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 02-OCT-2024, entry version 178. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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. The RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of RT 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., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., 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., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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., 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 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-312, AND IDENTIFICATION BY RP 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., Barca S., RA Marino M.L., Logozzi M., Federici C., Iessi E., 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., Iessi E., RA Venturi G., Meschini S., Canitano A., Bona R., Cara A., Fais S.; RT "TM9SF4 is a novel V-ATPase-interacting protein that modulates tumor pH RT alterations associated with drug resistance and invasiveness of colon RT 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 cell RT 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., Ayoub D., RA 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 transmembrane CC domains and ensures their efficient localization to the cell surface CC (PubMed:25999474). Regulates the assembly and activity of V-ATPase in CC colon cancer cells via its interaction with V-type proton ATPase CC subunit H (ATP6V1H) and contributes to V-ATPase-mediated pH alterations CC in cancer cells which play an important role in drug resistance and CC invasiveness of colon cancer cells (PubMed:25659576). Plays an CC important role in an atypical phagocytic activity of metastatic CC melanoma cells called cannibalism and is involved in the pH regulation CC of the 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 -!- INTERACTION: CC Q92544; P13726: F3; NbExp=2; IntAct=EBI-6138615, EBI-1040727; CC Q92544; P42345: MTOR; NbExp=4; IntAct=EBI-6138615, EBI-359260; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane CC protein {ECO:0000255}. Golgi apparatus {ECO:0000269|PubMed:25999474}. CC Early endosome {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 particular CC in those displaying granulocytic differentiation (at protein level). CC {ECO:0000269|PubMed:19893578, ECO:0000269|PubMed:25961573}. CC -!- INDUCTION: Transcriptionally repressed following hypoxia by HIF1A in CC 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 AlphaFoldDB; Q92544; -. DR SMR; Q92544; -. DR BioGRID; 115121; 142. DR IntAct; Q92544; 78. DR MINT; Q92544; -. DR STRING; 9606.ENSP00000381104; -. DR TCDB; 8.A.68.1.3; the endomembrane protein-70 (emp70) family. DR TCDB; 8.A.86.1.18; the chloroplast trigalactosyldiacylglycerol-5 (tgd5) family. DR GlyGen; Q92544; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q92544; -. DR PhosphoSitePlus; Q92544; -. DR SwissPalm; Q92544; -. DR BioMuta; TM9SF4; -. DR DMDM; 172045829; -. DR jPOST; Q92544; -. DR MassIVE; Q92544; -. DR PaxDb; 9606-ENSP00000381104; -. DR PeptideAtlas; Q92544; -. DR ProteomicsDB; 75305; -. DR Pumba; Q92544; -. DR ABCD; Q92544; 2 sequenced antibodies. DR Antibodypedia; 42955; 126 antibodies from 21 providers. DR DNASU; 9777; -. DR Ensembl; ENST00000398022.7; ENSP00000381104.2; ENSG00000101337.16. DR GeneID; 9777; -. DR KEGG; hsa:9777; -. DR MANE-Select; ENST00000398022.7; ENSP00000381104.2; NM_014742.4; NP_055557.2. DR UCSC; uc002wxj.2; human. DR AGR; HGNC:30797; -. DR CTD; 9777; -. DR DisGeNET; 9777; -. DR GeneCards; TM9SF4; -. DR HGNC; HGNC:30797; TM9SF4. DR HPA; ENSG00000101337; Low tissue specificity. DR MIM; 617727; gene. DR neXtProt; NX_Q92544; -. DR OpenTargets; ENSG00000101337; -. DR PharmGKB; PA134937613; -. DR VEuPathDB; HostDB:ENSG00000101337; -. DR eggNOG; KOG1278; Eukaryota. DR GeneTree; ENSGT00940000157198; -. DR InParanoid; Q92544; -. DR OMA; NLFLWAK; -. DR OrthoDB; 3078144at2759; -. DR PhylomeDB; Q92544; -. DR TreeFam; TF354239; -. DR PathwayCommons; Q92544; -. DR SignaLink; Q92544; -. DR SIGNOR; Q92544; -. DR BioGRID-ORCS; 9777; 17 hits in 1150 CRISPR screens. DR ChiTaRS; TM9SF4; human. DR GenomeRNAi; 9777; -. DR Pharos; Q92544; Tbio. DR PRO; PR:Q92544; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q92544; protein. DR Bgee; ENSG00000101337; Expressed in stromal cell of endometrium and 206 other cell types or tissues. DR ExpressionAtlas; Q92544; baseline and differential. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0016020; C: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:0072657; P:protein localization to membrane; IBA:GO_Central. 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:SF55; TRANSMEMBRANE 9 SUPERFAMILY MEMBER 4; 1. DR PANTHER; PTHR10766; TRANSMEMBRANE 9 SUPERFAMILY PROTEIN; 1. DR Pfam; PF02990; EMP70; 1. PE 1: Evidence at protein level; KW Endosome; Golgi apparatus; Membrane; Phosphoprotein; KW Proteomics identification; Reference proteome; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..642 FT /note="Transmembrane 9 superfamily member 4" FT /id="PRO_0000210178" FT TOPO_DOM 24..281 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 282..302 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 303..346 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 347..367 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 368..376 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 377..397 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 398..416 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 417..437 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 438..449 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 450..470 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 471..501 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 502..522 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 523..535 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 536..556 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 557..570 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 571..591 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 592..598 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 599..619 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 620..642 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOD_RES 312 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|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 //