VAC14_HUMAN
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 03-AUG-2022, entry version 143.
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:33098764, PubMed:18950639). 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; P48728-4: AMT; NbExp=3; IntAct=EBI-2107455, EBI-14394829;
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; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-2107455, EBI-11976299;
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; Q8IW40: CCDC103; NbExp=8; IntAct=EBI-2107455, EBI-10261970;
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; 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=5; IntAct=EBI-2107455, EBI-4290773;
CC Q08AM6; Q53EP0-3: FNDC3B; NbExp=3; IntAct=EBI-2107455, EBI-10242151;
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; 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; Q5TA45: INTS11; NbExp=3; IntAct=EBI-2107455, EBI-748258;
CC Q08AM6; P0C870: JMJD7; NbExp=3; IntAct=EBI-2107455, EBI-9090173;
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; Q16609: LPAL2; NbExp=3; IntAct=EBI-2107455, EBI-10238012;
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=5; 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; P30039: PBLD; NbExp=3; IntAct=EBI-2107455, EBI-750589;
CC Q08AM6; Q6PIM4: PCMTD2; NbExp=3; IntAct=EBI-2107455, EBI-10253759;
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=5; 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; 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; 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; Q96LM6: TEX37; NbExp=3; IntAct=EBI-2107455, EBI-743976;
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 Q08AM6; Q7Z2F6: ZNF720; NbExp=3; IntAct=EBI-2107455, EBI-2796279;
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};
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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_018052.3. [Q08AM6-1]
DR PDB; 7K1Y; EM; 5.25 A; B/D/E/G=1-782.
DR PDBsum; 7K1Y; -.
DR AlphaFoldDB; Q08AM6; -.
DR BioGRID; 120822; 205.
DR CORUM; Q08AM6; -.
DR IntAct; Q08AM6; 139.
DR MINT; Q08AM6; -.
DR STRING; 9606.ENSP00000261776; -.
DR GlyGen; Q08AM6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q08AM6; -.
DR MetOSite; Q08AM6; -.
DR PhosphoSitePlus; Q08AM6; -.
DR SwissPalm; Q08AM6; -.
DR BioMuta; VAC14; -.
DR DMDM; 121940040; -.
DR EPD; Q08AM6; -.
DR jPOST; Q08AM6; -.
DR MassIVE; Q08AM6; -.
DR MaxQB; Q08AM6; -.
DR PaxDb; Q08AM6; -.
DR PeptideAtlas; Q08AM6; -.
DR PRIDE; Q08AM6; -.
DR ProteomicsDB; 3649; -.
DR ProteomicsDB; 58681; -. [Q08AM6-1]
DR Antibodypedia; 16467; 106 antibodies from 22 providers.
DR DNASU; 55697; -.
DR Ensembl; ENST00000261776.10; ENSP00000261776.5; ENSG00000103043.15. [Q08AM6-1]
DR Ensembl; ENST00000536184.6; ENSP00000439284.2; ENSG00000103043.15. [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 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 neXtProt; NX_Q08AM6; -.
DR OpenTargets; ENSG00000103043; -.
DR Orphanet; 497906; Childhood-onset basal ganglia degeneration syndrome.
DR Orphanet; 3472; Yunis-Varon syndrome.
DR PharmGKB; PA142670633; -.
DR VEuPathDB; HostDB:ENSG00000103043; -.
DR eggNOG; KOG0212; Eukaryota.
DR GeneTree; ENSGT00390000008385; -.
DR HOGENOM; CLU_007740_1_0_1; -.
DR InParanoid; Q08AM6; -.
DR OMA; TYLRMQL; -.
DR OrthoDB; 306227at2759; -.
DR PhylomeDB; Q08AM6; -.
DR TreeFam; TF343690; -.
DR BioCyc; MetaCyc:ENSG00000103043-MON; -.
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 BioGRID-ORCS; 55697; 63 hits in 1079 CRISPR screens.
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 149 other tissues.
DR ExpressionAtlas; Q08AM6; baseline and differential.
DR Genevisible; Q08AM6; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0000306; C:extrinsic component of vacuolar membrane; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031902; C:late endosome membrane; TAS:Reactome.
DR GO; GO:0070772; C:PAS complex; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0038023; F:signaling receptor activity; NAS:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IBA:GO_Central.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR Gene3D; 1.25.10.10; -; 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; PTHR16023; 1.
DR Pfam; PF11916; Vac14_Fig4_bd; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
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; 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 492..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
