ID VPS54_HUMAN Reviewed; 977 AA. AC Q9P1Q0; Q5VIR5; Q86YF7; Q8N6G3; Q9NPV0; Q9NT07; Q9NUJ0; DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot. DT 10-MAY-2005, sequence version 2. DT 10-FEB-2021, entry version 146. DE RecName: Full=Vacuolar protein sorting-associated protein 54; DE AltName: Full=Hepatocellular carcinoma protein 8; DE AltName: Full=Tumor antigen HOM-HCC-8; DE AltName: Full=Tumor antigen SLP-8p; GN Name=VPS54; Synonyms=HCC8; 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 [MRNA] (ISOFORM 2). RC TISSUE=Hepatoma; RA Stenner-Liewen F., Luo G., Tuereci O., Sahin U., Liewen H., Koslowski M., RA Pfreundschuh M.; RT "HOM-HCC-8, a novel tumor antigen associated with hepatocellular RT carcinoma."; RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBUNIT. RX PubMed=15878329; DOI=10.1016/j.yexcr.2005.01.022; RA Liewen H., Meinhold-Heerlein I., Oliveira V., Schwarzenbacher R., Luo G., RA Wadle A., Jung M., Pfreundschuh M., Stenner-Liewen F.; RT "Characterization of the human GARP (Golgi associated retrograde protein) RT complex."; RL Exp. Cell Res. 306:24-34(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Skin, 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 579-977. RC TISSUE=Placenta; 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 [6] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18367545; DOI=10.1091/mbc.e07-11-1189; RA Perez-Victoria F.J., Mardones G.A., Bonifacino J.S.; RT "Requirement of the human GARP complex for mannose 6-phosphate-receptor- RT dependent sorting of cathepsin D to lysosomes."; RL Mol. Biol. Cell 19:2350-2362(2008). RN [7] RP INTERACTION WITH VPS51. RX PubMed=20685960; DOI=10.1091/mbc.e10-05-0392; RA Perez-Victoria F.J., Schindler C., Magadan J.G., Mardones G.A., RA Delevoye C., Romao M., Raposo G., Bonifacino J.S.; RT "Ang2/fat-free is a conserved subunit of the Golgi-associated retrograde RT protein complex."; RL Mol. Biol. Cell 21:3386-3395(2010). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE GARP COMPLEX. RX PubMed=25799061; DOI=10.1038/ncb3129; RA Schindler C., Chen Y., Pu J., Guo X., Bonifacino J.S.; RT "EARP is a multisubunit tethering complex involved in endocytic RT recycling."; RL Nat. Cell Biol. 17:639-650(2015). RN [10] RP IDENTIFICATION IN THE GARP COMPLEX, AND INTERACTION WITH EIPR1. RX PubMed=27440922; DOI=10.1091/mbc.e16-04-0209; RA Gershlick D.C., Schindler C., Chen Y., Bonifacino J.S.; RT "TSSC1 is novel component of the endosomal retrieval machinery."; RL Mol. Biol. Cell 27:2867-2878(2016). RN [11] RP INTERACTION WITH VPS51. RX PubMed=31721635; DOI=10.1091/mbc.e18-07-0469; RA Topalidou I., Cattin-Ortola J., Hummer B., Asensio C.S., Ailion M.; RT "EIPR1 controls dense-core vesicle cargo retention and EARP complex RT localization in insulin-secreting cells."; RL Mol. Biol. Cell 31:59-79(2020). CC -!- FUNCTION: Acts as component of the GARP complex that is involved in CC retrograde transport from early and late endosomes to the trans-Golgi CC network (TGN). The GARP complex is required for the maintenance of the CC cycling of mannose 6-phosphate receptors between the TGN and endosomes, CC this cycling is necessary for proper lysosomal sorting of acid CC hydrolases such as CTSD (PubMed:18367545). Within the GARP complex, CC required to tether the complex to the TGN. Not involved in endocytic CC recycling (PubMed:25799061). {ECO:0000269|PubMed:18367545, CC ECO:0000269|PubMed:25799061}. CC -!- SUBUNIT: Component of the Golgi-associated retrograde protein (GARP) CC complex, also called VFT (VPS fifty-three) complex, composed of VPS51, CC VPS52, VPS53 and VPS54 (PubMed:15878329, PubMed:25799061, CC PubMed:27440922). EIPR1 interacts with GARP complex and mediates its CC recruitment to the trans-Golgi network (PubMed:27440922). Interacts CC with VPS51 in an EIPR1-independent manner (PubMed:31721635). CC {ECO:0000269|PubMed:15878329, ECO:0000269|PubMed:25799061, CC ECO:0000269|PubMed:27440922, ECO:0000269|PubMed:31721635}. CC -!- INTERACTION: CC Q9P1Q0-4; P55212: CASP6; NbExp=3; IntAct=EBI-25835297, EBI-718729; CC Q9P1Q0-4; P06307: CCK; NbExp=3; IntAct=EBI-25835297, EBI-6624398; CC Q9P1Q0-4; P22607: FGFR3; NbExp=3; IntAct=EBI-25835297, EBI-348399; CC Q9P1Q0-4; Q14957: GRIN2C; NbExp=3; IntAct=EBI-25835297, EBI-8285963; CC Q9P1Q0-4; P06396: GSN; NbExp=3; IntAct=EBI-25835297, EBI-351506; CC Q9P1Q0-4; O00291: HIP1; NbExp=3; IntAct=EBI-25835297, EBI-473886; CC Q9P1Q0-4; P13473-2: LAMP2; NbExp=3; IntAct=EBI-25835297, EBI-21591415; CC Q9P1Q0-4; P62826: RAN; NbExp=3; IntAct=EBI-25835297, EBI-286642; CC Q9P1Q0-4; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-25835297, EBI-741480; CC Q9P1Q0-4; Q9Y649; NbExp=3; IntAct=EBI-25835297, EBI-25900580; CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network CC {ECO:0000269|PubMed:18367545, ECO:0000269|PubMed:25799061}. Membrane CC {ECO:0000250|UniProtKB:Q9JMK8}. Note=Associates with membranes in an CC EIPR1-independent manner. {ECO:0000250|UniProtKB:Q9JMK8}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q9P1Q0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9P1Q0-2; Sequence=VSP_013756; CC Name=3; CC IsoId=Q9P1Q0-3; Sequence=VSP_013752, VSP_013754, VSP_013755; CC Name=4; CC IsoId=Q9P1Q0-4; Sequence=VSP_013753; CC Name=5; CC IsoId=Q9P1Q0-5; Sequence=VSP_013751; CC -!- SIMILARITY: Belongs to the VPS54 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA92134.1; 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; AF102177; AAF37319.1; -; mRNA. DR EMBL; AY444798; AAS20945.1; -; mRNA. DR EMBL; AL137604; CAB70837.1; -; mRNA. DR EMBL; AL359939; CAB95772.1; -; mRNA. DR EMBL; CR749701; CAH18479.1; -; mRNA. DR EMBL; BC030275; AAH30275.1; -; mRNA. DR EMBL; BC041868; AAH41868.1; -; mRNA. DR EMBL; AK002205; BAA92134.1; ALT_INIT; mRNA. DR CCDS; CCDS33208.1; -. [Q9P1Q0-1] DR CCDS; CCDS46302.1; -. [Q9P1Q0-4] DR PIR; T46308; T46308. DR RefSeq; NP_001005739.1; NM_001005739.1. [Q9P1Q0-4] DR RefSeq; NP_057600.2; NM_016516.2. [Q9P1Q0-1] DR SMR; Q9P1Q0; -. DR BioGRID; 119600; 26. DR CORUM; Q9P1Q0; -. DR DIP; DIP-61627N; -. DR IntAct; Q9P1Q0; 22. DR STRING; 9606.ENSP00000272322; -. DR iPTMnet; Q9P1Q0; -. DR PhosphoSitePlus; Q9P1Q0; -. DR BioMuta; VPS54; -. DR DMDM; 82583721; -. DR jPOST; Q9P1Q0; -. DR MassIVE; Q9P1Q0; -. DR MaxQB; Q9P1Q0; -. DR PaxDb; Q9P1Q0; -. DR PeptideAtlas; Q9P1Q0; -. DR PRIDE; Q9P1Q0; -. DR ProteomicsDB; 83656; -. [Q9P1Q0-1] DR ProteomicsDB; 83657; -. [Q9P1Q0-2] DR ProteomicsDB; 83658; -. [Q9P1Q0-3] DR ProteomicsDB; 83659; -. [Q9P1Q0-4] DR ProteomicsDB; 83660; -. [Q9P1Q0-5] DR Antibodypedia; 30808; 140 antibodies. DR DNASU; 51542; -. DR Ensembl; ENST00000272322; ENSP00000272322; ENSG00000143952. [Q9P1Q0-1] DR Ensembl; ENST00000354504; ENSP00000346499; ENSG00000143952. [Q9P1Q0-3] DR Ensembl; ENST00000409558; ENSP00000386980; ENSG00000143952. [Q9P1Q0-4] DR GeneID; 51542; -. DR KEGG; hsa:51542; -. DR UCSC; uc002scp.4; human. [Q9P1Q0-1] DR CTD; 51542; -. DR DisGeNET; 51542; -. DR GeneCards; VPS54; -. DR HGNC; HGNC:18652; VPS54. DR HPA; ENSG00000143952; Low tissue specificity. DR MIM; 614633; gene. DR neXtProt; NX_Q9P1Q0; -. DR OpenTargets; ENSG00000143952; -. DR PharmGKB; PA134920394; -. DR VEuPathDB; HostDB:ENSG00000143952.19; -. DR eggNOG; KOG2115; Eukaryota. DR GeneTree; ENSGT00390000000583; -. DR HOGENOM; CLU_005185_1_0_1; -. DR InParanoid; Q9P1Q0; -. DR OMA; ANGMEMP; -. DR OrthoDB; 449680at2759; -. DR PhylomeDB; Q9P1Q0; -. DR TreeFam; TF313700; -. DR PathwayCommons; Q9P1Q0; -. DR Reactome; R-HSA-6811440; Retrograde transport at the Trans-Golgi-Network. DR BioGRID-ORCS; 51542; 222 hits in 895 CRISPR screens. DR ChiTaRS; VPS54; human. DR GenomeRNAi; 51542; -. DR Pharos; Q9P1Q0; Tbio. DR PRO; PR:Q9P1Q0; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9P1Q0; protein. DR Bgee; ENSG00000143952; Expressed in sperm and 229 other tissues. DR ExpressionAtlas; Q9P1Q0; baseline and differential. DR Genevisible; Q9P1Q0; HS. DR GO; GO:0005829; C:cytosol; IEA:GOC. DR GO; GO:0000938; C:GARP complex; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB. DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome. DR GO; GO:0019905; F:syntaxin binding; IBA:GO_Central. DR GO; GO:0006896; P:Golgi to vacuole transport; IBA:GO_Central. DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl. DR GO; GO:0007041; P:lysosomal transport; IMP:MGI. DR GO; GO:0050881; P:musculoskeletal movement; IEA:Ensembl. DR GO; GO:0060052; P:neurofilament cytoskeleton organization; IEA:Ensembl. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0040008; P:regulation of growth; IEA:Ensembl. DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:MGI. DR InterPro; IPR039745; Vps54. DR InterPro; IPR012501; Vps54_C. DR InterPro; IPR019515; VPS54_N. DR PANTHER; PTHR12965; PTHR12965; 1. DR Pfam; PF07928; Vps54; 1. DR Pfam; PF10475; Vps54_N; 1. PE 1: Evidence at protein level; KW Alternative splicing; Coiled coil; Golgi apparatus; Membrane; KW Phosphoprotein; Protein transport; Reference proteome; Transport. FT CHAIN 1..977 FT /note="Vacuolar protein sorting-associated protein 54" FT /id="PRO_0000148731" FT COILED 240..260 FT /evidence="ECO:0000255" FT COILED 480..507 FT /evidence="ECO:0000255" FT COILED 582..603 FT /evidence="ECO:0000255" FT MOD_RES 8 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT VAR_SEQ 1..838 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_013751" FT VAR_SEQ 1..117 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013752" FT VAR_SEQ 46..57 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013753" FT VAR_SEQ 118..126 FT /note="TVYQQEISQ -> MLPTKNRIK (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013754" FT VAR_SEQ 380..415 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013755" FT VAR_SEQ 964..977 FT /note="DLDLNMAEIWEQKR -> IWT (in isoform 2)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_013756" FT VARIANT 561 FT /note="S -> C (in dbSNP:rs34015596)" FT /id="VAR_052944" FT VARIANT 912 FT /note="M -> I (in dbSNP:rs11558741)" FT /id="VAR_061983" FT CONFLICT 130 FT /note="I -> V (in Ref. 1; AAF37319)" FT /evidence="ECO:0000305" FT CONFLICT 526 FT /note="E -> K (in Ref. 1; AAF37319)" FT /evidence="ECO:0000305" FT CONFLICT 601 FT /note="E -> G (in Ref. 1; AAF37319)" FT /evidence="ECO:0000305" FT CONFLICT 643 FT /note="E -> G (in Ref. 1; AAF37319)" FT /evidence="ECO:0000305" FT CONFLICT 650 FT /note="E -> A (in Ref. 1; AAF37319)" FT /evidence="ECO:0000305" FT CONFLICT 677..679 FT /note="EER -> VGG (in Ref. 1; AAF37319)" FT /evidence="ECO:0000305" FT CONFLICT 727 FT /note="K -> E (in Ref. 5; BAA92134)" FT /evidence="ECO:0000305" FT CONFLICT 844 FT /note="D -> G (in Ref. 4; AAH41868)" FT /evidence="ECO:0000305" FT CONFLICT 904 FT /note="L -> H (in Ref. 4; AAH41868)" FT /evidence="ECO:0000305" SQ SEQUENCE 977 AA; 110589 MW; 3290160E3460C836 CRC64; MASSHSSSPV PQGSSSDVFF KIEVDPSKHI RPVPSLPDVC PKEPTGDSHS LYVAPSLVTD QHRWTVYHSK VNLPAALNDP RLAKRESDFF TKTWGLDFVD TEVIPSFYLP QISKEHFTVY QQEISQREKI HERCKNICPP KDTFERTLLH THDKSRTDLE QVPKIFMKPD FALDDSLTFN SVLPWSHFNT AGGKGNRDAA SSKLLQEKLS HYLDIVEVNI AHQISLRSEA FFHAMTSQHE LQDYLRKTSQ AVKMLRDKIA QIDKVMCEGS LHILRLALTR NNCVKVYNKL KLMATVHQTQ PTVQVLLSTS EFVGALDLIA TTQEVLQQEL QGIHSFRHLG SQLCELEKLI DKMMIAEFST YSHSDLNRPL EDDCQVLEEE RLISLVFGLL KQRKLNFLEI YGEKMVITAK NIIKQCVINK VSQTEEIDTD VVVKLADQMR MLNFPQWFDL LKDIFSKFTI FLQRVKATLN IIHSVVLSVL DKNQRTRELE EISQQKNAAK DNSLDTEVAY LIHEGMFISD AFGEGELTPI AVDTTSQRNA SPNSEPCSSD SVSEPECTTD SSSSKEHTSS SAIPGGVDIM VSEDMKLTDS ELGKLANNIQ ELLYSASDIC HDRAVKFLMS RAKDGFLEKL NSMEFITLSR LMETFILDTE QICGRKSTSL LGALQSQAIK FVNRFHEERK TKLSLLLDNE RWKQADVPAE FQDLVDSLSD GKIALPEKKS GATEERKPAE VLIVEGQQYA VVGTVLLLIR IILEYCQCVD NIPSVTTDML TRLSDLLKYF NSRSCQLVLG AGALQVVGLK TITTKNLALS SRCLQLIVHY IPVIRAHFEA RLPPKQYSML RHFDHITKDY HDHIAEISAK LVAIMDSLFD KLLSKYEVKA PVPSACFRNI CKQMTKMHEA IFDLLPEEQT QMLFLRINAS YKLHLKKQLS HLNVINDGGP QNGLVTADVA FYTGNLQALK GLKDLDLNMA EIWEQKR //