TM127_HUMAN
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 03-AUG-2022, entry version 138.
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}.
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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; 5.
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; O75204; -.
DR PeptideAtlas; O75204; -.
DR PRIDE; O75204; -.
DR ProteomicsDB; 49868; -.
DR Antibodypedia; 32415; 44 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 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; MEETEPY; -.
DR OrthoDB; 507784at2759; -.
DR PhylomeDB; O75204; -.
DR TreeFam; TF328671; -.
DR PathwayCommons; O75204; -.
DR BioGRID-ORCS; 55654; 133 hits in 1085 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 195 other tissues.
DR ExpressionAtlas; O75204; baseline and differential.
DR Genevisible; O75204; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 PANTHER; PTHR28358; PTHR28358; 1.
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
