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Transmembrane protein 127

 TM127_HUMAN             Reviewed;         238 AA.
O75204; D3DXH0;
03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
01-NOV-1998, sequence version 1.
20-JUN-2018, entry version 119.
RecName: Full=Transmembrane protein 127;
Name=TMEM127;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=10493829; DOI=10.1006/geno.1999.5927;
Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R.,
Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
Harris P.C., Venter J.C., Adams M.D.;
"Genome duplications and other features in 12 Mb of DNA sequence from
human chromosome 16p and 16q.";
Genomics 60:295-308(1999).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15815621; DOI=10.1038/nature03466;
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
Waterston R.H., Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2
and 4.";
Nature 434:724-731(2005).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Ovary, and Testis;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
Greff Z., Keri G., Stemmann O., Mann M.;
"Kinase-selective enrichment enables quantitative phosphoproteomics of
the kinome across the cell cycle.";
Mol. Cell 31:438-448(2008).
[7]
FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN
PHEOCHROMOCYTOMA, AND VARIANT PCC MET-90.
PubMed=20154675; DOI=10.1038/ng.533;
Qin Y., Yao L., King E.E., Buddavarapu K., Lenci R.E., Chocron E.S.,
Lechleiter J.D., Sass M., Aronin N., Schiavi F., Boaretto F.,
Opocher G., Toledo R.A., Toledo S.P., Stiles C., Aguiar R.C.,
Dahia P.L.;
"Germline mutations in TMEM127 confer susceptibility to
pheochromocytoma.";
Nat. Genet. 42:229-233(2010).
[8]
ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22814378; DOI=10.1073/pnas.1210303109;
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
Aldabe R.;
"N-terminal acetylome analyses and functional insights of the N-
terminal acetyltransferase NatB.";
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
[9]
ACETYLATION AT MET-1.
PubMed=25732826; DOI=10.1016/j.celrep.2015.01.053;
Aksnes H., Van Damme P., Goris M., Starheim K.K., Marie M.,
Stoeve S.I., Hoel C., Kalvik T.V., Hole K., Glomnes N., Furnes C.,
Ljostveit S., Ziegler M., Niere M., Gevaert K., Arnesen T.;
"An organellar nalpha-acetyltransferase, naa60, acetylates cytosolic N
termini of transmembrane proteins and maintains Golgi integrity.";
Cell Rep. 10:1362-1374(2015).
[10]
VARIANTS PCC SER-53; ASN-70; ARG-73; MET-90; TRP-94; ARG-140 AND
TYR-140, CHARACTERIZATION OF VARIANTS ASN-70; TRP-94; ARG-140 AND
TYR-140, AND SUBCELLULAR LOCATION.
PubMed=21156949; DOI=10.1001/jama.2010.1830;
Yao L., Schiavi F., Cascon A., Qin Y., Inglada-Perez L., King E.E.,
Toledo R.A., Ercolino T., Rapizzi E., Ricketts C.J., Mori L.,
Giacche M., Mendola A., Taschin E., Boaretto F., Loli P., Iacobone M.,
Rossi G.P., Biondi B., Lima-Junior J.V., Kater C.E., Bex M.,
Vikkula M., Grossman A.B., Gruber S.B., Barontini M., Persu A.,
Castellano M., Toledo S.P., Maher E.R., Mannelli M., Opocher G.,
Robledo M., Dahia P.L.;
"Spectrum and prevalence of FP/TMEM127 gene mutations in
pheochromocytomas and paragangliomas.";
JAMA 304:2611-2619(2010).
-!- FUNCTION: Controls cell proliferation acting as a negative
regulator of TOR signaling pathway mediated by mTORC1. May act as
a tumor suppressor. {ECO:0000269|PubMed:20154675}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20154675,
ECO:0000269|PubMed:21156949}; Multi-pass membrane protein
{ECO:0000269|PubMed:20154675}. Cytoplasm
{ECO:0000269|PubMed:20154675, ECO:0000269|PubMed:21156949}.
Note=Association of TMEM127 with the cell membrane is enhanced by
inhibition of endocytosis. In the cytoplasm, it colocalizes with
markers of early endosomal structures, Golgi apparatus and
lysosomes. {ECO:0000269|PubMed:20154675,
ECO:0000269|PubMed:21156949}.
-!- TISSUE SPECIFICITY: Widely expressed.
{ECO:0000269|PubMed:20154675}.
-!- DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-
producing tumor of chromaffin tissue of the adrenal medulla or
sympathetic paraganglia. The cardinal symptom, reflecting the
increased secretion of epinephrine and norepinephrine, is
hypertension, which may be persistent or intermittent.
{ECO:0000269|PubMed:20154675, ECO:0000269|PubMed:21156949}.
Note=Disease susceptibility is associated with variations
affecting the gene represented in this entry.
-!- MISCELLANEOUS: Consistent with the observation that mTORC1
signaling regulates cell growth and size in many species, TMEM127
knockdown cells are larger and proliferate at higher rates
compared to control cell lines. In contrast, cell proliferation is
reduced in cells overexpressing TMEM127 (PubMed:20154675).
{ECO:0000305|PubMed:20154675}.
-!- SIMILARITY: Belongs to the TMEM127 family. {ECO:0000305}.
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; AK000514; BAA91220.1; -; mRNA.
EMBL; AC004020; AAC23494.1; -; Genomic_DNA.
EMBL; AC012307; AAY24224.1; -; Genomic_DNA.
EMBL; CH471207; EAW71376.1; -; Genomic_DNA.
EMBL; CH471207; EAW71377.1; -; Genomic_DNA.
EMBL; CH471207; EAW71378.1; -; Genomic_DNA.
EMBL; CH471207; EAW71379.1; -; Genomic_DNA.
EMBL; BC028575; AAH28575.1; -; mRNA.
EMBL; BC039892; AAH39892.1; -; mRNA.
CCDS; CCDS2018.1; -.
RefSeq; NP_001180233.1; NM_001193304.2.
RefSeq; NP_060319.1; NM_017849.3.
UniGene; Hs.164303; -.
UniGene; Hs.735706; -.
ProteinModelPortal; O75204; -.
SMR; O75204; -.
BioGrid; 120786; 1.
STRING; 9606.ENSP00000258439; -.
iPTMnet; O75204; -.
PhosphoSitePlus; O75204; -.
BioMuta; TMEM127; -.
EPD; O75204; -.
MaxQB; O75204; -.
PaxDb; O75204; -.
PeptideAtlas; O75204; -.
PRIDE; O75204; -.
ProteomicsDB; 49868; -.
Ensembl; ENST00000258439; ENSP00000258439; ENSG00000135956.
Ensembl; ENST00000432959; ENSP00000416660; ENSG00000135956.
GeneID; 55654; -.
KEGG; hsa:55654; -.
UCSC; uc002svq.4; human.
CTD; 55654; -.
DisGeNET; 55654; -.
EuPathDB; HostDB:ENSG00000135956.8; -.
GeneCards; TMEM127; -.
HGNC; HGNC:26038; TMEM127.
MalaCards; TMEM127; -.
MIM; 171300; phenotype.
MIM; 613403; gene.
neXtProt; NX_O75204; -.
OpenTargets; ENSG00000135956; -.
Orphanet; 319276; Clear cell renal carcinoma.
Orphanet; 29072; Hereditary pheochromocytoma-paraganglioma.
PharmGKB; PA143485647; -.
eggNOG; ENOG410IJHY; Eukaryota.
eggNOG; ENOG410XW58; LUCA.
GeneTree; ENSGT00390000005154; -.
HOGENOM; HOG000231823; -.
HOVERGEN; HBG053128; -.
InParanoid; O75204; -.
OMA; YCMNPQT; -.
OrthoDB; EOG091G0WXT; -.
PhylomeDB; O75204; -.
TreeFam; TF328671; -.
ChiTaRS; TMEM127; human.
GenomeRNAi; 55654; -.
PRO; PR:O75204; -.
Proteomes; UP000005640; Chromosome 2.
Bgee; ENSG00000135956; -.
CleanEx; HS_TMEM127; -.
ExpressionAtlas; O75204; baseline and differential.
Genevisible; O75204; HS.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005769; C:early endosome; IDA:MGI.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO; GO:0017137; F:Rab GTPase binding; IDA:MGI.
GO; GO:0007032; P:endosome organization; IEA:Ensembl.
GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB.
InterPro; IPR033331; TMEM127.
PANTHER; PTHR28358; PTHR28358; 1.
1: Evidence at protein level;
Acetylation; Cell membrane; Complete proteome; Cytoplasm; Membrane;
Phosphoprotein; Polymorphism; Reference proteome; Transmembrane;
Transmembrane helix; Tumor suppressor.
CHAIN 1 238 Transmembrane protein 127.
/FTId=PRO_0000251718.
TRANSMEM 96 116 Helical. {ECO:0000255}.
TRANSMEM 130 150 Helical. {ECO:0000255}.
TRANSMEM 169 189 Helical. {ECO:0000255}.
MOD_RES 1 1 N-acetylmethionine.
{ECO:0000244|PubMed:22814378,
ECO:0000269|PubMed:25732826}.
MOD_RES 17 17 Phosphoserine.
{ECO:0000244|PubMed:18691976}.
VARIANT 53 53 W -> S (in PCC; dbSNP:rs121908818).
{ECO:0000269|PubMed:21156949}.
/FTId=VAR_072273.
VARIANT 70 70 D -> N (in PCC; localized diffusely
within the cytoplasm; dbSNP:rs121908819).
{ECO:0000269|PubMed:21156949}.
/FTId=VAR_072274.
VARIANT 73 73 G -> R (in PCC; dbSNP:rs121908820).
{ECO:0000269|PubMed:21156949}.
/FTId=VAR_072275.
VARIANT 90 90 V -> M (in PCC; dbSNP:rs121908823).
{ECO:0000269|PubMed:20154675,
ECO:0000269|PubMed:21156949}.
/FTId=VAR_063595.
VARIANT 94 94 R -> W (in PCC; localized diffusely
within the cytoplasm; dbSNP:rs121908824).
{ECO:0000269|PubMed:21156949}.
/FTId=VAR_072276.
VARIANT 140 140 C -> R (in PCC; localized diffusely
within the cytoplasm; dbSNP:rs121908827).
{ECO:0000269|PubMed:21156949}.
/FTId=VAR_072277.
VARIANT 140 140 C -> Y (in PCC; localized diffusely
within the cytoplasm; dbSNP:rs121908828).
{ECO:0000269|PubMed:21156949}.
/FTId=VAR_072278.
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


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