ID TM127_HUMAN Reviewed; 238 AA. AC O75204; D3DXH0; DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 27-MAR-2024, entry version 146. DE RecName: Full=Transmembrane protein 127; GN Name=TMEM127; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10493829; DOI=10.1006/geno.1999.5927; RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., RA Adams M.D.; RT "Genome duplications and other features in 12 Mb of DNA sequence from human RT chromosome 16p and 16q."; RL Genomics 60:295-308(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [7] RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN RP PHEOCHROMOCYTOMA, AND VARIANT PCC MET-90. RX PubMed=20154675; DOI=10.1038/ng.533; RA Qin Y., Yao L., King E.E., Buddavarapu K., Lenci R.E., Chocron E.S., RA Lechleiter J.D., Sass M., Aronin N., Schiavi F., Boaretto F., Opocher G., RA Toledo R.A., Toledo S.P., Stiles C., Aguiar R.C., Dahia P.L.; RT "Germline mutations in TMEM127 confer susceptibility to pheochromocytoma."; RL Nat. Genet. 42:229-233(2010). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [9] RP ACETYLATION AT MET-1. RX PubMed=25732826; DOI=10.1016/j.celrep.2015.01.053; RA Aksnes H., Van Damme P., Goris M., Starheim K.K., Marie M., Stoeve S.I., RA Hoel C., Kalvik T.V., Hole K., Glomnes N., Furnes C., Ljostveit S., RA Ziegler M., Niere M., Gevaert K., Arnesen T.; RT "An organellar nalpha-acetyltransferase, naa60, acetylates cytosolic N RT termini of transmembrane proteins and maintains Golgi integrity."; RL Cell Rep. 10:1362-1374(2015). RN [10] RP VARIANTS PCC SER-53; ASN-70; ARG-73; MET-90; TRP-94; ARG-140 AND TYR-140, RP CHARACTERIZATION OF VARIANTS ASN-70; TRP-94; ARG-140 AND TYR-140, AND RP SUBCELLULAR LOCATION. RX PubMed=21156949; DOI=10.1001/jama.2010.1830; RA Yao L., Schiavi F., Cascon A., Qin Y., Inglada-Perez L., King E.E., RA Toledo R.A., Ercolino T., Rapizzi E., Ricketts C.J., Mori L., Giacche M., RA Mendola A., Taschin E., Boaretto F., Loli P., Iacobone M., Rossi G.P., RA Biondi B., Lima-Junior J.V., Kater C.E., Bex M., Vikkula M., Grossman A.B., RA Gruber S.B., Barontini M., Persu A., Castellano M., Toledo S.P., RA Maher E.R., Mannelli M., Opocher G., Robledo M., Dahia P.L.; RT "Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas RT and paragangliomas."; RL JAMA 304:2611-2619(2010). CC -!- FUNCTION: Controls cell proliferation acting as a negative regulator of CC TOR signaling pathway mediated by mTORC1. May act as a tumor CC suppressor. {ECO:0000269|PubMed:20154675}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20154675, CC ECO:0000269|PubMed:21156949}; Multi-pass membrane protein CC {ECO:0000269|PubMed:20154675}. Cytoplasm {ECO:0000269|PubMed:20154675, CC ECO:0000269|PubMed:21156949}. Note=Association of TMEM127 with the cell CC membrane is enhanced by inhibition of endocytosis. In the cytoplasm, it CC colocalizes with markers of early endosomal structures, Golgi apparatus CC and lysosomes. {ECO:0000269|PubMed:20154675, CC ECO:0000269|PubMed:21156949}. CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:20154675}. CC -!- DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing CC tumor of chromaffin tissue of the adrenal medulla or sympathetic CC paraganglia. The cardinal symptom, reflecting the increased secretion CC of epinephrine and norepinephrine, is hypertension, which may be CC persistent or intermittent. {ECO:0000269|PubMed:20154675, CC ECO:0000269|PubMed:21156949}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Consistent with the observation that mTORC1 signaling CC regulates cell growth and size in many species, TMEM127 knockdown cells CC are larger and proliferate at higher rates compared to control cell CC lines. In contrast, cell proliferation is reduced in cells CC overexpressing TMEM127 (PubMed:20154675). CC {ECO:0000305|PubMed:20154675}. CC -!- SIMILARITY: Belongs to the TMEM127 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK000514; BAA91220.1; -; mRNA. DR EMBL; AC004020; AAC23494.1; -; Genomic_DNA. DR EMBL; AC012307; AAY24224.1; -; Genomic_DNA. DR EMBL; CH471207; EAW71376.1; -; Genomic_DNA. DR EMBL; CH471207; EAW71377.1; -; Genomic_DNA. DR EMBL; CH471207; EAW71378.1; -; Genomic_DNA. DR EMBL; CH471207; EAW71379.1; -; Genomic_DNA. DR EMBL; BC028575; AAH28575.1; -; mRNA. DR EMBL; BC039892; AAH39892.1; -; mRNA. DR CCDS; CCDS2018.1; -. DR RefSeq; NP_001180233.1; NM_001193304.2. DR RefSeq; NP_060319.1; NM_017849.3. DR AlphaFoldDB; O75204; -. DR BioGRID; 120786; 6. DR STRING; 9606.ENSP00000258439; -. DR TCDB; 9.B.419.1.1; the transmembrane 127 (tmem127) family. DR iPTMnet; O75204; -. DR PhosphoSitePlus; O75204; -. DR BioMuta; TMEM127; -. DR EPD; O75204; -. DR jPOST; O75204; -. DR MassIVE; O75204; -. DR MaxQB; O75204; -. DR PaxDb; 9606-ENSP00000258439; -. DR PeptideAtlas; O75204; -. DR ProteomicsDB; 49868; -. DR Pumba; O75204; -. DR Antibodypedia; 32415; 49 antibodies from 18 providers. DR DNASU; 55654; -. DR Ensembl; ENST00000258439.8; ENSP00000258439.3; ENSG00000135956.9. DR Ensembl; ENST00000432959.1; ENSP00000416660.1; ENSG00000135956.9. DR GeneID; 55654; -. DR KEGG; hsa:55654; -. DR MANE-Select; ENST00000258439.8; ENSP00000258439.3; NM_017849.4; NP_060319.1. DR UCSC; uc002svq.4; human. DR AGR; HGNC:26038; -. DR CTD; 55654; -. DR DisGeNET; 55654; -. DR GeneCards; TMEM127; -. DR GeneReviews; TMEM127; -. DR HGNC; HGNC:26038; TMEM127. DR HPA; ENSG00000135956; Low tissue specificity. DR MalaCards; TMEM127; -. DR MIM; 171300; phenotype. DR MIM; 613403; gene. DR neXtProt; NX_O75204; -. DR OpenTargets; ENSG00000135956; -. DR Orphanet; 404511; Clear cell papillary renal cell carcinoma. DR Orphanet; 29072; Hereditary pheochromocytoma-paraganglioma. DR PharmGKB; PA143485647; -. DR VEuPathDB; HostDB:ENSG00000135956; -. DR eggNOG; ENOG502QTCN; Eukaryota. DR GeneTree; ENSGT00390000005154; -. DR InParanoid; O75204; -. DR OMA; CVFWVIA; -. DR OrthoDB; 5353936at2759; -. DR PhylomeDB; O75204; -. DR TreeFam; TF328671; -. DR PathwayCommons; O75204; -. DR BioGRID-ORCS; 55654; 137 hits in 1168 CRISPR screens. DR ChiTaRS; TMEM127; human. DR GenomeRNAi; 55654; -. DR Pharos; O75204; Tbio. DR PRO; PR:O75204; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; O75204; Protein. DR Bgee; ENSG00000135956; Expressed in leukocyte and 197 other cell types or tissues. DR ExpressionAtlas; O75204; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005769; C:early endosome; IDA:MGI. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IDA:MGI. DR GO; GO:0007032; P:endosome organization; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB. DR GO; GO:0032006; P:regulation of TOR signaling; IBA:GO_Central. DR InterPro; IPR033331; TMEM127. DR InterPro; IPR046795; TMEM127_TM. DR PANTHER; PTHR28358; TRANSMEMBRANE PROTEIN 127; 1. DR PANTHER; PTHR28358:SF1; TRANSMEMBRANE PROTEIN 127; 1. DR Pfam; PF20517; TMEM127; 1. DR Genevisible; O75204; HS. PE 1: Evidence at protein level; KW Acetylation; Cell membrane; Cytoplasm; Membrane; Phosphoprotein; KW Reference proteome; Transmembrane; Transmembrane helix; Tumor suppressor. FT CHAIN 1..238 FT /note="Transmembrane protein 127" FT /id="PRO_0000251718" FT TRANSMEM 96..116 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 130..150 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 169..189 FT /note="Helical" FT /evidence="ECO:0000255" FT REGION 1..27 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|PubMed:25732826, FT ECO:0007744|PubMed:22814378" FT MOD_RES 17 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT VARIANT 53 FT /note="W -> S (in PCC; dbSNP:rs121908818)" FT /evidence="ECO:0000269|PubMed:21156949" FT /id="VAR_072273" FT VARIANT 70 FT /note="D -> N (in PCC; localized diffusely within the FT cytoplasm; dbSNP:rs121908819)" FT /evidence="ECO:0000269|PubMed:21156949" FT /id="VAR_072274" FT VARIANT 73 FT /note="G -> R (in PCC; dbSNP:rs121908820)" FT /evidence="ECO:0000269|PubMed:21156949" FT /id="VAR_072275" FT VARIANT 90 FT /note="V -> M (in PCC; dbSNP:rs121908823)" FT /evidence="ECO:0000269|PubMed:20154675, FT ECO:0000269|PubMed:21156949" FT /id="VAR_063595" FT VARIANT 94 FT /note="R -> W (in PCC; localized diffusely within the FT cytoplasm; dbSNP:rs121908824)" FT /evidence="ECO:0000269|PubMed:21156949" FT /id="VAR_072276" FT VARIANT 140 FT /note="C -> R (in PCC; localized diffusely within the FT cytoplasm; dbSNP:rs121908827)" FT /evidence="ECO:0000269|PubMed:21156949" FT /id="VAR_072277" FT VARIANT 140 FT /note="C -> Y (in PCC; localized diffusely within the FT cytoplasm; dbSNP:rs121908828)" FT /evidence="ECO:0000269|PubMed:21156949" FT /id="VAR_072278" SQ SEQUENCE 238 AA; 25842 MW; 9A351F13EA9C6865 CRC64; MYAPGGAGLP GGRRRRSPGG SALPKQPERS LASALPGALS ITALCTALAE PAWLHIHGGT CSRQELGVSD VLGYVHPDLL KDFCMNPQTV LLLRVIAAFC FLGILCSLSA FLLDVFGPKH PALKITRRYA FAHILTVLQC ATVIGFSYWA SELILAQQQQ HKKYHGSQVY VTFAVSFYLV AGAGGASILA TAANLLRHYP TEEEEQALEL LSEMEENEPY PAEYEVINQF QPPPAYTP //