VAPA_HUMAN
ID VAPA_HUMAN Reviewed; 249 AA.
AC Q9P0L0; A6NDZ0; D3DUI3; O75453; Q5U0E7; Q9UBZ2;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Vesicle-associated membrane protein-associated protein A;
DE Short=VAMP-A;
DE Short=VAMP-associated protein A;
DE Short=VAP-A;
DE AltName: Full=33 kDa VAMP-associated protein;
DE Short=VAP-33;
GN Name=VAPA; Synonyms=VAP33;
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 1), SUBCELLULAR LOCATION, AND
RP INTERACTION WITH OCLN.
RC TISSUE=Liver;
RX PubMed=10523508; DOI=10.1242/jcs.112.21.3723;
RA Lapierre L.A., Tuma P.L., Navarre J., Goldenring J.R., Anderson J.M.;
RT "VAP-33 localizes to both an intracellular vesicle population and with
RT occludin at the tight junction.";
RL J. Cell Sci. 112:3723-3732(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Zhou H.J., Huang X.W., Zhou Y., Hu S.L., Yuan J.G., Qiang B.Q.;
RT "Cloning and isolating human 33kDa Vamp-associated protein cDNA.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-199 (ISOFORM 2).
RC TISSUE=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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-249 (ISOFORM 1), AND INTERACTION WITH VAMP1
RP AND VAMP2.
RC TISSUE=Pancreatic islet;
RX PubMed=9657962; DOI=10.1042/bj3330247;
RA Weir M.L., Klip A., Trimble W.S.;
RT "Identification of a human homologue of the vesicle-associated membrane
RT protein (VAMP)-associated protein of 33 kDa (VAP-33): a broadly expressed
RT protein that binds to VAMP.";
RL Biochem. J. 333:247-251(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-249 (ISOFORM 1).
RC TISSUE=B-cell;
RX PubMed=9920726; DOI=10.1006/bbrc.1998.9876;
RA Nishimura Y., Hayashi M., Inada H., Tanaka T.;
RT "Molecular cloning and characterization of mammalian homologues of vesicle-
RT associated membrane protein-associated (VAMP-associated) proteins.";
RL Biochem. Biophys. Res. Commun. 254:21-26(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-249 (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP FUNCTION, AND INTERACTION WITH VAPB; VAMP1; VAMP2; STX1A; BET1 AND SEC22C.
RX PubMed=11511104; DOI=10.1006/bbrc.2001.5437;
RA Weir M.L., Xie H., Klip A., Trimble W.S.;
RT "VAP-A binds promiscuously to both v- and tSNAREs.";
RL Biochem. Biophys. Res. Commun. 286:616-621(2001).
RN [10]
RP FUNCTION, INTERACTION WITH OSBPL3, AND SUBCELLULAR LOCATION.
RX PubMed=16143324; DOI=10.1016/j.yexcr.2005.08.003;
RA Lehto M., Hynynen R., Karjalainen K., Kuismanen E., Hyvaerinen K.,
RA Olkkonen V.M.;
RT "Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and
RT plasma membrane is controlled by multiple determinants.";
RL Exp. Cell Res. 310:445-462(2005).
RN [11]
RP INTERACTION WITH CERT1.
RX PubMed=16895911; DOI=10.1074/jbc.m605032200;
RA Kawano M., Kumagai K., Nishijima M., Hanada K.;
RT "Efficient trafficking of ceramide from the endoplasmic reticulum to the
RT Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif
RT of CERT.";
RL J. Biol. Chem. 281:30279-30288(2006).
RN [12]
RP FUNCTION, INTERACTION WITH ZFYVE27, MUTAGENESIS OF LYS-94 AND MET-96, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19289470; DOI=10.1074/jbc.m807938200;
RA Saita S., Shirane M., Natume T., Iemura S., Nakayama K.I.;
RT "Promotion of neurite extension by protrudin requires its interaction with
RT vesicle-associated membrane protein-associated protein.";
RL J. Biol. Chem. 284:13766-13777(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-125, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
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 INTERACTION WITH ZFYVE27 AND KIF5A.
RX PubMed=21976701; DOI=10.1091/mbc.e11-01-0068;
RA Matsuzaki F., Shirane M., Matsumoto M., Nakayama K.I.;
RT "Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes
RT in vesicular transport during process formation.";
RL Mol. Biol. Cell 22:4602-4620(2011).
RN [16]
RP INTERACTION WITH RSAD2, AND INTERACTION WITH HCV PROTEIN NS5A AND NS5B
RP (MICROBIAL INFECTION).
RX PubMed=21957124; DOI=10.1099/vir.0.033860-0;
RA Wang S., Wu X., Pan T., Song W., Wang Y., Zhang F., Yuan Z.;
RT "Viperin inhibits hepatitis C virus replication by interfering with binding
RT of NS5A to host protein hVAP-33.";
RL J. Gen. Virol. 93:83-92(2012).
RN [17]
RP INTERACTION WITH IFITM3.
RX PubMed=23601107; DOI=10.1016/j.chom.2013.03.006;
RA Amini-Bavil-Olyaee S., Choi Y.J., Lee J.H., Shi M., Huang I.C., Farzan M.,
RA Jung J.U.;
RT "The antiviral effector IFITM3 disrupts intracellular cholesterol
RT homeostasis to block viral entry.";
RL Cell Host Microbe 13:452-464(2013).
RN [18]
RP INTERACTION WITH STARD3 AND STARD3NL.
RX PubMed=24105263; DOI=10.1242/jcs.139295;
RA Alpy F., Rousseau A., Schwab Y., Legueux F., Stoll I., Wendling C.,
RA Spiegelhalter C., Kessler P., Mathelin C., Rio M.C., Levine T.P.,
RA Tomasetto C.;
RT "STARD3 or STARD3NL and VAP form a novel molecular tether between late
RT endosomes and the ER.";
RL J. Cell Sci. 126:5500-5512(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166; THR-170; SER-214;
RP SER-216 AND SER-219, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214, AND IDENTIFICATION BY
RP 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 [21]
RP FUNCTION, INTERACTION WITH OSBPL3, AND SUBCELLULAR LOCATION.
RX PubMed=25447204; DOI=10.1016/j.yexcr.2014.10.019;
RA Weber-Boyvat M., Kentala H., Lilja J., Vihervaara T., Hanninen R., Zhou Y.,
RA Peranen J., Nyman T.A., Ivaska J., Olkkonen V.M.;
RT "OSBP-related protein 3 (ORP3) coupling with VAMP-associated protein A
RT regulates R-Ras activity.";
RL Exp. Cell Res. 331:278-291(2015).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF LYS-94 AND MET-96.
RX PubMed=29858488; DOI=10.15252/embr.201745453;
RA Di Mattia T., Wilhelm L.P., Ikhlef S., Wendling C., Spehner D., Nomine Y.,
RA Giordano F., Mathelin C., Drin G., Tomasetto C., Alpy F.;
RT "Identification of MOSPD2, a novel scaffold for endoplasmic reticulum
RT membrane contact sites.";
RL EMBO Rep. 19:0-0(2018).
RN [24]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH VPS13A.
RX PubMed=30741634; DOI=10.7554/elife.43561;
RA Yeshaw W.M., van der Zwaag M., Pinto F., Lahaye L.L., Faber A.I.,
RA Gomez-Sanchez R., Dolga A.M., Poland C., Monaco A.P., van Ijzendoorn S.C.,
RA Grzeschik N.A., Velayos-Baeza A., Sibon O.C.;
RT "Human VPS13A is associated with multiple organelles and influences
RT mitochondrial morphology and lipid droplet motility.";
RL Elife 8:0-0(2019).
RN [25]
RP INTERACTION WITH PLEKHA3 AND SACM1L.
RX PubMed=30659099; DOI=10.1083/jcb.201812021;
RA Venditti R., Masone M.C., Rega L.R., Di Tullio G., Santoro M.,
RA Polishchuk E., Serrano I.C., Olkkonen V.M., Harada A., Medina D.L.,
RA La Montagna R., De Matteis M.A.;
RT "The activity of Sac1 across ER-TGN contact sites requires the four-
RT phosphate-adaptor-protein-1.";
RL J. Cell Biol. 218:783-797(2019).
RN [26]
RP STRUCTURE BY NMR OF 11-135, AND INTERACTION WITH OSBP.
RX PubMed=20178991; DOI=10.1074/jbc.m109.082602;
RA Furuita K., Jee J., Fukada H., Mishima M., Kojima C.;
RT "Electrostatic interaction between oxysterol-binding protein and VAMP-
RT associated protein A revealed by NMR and mutagenesis studies.";
RL J. Biol. Chem. 285:12961-12970(2010).
CC -!- FUNCTION: Binds to OSBPL3, which mediates recruitment of VAPA to plasma
CC membrane sites (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS
CC signaling which in turn attenuates integrin beta-1 (ITGB1) activation
CC at the cell surface (PubMed:25447204). With OSBPL3, may regulate ER
CC morphology (PubMed:16143324). May play a role in vesicle trafficking
CC (PubMed:11511104, PubMed:19289470). {ECO:0000269|PubMed:11511104,
CC ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:19289470,
CC ECO:0000269|PubMed:25447204}.
CC -!- SUBUNIT: Homodimer, and heterodimer with VAPB (PubMed:11511104).
CC Interacts with VAMP1, VAMP2, STX1A, BET1, SEC22C and with the C-
CC terminal domain of OCLN (PubMed:11511104, PubMed:9657962,
CC PubMed:10523508). Interacts with OSBPL1A (By similarity). Interacts
CC (via MSP domain) with ZFYVE27; may retain ZFYVE27 in the endoplasmic
CC reticulum and regulate its function in cell projections formation
CC (PubMed:19289470, PubMed:21976701). Interacts with OSBP
CC (PubMed:20178991). Interacts (via C-terminus) with RSAD2/viperin (via
CC C-terminus) (PubMed:21957124). Interacts with IFITM3 (PubMed:23601107).
CC Interacts with OSBPL3 (phosphorylated form) (PubMed:16143324,
CC PubMed:25447204). Interacts with KIF5A in a ZFYVE27-dependent manner
CC (PubMed:21976701). Interacts with STARD3 (via FFAT motif)
CC (PubMed:24105263). Interacts with STARD3NL (via FFAT motif)
CC (PubMed:24105263). Interacts with CERT1 (PubMed:16895911). Interacts
CC with PLEKHA3 and SACM1L to form a ternary complex (PubMed:30659099).
CC Interacts with VPS13A (via FFAT motif) (PubMed:30741634).
CC {ECO:0000250|UniProtKB:Q9Z270, ECO:0000269|PubMed:10523508,
CC ECO:0000269|PubMed:11511104, ECO:0000269|PubMed:16143324,
CC ECO:0000269|PubMed:16895911, ECO:0000269|PubMed:19289470,
CC ECO:0000269|PubMed:20178991, ECO:0000269|PubMed:21957124,
CC ECO:0000269|PubMed:21976701, ECO:0000269|PubMed:23601107,
CC ECO:0000269|PubMed:24105263, ECO:0000269|PubMed:25447204,
CC ECO:0000269|PubMed:30659099, ECO:0000269|PubMed:30741634,
CC ECO:0000269|PubMed:9657962}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HCV protein NS5A and NS5B
CC (PubMed:21957124). {ECO:0000269|PubMed:21957124}.
CC -!- INTERACTION:
CC Q9P0L0; Q96K78: ADGRG7; NbExp=3; IntAct=EBI-1059156, EBI-10290200;
CC Q9P0L0; P05090: APOD; NbExp=6; IntAct=EBI-1059156, EBI-715495;
CC Q9P0L0; Q13520: AQP6; NbExp=3; IntAct=EBI-1059156, EBI-13059134;
CC Q9P0L0; Q06432: CACNG1; NbExp=3; IntAct=EBI-1059156, EBI-9686780;
CC Q9P0L0; P11912: CD79A; NbExp=3; IntAct=EBI-1059156, EBI-7797864;
CC Q9P0L0; P49447: CYB561; NbExp=3; IntAct=EBI-1059156, EBI-8646596;
CC Q9P0L0; Q53TN4: CYBRD1; NbExp=3; IntAct=EBI-1059156, EBI-8637742;
CC Q9P0L0; O00559: EBAG9; NbExp=3; IntAct=EBI-1059156, EBI-8787095;
CC Q9P0L0; Q15125: EBP; NbExp=3; IntAct=EBI-1059156, EBI-3915253;
CC Q9P0L0; P00533: EGFR; NbExp=3; IntAct=EBI-1059156, EBI-297353;
CC Q9P0L0; Q9NS71: GKN1; NbExp=3; IntAct=EBI-1059156, EBI-3933251;
CC Q9P0L0; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-1059156, EBI-1052304;
CC Q9P0L0; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-1059156, EBI-18053395;
CC Q9P0L0; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-1059156, EBI-10266796;
CC Q9P0L0; O95214: LEPROTL1; NbExp=3; IntAct=EBI-1059156, EBI-750776;
CC Q9P0L0; P35372: OPRM1; NbExp=4; IntAct=EBI-1059156, EBI-2624570;
CC Q9P0L0; P22059: OSBP; NbExp=4; IntAct=EBI-1059156, EBI-2681902;
CC Q9P0L0; Q9BXW6: OSBPL1A; NbExp=4; IntAct=EBI-1059156, EBI-765918;
CC Q9P0L0; O15173: PGRMC2; NbExp=3; IntAct=EBI-1059156, EBI-1050125;
CC Q9P0L0; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-1059156, EBI-10192441;
CC Q9P0L0; Q96LZ7: RMDN2; NbExp=3; IntAct=EBI-1059156, EBI-2806908;
CC Q9P0L0; Q8WXG1: RSAD2; NbExp=10; IntAct=EBI-1059156, EBI-12736320;
CC Q9P0L0; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-1059156, EBI-17247926;
CC Q9P0L0; Q9BY50: SEC11C; NbExp=3; IntAct=EBI-1059156, EBI-2855401;
CC Q9P0L0; O60669: SLC16A7; NbExp=3; IntAct=EBI-1059156, EBI-3921243;
CC Q9P0L0; P78383: SLC35B1; NbExp=3; IntAct=EBI-1059156, EBI-12147661;
CC Q9P0L0; Q14849-1: STARD3; NbExp=4; IntAct=EBI-1059156, EBI-9819369;
CC Q9P0L0; Q8NBD8: TMEM229B; NbExp=3; IntAct=EBI-1059156, EBI-12195227;
CC Q9P0L0; Q53FP2: TMEM35A; NbExp=3; IntAct=EBI-1059156, EBI-11722971;
CC Q9P0L0; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-1059156, EBI-2548832;
CC Q9P0L0; Q9Y320: TMX2; NbExp=3; IntAct=EBI-1059156, EBI-6447886;
CC Q9P0L0; A0A024R8A9: USP20; NbExp=3; IntAct=EBI-1059156, EBI-14096082;
CC Q9P0L0; O95292: VAPB; NbExp=2; IntAct=EBI-1059156, EBI-1188298;
CC Q9P0L0; O95292-1: VAPB; NbExp=2; IntAct=EBI-1059156, EBI-9350848;
CC Q9P0L0; O95070: YIF1A; NbExp=3; IntAct=EBI-1059156, EBI-2799703;
CC Q9P0L0; O15209: ZBTB22; NbExp=3; IntAct=EBI-1059156, EBI-723574;
CC Q9P0L0; Q5T4F4: ZFYVE27; NbExp=5; IntAct=EBI-1059156, EBI-3892947;
CC Q9P0L0; PRO_0000037576 [P27958]; Xeno; NbExp=7; IntAct=EBI-1059156, EBI-8753518;
CC Q9P0L0; PRO_0000037577 [P27958]; Xeno; NbExp=5; IntAct=EBI-1059156, EBI-6904388;
CC Q9P0L0; PRO_0000278740 [Q03463]; Xeno; NbExp=4; IntAct=EBI-1059156, EBI-8803426;
CC Q9P0L0; PRO_0000278741 [Q03463]; Xeno; NbExp=3; IntAct=EBI-1059156, EBI-8803474;
CC Q9P0L0; PRO_0000045600 [Q99IB8]; Xeno; NbExp=3; IntAct=EBI-1059156, EBI-9096996;
CC Q9P0L0; PRO_0000045602 [Q99IB8]; Xeno; NbExp=2; IntAct=EBI-1059156, EBI-6927873;
CC Q9P0L0; PRO_0000037551 [Q9WMX2]; Xeno; NbExp=10; IntAct=EBI-1059156, EBI-6863748;
CC Q9P0L0; PRO_0000037552 [Q9WMX2]; Xeno; NbExp=4; IntAct=EBI-1059156, EBI-9005440;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10523508, ECO:0000269|PubMed:16143324,
CC ECO:0000269|PubMed:19289470, ECO:0000269|PubMed:25447204,
CC ECO:0000269|PubMed:30741634}; Single-pass type IV membrane protein
CC {ECO:0000269|PubMed:10523508, ECO:0000269|PubMed:19289470}. Cell
CC membrane {ECO:0000269|PubMed:25447204}; Single-pass type IV membrane
CC protein {ECO:0000305}. Cell junction, tight junction
CC {ECO:0000269|PubMed:10523508}. Nucleus membrane
CC {ECO:0000250|UniProtKB:Q9Z270}. Note=Present in the plasma membrane and
CC in intracellular vesicles, together with SNARE proteins. May also
CC associate with the cytoskeleton. Colocalizes with OCLN at the tight
CC junction in polarized epithelial cells. {ECO:0000269|PubMed:10523508}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9P0L0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9P0L0-2; Sequence=VSP_038648;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the VAMP-associated protein (VAP) (TC 9.B.17)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD09742.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF72105.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BG488667; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF044670; AAD09742.1; ALT_INIT; mRNA.
DR EMBL; AF154847; AAF72105.1; ALT_INIT; mRNA.
DR EMBL; AC006238; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471113; EAX01591.1; -; Genomic_DNA.
DR EMBL; CH471113; EAX01592.1; -; Genomic_DNA.
DR EMBL; BC002992; AAH02992.2; -; mRNA.
DR EMBL; BG488667; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF057358; AAC26508.1; -; mRNA.
DR EMBL; AF086627; AAD13576.1; -; mRNA.
DR EMBL; BT019618; AAV38424.1; -; mRNA.
DR CCDS; CCDS11847.2; -. [Q9P0L0-2]
DR CCDS; CCDS11848.2; -. [Q9P0L0-1]
DR RefSeq; NP_003565.4; NM_003574.5. [Q9P0L0-2]
DR RefSeq; NP_919415.2; NM_194434.2. [Q9P0L0-1]
DR PDB; 2RR3; NMR; -; A=11-135.
DR PDB; 6TQR; X-ray; 1.85 A; A/B/C/D=8-212.
DR PDBsum; 2RR3; -.
DR PDBsum; 6TQR; -.
DR AlphaFoldDB; Q9P0L0; -.
DR SMR; Q9P0L0; -.
DR BioGRID; 114651; 553.
DR ComplexPortal; CPX-489; VAPA-OSBP complex.
DR CORUM; Q9P0L0; -.
DR DIP; DIP-41135N; -.
DR IntAct; Q9P0L0; 295.
DR MINT; Q9P0L0; -.
DR TCDB; 1.R.1.1.1; the membrane contact site (mcs) family.
DR GlyGen; Q9P0L0; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q9P0L0; -.
DR MetOSite; Q9P0L0; -.
DR PhosphoSitePlus; Q9P0L0; -.
DR SwissPalm; Q9P0L0; -.
DR BioMuta; VAPA; -.
DR DMDM; 122066680; -.
DR EPD; Q9P0L0; -.
DR jPOST; Q9P0L0; -.
DR MassIVE; Q9P0L0; -.
DR MaxQB; Q9P0L0; -.
DR PeptideAtlas; Q9P0L0; -.
DR PRIDE; Q9P0L0; -.
DR ProteomicsDB; 83567; -. [Q9P0L0-1]
DR ProteomicsDB; 83568; -. [Q9P0L0-2]
DR TopDownProteomics; Q9P0L0-1; -. [Q9P0L0-1]
DR TopDownProteomics; Q9P0L0-2; -. [Q9P0L0-2]
DR Antibodypedia; 2287; 296 antibodies from 33 providers.
DR DNASU; 9218; -.
DR Ensembl; ENST00000340541.4; ENSP00000345656.4; ENSG00000101558.14. [Q9P0L0-2]
DR Ensembl; ENST00000400000.7; ENSP00000382880.3; ENSG00000101558.14. [Q9P0L0-1]
DR GeneID; 9218; -.
DR KEGG; hsa:9218; -.
DR MANE-Select; ENST00000400000.7; ENSP00000382880.3; NM_194434.3; NP_919415.2.
DR UCSC; uc002koj.4; human. [Q9P0L0-1]
DR CTD; 9218; -.
DR DisGeNET; 9218; -.
DR GeneCards; VAPA; -.
DR HGNC; HGNC:12648; VAPA.
DR HPA; ENSG00000101558; Low tissue specificity.
DR MIM; 605703; gene.
DR neXtProt; NX_Q9P0L0; -.
DR OpenTargets; ENSG00000101558; -.
DR PharmGKB; PA37272; -.
DR VEuPathDB; HostDB:ENSG00000101558; -.
DR GeneTree; ENSGT00940000154799; -.
DR HOGENOM; CLU_032848_0_1_1; -.
DR InParanoid; Q9P0L0; -.
DR OMA; QSVIAPE; -.
DR OrthoDB; 1332028at2759; -.
DR PhylomeDB; Q9P0L0; -.
DR TreeFam; TF317024; -.
DR PathwayCommons; Q9P0L0; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR SignaLink; Q9P0L0; -.
DR SIGNOR; Q9P0L0; -.
DR BioGRID-ORCS; 9218; 28 hits in 1078 CRISPR screens.
DR ChiTaRS; VAPA; human.
DR EvolutionaryTrace; Q9P0L0; -.
DR GeneWiki; VAPA; -.
DR GenomeRNAi; 9218; -.
DR Pharos; Q9P0L0; Tbio.
DR PRO; PR:Q9P0L0; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q9P0L0; protein.
DR Bgee; ENSG00000101558; Expressed in endothelial cell and 211 other tissues.
DR ExpressionAtlas; Q9P0L0; baseline and differential.
DR Genevisible; Q9P0L0; HS.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:ComplexPortal.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0033149; F:FFAT motif binding; IMP:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IMP:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0008219; P:cell death; IMP:UniProtKB.
DR GO; GO:0035627; P:ceramide transport; IMP:ComplexPortal.
DR GO; GO:0090114; P:COPII-coated vesicle budding; IMP:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IMP:UniProtKB.
DR GO; GO:0061025; P:membrane fusion; TAS:ProtInc.
DR GO; GO:0044828; P:negative regulation by host of viral genome replication; IDA:AgBase.
DR GO; GO:0031175; P:neuron projection development; IMP:UniProtKB.
DR GO; GO:0015914; P:phospholipid transport; IDA:ComplexPortal.
DR GO; GO:0044829; P:positive regulation by host of viral genome replication; IDA:AgBase.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR GO; GO:0070972; P:protein localization to endoplasmic reticulum; IMP:UniProtKB.
DR GO; GO:0006686; P:sphingomyelin biosynthetic process; IMP:ComplexPortal.
DR GO; GO:0015918; P:sterol transport; IDA:ComplexPortal.
DR GO; GO:0019076; P:viral release from host cell; IDA:AgBase.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR000535; MSP_dom.
DR InterPro; IPR008962; PapD-like_sf.
DR InterPro; IPR016763; VAP.
DR PANTHER; PTHR10809; PTHR10809; 2.
DR Pfam; PF00635; Motile_Sperm; 1.
DR PIRSF; PIRSF019693; VAMP-associated; 1.
DR SUPFAM; SSF49354; SSF49354; 1.
DR PROSITE; PS50202; MSP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell junction;
KW Cell membrane; Coiled coil; Endoplasmic reticulum; Host-virus interaction;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Tight junction;
KW Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:25944712"
FT CHAIN 2..249
FT /note="Vesicle-associated membrane protein-associated
FT protein A"
FT /id="PRO_0000213470"
FT TOPO_DOM 2..227
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 228..248
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT DOMAIN 14..131
FT /note="MSP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00132"
FT REGION 135..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 169..205
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:25944712"
FT MOD_RES 125
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 170
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 139
FT /note="L -> LGITPPGNAPTVTSMSSINNTVATPASYHTKDDPRGLSVLKQEKQK
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038648"
FT VARIANT 8
FT /note="M -> T (in dbSNP:rs1044163)"
FT /id="VAR_050440"
FT VARIANT 104
FT /note="P -> L (in dbSNP:rs1127666)"
FT /id="VAR_050441"
FT MUTAGEN 94
FT /note="K->D: Alters interaction with ZFYVE27 and prevents
FT binding to the FFAT motif in target proteins; when
FT associated with D-96."
FT /evidence="ECO:0000269|PubMed:19289470"
FT MUTAGEN 96
FT /note="M->D: Alters interaction with ZFYVE27 and prevents
FT binding to the FFAT motif in target proteins; when
FT associated with D-94."
FT /evidence="ECO:0000269|PubMed:19289470"
FT CONFLICT 10..11
FT /note="KH -> ND (in Ref. 6; AAC26508 and 8; AAV38424)"
FT /evidence="ECO:0000305"
FT CONFLICT 160
FT /note="P -> S (in Ref. 2; AAF72105)"
FT /evidence="ECO:0000305"
FT STRAND 15..27
FT /evidence="ECO:0007829|PDB:6TQR"
FT STRAND 33..40
FT /evidence="ECO:0007829|PDB:6TQR"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:6TQR"
FT STRAND 47..54
FT /evidence="ECO:0007829|PDB:6TQR"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:6TQR"
FT STRAND 59..68
FT /evidence="ECO:0007829|PDB:6TQR"
FT STRAND 73..80
FT /evidence="ECO:0007829|PDB:6TQR"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:6TQR"
FT HELIX 109..115
FT /evidence="ECO:0007829|PDB:6TQR"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:6TQR"
FT STRAND 122..131
FT /evidence="ECO:0007829|PDB:6TQR"
SQ SEQUENCE 249 AA; 27893 MW; 68B603F3A9FA5475 CRC64;
MASASGAMAK HEQILVLDPP TDLKFKGPFT DVVTTNLKLR NPSDRKVCFK VKTTAPRRYC
VRPNSGIIDP GSTVTVSVML QPFDYDPNEK SKHKFMVQTI FAPPNTSDME AVWKEAKPDE
LMDSKLRCVF EMPNENDKLN DMEPSKAVPL NASKQDGPMP KPHSVSLNDT ETRKLMEECK
RLQGEMMKLS EENRHLRDEG LRLRKVAHSD KPGSTSTASF RDNVTSPLPS LLVVIAAIFI
GFFLGKFIL
