VAPB_HUMAN
ID VAPB_HUMAN Reviewed; 243 AA.
AC O95292; A2A2F2; O95293; Q9P0H0;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Vesicle-associated membrane protein-associated protein B/C;
DE Short=VAMP-B/VAMP-C;
DE Short=VAMP-associated protein B/C;
DE Short=VAP-B/VAP-C;
GN Name=VAPB; ORFNames=UNQ484/PRO983;
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] (ISOFORMS 1 AND 2), AND INTERACTION WITH VAPA;
RP VAMP1 AND VAMP2.
RC TISSUE=Brain, and Heart;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 PROTEIN SEQUENCE OF 2-19.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP INTERACTION WITH HEPATITIS C NON-STRUCTURAL PROTEIN 5A (MICROBIAL
RP INFECTION), AND INTERACTION WITH HEPATITIS C RNA-DIRECTED RNA POLYMERASE
RP (MICROBIAL INFECTION).
RX PubMed=16227268; DOI=10.1128/jvi.79.21.13473-13482.2005;
RA Hamamoto I., Nishimura Y., Okamoto T., Aizaki H., Liu M., Mori Y., Abe T.,
RA Suzuki T., Lai M.M., Miyamura T., Moriishi K., Matsuura Y.;
RT "Human VAP-B is involved in hepatitis C virus replication through
RT interaction with NS5A and NS5B.";
RL J. Virol. 79:13473-13482(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP FUNCTION IN ENDOPLASMIC RETICULUM UNFOLDED PROTEIN RESPONSE, AND
RP CHARACTERIZATION OF VARIANT ALS8 SER-56.
RX PubMed=16891305; DOI=10.1074/jbc.m605049200;
RA Kanekura K., Nishimoto I., Aiso S., Matsuoka M.;
RT "Characterization of amyotrophic lateral sclerosis-linked P56S mutation of
RT vesicle-associated membrane protein-associated protein B (VAPB/ALS8).";
RL J. Biol. Chem. 281:30223-30233(2006).
RN [10]
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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-150; SER-156 AND SER-160, AND
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 [13]
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=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP INTERACTION WITH ZFYVE27.
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 [15]
RP FUNCTION IN ENDOPLASMIC RETICULUM UNFOLDED PROTEIN RESPONSE, VARIANT ALS8
RP ILE-46, CHARACTERIZATION OF VARIANTS ALS8 ILE-46 AND SER-56, SUBUNIT, AND
RP INTERACTION WITH VAPA; VAMP1 AND VAMP2.
RX PubMed=20940299; DOI=10.1074/jbc.m110.161398;
RA Chen H.J., Anagnostou G., Chai A., Withers J., Morris A., Adhikaree J.,
RA Pennetta G., de Belleroche J.S.;
RT "Characterization of the properties of a novel mutation in VAPB in familial
RT amyotrophic lateral sclerosis.";
RL J. Biol. Chem. 285:40266-40281(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-150; SER-156 AND SER-160, AND
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 [17]
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 [18]
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 [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP FUNCTION IN CELLULAR CALCIUM HOMEOSTASIS REGULATION, SUBCELLULAR LOCATION,
RP INTERACTION WITH RMDN3, AND CHARACTERIZATION OF VARIANT ALS8 SER-56.
RX PubMed=22131369; DOI=10.1093/hmg/ddr559;
RA De Vos K.J., Morotz G.M., Stoica R., Tudor E.L., Lau K.F., Ackerley S.,
RA Warley A., Shaw C.E., Miller C.C.;
RT "VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium
RT homeostasis.";
RL Hum. Mol. Genet. 21:1299-1311(2012).
RN [21]
RP INTERACTION WITH HEPATITIS C NON-STRUCTURAL PROTEIN 5A (MICROBIAL
RP INFECTION).
RX PubMed=22720086; DOI=10.1371/journal.pone.0039261;
RA Gupta G., Qin H., Song J.;
RT "Intrinsically unstructured domain 3 of hepatitis C Virus NS5A forms a
RT 'fuzzy complex' with VAPB-MSP domain which carries ALS-causing mutations.";
RL PLoS ONE 7:e39261-e39261(2012).
RN [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-146; THR-150; SER-156;
RP SER-158; SER-159; SER-160 AND SER-206, 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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158 AND SER-160, AND
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 [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-147, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [26]
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 [27]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF LYS-87 AND MET-89.
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 [28]
RP 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 [29]
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 [30]
RP VARIANT ALS8 SER-56, AND VARIANT SMAPAD SER-56.
RX PubMed=15372378; DOI=10.1086/425287;
RA Nishimura A.L., Mitne-Neto M., Silva H.C., Richieri-Costa A., Middleton S.,
RA Cascio D., Kok F., Oliveira J.R., Gillingwater T., Webb J., Skehel P.,
RA Zatz M.;
RT "A mutation in the vesicle-trafficking protein VAPB causes late-onset
RT spinal muscular atrophy and amyotrophic lateral sclerosis.";
RL Am. J. Hum. Genet. 75:822-831(2004).
CC -!- FUNCTION: Participates in the endoplasmic reticulum unfolded protein
CC response (UPR) by inducing ERN1/IRE1 activity. Involved in cellular
CC calcium homeostasis regulation. {ECO:0000269|PubMed:16891305,
CC ECO:0000269|PubMed:20940299, ECO:0000269|PubMed:22131369}.
CC -!- SUBUNIT: Homodimer, and heterodimer with VAPA (PubMed:20940299).
CC Interacts with VAMP1 and VAMP2 (PubMed:9920726, PubMed:20940299).
CC Interacts (via MSP domain) with ZFYVE27 (PubMed:21976701,
CC PubMed:19289470). Interacts with RMDN3 (PubMed:22131369). Interacts
CC with KIF5A in a ZFYVE27-dependent manner (PubMed:21976701). Interacts
CC with STARD3 (via FFAT motif) (PubMed:24105263). Interacts with STARD3NL
CC (via FFAT motif) (PubMed:24105263). Interacts with CERT1
CC (PubMed:16895911). Interacts with PLEKHA3 and SACM1L to form a ternary
CC complex (PubMed:30659099). Interacts with VPS13A (via FFAT motif)
CC (PubMed:30741634). {ECO:0000269|PubMed:16227268,
CC ECO:0000269|PubMed:16895911, ECO:0000269|PubMed:19289470,
CC ECO:0000269|PubMed:20940299, ECO:0000269|PubMed:21976701,
CC ECO:0000269|PubMed:22131369, ECO:0000269|PubMed:24105263,
CC ECO:0000269|PubMed:30659099, ECO:0000269|PubMed:30741634,
CC ECO:0000269|PubMed:9920726}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via MSP domain) with
CC hepatitis C virus (HCV) non-structural protein 5A (via disordered
CC domain D3) (PubMed:16227268, PubMed:22720086). Interacts with HCV RNA-
CC directed RNA polymerase (PubMed:16227268).
CC {ECO:0000269|PubMed:16227268, ECO:0000269|PubMed:22720086}.
CC -!- INTERACTION:
CC O95292; Q9NVV5-2: AIG1; NbExp=3; IntAct=EBI-1188298, EBI-11957045;
CC O95292; P63010-2: AP2B1; NbExp=3; IntAct=EBI-1188298, EBI-11529439;
CC O95292; Q13520: AQP6; NbExp=3; IntAct=EBI-1188298, EBI-13059134;
CC O95292; Q0P5N6: ARL16; NbExp=3; IntAct=EBI-1188298, EBI-10186132;
CC O95292; P11912: CD79A; NbExp=3; IntAct=EBI-1188298, EBI-7797864;
CC O95292; P49447: CYB561; NbExp=3; IntAct=EBI-1188298, EBI-8646596;
CC O95292; Q53TN4: CYBRD1; NbExp=3; IntAct=EBI-1188298, EBI-8637742;
CC O95292; O00559: EBAG9; NbExp=3; IntAct=EBI-1188298, EBI-8787095;
CC O95292; Q15125: EBP; NbExp=3; IntAct=EBI-1188298, EBI-3915253;
CC O95292; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-1188298, EBI-18535450;
CC O95292; P50402: EMD; NbExp=3; IntAct=EBI-1188298, EBI-489887;
CC O95292; Q8TBP5: FAM174A; NbExp=3; IntAct=EBI-1188298, EBI-18636064;
CC O95292; O00155: GPR25; NbExp=3; IntAct=EBI-1188298, EBI-10178951;
CC O95292; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-1188298, EBI-18053395;
CC O95292; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-1188298, EBI-10266796;
CC O95292; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-1188298, EBI-1044640;
CC O95292; Q9BXW6: OSBPL1A; NbExp=5; IntAct=EBI-1188298, EBI-765918;
CC O95292; O14684: PTGES; NbExp=3; IntAct=EBI-1188298, EBI-11161398;
CC O95292; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-1188298, EBI-7545592;
CC O95292; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-1188298, EBI-10192441;
CC O95292; Q96LZ7: RMDN2; NbExp=4; IntAct=EBI-1188298, EBI-2806908;
CC O95292; Q6P5S7: RNASEK; NbExp=3; IntAct=EBI-1188298, EBI-18397230;
CC O95292; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-1188298, EBI-17247926;
CC O95292; O00560: SDCBP; NbExp=3; IntAct=EBI-1188298, EBI-727004;
CC O95292; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-1188298, EBI-17295964;
CC O95292; Q96IK0: TMEM101; NbExp=3; IntAct=EBI-1188298, EBI-3922699;
CC O95292; Q8N6L7: TMEM252; NbExp=3; IntAct=EBI-1188298, EBI-8787626;
CC O95292; Q9Y320: TMX2; NbExp=3; IntAct=EBI-1188298, EBI-6447886;
CC O95292; Q5VTQ0: TTC39B; NbExp=3; IntAct=EBI-1188298, EBI-4289975;
CC O95292; A0A024R8A9: USP20; NbExp=3; IntAct=EBI-1188298, EBI-14096082;
CC O95292; Q9Y2K6: USP20; NbExp=3; IntAct=EBI-1188298, EBI-2511991;
CC O95292; Q9P0L0: VAPA; NbExp=2; IntAct=EBI-1188298, EBI-1059156;
CC O95292; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-1188298, EBI-358545;
CC O95292; O95070: YIF1A; NbExp=9; IntAct=EBI-1188298, EBI-2799703;
CC O95292; O15209: ZBTB22; NbExp=3; IntAct=EBI-1188298, EBI-723574;
CC O95292; Q96MV8: ZDHHC15; NbExp=3; IntAct=EBI-1188298, EBI-12837904;
CC O95292; Q5T4F4: ZFYVE27; NbExp=2; IntAct=EBI-1188298, EBI-3892947;
CC O95292; Q03137: Epha4; Xeno; NbExp=2; IntAct=EBI-1188298, EBI-1539152;
CC O95292; PRO_0000278740 [Q03463]; Xeno; NbExp=6; IntAct=EBI-1188298, EBI-8803426;
CC O95292; PRO_0000045600 [Q99IB8]; Xeno; NbExp=2; IntAct=EBI-1188298, EBI-9096996;
CC O95292-1; Q9P0L0: VAPA; NbExp=2; IntAct=EBI-9350848, EBI-1059156;
CC O95292-1; PRO_0000278741 [Q03463]; Xeno; NbExp=2; IntAct=EBI-9350848, EBI-8803474;
CC O95292-2; PRO_0000278741 [Q03463]; Xeno; NbExp=3; IntAct=EBI-9350855, EBI-8803474;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass type IV membrane protein {ECO:0000250}. Note=Present in
CC mitochondria-associated membranes that are endoplasmic reticulum
CC membrane regions closely apposed to the outer mitochondrial membrane.
CC {ECO:0000269|PubMed:22131369}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=VAP-B;
CC IsoId=O95292-1; Sequence=Displayed;
CC Name=2; Synonyms=VAP-C;
CC IsoId=O95292-2; Sequence=VSP_003277, VSP_003278;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Isoform 1 predominates.
CC -!- DISEASE: Amyotrophic lateral sclerosis 8 (ALS8) [MIM:608627]: A
CC neurodegenerative disorder affecting upper motor neurons in the brain
CC and lower motor neurons in the brain stem and spinal cord, resulting in
CC fatal paralysis. Sensory abnormalities are absent. The pathologic
CC hallmarks of the disease include pallor of the corticospinal tract due
CC to loss of motor neurons, presence of ubiquitin-positive inclusions
CC within surviving motor neurons, and deposition of pathologic
CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to
CC be multifactorial, involving both genetic and environmental factors.
CC The disease is inherited in 5-10% of the cases.
CC {ECO:0000269|PubMed:15372378, ECO:0000269|PubMed:16891305,
CC ECO:0000269|PubMed:20940299, ECO:0000269|PubMed:22131369}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Spinal muscular atrophy, proximal, adult, autosomal dominant
CC (SMAPAD) [MIM:182980]: A form of spinal muscular atrophy, a
CC neuromuscular disorder characterized by degeneration of the anterior
CC horn cells of the spinal cord, leading to symmetrical muscle weakness
CC and atrophy. SMAPAD is characterized by proximal muscle weakness that
CC begins in the lower limbs and then progresses to upper limbs, onset in
CC late adulthood (after third decade) and a benign course. Most of the
CC patients remain ambulatory 10 to 40 years after clinical onset.
CC {ECO:0000269|PubMed:15372378}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the VAMP-associated protein (VAP) (TC 9.B.17)
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Alsod; Note=ALS genetic mutations db;
CC URL="https://alsod.ac.uk";
CC -!- WEB RESOURCE: Name=Mendelian genes VAMP (vesicle-associated membrane
CC protein)-associated protein B and C (VAPB); Note=Leiden Open Variation
CC Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/VAPB";
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DR EMBL; AF086628; AAD13577.1; -; mRNA.
DR EMBL; AF086629; AAD13578.1; -; mRNA.
DR EMBL; AF160212; AAF67013.1; -; mRNA.
DR EMBL; AY358464; AAQ88829.1; -; mRNA.
DR EMBL; AL035455; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001712; AAH01712.1; -; mRNA.
DR CCDS; CCDS33498.1; -. [O95292-1]
DR CCDS; CCDS56198.1; -. [O95292-2]
DR PIR; JG0186; JG0186.
DR RefSeq; NP_001182606.1; NM_001195677.1. [O95292-2]
DR RefSeq; NP_004729.1; NM_004738.4. [O95292-1]
DR PDB; 2MDK; NMR; -; A=1-125.
DR PDB; 3IKK; X-ray; 2.50 A; A/B=1-125.
DR PDBsum; 2MDK; -.
DR PDBsum; 3IKK; -.
DR AlphaFoldDB; O95292; -.
DR BMRB; O95292; -.
DR SMR; O95292; -.
DR BioGRID; 114650; 392.
DR CORUM; O95292; -.
DR DIP; DIP-39816N; -.
DR IntAct; O95292; 182.
DR MINT; O95292; -.
DR STRING; 9606.ENSP00000417175; -.
DR TCDB; 1.R.1.1.1; the membrane contact site (mcs) family.
DR TCDB; 9.B.17.1.1; the vamp-associated protein (vap) family.
DR GlyGen; O95292; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; O95292; -.
DR PhosphoSitePlus; O95292; -.
DR SwissPalm; O95292; -.
DR BioMuta; VAPB; -.
DR EPD; O95292; -.
DR jPOST; O95292; -.
DR MassIVE; O95292; -.
DR MaxQB; O95292; -.
DR PaxDb; O95292; -.
DR PeptideAtlas; O95292; -.
DR PRIDE; O95292; -.
DR ProteomicsDB; 50788; -. [O95292-1]
DR ProteomicsDB; 50789; -. [O95292-2]
DR Antibodypedia; 2398; 358 antibodies from 33 providers.
DR DNASU; 9217; -.
DR Ensembl; ENST00000395802.7; ENSP00000379147.3; ENSG00000124164.16. [O95292-2]
DR Ensembl; ENST00000475243.6; ENSP00000417175.1; ENSG00000124164.16. [O95292-1]
DR GeneID; 9217; -.
DR KEGG; hsa:9217; -.
DR MANE-Select; ENST00000475243.6; ENSP00000417175.1; NM_004738.5; NP_004729.1.
DR UCSC; uc002xzd.3; human. [O95292-1]
DR CTD; 9217; -.
DR DisGeNET; 9217; -.
DR GeneCards; VAPB; -.
DR HGNC; HGNC:12649; VAPB.
DR HPA; ENSG00000124164; Low tissue specificity.
DR MalaCards; VAPB; -.
DR MIM; 182980; phenotype.
DR MIM; 605704; gene.
DR MIM; 608627; phenotype.
DR neXtProt; NX_O95292; -.
DR OpenTargets; ENSG00000124164; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR Orphanet; 209335; Autosomal dominant adult-onset proximal spinal muscular atrophy.
DR PharmGKB; PA37273; -.
DR VEuPathDB; HostDB:ENSG00000124164; -.
DR eggNOG; KOG0439; Eukaryota.
DR GeneTree; ENSGT00940000155769; -.
DR HOGENOM; CLU_032848_0_1_1; -.
DR InParanoid; O95292; -.
DR OMA; LRCTFEM; -.
DR PhylomeDB; O95292; -.
DR TreeFam; TF317024; -.
DR PathwayCommons; O95292; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR SignaLink; O95292; -.
DR SIGNOR; O95292; -.
DR BioGRID-ORCS; 9217; 13 hits in 1081 CRISPR screens.
DR ChiTaRS; VAPB; human.
DR EvolutionaryTrace; O95292; -.
DR GeneWiki; VAPB; -.
DR GenomeRNAi; 9217; -.
DR Pharos; O95292; Tbio.
DR PRO; PR:O95292; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; O95292; protein.
DR Bgee; ENSG00000124164; Expressed in endothelial cell and 208 other tissues.
DR ExpressionAtlas; O95292; baseline and differential.
DR Genevisible; O95292; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0033149; F:FFAT motif binding; IMP:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0090114; P:COPII-coated vesicle budding; IMP:UniProtKB.
DR GO; GO:0090158; P:endoplasmic reticulum membrane organization; IBA:GO_Central.
DR GO; GO:0007029; P:endoplasmic reticulum organization; IMP:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IMP:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IMP:UniProtKB.
DR GO; GO:0061817; P:endoplasmic reticulum-plasma membrane tethering; IBA:GO_Central.
DR GO; GO:0036498; P:IRE1-mediated unfolded protein response; IDA:UniProtKB.
DR GO; GO:0044830; P:modulation by host of viral RNA genome replication; IDA:AgBase.
DR GO; GO:0044828; P:negative regulation by host of viral genome replication; IDA:AgBase.
DR GO; GO:0046725; P:negative regulation by virus of viral protein levels in host cell; IDA:AgBase.
DR GO; GO:0044829; P:positive regulation by host of viral genome replication; IDA:AgBase.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0044790; P:suppression of viral release by host; IDA:AgBase.
DR GO; GO:0019076; P:viral release from host cell; IDA:AgBase.
DR DisProt; DP01248; -.
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;
KW Amyotrophic lateral sclerosis; Coiled coil; Direct protein sequencing;
KW Disease variant; Endoplasmic reticulum; Host-virus interaction;
KW Isopeptide bond; Membrane; Neurodegeneration; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation;
KW Unfolded protein response.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:25944712"
FT CHAIN 2..243
FT /note="Vesicle-associated membrane protein-associated
FT protein B/C"
FT /id="PRO_0000213473"
FT TOPO_DOM 2..222
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 223..243
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT DOMAIN 7..124
FT /note="MSP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00132"
FT COILED 159..196
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 146
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 150
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 206
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 147
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0007744|PubMed:25114211"
FT VAR_SEQ 71..99
FT /note="VMLQPFDYDPNEKSKHKFMVQSMFAPTDT -> GRRWTADEEDSAEQQPHFS
FT ISPNWEGRRP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9920726"
FT /id="VSP_003277"
FT VAR_SEQ 100..243
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9920726"
FT /id="VSP_003278"
FT VARIANT 46
FT /note="T -> I (in ALS8; it forms insoluble cytosolic
FT aggregates; cannot activate the UPR pathway through ERN1/
FT IRE1 induction; results in ubiquitinated aggregates
FT accumulation and cell death; dbSNP:rs281875284)"
FT /evidence="ECO:0000269|PubMed:20940299"
FT /id="VAR_067964"
FT VARIANT 56
FT /note="P -> S (in ALS8 and SMAPAD; it forms insoluble
FT cytosolic aggregates; cannot activate the UPR pathway;
FT affects interaction with RMDN3; affects cellular calcium
FT homeostasis; induces mislocalization to the non-ER
FT compartments; enhances homodimerization; dbSNP:rs74315431)"
FT /evidence="ECO:0000269|PubMed:15372378,
FT ECO:0000269|PubMed:16891305, ECO:0000269|PubMed:20940299,
FT ECO:0000269|PubMed:22131369"
FT /id="VAR_026743"
FT MUTAGEN 87
FT /note="K->D: Prevents binding to the FFAT motif in target
FT proteins; when associated with D-89."
FT /evidence="ECO:0000269|PubMed:29858488"
FT MUTAGEN 89
FT /note="M->D: Prevents binding to the FFAT motif in target
FT proteins; when associated with D-87."
FT /evidence="ECO:0000269|PubMed:29858488"
FT CONFLICT 60
FT /note="I -> V (in Ref. 2; AAF67013)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="I -> L (in Ref. 2; AAF67013)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="T -> P (in Ref. 2; AAF67013)"
FT /evidence="ECO:0000305"
FT CONFLICT 103..106
FT /note="EAVW -> DGTR (in Ref. 2; AAF67013)"
FT /evidence="ECO:0000305"
FT TURN 4..7
FT /evidence="ECO:0007829|PDB:2MDK"
FT STRAND 8..20
FT /evidence="ECO:0007829|PDB:3IKK"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:3IKK"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:3IKK"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:3IKK"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:3IKK"
FT STRAND 52..61
FT /evidence="ECO:0007829|PDB:3IKK"
FT STRAND 66..73
FT /evidence="ECO:0007829|PDB:3IKK"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:2MDK"
FT STRAND 88..94
FT /evidence="ECO:0007829|PDB:3IKK"
FT TURN 104..108
FT /evidence="ECO:0007829|PDB:3IKK"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:3IKK"
FT STRAND 115..124
FT /evidence="ECO:0007829|PDB:3IKK"
SQ SEQUENCE 243 AA; 27228 MW; 22AEEF9EC7FC0B3F CRC64;
MAKVEQVLSL EPQHELKFRG PFTDVVTTNL KLGNPTDRNV CFKVKTTAPR RYCVRPNSGI
IDAGASINVS VMLQPFDYDP NEKSKHKFMV QSMFAPTDTS DMEAVWKEAK PEDLMDSKLR
CVFELPAEND KPHDVEINKI ISTTASKTET PIVSKSLSSS LDDTEVKKVM EECKRLQGEV
QRLREENKQF KEEDGLRMRK TVQSNSPISA LAPTGKEEGL STRLLALVVL FFIVGVIIGK
IAL
