ID VAC14_HUMAN Reviewed; 782 AA. AC Q08AM6; B3KPJ5; B3KSM8; Q13174; Q6IA12; Q7L4Y1; Q9BW96; Q9H6V6; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2006, sequence version 1. DT 02-SEP-2026, entry version 162. DE RecName: Full=Protein VAC14 homolog; DE AltName: Full=Tax1-binding protein 2; GN Name=VAC14; Synonyms=TAX1BP2, TRX; 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] (ISOFORMS 1 AND 2). RC TISSUE=Trachea; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, and Lung; 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 244-366 (ISOFORM 1), TISSUE SPECIFICITY, AND RP INTERACTION WITH HTLV-1 PROTEIN TAX (MICROBIAL INFECTION). RX PubMed=8611628; DOI=10.1016/0167-4781(96)00012-7; RA Mireskandari A., Reid R.L., Kashanchi F., Dittmer J., Li W.B., Brady J.N.; RT "Isolation of a cDNA clone, TRX encoding a human T-cell lymphotrophic virus RT type-I Tax1 binding protein."; RL Biochim. Biophys. Acta 1306:9-13(1996). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 259-782 (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15542851; DOI=10.1128/mcb.24.23.10437-10447.2004; RA Sbrissa D., Ikonomov O.C., Strakova J., Dondapati R., Mlak K., Deeb R., RA Silver R., Shisheva A.; RT "A mammalian ortholog of Saccharomyces cerevisiae Vac14 that associates RT with and up-regulates PIKfyve phosphoinositide 5-kinase activity."; RL Mol. Cell. Biol. 24:10437-10447(2004). RN [7] RP INTERACTION WITH NOS1, AND MUTAGENESIS OF GLY-773; ASP-774; LEU-776; RP ASP-777; 780-VAL--LEU-782 AND LEU-782. RX PubMed=17161399; DOI=10.1016/j.febslet.2006.11.061; RA Lemaire J.F., McPherson P.S.; RT "Binding of Vac14 to neuronal nitric oxide synthase: Characterisation of a RT new internal PDZ-recognition motif."; RL FEBS Lett. 580:6948-6954(2006). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE PI(3,5)P2 RP REGULATORY COMPLEX. RX PubMed=17556371; DOI=10.1074/jbc.m611678200; RA Sbrissa D., Ikonomov O.C., Fu Z., Ijuin T., Gruenberg J., Takenawa T., RA Shisheva A.; RT "Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate RT synthesis and turnover that regulates the progression of endosomal RT transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex."; RL J. Biol. Chem. 282:23878-23891(2007). RN [9] RP SUBUNIT, IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, AND DOMAIN. RX PubMed=18950639; DOI=10.1016/j.jmb.2008.10.009; RA Sbrissa D., Ikonomov O.C., Fenner H., Shisheva A.; RT "ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 RT in a complex to promote PIKfyve activity and functionality."; RL J. Mol. Biol. 384:766-779(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-11 AND THR-499, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-517 AND SER-743, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] {ECO:0007744|PDB:7K1Y} RP STRUCTURE BY ELECTRON MICROSCOPY (5.25 ANGSTROMS) OF 1-782, FUNCTION, RP SUBUNIT, AND IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX. RX PubMed=33098764; DOI=10.1016/j.molcel.2020.10.003; RA Lees J.A., Li P., Kumar N., Weisman L.S., Reinisch K.M.; RT "Insights into Lysosomal PI(3,5)P2 Homeostasis from a Structural- RT Biochemical Analysis of the PIKfyve Lipid Kinase Complex."; RL Mol. Cell 80:736-743.e4(2020). RN [19] RP INVOLVEMENT IN SNDC, AND VARIANTS SNDC LEU-424; SER-582 AND LEU-583. RX PubMed=27292112; DOI=10.1016/j.ajhg.2016.05.008; RA Lenk G.M., Szymanska K., Debska-Vielhaber G., Rydzanicz M., Walczak A., RA Bekiesinska-Figatowska M., Vielhaber S., Hallmann K., Stawinski P., RA Buehring S., Hsu D.A., Kunz W.S., Meisler M.H., Ploski R.; RT "Biallelic mutations of VAC14 in pediatric-onset neurological disease."; RL Am. J. Hum. Genet. 99:188-194(2016). CC -!- FUNCTION: Scaffold protein component of the PI(3,5)P2 regulatory CC complex which regulates both the synthesis and turnover of CC phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Pentamerizes CC into a star-shaped structure and nucleates the assembly of the complex. CC The pentamer binds a single copy each of PIKFYVE and FIG4 and CC coordinates both PIKfyve kinase activity and FIG4 phosphatase activity, CC being required to maintain normal levels of phosphatidylinositol 3- CC phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate CC (PtdIns(5)P) (PubMed:33098764). Plays a role in the biogenesis of CC endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport CC intermediates from early endosomes. {ECO:0000269|PubMed:15542851, CC ECO:0000269|PubMed:17556371, ECO:0000269|PubMed:33098764}. CC -!- SUBUNIT: Forms pentamers (PubMed:18950639, PubMed:33098764). Component CC of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of CC PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex CC and serves as a scaffold by pentamerizing into a star-shaped structure, CC which can bind a single copy each of PIKFYVE and FIG4 and coordinates CC their activities (PubMed:17556371, PubMed:18950639, PubMed:33098764). CC Interacts with NOS1 (PubMed:17161399). {ECO:0000269|PubMed:17161399, CC ECO:0000269|PubMed:17556371, ECO:0000269|PubMed:18950639, CC ECO:0000269|PubMed:33098764}. CC -!- SUBUNIT: (Microbial infection) Interacts with HTLV-1 Tax. CC {ECO:0000269|PubMed:8611628}. CC -!- INTERACTION: CC Q08AM6; Q8NFV4-4: ABHD11; NbExp=3; IntAct=EBI-2107455, EBI-12318443; CC Q08AM6; Q9NUB1: ACSS1; NbExp=6; IntAct=EBI-2107455, EBI-10313831; CC Q08AM6; Q5BKX5-3: ACTMAP; NbExp=3; IntAct=EBI-2107455, EBI-11976299; CC Q08AM6; P48728-4: AMT; NbExp=3; IntAct=EBI-2107455, EBI-14394829; CC Q08AM6; Q02410: APBA1; NbExp=2; IntAct=EBI-2107455, EBI-368690; CC Q08AM6; Q99767: APBA2; NbExp=2; IntAct=EBI-2107455, EBI-81711; CC Q08AM6; Q03989: ARID5A; NbExp=3; IntAct=EBI-2107455, EBI-948603; CC Q08AM6; Q8WXK3: ASB13; NbExp=6; IntAct=EBI-2107455, EBI-707573; CC Q08AM6; Q8WXK3-2: ASB13; NbExp=3; IntAct=EBI-2107455, EBI-12015080; CC Q08AM6; P13637: ATP1A3; NbExp=3; IntAct=EBI-2107455, EBI-948169; CC Q08AM6; A0A0S2Z3D2: BCL2L1; NbExp=3; IntAct=EBI-2107455, EBI-16431449; CC Q08AM6; O14503: BHLHE40; NbExp=6; IntAct=EBI-2107455, EBI-711810; CC Q08AM6; Q9H0W9: C11orf54; NbExp=4; IntAct=EBI-2107455, EBI-740204; CC Q08AM6; Q9H0W9-3: C11orf54; NbExp=3; IntAct=EBI-2107455, EBI-12108466; CC Q08AM6; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-2107455, EBI-739879; CC Q08AM6; Q8N1A6: C4orf33; NbExp=8; IntAct=EBI-2107455, EBI-10264911; CC Q08AM6; P29466: CASP1; NbExp=4; IntAct=EBI-2107455, EBI-516667; CC Q08AM6; P29466-3: CASP1; NbExp=3; IntAct=EBI-2107455, EBI-12248206; CC Q08AM6; Q9NNX6: CD209; NbExp=4; IntAct=EBI-2107455, EBI-9257341; CC Q08AM6; Q9NNX6-10: CD209; NbExp=3; IntAct=EBI-2107455, EBI-12300031; CC Q08AM6; Q8N9R6: CDRT4; NbExp=7; IntAct=EBI-2107455, EBI-10176618; CC Q08AM6; P27658: COL8A1; NbExp=7; IntAct=EBI-2107455, EBI-747133; CC Q08AM6; P05813: CRYBA1; NbExp=3; IntAct=EBI-2107455, EBI-7043337; CC Q08AM6; P53672: CRYBA2; NbExp=3; IntAct=EBI-2107455, EBI-750444; CC Q08AM6; Q12959: DLG1; NbExp=3; IntAct=EBI-2107455, EBI-357481; CC Q08AM6; Q15700: DLG2; NbExp=2; IntAct=EBI-2107455, EBI-80426; CC Q08AM6; Q92796: DLG3; NbExp=3; IntAct=EBI-2107455, EBI-80440; CC Q08AM6; P78352: DLG4; NbExp=3; IntAct=EBI-2107455, EBI-80389; CC Q08AM6; Q8IW40: DNAAF19; NbExp=8; IntAct=EBI-2107455, EBI-10261970; CC Q08AM6; Q96AZ1: EEF1AKMT3; NbExp=3; IntAct=EBI-2107455, EBI-12108304; CC Q08AM6; Q08426: EHHADH; NbExp=3; IntAct=EBI-2107455, EBI-2339219; CC Q08AM6; P05198: EIF2S1; NbExp=3; IntAct=EBI-2107455, EBI-1056162; CC Q08AM6; P56537: EIF6; NbExp=3; IntAct=EBI-2107455, EBI-372243; CC Q08AM6; Q9Y247: FAM50B; NbExp=3; IntAct=EBI-2107455, EBI-742802; CC Q08AM6; Q92562: FIG4; NbExp=8; IntAct=EBI-2107455, EBI-4290773; CC Q08AM6; Q53EP0-3: FNDC3B; NbExp=3; IntAct=EBI-2107455, EBI-10242151; CC Q08AM6; Q68DX3: FRMPD2; NbExp=2; IntAct=EBI-2107455, EBI-53993476; CC Q08AM6; Q8TAK5: GABPB2; NbExp=3; IntAct=EBI-2107455, EBI-8468945; CC Q08AM6; A0A0S2Z4I0: GALT; NbExp=3; IntAct=EBI-2107455, EBI-16434744; CC Q08AM6; Q9BRX5: GINS3; NbExp=6; IntAct=EBI-2107455, EBI-2857315; CC Q08AM6; Q9BRX5-3: GINS3; NbExp=3; IntAct=EBI-2107455, EBI-16436971; CC Q08AM6; Q9BZE0: GLIS2; NbExp=3; IntAct=EBI-2107455, EBI-7251368; CC Q08AM6; P62873: GNB1; NbExp=3; IntAct=EBI-2107455, EBI-357130; CC Q08AM6; A4D2P6: GRID2IP; NbExp=2; IntAct=EBI-2107455, EBI-15893226; CC Q08AM6; Q9Y3R0: GRIP1; NbExp=5; IntAct=EBI-2107455, EBI-5349621; CC Q08AM6; Q9C0E4: GRIP2; NbExp=4; IntAct=EBI-2107455, EBI-949557; CC Q08AM6; Q8WUA4-2: GTF3C2; NbExp=3; IntAct=EBI-2107455, EBI-11957962; CC Q08AM6; Q9BSH5: HDHD3; NbExp=3; IntAct=EBI-2107455, EBI-745201; CC Q08AM6; V9HW53: HEL-S-277; NbExp=5; IntAct=EBI-2107455, EBI-10330115; CC Q08AM6; P35680: HNF1B; NbExp=3; IntAct=EBI-2107455, EBI-2798841; CC Q08AM6; P42858: HTT; NbExp=3; IntAct=EBI-2107455, EBI-466029; CC Q08AM6; Q14005: IL16; NbExp=2; IntAct=EBI-2107455, EBI-2831580; CC Q08AM6; Q5TA45: INTS11; NbExp=3; IntAct=EBI-2107455, EBI-748258; CC Q08AM6; P0C870: JMJD7; NbExp=3; IntAct=EBI-2107455, EBI-9090173; CC Q08AM6; Q7Z2F6: KRBOX5; NbExp=3; IntAct=EBI-2107455, EBI-2796279; CC Q08AM6; Q9NSB4: KRT82; NbExp=3; IntAct=EBI-2107455, EBI-1045341; CC Q08AM6; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-2107455, EBI-11992140; CC Q08AM6; Q7Z4W3: KRTAP19-3; NbExp=3; IntAct=EBI-2107455, EBI-12020132; CC Q08AM6; Q3LI72: KRTAP19-5; NbExp=6; IntAct=EBI-2107455, EBI-1048945; CC Q08AM6; Q3SYF9: KRTAP19-7; NbExp=6; IntAct=EBI-2107455, EBI-10241353; CC Q08AM6; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-2107455, EBI-12111050; CC Q08AM6; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-2107455, EBI-11962084; CC Q08AM6; Q16773: KYAT1; NbExp=4; IntAct=EBI-2107455, EBI-10238309; CC Q08AM6; Q14847-2: LASP1; NbExp=3; IntAct=EBI-2107455, EBI-9088686; CC Q08AM6; Q8N0U6: LINC00518; NbExp=3; IntAct=EBI-2107455, EBI-10264791; CC Q08AM6; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-2107455, EBI-739832; CC Q08AM6; Q16609: LPAL2; NbExp=3; IntAct=EBI-2107455, EBI-10238012; CC Q08AM6; Q86UL8: MAGI2; NbExp=4; IntAct=EBI-2107455, EBI-311035; CC Q08AM6; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2107455, EBI-16439278; CC Q08AM6; A6NJ78-4: METTL15; NbExp=3; IntAct=EBI-2107455, EBI-10174029; CC Q08AM6; Q15777: MPPED2; NbExp=6; IntAct=EBI-2107455, EBI-2350461; CC Q08AM6; Q96QG7: MTMR9; NbExp=3; IntAct=EBI-2107455, EBI-744593; CC Q08AM6; Q9NP98: MYOZ1; NbExp=3; IntAct=EBI-2107455, EBI-744402; CC Q08AM6; Q6ZNJ1: NBEAL2; NbExp=8; IntAct=EBI-2107455, EBI-2862306; CC Q08AM6; O14561: NDUFAB1; NbExp=3; IntAct=EBI-2107455, EBI-1246261; CC Q08AM6; Q9NPG2: NGB; NbExp=6; IntAct=EBI-2107455, EBI-10311409; CC Q08AM6; P29475: NOS1; NbExp=6; IntAct=EBI-2107455, EBI-7164065; CC Q08AM6; Q96HA8: NTAQ1; NbExp=5; IntAct=EBI-2107455, EBI-741158; CC Q08AM6; Q8WWZ8: OIT3; NbExp=3; IntAct=EBI-2107455, EBI-10277776; CC Q08AM6; Q8NHW6: OTOS; NbExp=3; IntAct=EBI-2107455, EBI-12038159; CC Q08AM6; Q8NI35: PATJ; NbExp=8; IntAct=EBI-2107455, EBI-724390; CC Q08AM6; P30039: PBLD; NbExp=3; IntAct=EBI-2107455, EBI-750589; CC Q08AM6; Q6PIM4: PCMTD2; NbExp=3; IntAct=EBI-2107455, EBI-10253759; CC Q08AM6; Q5T2W1: PDZK1; NbExp=3; IntAct=EBI-2107455, EBI-349819; CC Q08AM6; P16284: PECAM1; NbExp=3; IntAct=EBI-2107455, EBI-716404; CC Q08AM6; Q96FA3: PELI1; NbExp=3; IntAct=EBI-2107455, EBI-448369; CC Q08AM6; O43189: PHF1; NbExp=3; IntAct=EBI-2107455, EBI-530034; CC Q08AM6; Q8IUZ5: PHYKPL; NbExp=4; IntAct=EBI-2107455, EBI-751947; CC Q08AM6; Q9Y2I7: PIKFYVE; NbExp=7; IntAct=EBI-2107455, EBI-6138650; CC Q08AM6; B3KUN1: PPP2CA; NbExp=5; IntAct=EBI-2107455, EBI-10175948; CC Q08AM6; P67775: PPP2CA; NbExp=3; IntAct=EBI-2107455, EBI-712311; CC Q08AM6; O00743: PPP6C; NbExp=3; IntAct=EBI-2107455, EBI-359751; CC Q08AM6; Q9BSG0: PRADC1; NbExp=3; IntAct=EBI-2107455, EBI-10297527; CC Q08AM6; Q9NZ81: PRR13; NbExp=6; IntAct=EBI-2107455, EBI-740924; CC Q08AM6; P86479: PRR20C; NbExp=3; IntAct=EBI-2107455, EBI-10172814; CC Q08AM6; P86480: PRR20D; NbExp=3; IntAct=EBI-2107455, EBI-12754095; CC Q08AM6; O43251: RBFOX2; NbExp=4; IntAct=EBI-2107455, EBI-746056; CC Q08AM6; O75783: RHBDL1; NbExp=3; IntAct=EBI-2107455, EBI-12104986; CC Q08AM6; Q9BQY4: RHOXF2; NbExp=6; IntAct=EBI-2107455, EBI-372094; CC Q08AM6; Q0D2K3: RIPPLY1; NbExp=3; IntAct=EBI-2107455, EBI-10226430; CC Q08AM6; Q8TDP1: RNASEH2C; NbExp=3; IntAct=EBI-2107455, EBI-9027335; CC Q08AM6; Q96LW2: RSKR; NbExp=3; IntAct=EBI-2107455, EBI-1054572; CC Q08AM6; Q14160: SCRIB; NbExp=2; IntAct=EBI-2107455, EBI-357345; CC Q08AM6; O15389: SIGLEC5; NbExp=6; IntAct=EBI-2107455, EBI-750381; CC Q08AM6; Q53HV7: SMUG1; NbExp=4; IntAct=EBI-2107455, EBI-749970; CC Q08AM6; Q53HV7-2: SMUG1; NbExp=3; IntAct=EBI-2107455, EBI-12275818; CC Q08AM6; Q96H20: SNF8; NbExp=4; IntAct=EBI-2107455, EBI-747719; CC Q08AM6; Q96LM6: SPMIP9; NbExp=3; IntAct=EBI-2107455, EBI-743976; CC Q08AM6; Q5W111: SPRYD7; NbExp=4; IntAct=EBI-2107455, EBI-10248098; CC Q08AM6; Q5W111-2: SPRYD7; NbExp=3; IntAct=EBI-2107455, EBI-12408727; CC Q08AM6; Q8N8B7: TCEANC; NbExp=3; IntAct=EBI-2107455, EBI-954696; CC Q08AM6; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-2107455, EBI-11955057; CC Q08AM6; Q9NUW8: TDP1; NbExp=3; IntAct=EBI-2107455, EBI-2902553; CC Q08AM6; Q07157: TJP1; NbExp=2; IntAct=EBI-2107455, EBI-79553; CC Q08AM6; Q12888: TP53BP1; NbExp=6; IntAct=EBI-2107455, EBI-396540; CC Q08AM6; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-2107455, EBI-12068150; CC Q08AM6; Q08AM6: VAC14; NbExp=5; IntAct=EBI-2107455, EBI-2107455; CC Q08AM6; O95231: VENTX; NbExp=3; IntAct=EBI-2107455, EBI-10191303; CC Q08AM6; Q6RSH7: VHLL; NbExp=3; IntAct=EBI-2107455, EBI-10254232; CC Q08AM6; P08670: VIM; NbExp=3; IntAct=EBI-2107455, EBI-353844; CC Q08AM6; Q9BRX9: WDR83; NbExp=3; IntAct=EBI-2107455, EBI-7705033; CC Q08AM6; Q9BUR4: WRAP53; NbExp=3; IntAct=EBI-2107455, EBI-2563542; CC Q08AM6; Q6ZSB9: ZBTB49; NbExp=3; IntAct=EBI-2107455, EBI-2859943; CC Q08AM6; A0A0S2Z6A9: ZCWPW1; NbExp=3; IntAct=EBI-2107455, EBI-16429747; CC Q08AM6; Q8IZ26: ZNF34; NbExp=4; IntAct=EBI-2107455, EBI-10264496; CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:15542851, CC ECO:0000269|PubMed:17556371}. Microsome membrane CC {ECO:0000250|UniProtKB:Q80W92}. Note=Mainly associated with membranes CC of the late endocytic pathway. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q08AM6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q08AM6-2; Sequence=VSP_056097; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC {ECO:0000269|PubMed:8611628}. CC -!- DOMAIN: The C-terminal domain (residues 523-782) mediates pentameric CC interactions and is necessary for the formation and maintenance of the CC PI(3,5)P2 regulatory complex. {ECO:0000269|PubMed:18950639, CC ECO:0000269|PubMed:33098764}. CC -!- DISEASE: Striatonigral degeneration, childhood-onset (SNDC) CC [MIM:617054]: An autosomal recessive neurological disorder CC characterized by sudden childhood onset of developmental regression. CC Affected children develop impaired movements with dystonia, CC progressively become non-ambulatory and non-verbal, and exhibit CC striatal abnormalities on MRI. {ECO:0000269|PubMed:27292112}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the VAC14 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB03813.1; Type=Miscellaneous discrepancy; Note=Unknown C-terminal region.; Evidence={ECO:0000305}; CC Sequence=BAB15145.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AK025479; BAB15145.1; ALT_INIT; mRNA. DR EMBL; AK056433; BAG51707.1; -; mRNA. DR EMBL; AK093941; BAG52790.1; -; mRNA. DR EMBL; AC020763; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC027281; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000536; AAH00536.2; -; mRNA. DR EMBL; BC007214; AAH07214.2; -; mRNA. DR EMBL; BC125108; AAI25109.1; -; mRNA. DR EMBL; BC125109; AAI25110.1; -; mRNA. DR EMBL; U25801; AAB03813.1; ALT_SEQ; mRNA. DR EMBL; CR457343; CAG33624.1; -; mRNA. DR CCDS; CCDS10896.1; -. [Q08AM6-1] DR PIR; S68091; S68091. DR RefSeq; NP_060522.3; NM_018052.5. [Q08AM6-1] DR PDB; 7K1Y; EM; 5.25 A; B/D/E/G=1-782. DR AlphaFoldDB; Q08AM6; -. DR EMDB; EMD-22634; -. DR BioGRID; 120822; 231. DR ComplexPortal; CPX-26396; PtdIns(3,5)P2 regulatory complex. DR CORUM; Q08AM6; -. DR FunCoup; Q08AM6; 3271. DR IntAct; Q08AM6; 251. DR MINT; Q08AM6; -. DR NDEx; IQUERY-CP-VAC14; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000261776; -. DR BindingDB; Q08AM6; -. DR ChEMBL; CHEMBL6066525; -. DR GlyGen; Q08AM6; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q08AM6; -. DR MetOSite; Q08AM6; -. DR PhosphoSitePlus; Q08AM6; -. DR SwissPalm; Q08AM6; -. DR BioMuta; VAC14; -. DR DMDM; 121940040; -. DR jPOST; Q08AM6; -. DR MassIVE; Q08AM6; -. DR PaxDb; 9606-ENSP00000261776; -. DR PeptideAtlas; Q08AM6; -. DR ProteomicsDB; 3649; -. DR ProteomicsDB; 58681; -. [Q08AM6-1] DR Pumba; Q08AM6; -. DR Antibodypedia; 16467; 95 antibodies from 22 providers. DR DNASU; 55697; -. DR Ensembl; ENST00000261776.10; ENSP00000261776.5; ENSG00000103043.16. [Q08AM6-1] DR Ensembl; ENST00000536184.6; ENSP00000439284.2; ENSG00000103043.16. [Q08AM6-2] DR GeneID; 55697; -. DR KEGG; hsa:55697; -. DR MANE-Select; ENST00000261776.10; ENSP00000261776.5; NM_018052.5; NP_060522.3. DR UCSC; uc002ezm.4; human. [Q08AM6-1] DR AGR; HGNC:25507; -. DR ClinPGx; PA142670633; -. DR CTD; 55697; -. DR DisGeNET; 55697; -. DR GeneCards; VAC14; -. DR HGNC; HGNC:25507; VAC14. DR HPA; ENSG00000103043; Low tissue specificity. DR MalaCards; VAC14; -. DR MIM; 604632; gene. DR MIM; 617054; phenotype. DR OpenTargets; ENSG00000103043; -. DR Orphanet; 497906; Childhood-onset basal ganglia degeneration syndrome. DR Orphanet; 3472; Yunis-Varon syndrome. DR VEuPathDB; HostDB:ENSG00000103043; -. DR eggNOG; KOG0212; Eukaryota. DR GeneTree; ENSGT00390000008385; -. DR HOGENOM; CLU_007740_1_0_1; -. DR InParanoid; Q08AM6; -. DR OMA; QCYQHVS; -. DR OrthoDB; 5574975at2759; -. DR PAN-GO; Q08AM6; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q08AM6; -. DR BioCyc; MetaCyc:ENSG00000103043-MONOMER; -. DR PathwayCommons; Q08AM6; -. DR Reactome; R-HSA-1660514; Synthesis of PIPs at the Golgi membrane. DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane. DR Reactome; R-HSA-1660517; Synthesis of PIPs at the late endosome membrane. DR SignaLink; Q08AM6; -. DR SIGNOR; Q08AM6; -. DR Agora; ENSG00000103043; -. DR BioGRID-ORCS; 55697; 80 hits in 1169 CRISPR screens. DR CD-CODE; 8C2F96ED; Centrosome. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; VAC14; human. DR GeneWiki; VAC14; -. DR GenomeRNAi; 55697; -. DR Pharos; Q08AM6; Tbio. DR PRO; PR:Q08AM6; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q08AM6; protein. DR Bgee; ENSG00000103043; Expressed in stromal cell of endometrium and 151 other cell types or tissues. DR ExpressionAtlas; Q08AM6; baseline and differential. DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome. DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0031902; C:late endosome membrane; TAS:Reactome. DR GO; GO:0070772; C:PAS complex; IPI:ComplexPortal. DR GO; GO:0098830; C:presynaptic endosome; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0038023; F:signaling receptor activity; NAS:UniProtKB. DR GO; GO:1903100; P:1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate metabolic process; IDA:ComplexPortal. DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IBA:GO_Central. DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. DR FunFam; 1.25.10.10:FF:000631; Vac14, PIKFYVE complex component; 1. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 2. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR026825; Vac14. DR InterPro; IPR021841; VAC14_Fig4p-bd. DR PANTHER; PTHR16023:SF0; PROTEIN VAC14 HOMOLOG; 1. DR PANTHER; PTHR16023; TAX1 BINDING PROTEIN-RELATED; 1. DR Pfam; PF12755; Vac14_Fab1_bd; 1. DR Pfam; PF11916; Vac14_Fig4_bd; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR PDBsum; 7K1Y; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Disease variant; KW Endoplasmic reticulum; Endosome; Host-virus interaction; Membrane; KW Microsome; Neurodegeneration; Phosphoprotein; Proteomics identification; KW Reference proteome; Repeat. FT CHAIN 1..782 FT /note="Protein VAC14 homolog" FT /id="PRO_0000300485" FT REPEAT 5..42 FT /note="HEAT 1" FT REPEAT 89..126 FT /note="HEAT 2" FT REPEAT 171..208 FT /note="HEAT 3" FT REPEAT 212..249 FT /note="HEAT 4" FT REPEAT 438..475 FT /note="HEAT 5" FT REPEAT 560..598 FT /note="HEAT 6" FT REGION 335..372 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 471..517 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 773..777 FT /note="Mediates interaction with the PDZ domain of NOS1" FT COMPBIAS 478..488 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 506..517 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 11 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 499 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 517 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 743 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..568 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056097" FT VARIANT 424 FT /note="W -> L (in SNDC; dbSNP:rs762388639)" FT /evidence="ECO:0000269|PubMed:27292112" FT /id="VAR_077031" FT VARIANT 582 FT /note="A -> S (in SNDC; dbSNP:rs749094914)" FT /evidence="ECO:0000269|PubMed:27292112" FT /id="VAR_077032" FT VARIANT 583 FT /note="S -> L (in SNDC; dbSNP:rs879255645)" FT /evidence="ECO:0000269|PubMed:27292112" FT /id="VAR_077033" FT MUTAGEN 773 FT /note="G->A: Reduces interaction with NOS1." FT /evidence="ECO:0000269|PubMed:17161399" FT MUTAGEN 774 FT /note="D->A: Reduces interaction with NOS1." FT /evidence="ECO:0000269|PubMed:17161399" FT MUTAGEN 776 FT /note="L->A: Reduces interaction with NOS1." FT /evidence="ECO:0000269|PubMed:17161399" FT MUTAGEN 777 FT /note="D->A: Abolishes interaction with NOS1." FT /evidence="ECO:0000269|PubMed:17161399" FT MUTAGEN 780..782 FT /note="VVL->AAA: Reduces interaction with NOS1." FT /evidence="ECO:0000269|PubMed:17161399" FT MUTAGEN 782 FT /note="L->G: Reduces interaction with NOS1." FT /evidence="ECO:0000269|PubMed:17161399" FT CONFLICT 257 FT /note="A -> P (in Ref. 4; AAB03813)" FT /evidence="ECO:0000305" FT CONFLICT 263 FT /note="L -> P (in Ref. 4; AAB03813)" FT /evidence="ECO:0000305" FT CONFLICT 352 FT /note="T -> A (in Ref. 5; CAG33624)" FT /evidence="ECO:0000305" SQ SEQUENCE 782 AA; 87973 MW; B39AC1F4D619570F CRC64; MNPEKDFAPL TPNIVRALND KLYEKRKVAA LEIEKLVREF VAQNNTVQIK HVIQTLSQEF ALSQHPHSRK GGLIGLAACS IALGKDSGLY LKELIEPVLT CFNDADSRLR YYACEALYNI VKVARGAVLP HFNVLFDGLS KLAADPDPNV KSGSELLDRL LKDIVTESNK FDLVSFIPLL RERIYSNNQY ARQFIISWIL VLESVPDINL LDYLPEILDG LFQILGDNGK EIRKMCEVVL GEFLKEIKKN PSSVKFAEMA NILVIHCQTT DDLIQLTAMC WMREFIQLAG RVMLPYSSGI LTAVLPCLAY DDRKKSIKEV ANVCNQSLMK LVTPEDDELD ELRPGQRQAE PTPDDALPKQ EGTASGGPDG SCDSSFSSGI SVFTAASTER APVTLHLDGI VQVLNCHLSD TAIGMMTRIA VLKWLYHLYI KTPRKMFRHT DSLFPILLQT LSDESDEVIL KDLEVLAEIA SSPAGQTDDP GPLDGPDLQA SHSELQVPTP GRAGLLNTSG TKGLECSPST PTMNSYFYKF MINLLKRFSS ERKLLEVRGP FIIRQLCLLL NAENIFHSMA DILLREEDLK FASTMVHALN TILLTSTELF QLRNQLKDLK TLESQNLFCC LYRSWCHNPV TTVSLCFLTQ NYRHAYDLIQ KFGDLEVTVD FLAEVDKLVQ LIECPIFTYL RLQLLDVKNN PYLIKALYGL LMLLPQSSAF QLLSHRLQCV PNPELLQTED SLKAAPKSQK ADSPSIDYAE LLQHFEKVQN KHLEVRHQRS GRGDHLDRRV VL //