TM9S4_HUMAN
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 03-AUG-2022, entry version 167.
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; 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};
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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 BioGRID; 115121; 134.
DR IntAct; Q92544; 39.
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 jPOST; Q92544; -.
DR MassIVE; Q92544; -.
DR MaxQB; Q92544; -.
DR PaxDb; Q92544; -.
DR PeptideAtlas; Q92544; -.
DR PRIDE; Q92544; -.
DR ProteomicsDB; 75305; -.
DR ABCD; Q92544; 2 sequenced antibodies.
DR Antibodypedia; 42955; 120 antibodies from 20 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 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; CYPKNGT; -.
DR OrthoDB; 641127at2759; -.
DR PhylomeDB; Q92544; -.
DR TreeFam; TF354239; -.
DR PathwayCommons; Q92544; -.
DR SignaLink; Q92544; -.
DR SIGNOR; Q92544; -.
DR BioGRID-ORCS; 9777; 16 hits in 1072 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 204 other tissues.
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; IEA:UniProtKB-KW.
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; PTHR10766; 1.
DR Pfam; PF02990; EMP70; 1.
PE 1: Evidence at protein level;
KW Endosome; Golgi apparatus; Membrane; Phosphoprotein; Reference proteome;
KW Signal; Transmembrane; 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
