| TMEM171 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | TMEM171 , PRP2, transmembrane protein 171 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 2685751 HomoloGene: 18301 GeneCards: TMEM171 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Transmembrane protein 171 (TMEM171) is a protein that in humans is encoded by the TMEM171 gene. [5]
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | TMEM171 , PRP2, transmembrane protein 171 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 2685751 HomoloGene: 18301 GeneCards: TMEM171 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Transmembrane protein 171 (TMEM171) is a protein that in humans is encoded by the TMEM171 gene. [5]
TMEM171 is also known as PRP2 or proline-rich protein 2. It has 11,526 base pairs and 4 exons and is located on the long arm of chromosome 5, at 5q13.2, in humans. [6] It spans from 73,120,292 to 73,131,817 on the plus strand. It is flanked by FCHO2 and TNPO1 upstream and TMEM174 downstream. [6]
The predicted promoter region (GXP_7598) is 2034 base pairs long and extends past the first exon of TMEM171. [7] Transcription factors predicted to bind to the promoter region include p63 tumor protein, CCCTC binding factors, TATA binding factors, and thyroid hormone receptors. [8]
TMEM171 is moderately and differentially expressed, indicating that it is neither a housekeeping gene nor a tissue-enriched gene. [9] [10] Its expression is highest in the thyroid, mammary gland, stomach, duodenum, and kidney. It is also expressed at moderate levels in tissues including the spleen, ileum, colon, salivary gland, and expressed at lower levels in a variety of other tissues. [11] Conditional expression patterns of TMEM171 include decreased expression in papillary thyroid carcinoma, colon cancer, and gastric cancer, as well as increased expression in p63-depleted tissue and induced alveolar macrophages. [12] [13] [14] [15] [16]
TMEM171 has isoforms 1, 2, and X1, with 4 exons each. [5] The 3 transcripts undergo alternate in-frame splicing and are translated into proteins with 324, 323, and 305 amino acids, respectively. [17] [18] [19]
The 5' untranslated region has predicted sites for binding by SFRS1 and SFRS9 splicing factors and FUS, which couples transcription and splicing. The 3' untranslated region has predicted sites for binding by ELAVL1 and ZFP36, which both bind AU rich elements and may compete to stabilize or destabilize the mRNA. [20]
The longest protein isoform of TMEM171 is 324 amino acids in length and has an observed molecular weight of approximately 44 kDa. [17] [21] TMEM171 is an acidic protein overall, with a predicted isoelectric point of approximately 5. [22]
TMEM171 has fewer lysine residues than expected for a human protein. [23] Despite the fact that its alias is proline-rich protein 2, TMEM171 in humans does not have more proline residues than expected; however it does have a multiplet of 6 proline residues. More distant orthologs, including Xenopus tropicalis, do have significantly more proline residues than expected. TMEM171 has 3 hydrophobic segments, which correspond with transmembrane regions. [23]
TMEM171 has a conserved domain, pfam15471 (aa4:318), whose structure and function are not yet characterized. [5] Within the domain, there are 4 transmembrane domains, 2 non-cytosolic domains, and 3 cytosolic domains.
The structure of TMEM171 consists of approximately 25% beta strands and 15% alpha helices, with coils and disordered regions making up the rest of the structure. [24] The tertiary structure includes 2 predicted disulfide bridges, which occur between highly conserved cysteine residues in the non-cytosolic domains. [25]
TMEM171 undergoes methionine cleavage and N-terminal acetylation, which is one of the most common modifications of eukaryotic proteins. [28] N-linked glycosylation is predicted at a highly conserved NETD sequence within a non-cytosolic domain. [29] S-palmitoylation, which enhances surface hydrophobicity and membrane affinity, is predicted at 2 cytosolic cysteine residues in TMEM171. [30] TMEM171 is phosphorylated by unspecified kinases at several sites. [31] It also undergoes O-ß-GlcNAc modification at 4 sites, 3 of which are Yin-Yang sites due to O-ß-GlcNAc modification and phosphorylation competing for control of protein activation or deactivation. [32]
TMEM171's predicted location is in the plasma membrane, with both the N- and C-termini located inside the cell. [33] [34]
The proteins that are most likely to interact with TMEM171, based on affinity chromatography and two hybrid arrays, are MIER1, EMSY, CHPT1, HDLBP, NEDD4, WWOX, and TTHY3. [35] There is strong evidence for a direct interaction between TMEM171 an MIER1, which is a transcriptional repressor that is associated with central hypothyroidism. [36]
TMEM171 is down-regulated in papillary thyroid carcinoma and two SNPs, with the non-synonymous mutations R86G and N139K, are identified risk SNPs for papillary thyroid carcinoma. [37] [38] [39] TMEM171 is also down-regulated in gastric cancer and colon cancer. [13] [14] More specifically, it is down-regulated in right-sided colon cancer relative to left-sided colon cancer, which typically has a better prognosis. [40] In renal cancer, high expression of TMEM171 is a favorable prognostic marker. [41] In triple-negative breast cancer cells, immuno-activation by tumor necrosis factor alpha (TNFα) was found to up-regulate TMEM171. [42]
TMEM171 has signatures of balancing selection, which include a significant excess of polymorphisms and intermediate-frequency alleles. [43]
TMEM171 has no paralogs or paralogous domains. TMEM171 has 208 identified orthologs. [5] All orthologs are vertebrates, including mammals, amphibians, reptiles, birds, lobe-finned fish, and cartilaginous fish. The following table provides a sample of the ortholog space of TMEM171.
| Genus and Species | NCBI Accession Number | Date of Divergence (MYA) [44] | Sequence Length | Sequence Identity [45] |
| Homo sapiens (Human) | NP_775761.4 | 0 | 324 | 100% |
| Pan troglodytes (Chimpanzee) | XP_009447304.1 | 6 | 324 | 99% |
| Saimiri boliveiensis (Black-capped squirrel monkey) | XP_010334830.1 | 42.6 | 324 | 91% |
| Mus musculus (Mouse) | XP_006517772.1 | 88 | 323 | 75% |
| Myotis lucifugus (Little brown bat) | XP_006081400.1 | 94 | 325 | 82% |
| Vulpes vulpes (Fox) | XP_025838976.1 | 94 | 321 | 73% |
| Chrysochloris asiatica (Cape golden mole) | XP_006875335.1 | 102 | 326 | 73% |
| Sarcophilus harrisii (Tasmanian devil) | XP_003759514.1 | 160 | 332 | 67% |
| Empidonax traillii (Willow flycatcher) | XP_027739189.1 | 320 | 333 | 52% |
| Anas platyrhynchos (Mallard) | XP_027302666.1 | 320 | 330 | 47% |
| Xenopus tropicalis (Western clawed frog) | XP_012815192.1 | 353 | 332 | 54% |
| Rhincodon typus (Whale shark) | XP_020374629.1 | 465 | 311 | 36% |
| Callorhinchus milii (Australian ghost shark; Elephant fish) | XP_007898003.1 | 465 | 293 | 31% |
Proline-rich 12 (PRR12) is a protein of unknown function encoded by the gene PRR12.
Transmembrane protein 251, also known as C14orf109 or UPF0694, is a protein that in humans is encoded by the TMEM251 gene. One notable feature of this protein is the presence of proline residues on one of its predicted transmembrane domains., which is a determinant of the intramitochondrial sorting of inner membrane proteins.
C8orf48 is a protein that in humans is encoded by the C8orf48 gene. C8orf48 is a nuclear protein specifically predicted to be located in the nuclear lamina. C8orf48 has been found to interact with proteins that are involved in the regulation of various cellular responses like gene expression, protein secretion, cell proliferation, and inflammatory responses. This protein has been linked to breast cancer and papillary thyroid carcinoma.
Transmembrane Protein 217 is a protein encoded by the gene TMEM217. TMEM217 has been found to have expression correlated with the lymphatic system and endothelial tissues and has been predicted to have a function linked to the cytoskeleton.
SHLD1 or shieldin complex subunit 1 is a gene on chromosome 20. The C20orf196 gene encodes an mRNA that is 1,763 base pairs long, and a protein that is 205 amino acids long.
Chromosome 1 open reading frame 198 (C1orf198) is a protein that in humans is encoded by the C1orf198 gene. This particular gene does not have any paralogs in Homo sapiens, but many orthologs have been found throughout the Eukarya domain. C1orf198 has high levels of expression in all tissues throughout the human body, but is most highly expressed in lung, brain, and spinal cord tissues. Its function is most likely involved in lung development and hypoxia-associated events in the mitochondria, which are major consumers of oxygen in cells and are severely affected by decreases in available cellular oxygen.
Transmembrane protein 179 is a protein that in humans is encoded by the TMEM179 gene. The function of transmembrane protein 179 is not yet well understood, but it is believed to have a function in the nervous system.
WD Repeat and Coiled-coiled containing protein (WDCP) is a protein which in humans is encoded by the WDCP gene. The function of the protein is not completely understood, but WDCP has been identified in a fusion protein with anaplastic lymphoma kinase found in colorectal cancer. WDCP has also been identified in the MRN complex, which processes double-stranded breaks in DNA.
Transmembrane Protein 81 or TMEM81 is a protein that in humans is encoded by the TMEM81 gene. TMEM81 is a poorly-characterized transmembrane protein which contains an extracellular immunoglobulin domain.
TMEM267 is a protein that in humans is encoded by the TMEM267 gene. It is a possible oncogene which encodes a transmembrane protein. The function of TMEM267 most likely involves transportation of molecules from the cytosol, as the presence of motifs and domains involved in transportation were conserved in orthologs. TMEM267 has orthologs in many species and is expressed at highest levels in the thyroid.
SH3 Domain Binding Kinase Family Member 3 is an enzyme that in humans is encoded by the SBK3 gene. SBK3 is a member of the serine/threonine protein kinase family. The SBK3 protein is known to exhibit transferase activity, especially phosphotransferase activity, and tyrosine kinase activity. It is well-conserved throughout mammalian organisms and has two paralogs: SBK1 and SBK2.
Family with Sequence Similarity 155 Member B is a protein in humans that is encoded by the FAM155B gene. It belongs to a family of proteins whose function is not yet well understood by the scientific community. It is a transmembrane protein that is highly expressed in the heart, thyroid, and brain.
Transmembrane emp24 domain-containing protein 5 is a protein that in humans is encoded by the TMED5 gene.
OCEL1, also called Occludin//ELL Domain Containing 1, is a protein encoding gene located at chromosome 19p13.11 in the human genome. Other aliases for the gene include FLJ22709, FWP009, and S863-9. The function of OCEL1 has not yet been identified.
Transmembrane protein 101 (TMEM101) is a protein that in humans is encoded by the TMEM101 gene. The TMEM101 protein has been demonstrated to activate the NF-κB signaling pathway. High levels of expression of TMEM101 have been linked to breast cancer.
C1orf159 is a protein that in human is encoded by the C1orf159 gene located on chromosome 1. This gene is also found to be an unfavorable prognosis marker for renal and liver cancer, and a favorable prognosis marker for urothelial cancer.
NADP Dependent Oxidoreductase Domain Containing 1 (NOXRED1) is a human protein encoded by the gene NADP-Dependent Oxidoreductase Domain Containing 1 (NOXRED1). An alias of this gene is Chromosome 14 Open Reading Frame 148 (c14orf148). This gene is located on chromosome 14, at 14q24.3. NOXRED1 is predicted to be involved in pyrroline-5-carboxylate reductase activity as part of the L-proline biosynthetic pathway. It is expressed in a wide variety of tissues at a relatively low level, including the testes, thyroid, skin, small intestine, brain, kidney, colon, and more.
Transmembrane protein 248, also known as C7orf42, is a gene that in humans encodes the TMEM248 protein. This gene contains multiple transmembrane domains and is composed of seven exons.TMEM248 is predicted to be a component of the plasma membrane and be involved in vesicular trafficking. It has low tissue specificity, meaning it is ubiquitously expressed in tissues throughout the human body. Orthology analyses determined that TMEM248 is highly conserved, having homology with vertebrates and invertebrates. TMEM248 may play a role in cancer development. It was shown to be more highly expressed in cases of colon, breast, lung, ovarian, brain, and renal cancers.
Transmembrane protein 82 (TMEM82) is a protein encoded by the TMEM82 gene in humans.
CIMAP1C is a gene in humans that encodes the CIMAP1C protein. It is also often referred to as ODF3L1. CIMAP1C is expressed in low levels throughout the body with high expression levels in the testes. It is highly conserved in mammals and reptiles but not present in birds or amphibians, indicating it arose around 300 million years ago.
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