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https://en.wikipedia.org/wiki/ATP1B1
Sodium/potassium-transporting ATPase subunit beta-1 is an enzyme that in humans is encoded by the ATP1B1 gene. The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, and to the subfamily of Na+/K+-ATPases. Na+/K+-ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+-ATPase is encoded by multiple genes. This gene encodes a beta 1 subunit. Alternatively spliced transcript variants encoding different isoforms have been identified. References Further reading External links
https://en.wikipedia.org/wiki/PRDM1
PR domain zinc finger protein 1, or B lymphocyte-induced maturation protein-1 (BLIMP-1), is a protein in humans encoded by the gene PRDM1 located on chromosome 6q21. BLIMP-1 is considered a 'master regulator' of hematopoietic stem cells, and plays a critical role in the development of plasma B cells, T cells, dendritic cells (DCs), macrophages, and osteoclasts. Pattern Recognition Receptors (PRRs) can activate BLIMP-1, both as a direct target and through downstream activation. BLIMP-1 is a transcription factor that triggers expression of many downstream signaling cascades. As a fine-tuned and contextual rheostat of the immune system, BLIMP-1 up- or down-regulates immune responses depending on the precise scenarios. BLIMP-1 is highly expressed in exhausted T-cells – clones of dysfunctional T-cells with diminished functions due to chronic immune response against cancer, viral infections, or organ transplant. Function As a potent repressor of beta-interferon (IFN-β), BLIMP-1 competes for interferon regulatory factors (IRF) binding sites in the IFN-β promoter due to its sequence similarity with IRF1 and IRF2. However, BLIMP-1 cools down and activates immune responses in a highly contextual manner. BLIMP-1 represses NFκB/TNF-R pathway repressor NLRP12, thus indirectly activating the immune response. BLIMP-1 expression is also upregulated by danger signals from double-stranded RNA (specific to virus), lipopolysaccharides (specific to gram-negative bacteria), unmethylated CpG DNA
https://en.wikipedia.org/wiki/LIMK2
LIM domain kinase 2 is an enzyme that in humans is encoded by the LIMK2 gene. Function There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. The protein encoded by this gene is phosphorylated and activated by ROCK, a downstream effector of Rho, and the encoded protein, in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. It is thought that this pathway contributes to Rho-induced reorganization of the actin cytoskeleton. At least three transcript variants encoding different isoforms have been found for this gene. References Further reading External links LIMK2 Info with links in the Cell Migration Gateway
https://en.wikipedia.org/wiki/NASP%20%28gene%29
Nuclear autoantigenic sperm protein is a protein that in humans is encoded by the NASP gene. Multiple isoforms are encoded by transcript variants of this gene. Function This gene encodes a histone H1 binding protein that is involved in transporting histones into the nucleus of dividing cells. The somatic form is expressed in all mitotic cells, is localized to the nucleus, and is coupled to the cell cycle. The testicular form is expressed in embryonic tissues, tumor cells, and the testis. In male germ cells, this protein is localized to the cytoplasm of primary spermatocytes, the nucleus of spermatids, and the periacrosomal region of mature spermatozoa. References Further reading Human proteins
https://en.wikipedia.org/wiki/NTHL1
Endonuclease III-like protein 1 is an enzyme that in humans is encoded by the NTHL1 gene. As reviewed by Li et al., NTHL1 is a bifunctional DNA glycosylase that has an associated beta-elimination activity. NTHL1 is usually involved in removing oxidative pyrimidine lesions through base excision repair. NTHL1 catalyses the first step in base excision repair. It cleaves the N-glycosylic bond between the damaged base and its associated sugar residue and then cleaves the phosphodiester bond 3' to the AP site, leaving a 3'-unsaturated aldehyde after beta-elimination and a 5'-phosphate at the termini of the repair gap. Low expression of NTHL1 is associated with initiation and development of astrocytoma. Low expression of NTHL1 is also found in follicular thyroid tumors. A germ line homozygous mutation in NTHL1 causes a cancer susceptibility syndrome similar to Lynch syndrome. References Further reading
https://en.wikipedia.org/wiki/PAX4
Paired box gene 4, also known as PAX4, is a protein which in humans is encoded by the PAX4 gene. Function This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The paired box gene 4 is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells. See also Pax genes Maturity onset diabetes of the young type 9 References Further reading External links Transcription factors
https://en.wikipedia.org/wiki/PDE4B
cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene. This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of cellular responses to extracellular signals, such as hormones, light, and neurotransmitters. The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes cAMP. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. Clinical relevance Altered activity of this protein has been associated with schizophrenia and bipolar disorder. PDE4B is believed to be the PDE4 subtype involved in the antipsychotic effects of PDE4 inhibitors such as rolipram. PDE4B is involved in dopamine-associated and stress-related behaviours. It has also recently been found to modulate cognition, as reduction in PDE4B activity improves memory and long-term plasticity in mouse models, possibly supporting further therapeutic applications. Inhibitors AN2728, a boron-containing drug candidate that as of 2015 was under development by Anacor Pharmaceuticals for the topical treatment of psoriasis and atopic dermatitis (atopic eczema). mainly acting on PDE4B. References Further reading
https://en.wikipedia.org/wiki/PDE6B
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the PDE6B gene. PDE6 is crucial in transmission and amplification of visual signal. The existence of this beta subunit is essential for normal PDE6 functioning. Mutations in this subunit are responsible for retinal degeneration such as retinitis pigmentosa or congenital stationary night blindness. Structure PDE6 is a protein complex located on the photoreceptor's outer segment, and plays an important role in the phototransduction cascade. There are two types of photoreceptors: cones and rods. The rod and cone PDE6 complexes have different structures. PDE6β together with PDE6α and two identical inhibitory subunits, PDE6γ, form the rod PDE6 holoenzyme while the cone PDE6 complex only consists of two identical PDE6α' catalytic subunits. PDE6β, one of the catalytic units in rod PDE6, is composed of three domains: two N-terminal GAF domains and one C-terminal catalytic domain. The non-catalytic GAF domains are responsible for cGMP binding. The C-terminal interacts with cell membrane by isoprenylation and S-carboxylmethylation. Function Absorption of photons by rhodopsin triggers a signal transduction cascade in rod photoreceptors. This phototransduction cascade leads to hydrolysis of cGMP by cGMP-phosphodiesterase (PDE) that closes cGMP-gated channels and hyperpolarizes the cell. PDE6β is necessary for the formation of a functional phosphodiesteras
https://en.wikipedia.org/wiki/PHKA2
Phosphorylase b kinase regulatory subunit alpha, liver isoform is an enzyme that in humans is encoded by the PHKA2 gene. References Further reading External links GeneReviews/NCBI/NIH/UW entry on Phosphorylase Kinase Deficiency, Glycogen Storage Disease Type IX EC 2.7.11
https://en.wikipedia.org/wiki/PIK3C3
Phosphatidylinositol 3-kinase catalytic subunit type 3 is an enzyme subunit that in humans is encoded by the PIK3C3 gene. It's a class III phosphoinositide 3-kinase. References Further reading
https://en.wikipedia.org/wiki/POLD1
The gene polymerase delta 1 (POLD1) encodes the large, POLD1/p125, catalytic subunit of the DNA polymerase delta (Polδ) complex. The Polδ enzyme is responsible for synthesizing the lagging strand of DNA, and has also been implicated in some activities at the leading strand (Figure 1). The POLD1/p125 subunit encodes both DNA polymerizing and exonuclease domains, which provide the protein an important second function in proofreading to ensure replication accuracy during DNA synthesis, and in a number of types of replication-linked DNA repair following DNA damage. Germline mutations impairing activity of POLD1 have been implicated in several types of hereditary cancer, in some sporadic cancers, and in a developmental syndrome of premature aging, Mandibular hypoplasia, Deafness, and Progeroid features and Lipodystrophy (MDPL/MDP syndrome). Studies of POLD1 emphasize the importance of maintaining genomic stability to limit tumorigenesis. It is currently unclear whether the enhanced tumorigenesis associated with POLD1 defects is the result of increased base substitutions or due to fork collapse and production of DNA double strand breaks (DSBs). Recent reviews have addressed important functions of POLD1 and Polδ. Discovery The first DNA polymerase, DNA polymerase I, was discovered by Arthur Kornberg and his colleagues in 1956, reviewed in. In 1976, Byrnes et al. discovered a third DNA polymerase activity in mammalian cells that was called polymerase delta (δ). It was purifie
https://en.wikipedia.org/wiki/PPP2R3A
Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha is an enzyme that in humans is encoded by the PPP2R3A gene. Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the alpha subfamily of regulatory subunit B''. Alternative splicing results in multiple transcript variants encoding different isoforms. Interactions PPP2R3A has been shown to interact with CDC6 and PPP2R4. References Further reading
https://en.wikipedia.org/wiki/PPP2R5D
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform is an enzyme that in humans is encoded by the PPP2R5D gene. Mutations in PPP2R5D cause Jordan's Syndrome. Function The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a delta isoform of the regulatory subunit B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. Interactions PPP2R5D has been shown to interact with: HAND2, PPP2CA, PPP2R1B, and liprin-alpha-1. References Further reading
https://en.wikipedia.org/wiki/Pregnancy-specific%20beta-1-glycoprotein%201
Pregnancy-specific beta-1-glycoprotein 1 (PSBG-1) also known as CD66f (Cluster of Differentiation 66f), is a protein that in humans is encoded by the PSG1 gene and is a member of the carcinoembryonic antigen (CEA) gene family. Pregnancy-specific glycoproteins (PSGs) are a complex consisting of carbohydrate and protein, which is present in the mammalian body specifically during pregnancy. This glycoprotein is the most abundant protein found in the maternal bloodstream during the later stages of pregnancy and it is of vital importance in fetal development. The PSG functions primarily as an immunomodulator to protect the growing fetus. Structure PSG is a member of the immunoglobulin (Ig) superfamily and contains four immunoglobulin domains. The complete isolation of certain glycoproteins, later classified as pregnancy-specific, within human blood serum occurred in the early 1980s, when experimental techniques like molecular cloning became common practice. The serum was being collected during the first trimester of pregnancy to test for other vital molecules that are present during pregnancy and it was in those samples that they were able to isolate the PSGs specifically and characterize their structure. PSGs have been studied extensively in multiple mammalian species; mammals including rodents, monkeys, elk, moose, cows, sheep, and humans. Mice are the primary subject in significant portion of PSG studies. Specific structure can vary between species regarding different su
https://en.wikipedia.org/wiki/RAB1A
Ras-related protein Rab-1A is a protein that in humans is encoded by the RAB1A gene. Interactions RAB1A has been shown to interact with: CHML, GOLGA2, GOLGA5, MICAL1 RABAC1, and CHM. References Further reading
https://en.wikipedia.org/wiki/SAG%20%28gene%29
S-arrestin is a protein that in humans is encoded by the SAG gene. Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. S-arrestin, also known as S-antigen, is a major soluble protein in photoreceptor cells that is involved in desensitization of the photoactivated transduction cascade. It is expressed in the retina and the pineal gland and inhibits coupling of rhodopsin to transducin in vitro. Additionally, S-arrestin is highly antigenic, and is capable of inducing experimental autoimmune uveoretinitis. Mutations in this gene have been associated with Oguchi disease, a rare autosomal recessive form of night blindness. References Further reading
https://en.wikipedia.org/wiki/SMARCC2
SWI/SNF complex subunit SMARCC2 is a protein that in humans is encoded by the SMARCC2 gene. Function The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and contains a predicted leucine zipper motif typical of many transcription factors. Two transcript variants encoding different isoforms have been found for this gene. Interactions SMARCC2 has been shown to interact with BAZ1B and SMARCA4. References Further reading External links
https://en.wikipedia.org/wiki/TFCP2
Alpha-globin transcription factor CP2 is a protein that in humans is encoded by the TFCP2 gene. TFCP2 is also called Late SV40 factor (LSF) and it is induced by well known oncogene AEG-1. LSF also acts as an oncogene in hepatocellular carcinoma. LSF enhances angiogenesis by transcriptionally up-regulating matrix metalloproteinase-9 (MMP9). Along with its main oncogene function in hepatocellular carcinoma (HCC) it plays multifaceted role in chemoresistance, epithelial-mesenchymal transition (EMT), allergic response, inflammation and Alzheimer's disease. The small molecule FQI1 (factor quinolinone inhibitor 1) prevents LSF from binding to HCC DNA which results in HCC cell death. Interactions TFCP2 has been shown to interact with APBB1 and RNF2. References Further reading Transcription factors
https://en.wikipedia.org/wiki/RAE1
mRNA export factor is a protein that in humans is encoded by the RAE1 gene. Mutations in the Schizosaccharomyces pombe Rae1 and Saccharomyces cerevisiae Gle2 genes have been shown to result in accumulation of poly(A)-containing mRNA in the nucleus, suggesting that the encoded proteins are involved in RNA export. The protein encoded by this gene is a homolog of yeast Rae1. It contains four WD40 motifs, and has been shown to localize to distinct foci in the nucleoplasm, to the nuclear rim, and to meshwork-like structures throughout the cytoplasm. This gene is thought to be involved in nucleocytoplasmic transport, and in directly or indirectly attaching cytoplasmic mRNPs to the cytoskeleton. Alternatively spliced transcript variants encoding the same protein have been found for this gene. Interactions RAE1 has been shown to interact with NUP98. References Further reading
https://en.wikipedia.org/wiki/PLCE1
Phospholipase C epsilon 1 (PLCE1) is an enzyme that in humans is encoded by the PLCE1 gene. This gene encodes a phospholipase enzyme (PLCE1) that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). Mutations in this gene cause early-onset nephrotic syndrome and have been associated with respiratory chain deficiency with diffuse mesangial sclerosis. Structure PLCE1 is located on the q arm of chromosome 10 in position 23.33 and has 39 exons. PLCE1, the protein encoded by this gene, is located on the Golgi apparatus, the cell membrane, and in the cytosol. It contains 3 turns, 15 beta strands, and 6 alpha helixes. PLCE1 contains a 260 amino acid Ras-GEF domain at p. 531-790, a 149 amino acid PI-PLC X-box domain at p. 1392-1540, a 117 amino acid PI-PLC Y-box domain at p. 1730 – 1846, a 101 amino acid C2 domain at p. 1856 – 1956, a 103 amino acid Ras-associating 1 domain at p. 2012 – 2114, and a 104 amino acid Ras-associating 2 domain at p. 2135 – 2238. There is a region of 79 amino acids from p. 1686 – 1764 that is required for PLCE1 to be activated by RHOA, RHOB, GNA12, GNA13 and G-beta gamma. PLCE1 also has a Ca2+ cofactor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Function PLCE1 belongs to the phospholipase family that catalyzes the hydrolysis of polyphosphoinositides such as phosphatidylinositol-4,5-bisphosphate (PtdIn
https://en.wikipedia.org/wiki/MBD3
Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the MBD3 gene. Function DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). However, unlike the other family members, MBD3 is not capable of binding to methylated DNA but instead binds to hydroxymethylated DNA. The predicted MBD3 protein shares 71% and 94% identity with MBD2 (isoform 1) and mouse Mbd3. MBD3 is a subunit of the NuRD, a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. MBD3 mediates the association of metastasis-associated protein 2 (MTA2) with the core histone deacetylase complex. MBD3 also contains the coiled‐coil domain common to all three MBD3 isoforms. The coiled‐coil domain, but not the MBD domain, helps to maintain pluripotency of embryonic stem cells via the recruitment of polycomb repressive complex 2 to a subset of genes linked to development and organogenesis, thus establishing stable transcriptional repression. Interactions MBD3 has been shown to interact with: AURKA, GATAD2B, HDAC1, MTA2, and MBD2. References Further reading Human proteins
https://en.wikipedia.org/wiki/TDP1
Tyrosyl-DNA phosphodiesterase 1 is an enzyme that in humans is encoded by the TDP1 gene. The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of Type I topoisomerase and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1). While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same isoform. References Further reading External links GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia with Axonal Neuropathy, Autosomal Recessive
https://en.wikipedia.org/wiki/DEFB103A
Beta-defensin 103 is a protein that in humans is encoded by the DEFB103A gene. Function Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 103B, which has broad spectrum antimicrobial activity and may play an important role in innate epithelial defense. In dogs, the product of the same genetic locus, β-Defensin 103, also plays a role in pigmentation, being an agonist of the melanocortin 1 receptor. References Further reading Defensins
https://en.wikipedia.org/wiki/SMURF1
E3 ubiquitin-protein ligase SMURF1 is an enzyme that in humans is encoded by the SMURF1 gene. The SMURF1 Gene encodes a protein with a size of 757 amino acids and the molecular mass of this protein is 86114 Da. Function Smad ubiquitination regulatory factor 1 (Smurf1) is part of a gene that encodes a ubiquitin ligase and is specific for receptor-regulated SMAD proteins in the bone morphogenetic protein (BMP) pathway. A similar protein in Xenopus is involved in embryonic pattern formation. Alternative splicing results in multiple transcript variants encoding different isoforms. An additional transcript variant has been identified, but its full length sequence has not been determined. HIV The inhibition of HIV-1 replication in HeLa P4/R5 cells can be achieved by siRNA-mediated knockdown of SMURF1. Cancer Breast SMURF1 and SMURF2 have shown to exhibit E3 ligase-dependent and E3 ligase-independent activities in a multitude of different cell types whereby smurfs can act as tumor promoters or tumor suppressors by regulating biological tumorigenesis-related processes. Recent research in breast cancer explains a relationship between SMURF1 and ER alpha (Estrogen receptor alpha) during breast cancer growth. Since ER alpha is expressed in most breast cancers and is attributed to contributing to the progression of estrogen-dependent cancer, it has been supported that the reduction of SMURF1 decreases the proliferation of ER alpha-positive cells in vitro and in vivo. Thus, it
https://en.wikipedia.org/wiki/CLEC7A
C-type lectin domain family 7 member A or Dectin-1 is a protein that in humans is encoded by the CLEC7A gene. CLEC7A is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with a partial immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid dendritic cells, monocytes, macrophages and B cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. Structure Dectin-1 is a transmembrane protein containing an immunoreceptor tyrosine-based activation (ITAM)-like motif in its intracellular tail (which is involved in cellular activation) and one C-type lectin-like domain (carbohydrate-recognition domain, CRD) in the extracellular region (which recognizes β-glucans and endogenous ligands on T cells). The CRD is separated from the membrane by a stalk region. CLEC7A contains putative sites of N-linked glycosylation in the stalk region. CLEC7A is expressed by macrophages, neutrophils and dendritic cells. Expression has also been studied on other imm
https://en.wikipedia.org/wiki/Carbonic%20anhydrase%204
Carbonic anhydrase 4 is an enzyme that in humans is encoded by the CA4 gene. Function Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA IV is a glycosylphosphatidyl-inositol-anchored membrane isozyme expressed on the luminal surfaces of pulmonary (and certain other) capillaries and of proximal renal tubules. Its exact function is not known, however, it may have a role in inherited renal abnormalities of bicarbonate transport. CA IV has been identified in pulmonary epithelium of many mammalian species and may be uniquely adaptive for gas exchange necessary for the high metabolic requirements of mammals. A majority of the produced by metabolism is transported as bicarbonate (). At the tissue capillary, diffuses from tissue to plasma. Other forms of carbonic anhydrase enzyme are not present in the plasma, restricting the equilibrium reaction of + = = H+ . in the plasma diffuses into the Red Blood Cell. CA is present within the Red Blood Cell, facilitating the conversion of to . so produced is transferred by the /Cl- "shuttle" from the interior of the Red Blood Cell to the plasma. does not
https://en.wikipedia.org/wiki/CAMK2D
Calcium/calmodulin-dependent protein kinase type II delta chain is an enzyme that in humans is encoded by the CAMK2D gene. The product of this gene belongs to the serine/threonine protein kinase family and to the Ca2+/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a delta chain. Four alternatively spliced transcript variants that encode three different isoforms have been characterized to date. Distinct isoforms of this chain have different expression patterns. References Further reading External links EC 2.7.11
https://en.wikipedia.org/wiki/USP7
Ubiquitin-specific-processing protease 7 (USP7), also known as ubiquitin carboxyl-terminal hydrolase 7 or herpesvirus-associated ubiquitin-specific protease (HAUSP), is an enzyme that in humans is encoded by the USP7 gene. Function Regulation of the p53 tumor suppressor USP7 or HAUSP is a ubiquitin specific protease or a deubiquitylating enzyme that cleaves ubiquitin from its substrates. Since ubiquitylation (polyubiquitination) is most commonly associated with the stability and degradation of cellular proteins, HAUSP activity generally stabilizes its substrate proteins. HAUSP is most popularly known as a direct antagonist of Mdm2, the E3 ubiquitin ligase for the tumor suppressor protein, p53. Normally, p53 levels are kept low in part due to Mdm2-mediated ubiquitylation and degradation of p53. In response to oncogenic insults, HAUSP can deubiquitinate p53 and protect p53 from Mdm2-mediated degradation, indicating that it may possess a tumor suppressor function for the immediate stabilization of p53 in response to stress. Another important role of HAUSP function involves the oncogenic stabilization of p53. Oncogenes such as Myc and E1A are thought to activate p53 through a p19 alternative reading frame (p19ARF, also called ARF)-dependent pathway, although some evidence suggests ARF is not essential in this process. A possibility is that HAUSP provides an alternative pathway for safeguarding the cell against oncogenic insults. Role in transcriptional regulation USP7
https://en.wikipedia.org/wiki/RDBP
Negative elongation factor E is a protein that in humans is encoded by the RDBP gene. Function The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC class III) region on chromosome 6. Interactions RDBP has been shown to interact with: Cofactor of BRCA1, TH1L, and WHSC2. References Further reading External links
https://en.wikipedia.org/wiki/Signal%20transducing%20adaptor%20molecule
Signal transducing adapter molecule 1 is a protein that in humans is encoded by the STAM gene. Function This gene was identified by the rapid tyrosine-phosphorylation of its product in response to cytokine stimulation. The encoded protein contains an SH3 domain and the immunoreceptor tyrosine-based activation motif (ITAM). This protein associates with JAK3 and JAK2 kinases via its ITAM region, and is phosphorylated by the JAK kinases upon cytokine stimulation, which suggests the function of this protein is as an adaptor molecule involved in the downstream signaling of cytokine receptors. HGS/HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) has been found to bind and counteract the function of this protein. STAM1 contains multiple amino acid sites that are phosphorylated and ubiquitinated. Interactions Signal transducing adaptor molecule has been shown to interact with HGS, Janus kinase 2. MAP3K1, STAMBP, and TIMM8A. References Further reading
https://en.wikipedia.org/wiki/STX7
Syntaxin-7 is a protein that in humans is encoded by the STX7 gene. In melanocytic cells STX7 gene expression may be regulated by MITF. Interactions STX7 has been shown to interact with STX8, VPS18, Vesicle-associated membrane protein 8 and VPS11. References Further reading
https://en.wikipedia.org/wiki/SOAT2
Sterol O-acyltransferase 2, also known as SOAT2, is an enzyme that in humans is encoded by the SOAT2 gene. Function This gene is a member of a small family of Acyl-CoA:cholesterol acyltransferases. The gene encodes a membrane-bound enzyme localized in the endoplasmic reticulum that produces intracellular cholesterol esters from long-chain fatty acyl CoA and cholesterol. The cholesterol esters are then stored as cytoplasmic lipid droplets inside the cell. The enzyme is implicated in cholesterol absorption in the intestine and in the assembly and secretion of apolipoprotein B-containing lipoproteins such as very-low-density lipoprotein (VLDL). Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. References Further reading
https://en.wikipedia.org/wiki/EIF3A
Eukaryotic translation initiation factor 3 subunit A (eIF3a) is a protein that in humans is encoded by the EIF3A gene. It is one of the subunits of Eukaryotic initiation factor 3 (eIF3) a multiprotein complex playing major roles in translation initiation in eukaryotes. Interactions EIF3A has been shown to interact with: DISC1, EIF3B, EIF3C, EIF3D, EIF3EIP, EIF3F, EIF3G, EIF3H, EIF3I EIF3J, EIF3K, EIF3S6, EIF4B, EIF4G2, and FBXO32. See also Eukaryotic initiation factor 3 (eIF3) References Further reading
https://en.wikipedia.org/wiki/TRIM24
Tripartite motif-containing 24 (TRIM24) also known as transcriptional intermediary factor 1α (TIF1α) is a protein that, in humans, is encoded by the TRIM24 gene. Function The protein encoded by this gene mediates transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors, including the estrogen, retinoic acid, and vitamin D3 receptors. The protein localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. The protein is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains – a RING, a B-box type 1 and a B-box type 2 – and a coiled-coil region. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. Interactions TRIM24 has been shown to interact with Mineralocorticoid receptor, TRIM33, Estrogen receptor alpha and Retinoid X receptor alpha. See also Transcription coregulator References Further reading External links Gene expression Transcription coregulators
https://en.wikipedia.org/wiki/SAP30
Sin3A-associated protein, 30kDa, also known as SAP30, is a protein which in humans is encoded by the SAP30 gene. Function Histone acetylation plays a key role in the regulation of eukaryotic gene expression. Histone acetylation and deacetylation are catalyzed by multisubunit complexes. The protein encoded by this gene is a component of the histone deacetylase complex, which includes SIN3A, SAP18, HDAC1, HDAC2, RbAp46, RbAp48, and other polypeptides. This complex is active in deacetylating core histone octamers, but inactive in deacetylating nucleosomal histones. A pseudogene of this gene is located on chromosome 3. Mammals have one paralog of SAP30, named SAP30-like (SAP30L), which shares 70% sequence identity with SAP30. SAP30 and SAP30L together constitute a well-conserved SAP30 protein family. Also SAP30L interacts with several components of the Sin3A corepressor complex and induces transcriptional repression via recruitment of Sin3A and histone deacetylases. Proteins of the SAP30 family (SAP30 proteins) have a functional nucleolar localization signal and they are able to target Sin3A to the nucleolus. SAP30 proteins have sequence-independent contact with DNA by their N-terminal zinc-dependent module and their acidic central region contributes to histone and nucleosome interactions. The DNA binding of SAP30 proteins is regulated by the nuclear signalling lipids, phosphoinositides (PI). SAP30 proteins provide the first example in which the DNA and PIs seem to stand in
https://en.wikipedia.org/wiki/SGCE
Epsilon-sarcoglycan is a protein that in humans is encoded by the SGCE gene. The SGCE gene encodes the epsilon member of the sarcoglycan family, transmembrane components of the dystrophin-glycoprotein complex, which links the cytoskeleton to the extracellular matrix.[supplied by OMIM] See also Myoclonic dystonia References Further reading External links GeneReviews/NIH/NCBI/UW entry on Myoclonus-Dystonia LOVD mutation database: SGCE
https://en.wikipedia.org/wiki/DOK2
Docking protein 2 is a protein that in humans is encoded by the DOK2 gene. Function The protein encoded by this gene is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the chronic phase. It may be a critical substrate for p210(bcr/abl), a chimeric protein whose presence is associated with CML. This encoded protein binds p120 (RasGAP) from CML cells. Interactions DOK2 has been shown to interact with INPP5D and TEK tyrosine kinase. References Further reading
https://en.wikipedia.org/wiki/SART1
U4/U6.U5 tri-snRNP-associated protein 1 is a protein that in humans is encoded by the SART1 gene. This gene encodes two proteins, the SART1(800) protein expressed in the nucleus of the majority of proliferating cells, and the SART1(259) protein expressed in the cytosol of epithelial cancers. The SART1(259) protein is translated by the mechanism of -1 frameshifting during posttranscriptional regulation. The two encoded proteins are thought to be involved in the regulation of proliferation. Both proteins have tumor-rejection antigens. The SART1(259) protein possesses tumor epitopes capable of inducing HLA-A2402-restricted cytotoxic T lymphocytes in cancer patients. This SART1(259) antigen may be useful in specific immunotherapy for cancer patients and may serve as a paradigmatic tool for the diagnosis and treatment of patients with atopy. The SART1(259) protein is found to be essential for the recruitment of the tri-snRNP to the pre-spliceosome in the spliceosome assembly pathway. References Further reading Spliceosome
https://en.wikipedia.org/wiki/PRPF3
U4/U6 small nuclear ribonucleoprotein Prp3 is a protein that in humans is encoded by the PRPF3 gene. Function The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. PRPF3 is one of several proteins that associate with U4 and U6 snRNPs.[supplied by OMIM] Interactions PRPF3 has been shown to interact with DVL3. References Further reading External links GeneReviews/NIH/NCBI/UW entry on Retinitis Pigmentosa Overview Spliceosome
https://en.wikipedia.org/wiki/CTDP1
RNA polymerase II subunit A C-terminal domain phosphatase is an enzyme that in humans is encoded by the CTDP1 gene. This gene encodes a protein which interacts with the carboxy-terminus of transcription initiation factor TFIIF, a transcription factor which regulates elongation as well as initiation by RNA polymerase II. The protein may also represent a component of an RNA polymerase II holoenzyme complex. Alternative splicing of this gene results in two transcript variants encoding 2 different isoforms. Interactions CTDP1 has been shown to interact with WD repeat-containing protein 77, GTF2F1 and POLR2A. References External links Further reading
https://en.wikipedia.org/wiki/NRXN1
Neurexin-1-alpha is a protein that in humans is encoded by the NRXN1 gene. Neurexins are a family of proteins that function in the vertebrate nervous system as cell adhesion molecules and receptors. They are encoded by several unlinked genes of which two, NRXN1 and NRXN3, are among the largest known human genes. Three of the genes (NRXN1-3) utilize two alternate promoters and include numerous alternatively spliced exons to generate thousands of distinct mRNA transcripts and protein isoforms. The majority of transcripts are produced from the upstream promoter and encode alpha-neurexin isoforms; a much smaller number of transcripts are produced from the downstream promoter and encode beta-neurexin isoforms. The alpha-neurexins contain epidermal growth factor-like (EGF-like) sequences and laminin G domains, and have been shown to interact with neurexophilins. The beta-neurexins lack EGF-like sequences and contain fewer laminin G domains than alpha-neurexins. Function Neurexins are presynaptic membrane cell-adhesion molecules that bind primarily to neuroligins, proteins that have been associated with autism. Autism is characterized by a wide range of social and cognitive deficits, which are partially attributed to faulty synaptic communication between neurons. This lack of communication is oftentimes tied to mutations in NRXN1. Structural variants of NRXN1a (neurexin1 alpha) are consistent with mutations predisposing autism. These alpha neurexins are involved in communication
https://en.wikipedia.org/wiki/EIF2AK3
Eukaryotic translation initiation factor 2-alpha kinase 3, also known as protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), is an enzyme that in humans is encoded by the EIF2AK3 gene. Function The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Clinical significance Patients with mutations in this gene develop Wolcott-Rallison syndrome. Interactions EIF2AK3 has been shown to interact with DNAJC3, NFE2L2, and endoplasmic reticulum chaperone BiP (Hsp70). Inhibitors GSK2606414 3-Fluoro-GSK2606414 References Further reading EC 2.7.11
https://en.wikipedia.org/wiki/MED24
Mediator of RNA polymerase II transcription subunit 24 is an enzyme that in humans is encoded by the MED24 gene. Function This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. Multiple transcript variants encoding different isoforms have been found for this gene. Interactions MED24 has been shown to interact with Estrogen receptor alpha, Cyclin-dependent kinase 8, Calcitriol receptor and BRCA1. References Further reading
https://en.wikipedia.org/wiki/ABCC5
Multidrug resistance-associated protein 5 is a protein that in humans is encoded by the ABCC5 gene. Function The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions in the cellular export of its substrate, cyclic nucleotides. This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. Studies show that this protein provides resistance to thiopurine anticancer drugs, 6-mercaptopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. This protein may be involved in resistance to thiopurines in acute lymphoblastic leukemia and antiretroviral nucleoside analogs in HIV-infected patients. Alternative splicing of this gene has been detected; however, the complete sequence and translation initiation site is unclear. Interactive pathway map See also ATP-binding cassette transporter References Further reading External links ATP-binding cassette transporters
https://en.wikipedia.org/wiki/DNM1L
Dynamin-1-like protein is a GTPase that regulates mitochondrial fission. In humans, dynamin-1-like protein, which is typically referred to as dynamin-related protein 1 (Drp1), is encoded by the DNM1L gene and is part of the dynamin superfamily (DSP) family of proteins. Structure Drp1, which is a member of the dynamin superfamily of proteins, consists of a GTPase and GTPase effector domain that are separated from each other by a helical segment of amino acids. There are 3 mouse and 6 human isoforms of Drp1, including a brain-specific variant. Drp1 exists as homooligomers and its function relies on its oligomerization ability. Function Mitochondria routinely undergo fission and fusion events that maintain a dynamic reticular network. Drp1 is a fundamental component of mitochondrial fission. Indeed, Drp1 deficient neurons have large, strongly interconnected mitochondria due to dysfunctional fission machinery. Fission helps facilitate mitophagy, which is the breakdown and recycling of damaged mitochondria. Dysfunction in the DRP activity may result in mutated DNA or malfunctioning proteins diffusing throughout the mitochondrial system. In addition, fission results in fragmented mitochondria more capable of producing of reactive oxygen species, which can disrupt normal biochemical processes inside of cells. ROS can be formed from incomplete transfer of electrons through the electron transport chain. Furthermore, fission influences calcium flux within the cell, linking Drp1
https://en.wikipedia.org/wiki/ACTR1A
Alpha-centractin (yeast) or ARP1 is a protein that in humans is encoded by the ACTR1A gene. Function This gene encodes a 42.6 kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 8-13 copies per dynactin molecule, and is the most abundant molecule in the dynactin complex. It is an actin-related protein, and is approximately 60% identical at the amino acid level to conventional actin. ARP1 forms a 37 nm filament-like structure and is the core of the dynactin complex. It only exists in the dynactin complex in vivo. Highly purified, native Arp1 polymerize rapidly at extremely low concentrations into short filaments in vitro that were similar, but not identical, in length to those in dynactin. With time, these Arp1 filaments appeared to anneal to form longer assemblies but never attained the length of conventional actin filaments. As for conventional actin, Arp1 can bind and hydrolyze ATP, and Arp1 assembly is accompanied by nucleotide hydrolysis. It has been reported that Arp1 interacts with other dynactin components including DCTN1/p150Glued, DCTN4/p62 and Actr10/Arp11. Arp1 has been shown as the domain for dyna
https://en.wikipedia.org/wiki/STX6
Syntaxin-6 is a protein that in humans is encoded by the STX6 gene. Interactions STX6 has been shown to interact with SNAP23, VAMP3 and VAMP4. N terminal protein domain The protein domain Syntaxin 6 N terminal protein domain is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) found in endosomal transport vesicles. It is part of the family, of target SNAREs (t-SNAREs). It is a vital aid to exporting and importing cell cargo through a process called cell trafficking. Its SNARE motif shows significant homology to both syntaxin 1a and S25C, indicating similarity through evolutionary conservation. The structure of the syntaxin 6 N-terminal domain shows strong structural similarity with the N-terminal domains of syntaxin 1a, Sso1p, and Vam3p; despite a very low level of sequence similarity. SNARE functions essentially as a tether to hold the vesicle. The cytoplasmic regions of SNARE found on transport vesicles and target membranes interact, then a four-helix coiled coil forms. This links the cell membrane and vesicles together in such a way that it overcomes the energetic barrier to fusing two lipid bilayers. This is the way cell cargo is exchanged. This particular entry focuses on the N-terminal domain of Syntaxin 6. Structure Members of this entry, which are found in the amino terminus of various SNARE proteins, adopt a structure consisting of an antiparallel three-helix bundle. Their exact function has not been determined, though it is kn
https://en.wikipedia.org/wiki/NDEL1
Nuclear distribution protein nudE-like 1 is a protein that in humans is encoded by the NDEL1 gene. This gene encodes a thiol-activated oligopeptidase that is phosphorylated in M phase of the cell cycle. Phosphorylation regulates the cell cycle-dependent distribution of this protein, with a fraction of the protein bound strongly to centrosomes in interphase and localized to mitotic spindles in early M phase. Overall, this protein plays a role in nervous system development. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. Interactions NDEL1 has been shown to interact with Cyclin-dependent kinase 5, YWHAE, PAFAH1B1 and DISC1. References Further reading Human proteins
https://en.wikipedia.org/wiki/JAM3
Junctional adhesion molecule C is a protein that in humans is encoded by the JAM3 gene. Gene This gene is located on the long arm of chromosome 11 (11q25) on the Watson strand. It is 83,077 bases in length. The encoded protein is 310 amino acids long with a predicted molecular weight of 35.02 kiloDaltons. Function Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. The protein encoded by this immunoglobulin superfamily gene member is localized in the tight junctions between high endothelial cells. Unlike other proteins in this family, this protein is unable to adhere to leukocyte cell lines and only forms weak homotypic interactions. The encoded protein is a member of the junctional adhesion molecule protein family and acts as a receptor for another member of this family. Interactions JAM3 has been shown to interact with PARD3. Clinical significance Loss-of-function mutations in this gene cause a rare syndrome - autosomal recessive hemorrhagic destruction of the brain, subependymal calcification and congenital cataracts. References Further reading
https://en.wikipedia.org/wiki/ALCAM
CD166 antigen is a 100-105 kD typeI transmembrane glycoprotein that is a member of the immunoglobulin superfamily of proteins. In humans it is encoded by the ALCAM gene. It is also called CD166 (cluster of differentiation 166), MEMD, SC-1/DM-GRASP/BEN in the chicken, and KG-CAM in the rat. Some literature sources have also cited it as the CD6 ligand (CD6L). It is expressed on activated T cells, activated monocytes, epithelial cells, fibroblasts, neurons, melanoma cells, and also in sweat and sebaceous glands. CD166 protein expression is reported to be upregulated in a cell line deriving from a metastasizing melanoma. CD166 plays an important role in mediating adhesion interactions between thymic epithelial cells and CD6+ cells during intrathymic T cell development. Recently, CD166 has also been used as a potential cancer stem cell marker. References Further reading External links Clusters of differentiation
https://en.wikipedia.org/wiki/CHD4
Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the CHD4 gene. CHD4 is the core nucleosome-remodelling component of the Nucleosome Remodelling and Deacetylase (NuRD) complex. Function The product of this gene belongs to the SNF2/RAD54 helicase family. It represents the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Patients with dermatomyositis develop antibodies against this protein. Interactions CHD4 has been shown to interact with HDAC1, Histone deacetylase 2, MTA2, SATB1 and Ataxia telangiectasia and Rad3 related. Clinical Mutations in this gene have been associated with a condition known as Sifrim-Hitz-Weiss syndrome. This condition is characterized by Brain anomalies Macrocephaly Deafness Ophthalmic abnormalities Dysmorphic features Congenital heart defects Hypogonadism in males Skeletal and limb anomalies Global developmental delay Mild to moderate intellectual disability References External links Further reading
https://en.wikipedia.org/wiki/COPA%20%28gene%29
Coatomer subunit alpha is a protein that in humans is encoded by the COPA gene. Function In eukaryotic cells, protein transport between the endoplasmic reticulum and Golgi compartments is mediated in part by non-clathrin-coated vesicular coat proteins (COPs). Seven coat proteins have been identified, and they represent subunits of a complex known as coatomer. The subunits are designated alpha-COP, beta-COP, beta-prime-COP, gamma-COP, delta-COP, epsilon-COP, and zeta-COP. The alpha-COP, encoded by COPA, shares high sequence similarity with RET1, the homologous alpha subunit of the coatomer complex in yeast. Also, the N-terminal 25 amino acids of alpha-COP encode the bioactive peptide, xenin, which stimulates exocrine pancreatic secretion and may act as a gastrointestinal hormone. Alternative splicing results in multiple splice forms encoding distinct isoforms. Interactions COPA (gene) has been shown to interact with COPE and COPB1. References External links Further reading
https://en.wikipedia.org/wiki/CLDN7
Claudin-7 is a protein that in humans is encoded by the CLDN7 gene. It belongs to the group of claudins. Claudins, such as CLDN7, are involved in the formation of tight junctions between epithelial cells. Tight junctions restrict lateral diffusion of lipids and membrane proteins, and thereby physically define the border between the apical and basolateral compartments of epithelial cells (Zheng et al., 2003).[supplied by OMIM] References External links Further reading
https://en.wikipedia.org/wiki/Cathepsin%20H
Cathepsin H is a protein that in humans is encoded by the CTSH gene. The protein encoded by this gene is a cysteine cathepsin, a lysosomal cysteine protease important in the overall degradation of lysosomal proteins. It is composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. The encoded protein, which belongs to the peptidase C1 protein family, can act both as an aminopeptidase and as an endopeptidase. Increased expression of this gene has been correlated with malignant progression of prostate tumors. Two transcript variants encoding different isoforms have been found for this gene. References Further reading External links The MEROPS online database for peptidases and their inhibitors: C01.040 Proteases EC 3.4.22 Cathepsins
https://en.wikipedia.org/wiki/CYP2C18
Cytochrome P450 2C18 is a protein that in humans is encoded by the CYP2C18 gene. Function This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum but its specific substrate has not yet been determined. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. An additional gene, CYP2C17, was once thought to exist; however, CYP4217 is now considered an artefact based on a chimera of CYP2C18 and CYP2C19. CYP2C18 also possesses epoxygenase activity: it can attack various long-chain polyunsaturated fatty acids at their double (i.e. alkene) bonds to form epoxide products that act as signaling agents. It metabolizes: 1) arachidonic acid to various epoxyeicosatrienoic acids (also termed EETs); 2) linoleic acid to 9,10-epoxy octadecenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); 3) docosahexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and 4) eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs). While CYP2C19, CYP2C8, CYP2C9, CYP2J2, and possibly CYP2S1 are the main producers of EETs and, very likely EEQs, EDPs, and the epoxides of linoleic
https://en.wikipedia.org/wiki/DMP1
Dentin matrix acidic phosphoprotein 1 is a protein that in humans is encoded by the DMP1 gene. Dentin matrix acidic phosphoprotein is an extracellular matrix protein and a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family (other members being DSPP, IBSP, MEPE, and SPP1). This protein, which is critical for proper mineralization of bone and dentin, is present in diverse cells of bone and tooth tissues. The protein contains a large number of acidic domains, multiple phosphorylation sites, a functional arg-gly-asp cell attachment sequence, and a DNA binding domain. In undifferentiated osteoblasts it is primarily a nuclear protein that regulates the expression of osteoblast-specific genes. During osteoblast maturation the protein becomes phosphorylated and is exported to the extracellular matrix, where it orchestrates mineralized matrix formation. Mutations in the gene are known to cause autosomal recessive hypophosphatemia, a disease that manifests as rickets and osteomalacia. The gene structure is conserved in mammals. Two transcript variants encoding different isoforms have been described for this gene. References Cell Cycle-Dependent Nuclear Localization of DMP1 J.O. MANCERA1, T. JHALA2, S. WANG2, C. QIN2, R. D'SOUZA2, and Y. LU2, 1School of Dentistry, Meharry Medical College, Nashville, TN, 2Department of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, Dallas, TX Further reading Extracellular matrix pro
https://en.wikipedia.org/wiki/DYNC1H1
Cytoplasmic dynein 1 heavy chain 1 is a protein that in humans is encoded by the DYNC1H1 gene. Interactions DYNC1H1 has been shown to interact with PAFAH1B1 and CDC5L. Clinical relevance Mutations in this gene have been shown to cause dominant axonal Charcot-Marie-Tooth disease as well as spinal muscular atrophy with lower extremity predominance 1 (SMA-LED1). References Further reading External links
https://en.wikipedia.org/wiki/EEF1G
Elongation factor 1-gamma is a protein that in humans is encoded by the EEF1G gene. Function This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit contains an N-terminal glutathione transferase domain, which may be involved in regulating the assembly of multisubunit complexes containing this elongation factor and aminoacyl-tRNA synthetases. Interactions EEF1G has been shown to interact with: EEF1B2, EEF1D, HARS, LZTS1, LARS, and RECQL5. References Further reading
https://en.wikipedia.org/wiki/HuD%20%28protein%29
HuD otherwise known as ELAV-like protein 4 is a protein that in humans is encoded by the ELAVL4 gene. The HuD/ELAVL4 protein is an RNA-binding protein. HuD contains three RRM protein domains, enabling RNA binding. HuD is expressed only in neurons and it binds to AU-rich element-containing mRNAs. As a result of this interaction the half-life of the transcript is increased. HuD is important in neurons during brain development and plasticity. Interactions HuD (protein) has been shown to interact with NXF1. References Further reading
https://en.wikipedia.org/wiki/EPHA8
Ephrin type-A receptor 8 is a protein that in humans is encoded by the EPHA8 gene. Function This gene encodes a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. The protein encoded by this gene functions as a receptor for ephrin A2, A3 and A5 and plays a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system. Interactions EPHA8 has been shown to interact with FYN. References Further reading Tyrosine kinase receptors
https://en.wikipedia.org/wiki/ERV3
HERV-R_7q21.2 provirus ancestral envelope (Env) polyprotein is a protein that in humans is encoded by the ERV3 gene. Function The human genome includes many retroelements including the human endogenous retroviruses (HERVs), which compose about 7-8% of the human genome. ERV3, one of the most studied HERVs, is thought to have integrated 30 to 40 million years ago and is present in higher primates with the exception of gorillas. Taken together, the observation of genome conservation, the detection of transcript expression, and the presence of conserved ORFs is circumstantial evidence for a functional role. Similar endogenous retroviral Env genes like syncytin-1 have important roles in placental formation and embryonic development by enabling cell-cell fusion. Despite its origin as an Env gene, ERV3 has a premature stop codon that precludes any cell-cell fusion functionality. However, it does have an immunosuppressive function that helps the fetus evade a damaging maternal immune response, which may explain its high expression in the placenta. There is speculation that ERV3 originally did have cell-cell fusion functionality in the placenta, but that it was eventually supplanted by other Env genes like syncytin, leading to a loss of this function. Another functional role is suggested by the observation that downregulation of ERV3 is reported in choriocarcinoma. References Further reading External links Transcription factors
https://en.wikipedia.org/wiki/MECOM
MDS1 and EVI1 complex locus protein EVI1 (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or positive regulatory domain zinc finger protein 3 (PRDM3) is a protein that in humans is encoded by the MECOM gene. EVI1 was first identified as a common retroviral integration site in AKXD murine myeloid tumors. It has since been identified in a plethora of other organisms, and seems to play a relatively conserved developmental role in embryogenesis. EVI1 is a nuclear transcription factor involved in many signaling pathways for both coexpression and coactivation of cell cycle genes. Gene structure The EVI1 gene is located in the human genome on chromosome 3 (3q26.2). The gene spans 60 kilobases and encodes 16 exons, 10 of which are protein-coding. The first in-frame ATG start codon is in exon 3. mRNA A large number of transcript variations exist, encoding different isoforms or chimeric proteins. Some of the most common ones are: EVI_1a, EVI_1b, EVI_1c, EVI_1d, and EVI_3L are all variants in the 5' untranslated region, and all except EVI_1a are specific to human cells. −Rp9 variant is quite common in human and mouse cells, lacks 9 amino acids in the repression domain. Δ324 found at low levels in human and mouse cells - an alternative splice variant encoding an 88kDa protein lacking zinc fingers 6 and 7 Δ105 variant is unique to mice, and results in a protein truncated by 105 amino acids at the acidic C-terminus. Fusion transcripts with upstream
https://en.wikipedia.org/wiki/FABP1
FABP1 is a human gene coding for the protein product FABP1 (Fatty Acid-Binding Protein 1). It is also frequently known as liver-type fatty acid-binding protein (LFABP). FABP1 is primarily expressed in the liver where it is involved in the binding, transport and metabolism of long-chain fatty acids (LCFAs), endocannabinoids, phytocannabinoids (and less so for synthetic cannabinoid receptor (CBR) agonists and antagonists) and other hydrophobic molecules. Altered expression of the protein has been linked to metabolic conditions including obesity. Discovery The fatty acid-binding proteins (FABPs) were initially discovered in 1972 with experiments using 14C labelled oleate to identify the presence of a soluble fatty acid carrier in the enterocyte responsible for intestinal absorption of (LCFAs). Since then, ten members of the FABP family have been identified on the human genome. Nine are well established (FABP1-9) with a recently discovered tenth (FABP12). Each FABP corresponds to particular organs/tissue around the body where they play a role in fatty-acid uptake, transport and metabolism. Gene location The human FABP1 gene is located on the short (p) arm of chromosome 2 from base pair 88,122,982 to base pair 88,128,131. Protein structure FABP1 has been found to have a unique structure compared to other members of the FABP family, allowing it to bind multiple ligands simultaneously. It also has a larger solvent-accessible core compared to other FABPs allowing more dive
https://en.wikipedia.org/wiki/FABP5
Fatty acid-binding protein, epidermal is a protein that in humans is encoded by the FABP5 gene. Function This gene encodes the fatty acid binding protein found in epidermal cells, and was first identified as being upregulated in psoriasis tissue. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism. The phytocannabinoids (THC and CBD) inhibit endocannabinoid anandamide (AEA) uptake by targeting FABP5, and competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids. Results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis. Interactions FABP5 has been shown to interact with S100A7. References Further reading
https://en.wikipedia.org/wiki/FOXM1
Forkhead box protein M1 is a protein that in humans is encoded by the FOXM1 gene. The protein encoded by this gene is a member of the FOX family of transcription factors. Its potential as a target for future cancer treatments led to it being designated the 2010 Molecule of the Year. Function FOXM1 is known to play a key role in cell cycle progression where endogenous FOXM1 expression peaks at S and G2/M phases. FOXM1-null mouse embryos were neonatal lethal as a result of the development of polyploid cardiomyocytes and hepatocytes, highlighting the role of FOXM1 in mitotic division. More recently a study using transgenic/knockout mouse embryonic fibroblasts and human osteosarcoma cells (U2OS) has shown that FOXM1 regulates expression of a large array of G2/M-specific genes, such as Plk1, cyclin B2, Nek2 and CENPF, and plays an important role in maintenance of chromosomal segregation and genomic stability. Cancer link FOXM1 gene is now known as a human proto-oncogene. Abnormal upregulation of FOXM1 is involved in the oncogenesis of basal cell carcinoma, the most common human cancer worldwide. FOXM1 upregulation was subsequently found in the majority of solid human cancers including liver, breast, lung, prostate, cervix of uterus, colon, and brain. Isoforms There are three FOXM1 isoforms in humans, A, B and C. Isoform FOXM1A has been shown to be a gene transcriptional repressor whereas the remaining isoforms (B and C) are both transcriptional activators. Hence, it is no
https://en.wikipedia.org/wiki/TNIP1
TNFAIP3-interacting protein 1, also known as ABIN-1, is a protein that in humans is encoded by the TNIP1 gene. Association with autoimmune diseases Genetic variations within the region of the TNIP1 gene have been shown to have association with several autoimmune diseases: Systemic Sclerosis; Psoriasis; Psoriatic arthritis; Systemic Lupus Erythematosus Type-1 autoimmune hepatitis Lupus nephritis TNIP1 dysfunction or deficiency contributes to hyperinflammarion and may predispose healthy cells to the inflammatory response to otherwise innocuous TLR ligand exposure. Association with neurodegenerative diseases A recent genome-wide association study (GWAS) has found that genetic variations in TNIP1 are associated with late-onset sporadic Alzheimer’s disease (LOAD). Interactions TNIP1 contains multiple amino acid sites that are phosphorylated and ubiquitinated, and has been shown to interact with TNFAIP3, MAP3K1, and MAPK1. Regulation TNIP1 was shown to be part of a transcription module controlled by BCL3. BCL3 gen was found to be strongly associated with Aβ42 after conditioning for APOE and was found as upregulated in the brain of patients with LOAD. References Further reading External links
https://en.wikipedia.org/wiki/Tubulin%20beta-4B%20chain
Tubulin beta-4B chain formerly known as tubulin beta-2C chain is a protein that in humans is encoded by the TUBB4B gene. References Further reading External links
https://en.wikipedia.org/wiki/SEMA4D
Semaphorin-4D (SEMA4D) also known as Cluster of Differentiation 100 (CD100), is a protein of the semaphorin family that in humans is encoded by the SEMA4D gene. Function Semaphorin 4D (Sema 4D) is an axon guidance molecule which is secreted by oligodendrocytes and induces growth cone collapse in the central nervous system. By binding plexin B1 receptor it functions as an R-Ras GTPase-activating protein (GAP) and repels axon growth cones in both the mature central nervous system. In the immune system, CD100 binds CD72 to activate B cells and dendritic cells, though much about this interaction is still under investigation. During skin damage repairs, SEMA4D interacts with Plexin B2 on Gamma delta T cells to play a role in the healing process. See also Cluster of differentiation References Further reading External links Clusters of differentiation
https://en.wikipedia.org/wiki/Ubiquitin%20D
Ubiquitin D is a protein that in humans is encoded by the UBD gene, also known as FAT10. UBD acts like ubiquitin, by covalently modifying proteins and tagging them for destruction in the proteasome. Ubiquitin Ubiquitin is a protein composed of 76 amino acids. In order for ubiquitin to bind to other proteins, it must go through an activation process by E1, an ATP-dependent ubiquitin activating enzyme. The carboxyl terminal (C-terminus) of ubiquitin is linked to the cysteine residue of the E1 protein by a high energy thioester linkage and activated. This reaction requires ATP and proceeds through a covalent AMP-ubiquitin intermediate. Importance of Ubiquitin Proteolysis in cells is an essential process to prevent the production of unwanted or abnormal proteins. During protein degradation, the process in which proteolytic enzymes act in an ATP-dependent manner mainly occurs in the degradation of substrate proteins with short half-lives. In particular, in eukaryotic cells, the proteolysis process by the binding of ubiquitin composed of 76 amino acids plays an important role in regulating the half-life and function of proteins. Ubiquitin-binding E1, E2, and E3 enzymes E1, E2 proteins and E3 enzymes are essential for attaching ubiquitin to matrix proteins. Among them, only one type of E1 protein exists in an individual, and it is known that the number is the highest. About a dozen E2 proteins are known to exist in yeast as transfer proteins that transfer ubiquitin from E1 t
https://en.wikipedia.org/wiki/GNLY
Granulysin (GNLY) is a protein expressed in most mammals which functions as an antimicrobial peptide released by killer lymphocytes in cytotoxic granules. It is a pore-forming peptide, as it can puncture a microbial cell wall, allowing for other death-inducing enzymes to enter the microbe and cause microptosis. GNLY is inhibited by cholesterol, and is most effective in helping to kill cholesterol-deficient microbes. It is part of the saponin-like protein family, and its gene is found on the 2nd chromosome in humans. It is distinguished by its 5 α-helical structure. Its expression is restricted to cytotoxic immune cells such as cytotoxic T cells, NK cells, NKT cells and γδ T cells. Orthologs of this protein are found in most mammal species, such as in cows and pigs, however not in rodents. Granulysin is also an active player in many diseases, including Leprosy and Toxic Epidermal Necrolysis. Structure Granulysin has a five alpha-helix structure, and is part of the saposin-like protein family. It is expressed in 2 forms: a 15kDa precursor protein, the translation product, and a 9kDa cytotoxic protein, which is formed after cleavage of the amino and carbonyl ends of the 15kDa protein. The 15 kDa form consists of 145 amino acids, and is an inactive protein. It exists in its own granule after translation, and release of the protein is triggered by Protein Kinase C (PKC). Its C- and N-Termini function to properly direct the molecule to cytotoxic granules, and are subsequently
https://en.wikipedia.org/wiki/STAMBP
STAM-binding protein is a protein that in humans is encoded by the STAMBP gene. Function Cytokine-mediated signal transduction in the JAK-STAT cascade requires the involvement of adaptor molecules. One such signal-transducing adaptor molecule contains an SH3 domain that is required for induction of MYC and cell growth. The protein encoded by this gene binds to the SH3 domain of the signal-transducing adaptor molecule, and plays a critical role in cytokine-mediated signaling for MYC induction and cell cycle progression. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. Mutations in this gene have been associated to cases of microcephaly (doi:10.1038/ng.2602) Interactions STAMBP has been shown to interact with RNF11, Signal transducing adaptor molecule and GRAP2. References Further reading
https://en.wikipedia.org/wiki/GADD45G
Growth arrest and DNA-damage-inducible protein GADD45 gamma is a protein that in humans is encoded by the GADD45G gene on chromosome 9. GADD45G is also known as CR6, DDIT2, GRP17, OIG37, and GADD45gamma. GADD45G is involved in several different processes, including sexual development, human-specific brain development, tumor suppression, and the cellular stress response. GADD45G interacts with several other proteins that are involved in DNA repair, cell cycle control, apoptosis, and senescence. Low expression of GADD45G has been associated with many types of cancer. History GADD45G was originally cloned by Beadling under the name CR6 in 1993. In this experiment, several genes including GADD45G were noted for being induced by IL-2, and they were identified as immediate early response genes in T lymphocytes. Its role as a tumor suppressor was discovered in 1999 by Zhang. It received the name OIG37 from Nakayama due to its regulation by Oncostatin M, which was found to be able to inhibit growth. Finally, it also became known as Gadd-related protein 17 during its isolation from a cDNA library by Suzuki due to its homology with Gadd45. Structure and function GADD45G is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. GADD45G is in tu
https://en.wikipedia.org/wiki/MORF4L1
Mortality factor 4-like protein 1 is a protein that in humans is encoded by the MORF4L1 gene. Interactions MORF4L1 has been shown to interact with MYST1, Retinoblastoma protein and MRFAP1. References Further reading
https://en.wikipedia.org/wiki/AMFR
Autocrine motility factor receptor, isoform 2 is a protein that in humans is encoded by the AMFR gene. Autocrine motility factor is a tumor motility-stimulating protein secreted by tumor cells. The protein encoded by this gene is a glycosylated transmembrane protein and a receptor for autocrine motility factor. The receptor, which shows some sequence similarity to tumor protein p53, is localized to the leading and trailing edges of carcinoma cells. Model organisms Model organisms have been used in the study of AMFR function. A conditional knockout mouse line, called Amfrtm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty six tests were carried out on mutant mice and one significant abnormality was observed: Fewer than expected homozygous mutant mice survived until weaning. Interactions AMFR has been shown to interact with Valosin-containing protein. References External links Further reading Genes mutated in mice
https://en.wikipedia.org/wiki/APBA2
Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the APBA2 gene. Structure This protein has phosphotyrosine-binding domain (PTB domain or PID) in the middle and two PDZ domains at C-terminal. Function The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adaptor protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilises APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. Interactions APBA2 has been shown to interact with CLSTN1, RELA and amyloid precursor protein. References External links Further reading
https://en.wikipedia.org/wiki/Growth%20hormone%202
Growth hormone 2 (GH2), also known more commonly as placental growth hormone (PGH) or growth hormone variant (GH-V), is a protein that in humans is encoded by the GH2 gene. It is produced by and secreted from the placenta during pregnancy, and becomes the predominant form of growth hormone (GH) in the body during this time. Its cogener is growth hormone 1 (GH1), or pituitary growth hormone. The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones, playing an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17, where they are interspersed in the same transcriptional orientation; an arrangement that is thought to have evolved through a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and the potential for specialization. As in the case of its pituitary counterpart, growth hormone 1, the predominant isoform of this particular family member shows similar somatogenic activity with reduced lactogenic activity. Mutations in this gene lead to placental growth hormone/lactogen deficiency. See also Growth hormone Somatotropin family References Further reading External links Hormones of the pregnant female Hormones of the somatotropic axis
https://en.wikipedia.org/wiki/GJA4
Gap junction alpha-4 protein, also known as Connexin-37 or Cx37, is a protein that in humans is encoded by the GJA4 gene. This protein, like other Connexin proteins, forms connections between cells known as gap junctions. Connexin 37 can be found in many tissues including the ovary, heart, and kidney. References Further reading Connexins
https://en.wikipedia.org/wiki/Glypican%201
Glypican-1 (GPC1) is a protein that in humans is encoded by the GPC1 gene. GPC1 is encoded by human GPC1 gene located at 2q37.3. GPC1 contains 558 amino acids with three predicted heparan sulfate chains. Function Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with three heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. Interactions Glypican 1 has been shown to interact with SLIT2. Clinical significance This protein is involved in the misfolding of normal prion proteins in the cell membrane to the infectious prion form. In 2015 it was reported that the presence of this protein in exosomes in patients' blood is able to detect early pancreatic cancer with absolute specificity and sensitivity. However this conclusion is disputed. and in more recent overviews of potential markers for pancreatic cancer, Glypican 1 is not mentioned. Antibodies against GPC1 have been developed. GPC1 has been evaluated as a potential target for cancer therapy, including antibody-drug conjugates, CAR-T cell therapy, radiotherapy, bispecific T cell engager and immunotoxins in preclinical studies.  HM2 is a mouse monoclonal antibody targeting the C-terminal region of GPC1 developed by the labora
https://en.wikipedia.org/wiki/BRF1%20%28gene%29
Transcription factor IIIB 90 kDa subunit is a protein that in humans is encoded by the BRF1 gene. Function This gene encodes one of the three subunits of the RNA polymerase III transcription factor complex. This complex plays a central role in transcription initiation by RNA polymerase III on genes encoding tRNA, 5S rRNA, and other small structural RNAs. The gene product belongs to the TF2B family. Three alternatively spliced variants encoding three different isoforms, that function at different promoters transcribed by RNA polymerase III, have been identified. A transcript encoding a fourth isoform has not yet been completely characterized. Interactions BRF1 (gene) has been shown to interact with: RB1, RBL1, RBL2, and TBP References Further reading External links
https://en.wikipedia.org/wiki/HIST1H1B
Histone H1.5 is a protein that in humans is encoded by the HIST1H1B gene. Histones are basic nuclear proteins responsible for nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a member of the histone H1 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the small histone gene cluster on chromosome 6p22-p21.3. References Further reading
https://en.wikipedia.org/wiki/Hemoglobin%20subunit%20zeta
Hemoglobin subunit zeta is a protein that in humans is encoded by the HBZ gene. Zeta-globin is an alpha-like hemoglobin. The zeta-globin polypeptide is synthesized in the yolk sac of the early embryo, while alpha-globin is produced throughout fetal and adult life. The zeta-globin gene is a member of the human alpha-globin gene cluster that includes five functional genes and two pseudogenes. The order of genes is: 5' - zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta1 - 3'. References Further reading Hemoglobins
https://en.wikipedia.org/wiki/HDLBP
Vigilin is a 110 kDa protein that in humans is encoded by the HDLBP gene. References Further reading
https://en.wikipedia.org/wiki/HMOX2
Heme oxygenase 2 is an enzyme that in humans is encoded by the HMOX2 gene. Function Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 (this enzyme) belong to the heme oxygenase family. References Further reading
https://en.wikipedia.org/wiki/HOXB5
Homeobox protein Hox-B5 is a protein that in humans is encoded by the HOXB5 gene. Function This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in lung and gut development. Increased expression of this gene is associated with a distinct biologic subset of acute myeloid leukemia (AML) and the occurrence of bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM) tissue. See also Homeobox References Further reading External links Transcription factors
https://en.wikipedia.org/wiki/DNAJA1
DnaJ homolog subfamily A member 1 is a protein that in humans is encoded by the DNAJA1 gene. Interactions DNAJA1 has been shown to interact with PTTG1. References Further reading Heat shock proteins
https://en.wikipedia.org/wiki/HSPB2
Heat shock protein beta-2 is a protein that in humans is encoded by the HSPB2 gene. Interactions HSPB2 has been shown to interact with: CRYAB, HSPB8, Myotonic dystrophy protein kinase and TRAF6. References Further reading
https://en.wikipedia.org/wiki/IGHM
Ig mu chain C region is a protein that in humans is encoded by the IGHM gene. It is associated with agammaglobulinemia-1. References Further reading Proteins Antibodies
https://en.wikipedia.org/wiki/IGSF1
Immunoglobulin superfamily, member 1 is a plasma membrane glycoprotein encoded by the IGSF1 gene, which maps to the X chromosome in humans and other mammalian species. Function IGSF1's function in normal cells is unresolved. The protein is a member of the immunoglobulin (Ig) superfamily. It was predicted to contain 12 Ig loops, a transmembrane domain, and a short cytoplasmic tail. However, during translation of the protein, it is cleaved into amino- and carboxy-terminal domains (NTD and CTD, respectively). Only the CTD is trafficked to the plasma membrane. The NTD is trapped within the endoplasmic reticulum (ER). Pathogenic mutations in the IGSF1 gene block the transport of the CTD to the plasma membrane. Clinical relevance Mutations in IGSF1 cause a condition called IGSF1 deficiency syndrome or central hypothyroidism/testicular enlargement (CHTE). The condition, which affects an estimated 1:100,000 people, is more common in males than females. Most affected males are discovered through neonatal screening for hypothyroidism. The extent of hypothyroidism is variable, but most male cases require treatment with thyroid hormone replacement. Males with IGSF1 deficiency exhibit enlarged testicles (also known as macroorchidism) and a delay in the development of secondary sexual characteristics. Post-pubertally, there is no evidence of impaired fertility in these men. The IGSF1 gene is also active in the brain and in the developing liver. It can also become reactivated in liv
https://en.wikipedia.org/wiki/INCENP
Inner centromere protein is a protein that in humans is encoded by the INCENP gene. It is a regulatory protein in the chromosome passenger complex (CPC). It is involved in regulation of the catalytic proteins Aurora B and Aurora C. It acts in association with two other proteins - Survivin and Borealin. These proteins form a tight three-helical bundle. The N-terminal domain of INCENP is the domain involved in formation of this three-helical bundle while its C-terminal domain is responsible for the interaction with Aurora B. In mammalian cells, two broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and 'passenger' (or transiently interacting) proteins. The constitutive proteins include CENPA (centromere protein A), CENPB, CENPC1, and CENPD. The term 'passenger proteins' encompasses a broad collection of proteins that localize to the centromere during specific stages of the cell cycle. These include CENPE; MCAK; KID; cytoplasmic dynein (e.g., DYNC1H1); CliPs (e.g. CLIP1); and CENPF/mitosin (CENPF). The inner centromere proteins (INCENPs), the initial members of the passenger protein group, display a broad localization along chromosomes in the early stages of mitosis but gradually become concentrated at centromeres as the cell cycle progresses into mid-metaphase. During telophase, the proteins are located within the midbody in the intercellular bridge, where they are discarded after cytokinesis. Interactions INCENP h
https://en.wikipedia.org/wiki/ITIH2
Inter-alpha-trypsin inhibitor heavy chain H2 is a protein that in humans is encoded by the ITIH2 gene. It is known to contain a Gla domain, and thus be dependent for production on post translational modification requiring vitamin K. Its function is also presumably dependent on calcium ions. See also Inter-alpha-trypsin inhibitor ITIH1 ITIH3 ITIH4 References Further reading
https://en.wikipedia.org/wiki/KCNJ4
Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene. Function Several different potassium channels are known to be involved with electrical signaling in the nervous system. One class is activated by depolarization whereas a second class is not. The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into the cell rather than out of it. This asymmetry in potassium ion conductance plays a key role in the excitability of muscle cells and neurons. The protein encoded by this gene is an integral membrane protein and member of the inward rectifier potassium channel family. The encoded protein has a small unitary conductance compared to other members of this protein family. Two transcript variants encoding the same protein have been found for this gene. Interactions KCNJ4 has been shown to interact with: CASK, DLG1 DLG4, LIN7B, and LIN7C. See also Inward-rectifier potassium ion channel References Further reading External links
https://en.wikipedia.org/wiki/RHOQ
Rho-related GTP-binding protein RhoQ is a protein that in humans is encoded by the RHOQ gene. TC10 is a member of the RAS superfamily of small GTP-binding proteins (see HRAS, MIM 190020) involved in insulin-stimulated glucose uptake.[supplied by OMIM] In melanocytic cells RHOQ gene expression may be regulated by MITF. Interactions RHOQ has been shown to interact with EXOC7, GOPC, PARD6B, WASL, CDC42EP2, TRIP10 and CDC42EP3. References Further reading
https://en.wikipedia.org/wiki/SF3B1
Splicing factor 3B subunit 1 is a protein that in humans is encoded by the SF3B1 gene. Function This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms. Interactions SF3B1 has been shown to interact with: CDC5L, DDX42, PPP1R8, SF3B2, SF3B3, SF3B14, Clinical relevance Mutations in this gene have been recurrently seen in cases of advanced chronic lymphocytic leukemia, myelodysplastic syndromes and breast cancer. SF3B1 mutations are found in 60%-80% of patients with refractory anemia with ring sideroblasts (RARS; which is a myelodysplastic syndrome) or RARS with thrombocytosis (RARS-T; which is a myelodysplastic syndrome/myeloproliferative neoplasm). There is also an emerging body of evidence to suggest implications of SF3B1 mutations being involved in orbital melanoma. References Further reading
https://en.wikipedia.org/wiki/HEY1
Hairy/enhancer-of-split related with YRPW motif protein 1 is a protein that in humans is encoded by the HEY1 gene. Function This gene encodes a nuclear protein belonging to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcriptional repressors. Expression of this gene is induced by the Notch and c-Jun signal transduction pathways. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternative splicing results in multiple transcript variants. References Further reading External links Transcription factors
https://en.wikipedia.org/wiki/FBXO5
F-box only protein 5 is a protein that in humans is encoded by the FBXO5 gene. Function This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. This protein is similar to xenopus early mitotic inhibitor-1 (Emi1), which is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Moreover, Emi1 also assembles a CRL1 complex that targets RAD51 for ubiquitin-mediated degradation. Disease Gene and protein expression of FBXO5/Emi1 are increased in many human cancers and increased expression has been shown to cause chromosome instability and cancer. Interactions FBXO5 has been shown to interact with: CDC20, FZR1, SKP1A. and RAD51. References Further reading
https://en.wikipedia.org/wiki/Interleukin%2036%20receptor%20antagonist
Interleukin 36 receptor antagonist (IL-36RA) is a member of the interleukin-36 family of cytokines. It was previously named Interleukin-1 family member 5 (IL1F5). The protein is known to inhibit the effects of Interleukin-36 cytokines (IL-36α, IL-36β and IL-36γ) via competing with their receptor IL-36R/IL1RL2 and thereby inhibiting their proinflammatory effects. Roles in disease Mutations in the IL-36RN gene resulting in a decrease or production of defective IL-36RA protein have been shown to cause inflammatory skin diseases including generalised pustular psoriasis, acrodermatitis continua suppurativa Hallopeau (ACH) and acute generalized exanthematous pustulosis (AGEP). References Further reading Cytokine receptors
https://en.wikipedia.org/wiki/PDCD4
Programmed cell death protein 4 is a protein that in humans is encoded by the PDCD4 gene. It is one of the targets of an oncomiR, MIRN21. Function This gene encodes a protein localized to the nucleus in proliferating cells. Expression of this gene is modulated by cytokines in natural killer and T cells. The gene product is thought to play a role in apoptosis but the specific role has not yet been determined. Two transcripts encoding different isoforms have been identified. Interactions PDCD4 has been shown to interact with RPS13, ribosomal protein L5, p62, LC3 and Ubiquitin [9] References 9. Manirujjaman M, Ozaki I, Murata Y, Guo J, Xia J, Nishioka K, Perveen R,Takahashi H, Anzai K, Matsuhashi S (2020). "Degradation of the Tumor Suppressor PDCD4 Is Impaired by the Suppression of p62/SQSTM1 and Autophagy". Cells. 9(1): 218. doi.org/10.3390/cells9010218. Further reading
https://en.wikipedia.org/wiki/NCR3
Natural cytotoxicity triggering receptor 3 is a protein that in humans is encoded by the NCR3 gene. NCR3 has also been designated as CD337 (cluster of differentiation 337) and as NKp30. NCR3 belongs to the family of NCR membrane receptors together with NCR1 (NKp46) and NCR2 (NKp44). Identification NKp30 receptor was first identified in 1999. According to Western blot analysis specific monoclonal antibodies reacted with 30kDa molecule, therefore was the protein named NKp30. Structure Gene for NKp30 is located in the MHC class III region of the human MHC locus and encodes 190 amino acid long type I transmembrane receptor which belongs to immunoglobulin super family (IgSF). NKp30 has a mass of 30 kDa and includes one Ig-like extracellular domain which is 138 amino acids long, a 19 amino acid transmembrane (TM) domain and a 33 amino acid cytoplasmic tail. The Ig-like domain consists of 2 antiparallel beta-sheets linked by a disulphide bond. The extracellular domain contains two potential sites for N-linked glycosylation involved in ligand binding. The TM domain contains a positivelly charged arginine residue, which associates with negatively charged aspartate in TM domain of ITAM adaptor molecules CD3ζ and FCεRIγ. This is a common feature of other NK cell activating receptors as well. Accordingly the cytoplasmic tail lacks typical ITAM consensus sequence. Splicing variants We can find six different splicing variants on the cell surface. NKp30a, NKp30b and NKp30c encode mole
https://en.wikipedia.org/wiki/KCNJ8
Potassium inwardly-rectifying channel, subfamily J, member 8, also known as KCNJ8, is a human gene encoding the Kir6.1 protein. A mutation in KCNJ8 has been associated with cardiac arrest in the early repolarization syndrome. Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. Kir6.1 is an integral membrane protein and inward-rectifier type potassium channel. Kir6.1, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins. See also Inward-rectifier potassium ion channel References Further reading External links Ion channels
https://en.wikipedia.org/wiki/KCNMB1
Calcium-activated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNMB1 gene. Function MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the product of this gene, the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits. Beta subunits (beta 1-4) are highly tissue specific in their expression, with beta-1 being present predominantly on vascular smooth muscle. Endothelial cells are not known to express beta-1 subunits. Beta-1 is also known to be expressed in urinary bladder and in some regions of the brain. Association of the beta-1 subunit with the BK channel increases the apparent Ca2+ sensitivity of the channel and decreases voltage dependence. See also BK channel Voltage-gated potassium channel References Further reading Ion channels