VWC2L_HUMAN
ID VWC2L_HUMAN Reviewed; 222 AA.
AC B2RUY7; A6NC69; B2RUW7; B7X8X1;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=von Willebrand factor C domain-containing protein 2-like;
DE Short=VWC2-like protein;
DE AltName: Full=Brorin-like;
DE Flags: Precursor;
GN Name=VWC2L;
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).
RX PubMed=19852960; DOI=10.1016/j.febslet.2009.10.044;
RA Miwa H., Miyake A., Kouta Y., Shimada A., Yamashita Y., Nakayama Y.,
RA Yamauchi H., Konishi M., Itoh N.;
RT "A novel neural-specific BMP antagonist, Brorin-like, of the Chordin
RT family.";
RL FEBS Lett. 583:3643-3648(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Mochida Y., Yamauchi M.;
RT "A novel cysteine-knot protein regulates matrix mineralization.";
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain cortex;
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: May play a role in neurogenesis. May play a role in bone
CC differentiation and matrix mineralization. {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 VWC2L. Alone or in
CC combination, these auxiliary subunits control the gating and
CC pharmacology of the AMPAR complex and profoundly impact their
CC biogenesis and protein processing (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC B2RUY7; Q8WW18: C17orf50; NbExp=3; IntAct=EBI-11747707, EBI-12877892;
CC B2RUY7; Q6P5X5: C22orf39; NbExp=5; IntAct=EBI-11747707, EBI-7317823;
CC B2RUY7; Q6PRD7: CEMP1; NbExp=3; IntAct=EBI-11747707, EBI-12907646;
CC B2RUY7; Q9UGL9: CRCT1; NbExp=3; IntAct=EBI-11747707, EBI-713677;
CC B2RUY7; P42830: CXCL5; NbExp=3; IntAct=EBI-11747707, EBI-12175919;
CC B2RUY7; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11747707, EBI-3867333;
CC B2RUY7; Q30KQ8: DEFB112; NbExp=3; IntAct=EBI-11747707, EBI-17470374;
CC B2RUY7; Q9NWN3: FBXO34; NbExp=3; IntAct=EBI-11747707, EBI-719816;
CC B2RUY7; Q13643: FHL3; NbExp=4; IntAct=EBI-11747707, EBI-741101;
CC B2RUY7; P49639: HOXA1; NbExp=3; IntAct=EBI-11747707, EBI-740785;
CC B2RUY7; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-11747707, EBI-10171774;
CC B2RUY7; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-11747707, EBI-1052037;
CC B2RUY7; Q3LHN2: KRTAP19-2; NbExp=3; IntAct=EBI-11747707, EBI-12196745;
CC B2RUY7; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-11747707, EBI-11962058;
CC B2RUY7; Q5T751: LCE1C; NbExp=3; IntAct=EBI-11747707, EBI-12224199;
CC B2RUY7; Q5TA76: LCE3A; NbExp=6; IntAct=EBI-11747707, EBI-9394625;
CC B2RUY7; Q5TCM9: LCE5A; NbExp=3; IntAct=EBI-11747707, EBI-11955689;
CC B2RUY7; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11747707, EBI-16439278;
CC B2RUY7; Q92570: NR4A3; NbExp=3; IntAct=EBI-11747707, EBI-13644623;
CC B2RUY7; P32242: OTX1; NbExp=5; IntAct=EBI-11747707, EBI-740446;
CC B2RUY7; P57078-2: RIPK4; NbExp=3; IntAct=EBI-11747707, EBI-12854608;
CC B2RUY7; A0A024R4B0: SPATA3; NbExp=3; IntAct=EBI-11747707, EBI-14123856;
CC B2RUY7; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-11747707, EBI-5235829;
CC B2RUY7; Q06418: TYRO3; NbExp=3; IntAct=EBI-11747707, EBI-3951628;
CC B2RUY7; P17024: ZNF20; NbExp=3; IntAct=EBI-11747707, EBI-717634;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Synapse {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=B2RUY7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=B2RUY7-2; Sequence=VSP_035088, VSP_035089;
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB374231; BAH04176.1; -; mRNA.
DR EMBL; EU541473; ACD62527.1; -; mRNA.
DR EMBL; AC107218; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC146903; AAI46904.1; -; mRNA.
DR EMBL; BC146911; AAI46912.1; -; mRNA.
DR EMBL; BC146931; AAI46932.1; -; mRNA.
DR EMBL; BC146935; AAI46936.1; -; mRNA.
DR CCDS; CCDS46509.1; -. [B2RUY7-1]
DR RefSeq; NP_001073969.1; NM_001080500.3. [B2RUY7-1]
DR AlphaFoldDB; B2RUY7; -.
DR BioGRID; 135334; 38.
DR IntAct; B2RUY7; 25.
DR STRING; 9606.ENSP00000308976; -.
DR iPTMnet; B2RUY7; -.
DR PhosphoSitePlus; B2RUY7; -.
DR BioMuta; VWC2L; -.
DR MassIVE; B2RUY7; -.
DR PaxDb; B2RUY7; -.
DR PeptideAtlas; B2RUY7; -.
DR PRIDE; B2RUY7; -.
DR Antibodypedia; 52490; 12 antibodies from 6 providers.
DR DNASU; 402117; -.
DR Ensembl; ENST00000312504.10; ENSP00000308976.5; ENSG00000174453.10. [B2RUY7-1]
DR GeneID; 402117; -.
DR KEGG; hsa:402117; -.
DR MANE-Select; ENST00000312504.10; ENSP00000308976.5; NM_001080500.4; NP_001073969.1.
DR UCSC; uc002vet.3; human. [B2RUY7-1]
DR CTD; 402117; -.
DR DisGeNET; 402117; -.
DR GeneCards; VWC2L; -.
DR HGNC; HGNC:37203; VWC2L.
DR HPA; ENSG00000174453; Group enriched (brain, retina).
DR MIM; 619794; gene.
DR neXtProt; NX_B2RUY7; -.
DR OpenTargets; ENSG00000174453; -.
DR PharmGKB; PA165697841; -.
DR VEuPathDB; HostDB:ENSG00000174453; -.
DR eggNOG; ENOG502RAAU; Eukaryota.
DR GeneTree; ENSGT00720000108792; -.
DR HOGENOM; CLU_100254_0_1_1; -.
DR InParanoid; B2RUY7; -.
DR OMA; PICKHGP; -.
DR OrthoDB; 1478107at2759; -.
DR PhylomeDB; B2RUY7; -.
DR TreeFam; TF329913; -.
DR PathwayCommons; B2RUY7; -.
DR SignaLink; B2RUY7; -.
DR BioGRID-ORCS; 402117; 11 hits in 1066 CRISPR screens.
DR ChiTaRS; VWC2L; human.
DR GenomeRNAi; 402117; -.
DR Pharos; B2RUY7; Tdark.
DR PRO; PR:B2RUY7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; B2RUY7; protein.
DR Bgee; ENSG00000174453; Expressed in superior frontal gyrus and 26 other tissues.
DR ExpressionAtlas; B2RUY7; baseline and differential.
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:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR InterPro; IPR042979; VWC2/VWC2L.
DR InterPro; IPR001007; VWF_dom.
DR PANTHER; PTHR46252; PTHR46252; 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 Alternative splicing; Developmental protein; Reference proteome; Repeat;
KW Secreted; Signal; Synapse.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..222
FT /note="von Willebrand factor C domain-containing protein 2-
FT like"
FT /id="PRO_0000348060"
FT DOMAIN 51..110
FT /note="VWFC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 114..172
FT /note="VWFC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT VAR_SEQ 131..138
FT /note="PSPCEWCR -> VCVTLHIY (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_035088"
FT VAR_SEQ 139..222
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_035089"
SQ SEQUENCE 222 AA; 24570 MW; 7047CE3CBA835B54 CRC64;
MALHIHEACI LLLVIPGLVT SAAISHEDYP ADEGDQISSN DNLIFDDYRG KGCVDDSGFV
YKLGERFFPG HSNCPCVCAL DGPVCDQPEC PKIHPKCTKV EHNGCCPECK EVKNFCEYHG
KNYKILEEFK PSPCEWCRCE PSNEVHCVVA DCAVPECVNP VYEPEQCCPV CKNGPNCFAG
TTIIPAGIEV KVDECNICHC HNGDWWKPAQ CSKRECQGKQ TV
