ID TM9S4_HUMAN Reviewed; 642 AA. AC Q92544; B0QYT7; Q9NUA3; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 26-FEB-2008, sequence version 2. DT 28-FEB-2018, entry version 139. DE RecName: Full=Transmembrane 9 superfamily member 4; DE AltName: Full=Tumor cannibalism associated protein 1 {ECO:0000303|PubMed:19893578}; DE Flags: Precursor; GN Name=TM9SF4; Synonyms=KIAA0255, TUCAP1 {ECO:0000303|PubMed:19893578}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Bone marrow; RX PubMed=9039502; DOI=10.1093/dnares/3.5.321; RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., RA Tanaka A., Kotani H., Miyajima N., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. VI. RT The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by RT analysis of cDNA clones from cell line KG-1 and brain."; RL DNA Res. 3:321-329(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Muscle; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-312, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=19893578; DOI=10.1038/embor.2009.236; RA Lozupone F., Perdicchio M., Brambilla D., Borghi M., Meschini S., RA Barca S., Marino M.L., Logozzi M., Federici C., Iessi E., RA de Milito A., Fais S.; RT "The human homologue of Dictyostelium discoideum phg1A is expressed by RT human metastatic melanoma cells."; RL EMBO Rep. 10:1348-1354(2009). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=25999474; DOI=10.1242/jcs.164848; RA Perrin J., Le Coadic M., Vernay A., Dias M., Gopaldass N., RA Ouertatani-Sakouhi H., Cosson P.; RT "TM9 family proteins control surface targeting of glycine-rich RT transmembrane domains."; RL J. Cell Sci. 128:2269-2277(2015). RN [8] RP FUNCTION, AND INTERACTION WITH ATP6V1H. RX PubMed=25659576; DOI=10.1038/onc.2014.437; RA Lozupone F., Borghi M., Marzoli F., Azzarito T., Matarrese P., RA Iessi E., Venturi G., Meschini S., Canitano A., Bona R., Cara A., RA Fais S.; RT "TM9SF4 is a novel V-ATPase-interacting protein that modulates tumor RT pH alterations associated with drug resistance and invasiveness of RT colon cancer cells."; RL Oncogene 34:5163-5174(2015). RN [9] RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY. RX PubMed=25961573; DOI=10.1371/journal.pone.0126968; RA Paolillo R., Spinello I., Quaranta M.T., Pasquini L., Pelosi E., RA Lo Coco F., Testa U., Labbaye C.; RT "Human TM9SF4 is a new gene down-regulated by hypoxia and involved in RT cell adhesion of leukemic cells."; RL PLoS ONE 10:E0126968-E0126968(2015). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). CC -!- FUNCTION: Associates with proteins harboring glycine-rich CC transmembrane domains and ensures their efficient localization to CC the cell surface (PubMed:25999474). Regulates the assembly and CC activity of V-ATPase in colon cancer cells via its interaction CC with V-type proton ATPase subunit H (ATP6V1H) and contributes to CC V-ATPase-mediated pH alterations in cancer cells which play an CC important role in drug resistance and invasiveness of colon cancer CC cells (PubMed:25659576). Plays an important role in an atypical CC phagocytic activity of metastatic melanoma cells called CC cannibalism and is involved in the pH regulation of the CC intracellular vesicles in tumor cells (PubMed:19893578). CC {ECO:0000269|PubMed:19893578, ECO:0000269|PubMed:25659576, CC ECO:0000269|PubMed:25999474}. CC -!- SUBUNIT: Interacts with ATP6V1H in colon cancer cells CC (PubMed:25659576). {ECO:0000269|PubMed:25659576}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane CC protein {ECO:0000255}. Golgi apparatus CC {ECO:0000269|PubMed:25999474}. Early endosome CC {ECO:0000269|PubMed:19893578}. CC -!- TISSUE SPECIFICITY: Highly expressed in metastatic melanoma cells CC whereas it is undetectable in primary melanoma cells, healthy skin CC tissues and peripheral blood lymphocytes. Expressed in CD34(+) CC hematopoietic progenitor cells and during monocyte and granulocyte CC differentiation. Overexpressed in acute myeloid leukemia, in CC particular in those displaying granulocytic differentiation (at CC protein level). {ECO:0000269|PubMed:19893578, CC ECO:0000269|PubMed:25961573}. CC -!- INDUCTION: Transcriptionally repressed following hypoxia by HIF1A CC in leukemic cells. {ECO:0000269|PubMed:25961573}. CC -!- SIMILARITY: Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH21107.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA13385.2; Type=Erroneous initiation; Evidence={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; D87444; BAA13385.2; ALT_INIT; mRNA. DR EMBL; AL049539; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471077; EAW76391.1; -; Genomic_DNA. DR EMBL; BC021107; AAH21107.1; ALT_INIT; mRNA. DR EMBL; BC022850; AAH22850.2; -; mRNA. DR CCDS; CCDS13196.2; -. DR RefSeq; NP_055557.2; NM_014742.3. DR RefSeq; XP_005260679.1; XM_005260622.4. DR UniGene; Hs.654665; -. DR ProteinModelPortal; Q92544; -. DR BioGrid; 115121; 51. DR IntAct; Q92544; 32. DR MINT; Q92544; -. DR STRING; 9606.ENSP00000381104; -. DR TCDB; 8.A.68.1.3; the endomembrane protein-70 (emp70) family. DR iPTMnet; Q92544; -. DR PhosphoSitePlus; Q92544; -. DR SwissPalm; Q92544; -. DR BioMuta; TM9SF4; -. DR DMDM; 172045829; -. DR EPD; Q92544; -. DR MaxQB; Q92544; -. DR PaxDb; Q92544; -. DR PeptideAtlas; Q92544; -. DR PRIDE; Q92544; -. DR Ensembl; ENST00000398022; ENSP00000381104; ENSG00000101337. DR GeneID; 9777; -. DR KEGG; hsa:9777; -. DR UCSC; uc002wxj.2; human. DR CTD; 9777; -. DR DisGeNET; 9777; -. DR EuPathDB; HostDB:ENSG00000101337.15; -. DR GeneCards; TM9SF4; -. DR H-InvDB; HIX0015722; -. DR HGNC; HGNC:30797; TM9SF4. DR HPA; HPA064099; -. DR MIM; 617727; gene. DR neXtProt; NX_Q92544; -. DR OpenTargets; ENSG00000101337; -. DR PharmGKB; PA134937613; -. DR eggNOG; KOG1278; Eukaryota. DR eggNOG; ENOG410XPIW; LUCA. DR GeneTree; ENSGT00530000062897; -. DR HOGENOM; HOG000216679; -. DR HOVERGEN; HBG054197; -. DR InParanoid; Q92544; -. DR KO; K17086; -. DR OMA; HEYFVHL; -. DR OrthoDB; EOG091G03BD; -. DR PhylomeDB; Q92544; -. DR TreeFam; TF354239; -. DR ChiTaRS; TM9SF4; human. DR GenomeRNAi; 9777; -. DR PRO; PR:Q92544; -. DR Proteomes; UP000005640; Chromosome 20. DR Bgee; ENSG00000101337; -. DR CleanEx; HS_TM9SF4; -. DR ExpressionAtlas; Q92544; baseline and differential. DR Genevisible; Q92544; HS. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central. DR GO; GO:0007155; P:cell adhesion; IMP:UniProtKB. DR GO; GO:0006909; P:phagocytosis; IMP:UniProtKB. DR GO; GO:0070863; P:positive regulation of protein exit from endoplasmic reticulum; IMP:UniProtKB. DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IMP:UniProtKB. DR GO; GO:0051453; P:regulation of intracellular pH; IMP:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0070072; P:vacuolar proton-transporting V-type ATPase complex assembly; IMP:UniProtKB. DR InterPro; IPR004240; EMP70. DR PANTHER; PTHR10766; PTHR10766; 1. DR Pfam; PF02990; EMP70; 1. PE 1: Evidence at protein level; KW Complete proteome; Endosome; Golgi apparatus; Membrane; KW Phosphoprotein; Reference proteome; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 23 {ECO:0000255}. FT CHAIN 24 642 Transmembrane 9 superfamily member 4. FT /FTId=PRO_0000210178. FT TOPO_DOM 24 281 Extracellular. {ECO:0000255}. FT TRANSMEM 282 302 Helical. {ECO:0000255}. FT TOPO_DOM 303 346 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 347 367 Helical. {ECO:0000255}. FT TOPO_DOM 368 376 Extracellular. {ECO:0000255}. FT TRANSMEM 377 397 Helical. {ECO:0000255}. FT TOPO_DOM 398 416 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 417 437 Helical. {ECO:0000255}. FT TOPO_DOM 438 449 Extracellular. {ECO:0000255}. FT TRANSMEM 450 470 Helical. {ECO:0000255}. FT TOPO_DOM 471 501 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 502 522 Helical. {ECO:0000255}. FT TOPO_DOM 523 535 Extracellular. {ECO:0000255}. FT TRANSMEM 536 556 Helical. {ECO:0000255}. FT TOPO_DOM 557 570 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 571 591 Helical. {ECO:0000255}. FT TOPO_DOM 592 598 Extracellular. {ECO:0000255}. FT TRANSMEM 599 619 Helical. {ECO:0000255}. FT TOPO_DOM 620 642 Cytoplasmic. {ECO:0000255}. FT MOD_RES 312 312 Phosphotyrosine. FT {ECO:0000244|PubMed:18088087}. SQ SEQUENCE 642 AA; 74519 MW; 91E8F925D64A5AE7 CRC64; MATAMDWLPW SLLLFSLMCE TSAFYVPGVA PINFHQNDPV EIKAVKLTSS RTQLPYEYYS LPFCQPSKIT YKAENLGEVL RGDRIVNTPF QVLMNSEKKC EVLCSQSNKP VTLTVEQSRL VAERITEDYY VHLIADNLPV ATRLELYSNR DSDDKKKEKD VQFEHGYRLG FTDVNKIYLH NHLSFILYYH REDMEEDQEH TYRVVRFEVI PQSIRLEDLK ADEKSSCTLP EGTNSSPQEI DPTKENQLYF TYSVHWEESD IKWASRWDTY LTMSDVQIHW FSIINSVVVV FFLSGILSMI IIRTLRKDIA NYNKEDDIED TMEESGWKLV HGDVFRPPQY PMILSSLLGS GIQLFCMILI VIFVAMLGML SPSSRGALMT TACFLFMFMG VFGGFSAGRL YRTLKGHRWK KGAFCTATLY PGVVFGICFV LNCFIWGKHS SGAVPFPTMV ALLCMWFGIS LPLVYLGYYF GFRKQPYDNP VRTNQIPRQI PEQRWYMNRF VGILMAGILP FGAMFIELFF IFSAIWENQF YYLFGFLFLV FIILVVSCSQ ISIVMVYFQL CAEDYRWWWR NFLVSGGSAF YVLVYAIFYF VNKLDIVEFI PSLLYFGYTA LMVLSFWLLT GTIGFYAAYM FVRKIYAAVK ID //