VWC2_HUMAN
ID VWC2_HUMAN Reviewed; 325 AA.
AC Q2TAL6; Q6UXE2;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Brorin;
DE AltName: Full=Brain-specific chordin-like protein;
DE AltName: Full=von Willebrand factor C domain-containing protein 2;
DE Flags: Precursor;
GN Name=VWC2; ORFNames=UNQ739/PRO1434;
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].
RX PubMed=17400546; DOI=10.1074/jbc.m701570200;
RA Koike N., Kassai Y., Kouta Y., Miwa H., Konishi M., Itoh N.;
RT "Brorin, a novel secreted bone morphogenetic protein antagonist, promotes
RT neurogenesis in mouse neural precursor cells.";
RL J. Biol. Chem. 282:15843-15850(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
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].
RC TISSUE=Brain;
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).
CC -!- FUNCTION: BMP antagonist which may play a role in neural development.
CC Promotes cell adhesion (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Peripherally associated with AMPAR complex. AMPAR complex
CC consists of an inner core made of 4 pore-forming GluA/GRIA proteins
CC (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged
CC in a twofold symmetry. One of the two pairs of distinct binding sites
CC is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors
CC CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR
CC complex is complemented by outer core constituents binding directly to
CC the GluA/GRIA proteins at sites distinct from the interaction sites of
CC the inner core constituents. Outer core constituents include at least
CC PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the
CC inner and outer core serve as a platform for other, more peripherally
CC associated AMPAR constituents, including VWC2. Alone or in combination,
CC these auxiliary subunits control the gating and pharmacology of the
CC AMPAR complex and profoundly impact their biogenesis and protein
CC processing (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q2TAL6; Q6UXT9: ABHD15; NbExp=3; IntAct=EBI-11957238, EBI-2824666;
CC Q2TAL6; Q6UY14-3: ADAMTSL4; NbExp=6; IntAct=EBI-11957238, EBI-10173507;
CC Q2TAL6; Q8N5M1: ATPAF2; NbExp=3; IntAct=EBI-11957238, EBI-1166928;
CC Q2TAL6; P49069: CAMLG; NbExp=3; IntAct=EBI-11957238, EBI-1748958;
CC Q2TAL6; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-11957238, EBI-744545;
CC Q2TAL6; Q8NE01: CNNM3; NbExp=5; IntAct=EBI-11957238, EBI-741032;
CC Q2TAL6; Q49AN0: CRY2; NbExp=3; IntAct=EBI-11957238, EBI-2212355;
CC Q2TAL6; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11957238, EBI-3867333;
CC Q2TAL6; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-11957238, EBI-744099;
CC Q2TAL6; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-11957238, EBI-6658203;
CC Q2TAL6; Q969U6: FBXW5; NbExp=3; IntAct=EBI-11957238, EBI-741068;
CC Q2TAL6; Q9BTY2: FUCA2; NbExp=3; IntAct=EBI-11957238, EBI-9050116;
CC Q2TAL6; O43681: GET3; NbExp=3; IntAct=EBI-11957238, EBI-2515857;
CC Q2TAL6; Q9Y223-2: GNE; NbExp=3; IntAct=EBI-11957238, EBI-11975289;
CC Q2TAL6; Q9GZV7: HAPLN2; NbExp=3; IntAct=EBI-11957238, EBI-11956675;
CC Q2TAL6; P49639: HOXA1; NbExp=6; IntAct=EBI-11957238, EBI-740785;
CC Q2TAL6; P84074: HPCA; NbExp=3; IntAct=EBI-11957238, EBI-12197079;
CC Q2TAL6; P37235: HPCAL1; NbExp=3; IntAct=EBI-11957238, EBI-749311;
CC Q2TAL6; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-11957238, EBI-2556193;
CC Q2TAL6; Q5T749: KPRP; NbExp=3; IntAct=EBI-11957238, EBI-10981970;
CC Q2TAL6; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-11957238, EBI-10171774;
CC Q2TAL6; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-11957238, EBI-11953846;
CC Q2TAL6; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-11957238, EBI-10241252;
CC Q2TAL6; Q9BYR9: KRTAP2-4; NbExp=3; IntAct=EBI-11957238, EBI-14065470;
CC Q2TAL6; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-11957238, EBI-3958099;
CC Q2TAL6; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-11957238, EBI-11962058;
CC Q2TAL6; Q5T751: LCE1C; NbExp=3; IntAct=EBI-11957238, EBI-12224199;
CC Q2TAL6; Q5T754: LCE1F; NbExp=3; IntAct=EBI-11957238, EBI-11958008;
CC Q2TAL6; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-11957238, EBI-11973993;
CC Q2TAL6; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-11957238, EBI-10246750;
CC Q2TAL6; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-11957238, EBI-9394625;
CC Q2TAL6; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-11957238, EBI-6658837;
CC Q2TAL6; Q5T5B0: LCE3E; NbExp=3; IntAct=EBI-11957238, EBI-10245456;
CC Q2TAL6; Q5TA78: LCE4A; NbExp=3; IntAct=EBI-11957238, EBI-10246358;
CC Q2TAL6; Q9P121-3: NTM; NbExp=3; IntAct=EBI-11957238, EBI-12027160;
CC Q2TAL6; P32242: OTX1; NbExp=3; IntAct=EBI-11957238, EBI-740446;
CC Q2TAL6; P16118: PFKFB1; NbExp=3; IntAct=EBI-11957238, EBI-709807;
CC Q2TAL6; Q12837: POU4F2; NbExp=3; IntAct=EBI-11957238, EBI-17236143;
CC Q2TAL6; Q8WWY3: PRPF31; NbExp=3; IntAct=EBI-11957238, EBI-1567797;
CC Q2TAL6; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-11957238, EBI-748391;
CC Q2TAL6; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-11957238, EBI-744081;
CC Q2TAL6; Q9NUL5-4: SHFL; NbExp=3; IntAct=EBI-11957238, EBI-11955083;
CC Q2TAL6; O43609: SPRY1; NbExp=3; IntAct=EBI-11957238, EBI-3866665;
CC Q2TAL6; Q8WVR3: TRAPPC14; NbExp=3; IntAct=EBI-11957238, EBI-719893;
CC Q2TAL6; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-11957238, EBI-741480;
CC Q2TAL6; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-11957238, EBI-947187;
CC Q2TAL6; Q6EMK4: VASN; NbExp=3; IntAct=EBI-11957238, EBI-10249550;
CC Q2TAL6; P25490: YY1; NbExp=3; IntAct=EBI-11957238, EBI-765538;
CC Q2TAL6; Q9P2F9: ZNF319; NbExp=3; IntAct=EBI-11957238, EBI-11993110;
CC Q2TAL6; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-11957238, EBI-740727;
CC Q2TAL6; Q9ULM2: ZNF490; NbExp=3; IntAct=EBI-11957238, EBI-1105370;
CC Q2TAL6; Q6ZNH5: ZNF497; NbExp=3; IntAct=EBI-11957238, EBI-10486136;
CC Q2TAL6; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-11957238, EBI-6427977;
CC Q2TAL6; Q9H7X3: ZNF696; NbExp=3; IntAct=EBI-11957238, EBI-11090299;
CC Q2TAL6; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-11957238, EBI-10251462;
CC Q2TAL6; Q96EG3: ZNF837; NbExp=3; IntAct=EBI-11957238, EBI-11962574;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000250}. Synapse {ECO:0000250}.
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DR EMBL; AB292671; BAF51551.1; -; mRNA.
DR EMBL; AY358393; AAQ88759.1; -; mRNA.
DR EMBL; CH471128; EAW60985.1; -; Genomic_DNA.
DR EMBL; CH236955; EAL23904.1; -; Genomic_DNA.
DR EMBL; BC110857; AAI10858.1; -; mRNA.
DR CCDS; CCDS5508.1; -.
DR RefSeq; NP_940972.2; NM_198570.4.
DR AlphaFoldDB; Q2TAL6; -.
DR SMR; Q2TAL6; -.
DR BioGRID; 131984; 61.
DR IntAct; Q2TAL6; 56.
DR STRING; 9606.ENSP00000341819; -.
DR BioMuta; VWC2; -.
DR DMDM; 121941771; -.
DR MassIVE; Q2TAL6; -.
DR PaxDb; Q2TAL6; -.
DR PeptideAtlas; Q2TAL6; -.
DR PRIDE; Q2TAL6; -.
DR ProteomicsDB; 61467; -.
DR Antibodypedia; 62692; 60 antibodies from 12 providers.
DR DNASU; 375567; -.
DR Ensembl; ENST00000340652.5; ENSP00000341819.3; ENSG00000188730.5.
DR GeneID; 375567; -.
DR KEGG; hsa:375567; -.
DR MANE-Select; ENST00000340652.5; ENSP00000341819.3; NM_198570.5; NP_940972.2.
DR UCSC; uc003tot.2; human.
DR CTD; 375567; -.
DR DisGeNET; 375567; -.
DR GeneCards; VWC2; -.
DR HGNC; HGNC:30200; VWC2.
DR HPA; ENSG00000188730; Group enriched (brain, heart muscle, ovary).
DR MIM; 611108; gene.
DR neXtProt; NX_Q2TAL6; -.
DR OpenTargets; ENSG00000188730; -.
DR PharmGKB; PA147357154; -.
DR VEuPathDB; HostDB:ENSG00000188730; -.
DR eggNOG; ENOG502QW4Q; Eukaryota.
DR GeneTree; ENSGT00720000108792; -.
DR HOGENOM; CLU_073865_0_0_1; -.
DR InParanoid; Q2TAL6; -.
DR OMA; RHECKQM; -.
DR OrthoDB; 1478107at2759; -.
DR PhylomeDB; Q2TAL6; -.
DR TreeFam; TF329913; -.
DR PathwayCommons; Q2TAL6; -.
DR SignaLink; Q2TAL6; -.
DR BioGRID-ORCS; 375567; 9 hits in 1061 CRISPR screens.
DR ChiTaRS; VWC2; human.
DR GenomeRNAi; 375567; -.
DR Pharos; Q2TAL6; Tdark.
DR PRO; PR:Q2TAL6; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q2TAL6; protein.
DR Bgee; ENSG00000188730; Expressed in cerebellar cortex and 71 other tissues.
DR Genevisible; Q2TAL6; HS.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; IBA:GO_Central.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005604; C:basement membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISS:HGNC-UCL.
DR GO; GO:0005614; C:interstitial matrix; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISS:HGNC-UCL.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:HGNC-UCL.
DR InterPro; IPR042979; VWC2/VWC2L.
DR InterPro; IPR001007; VWF_dom.
DR PANTHER; PTHR46252; PTHR46252; 1.
DR Pfam; PF00093; VWC; 1.
DR SMART; SM00214; VWC; 2.
DR PROSITE; PS01208; VWFC_1; 1.
DR PROSITE; PS50184; VWFC_2; 1.
PE 1: Evidence at protein level;
KW Basement membrane; Extracellular matrix; Reference proteome; Repeat;
KW Secreted; Signal; Synapse.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..325
FT /note="Brorin"
FT /id="PRO_0000307159"
FT DOMAIN 153..212
FT /note="VWFC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 216..274
FT /note="VWFC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT REGION 37..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 114..116
FT /note="Mediates cell adhesion"
FT /evidence="ECO:0000250"
FT COMPBIAS 41..82
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 120
FT /note="A -> G (in dbSNP:rs769604)"
FT /id="VAR_035371"
FT CONFLICT 52
FT /note="S -> T (in Ref. 1; BAF51551 and 2; AAQ88759)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 325 AA; 35282 MW; A38B673AB376B64D CRC64;
MPSSTAMAVG ALSSSLLVTC CLMVALCSPS IPLEKLAQAP EQPGQEKREH ASRDGPGRVN
ELGRPARDEG GSGRDWKSKS GRGLAGREPW SKLKQAWVSQ GGGAKAGDLQ VRPRGDTPQA
EALAAAAQDA IGPELAPTPE PPEEYVYPDY RGKGCVDESG FVYAIGEKFA PGPSACPCLC
TEEGPLCAQP ECPRLHPRCI HVDTSQCCPQ CKERKNYCEF RGKTYQTLEE FVVSPCERCR
CEANGEVLCT VSACPQTECV DPVYEPDQCC PICKNGPNCF AETAVIPAGR EVKTDECTIC
HCTYEEGTWR IERQAMCTRH ECRQM
