VWA1_HUMAN
ID VWA1_HUMAN Reviewed; 445 AA.
AC Q6PCB0; A8K692; B3KUA1; E9PB53; Q7L5D7; Q9H6J5;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=von Willebrand factor A domain-containing protein 1 {ECO:0000305};
DE Flags: Precursor;
GN Name=VWA1 {ECO:0000312|HGNC:HGNC:30910};
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=Placenta, and Prostate;
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=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas, and Placenta;
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 [5]
RP PHOSPHORYLATION AT SER-74; SER-80; TYR-83 AND SER-93.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [6]
RP INVOLVEMENT IN HMNMYO, AND VARIANTS HMNMYO 32-ARG--PRO-445 DEL AND
RP 63-PRO--ALA-70 DEL.
RX PubMed=33459760; DOI=10.1093/brain/awaa418;
RA Deschauer M., Hengel H., Rupprich K., Kreiss M., Schlotter-Weigel B.,
RA Grimmel M., Admard J., Schneider I., Alhaddad B., Gazou A., Sturm M.,
RA Vorgerd M., Balousha G., Balousha O., Falna M., Kirschke J.S., Kornblum C.,
RA Jordan B., Kraya T., Strom T.M., Weis J., Schoels L., Schara U., Zierz S.,
RA Riess O., Meitinger T., Haack T.B.;
RT "Bi-allelic truncating mutations in VWA1 cause neuromyopathy.";
RL Brain 144:574-583(2021).
RN [7]
RP INVOLVEMENT IN HMNMYO.
RX PubMed=33559681; DOI=10.1093/brain/awaa420;
RG Genomics England Research Consortium;
RA Pagnamenta A.T., Kaiyrzhanov R., Zou Y., Da'as S.I., Maroofian R.,
RA Donkervoort S., Dominik N., Lauffer M., Ferla M.P., Orioli A., Giess A.,
RA Tucci A., Beetz C., Sedghi M., Ansari B., Barresi R., Basiri K.,
RA Cortese A., Elgar G., Fernandez-Garcia M.A., Yip J., Foley A.R.,
RA Gutowski N., Jungbluth H., Lassche S., Lavin T., Marcelis C., Marks P.,
RA Marini-Bettolo C., Medne L., Moslemi A.R., Sarkozy A., Reilly M.M.,
RA Muntoni F., Millan F., Muraresku C.C., Need A.C., Nemeth A.H.,
RA Neuhaus S.B., Norwood F., O'Donnell M., O'Driscoll M., Rankin J., Yum S.W.,
RA Zolkipli-Cunningham Z., Brusius I., Wunderlich G., Karakaya M., Wirth B.,
RA Fakhro K.A., Tajsharghi H., Boennemann C.G., Taylor J.C., Houlden H.;
RT "An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary
RT motor neuropathy.";
RL Brain 144:584-600(2021).
CC -!- FUNCTION: Promotes matrix assembly (By similarity). Involved in the
CC organization of skeletal muscles and in the formation of neuromuscular
CC junctions (Probable). {ECO:0000250|UniProtKB:Q8R2Z5,
CC ECO:0000305|PubMed:33559681}.
CC -!- SUBUNIT: Homodimer or homomultimer; disulfide-linked. Interacts with
CC HSPG2. {ECO:0000250|UniProtKB:Q8R2Z5}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000250|UniProtKB:Q8R2Z5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6PCB0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PCB0-2; Sequence=VSP_028617;
CC Name=3;
CC IsoId=Q6PCB0-3; Sequence=VSP_046651, VSP_046652;
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8R2Z5}.
CC -!- DISEASE: Neuropathy, hereditary motor, with myopathic features (HMNMYO)
CC [MIM:619216]: An autosomal recessive, neuromyopathic disorder that
CC manifests in childhood or adulthood with proximal and distal muscle
CC weakness predominantly of the lower limbs. Affected individuals have
CC difficulty climbing stairs and problems standing on the heels. Most
CC patients have foot deformities, and some may have leg muscle atrophy.
CC Muscle biopsy and electrophysiologic studies are consistent with both a
CC myopathic process and an axonal motor neuropathy.
CC {ECO:0000269|PubMed:33459760, ECO:0000269|PubMed:33559681}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; AK025868; BAB15264.1; -; mRNA.
DR EMBL; AK096773; BAG53363.1; -; mRNA.
DR EMBL; AK291557; BAF84246.1; -; mRNA.
DR EMBL; AL391244; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471183; EAW56197.1; -; Genomic_DNA.
DR EMBL; CH471183; EAW56198.1; -; Genomic_DNA.
DR EMBL; BC003543; AAH03543.2; -; mRNA.
DR EMBL; BC059409; AAH59409.1; -; mRNA.
DR CCDS; CCDS27.1; -. [Q6PCB0-1]
DR CCDS; CCDS28.2; -. [Q6PCB0-3]
DR RefSeq; NP_073745.2; NM_022834.4. [Q6PCB0-1]
DR RefSeq; NP_954572.2; NM_199121.2. [Q6PCB0-3]
DR AlphaFoldDB; Q6PCB0; -.
DR SMR; Q6PCB0; -.
DR BioGRID; 122329; 28.
DR IntAct; Q6PCB0; 14.
DR STRING; 9606.ENSP00000417185; -.
DR GlyGen; Q6PCB0; 3 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q6PCB0; -.
DR PhosphoSitePlus; Q6PCB0; -.
DR BioMuta; VWA1; -.
DR DMDM; 74749155; -.
DR jPOST; Q6PCB0; -.
DR MassIVE; Q6PCB0; -.
DR MaxQB; Q6PCB0; -.
DR PaxDb; Q6PCB0; -.
DR PeptideAtlas; Q6PCB0; -.
DR PRIDE; Q6PCB0; -.
DR ProteomicsDB; 67054; -. [Q6PCB0-1]
DR ProteomicsDB; 67055; -. [Q6PCB0-2]
DR Antibodypedia; 26362; 73 antibodies from 22 providers.
DR DNASU; 64856; -.
DR Ensembl; ENST00000338660.5; ENSP00000423404.1; ENSG00000179403.12. [Q6PCB0-3]
DR Ensembl; ENST00000476993.2; ENSP00000417185.1; ENSG00000179403.12. [Q6PCB0-1]
DR GeneID; 64856; -.
DR KEGG; hsa:64856; -.
DR MANE-Select; ENST00000476993.2; ENSP00000417185.1; NM_022834.5; NP_073745.2.
DR UCSC; uc001afr.4; human. [Q6PCB0-1]
DR CTD; 64856; -.
DR DisGeNET; 64856; -.
DR GeneCards; VWA1; -.
DR HGNC; HGNC:30910; VWA1.
DR HPA; ENSG00000179403; Tissue enhanced (seminal).
DR MalaCards; VWA1; -.
DR MIM; 611901; gene.
DR MIM; 619216; phenotype.
DR neXtProt; NX_Q6PCB0; -.
DR OpenTargets; ENSG00000179403; -.
DR Orphanet; 314485; Young adult-onset distal hereditary motor neuropathy.
DR PharmGKB; PA142670612; -.
DR VEuPathDB; HostDB:ENSG00000179403; -.
DR eggNOG; KOG1217; Eukaryota.
DR eggNOG; KOG3544; Eukaryota.
DR GeneTree; ENSGT00940000160734; -.
DR HOGENOM; CLU_2867092_0_0_1; -.
DR InParanoid; Q6PCB0; -.
DR OMA; PEGVLNC; -.
DR OrthoDB; 67372at2759; -.
DR PhylomeDB; Q6PCB0; -.
DR TreeFam; TF316402; -.
DR PathwayCommons; Q6PCB0; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; Q6PCB0; -.
DR BioGRID-ORCS; 64856; 25 hits in 1069 CRISPR screens.
DR ChiTaRS; VWA1; human.
DR GenomeRNAi; 64856; -.
DR Pharos; Q6PCB0; Tbio.
DR PRO; PR:Q6PCB0; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6PCB0; protein.
DR Bgee; ENSG00000179403; Expressed in tibial nerve and 162 other tissues.
DR ExpressionAtlas; Q6PCB0; baseline and differential.
DR Genevisible; Q6PCB0; HS.
DR GO; GO:0005604; C:basement membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005614; C:interstitial matrix; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0048266; P:behavioral response to pain; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR030758; Vwa1.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR PANTHER; PTHR24020:SF51; PTHR24020:SF51; 1.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF00092; VWA; 1.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR SUPFAM; SSF53300; SSF53300; 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Basement membrane; Disease variant; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Neuropathy; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..445
FT /note="von Willebrand factor A domain-containing protein 1"
FT /id="PRO_0000307156"
FT DOMAIN 34..213
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 214..304
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 334..427
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 302..325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 411..445
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 424..438
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 74
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 80
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 83
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 93
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..212
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_028617"
FT VAR_SEQ 26..64
FT /note="PPASAPRGDLMFLLDSSASVSHYEFSRVREFVGQLVAPL -> AQGPGRHRV
FT HCQHRPRQLPGAVSRCLSPCREAPALCGRG (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046651"
FT VAR_SEQ 65..445
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046652"
FT VARIANT 32..445
FT /note="Missing (in HMNMYO)"
FT /evidence="ECO:0000269|PubMed:33459760"
FT /id="VAR_085457"
FT VARIANT 63..70
FT /note="Missing (in HMNMYO; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33459760"
FT /id="VAR_085458"
FT CONFLICT 9
FT /note="L -> Q (in Ref. 1; BAF84246)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 445 AA; 46804 MW; D9FBDE9C0A4DEBDF CRC64;
MLPWTALGLA LSLRLALARS GAERGPPASA PRGDLMFLLD SSASVSHYEF SRVREFVGQL
VAPLPLGTGA LRASLVHVGS RPYTEFPFGQ HSSGEAAQDA VRASAQRMGD THTGLALVYA
KEQLFAEASG ARPGVPKVLV WVTDGGSSDP VGPPMQELKD LGVTVFIVST GRGNFLELSA
AASAPAEKHL HFVDVDDLHI IVQELRGSIL DAMRPQQLHA TEITSSGFRL AWPPLLTADS
GYYVLELVPS AQPGAARRQQ LPGNATDWIW AGLDPDTDYD VALVPESNVR LLRPQILRVR
TRPGEAGPGA SGPESGAGPA PTQLAALPAP EEAGPERIVI SHARPRSLRV SWAPALGSAA
ALGYHVQFGP LRGGEAQRVE VPAGRNCTTL QGLAPGTAYL VTVTAAFRSG RESALSAKAC
TPDGPRPRPR PVPRAPTPGT ASREP
