VWA2_HUMAN
ID VWA2_HUMAN Reviewed; 755 AA.
AC Q5GFL6; A1A5D4; B5MDJ8; Q6ZS39; Q6ZWJ7; Q708C5; Q70UZ8;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=von Willebrand factor A domain-containing protein 2;
DE AltName: Full=A domain-containing protein similar to matrilin and collagen;
DE Short=AMACO;
DE AltName: Full=Colon cancer secreted protein 2;
DE Short=CCSP-2;
DE Flags: Precursor;
GN Name=VWA2; Synonyms=AMACO;
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), AND VARIANT THR-9.
RC TISSUE=Placenta;
RX PubMed=14506275; DOI=10.1074/jbc.m307794200;
RA Sengle G., Kobbe B., Moergelin M., Paulsson M., Wagener R.;
RT "Identification and characterization of AMACO, a new member of the von
RT Willebrand factor A-like domain protein superfamily with a regulated
RT expression in the kidney.";
RL J. Biol. Chem. 278:50240-50249(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP PROTEOLYTIC PROCESSING, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15580307; DOI=10.1038/sj.onc.1208134;
RA Xin B., Platzer P., Fink S.P., Reese L., Nosrati A., Willson J.K.V.,
RA Wilson K., Markowitz S.;
RT "Colon cancer secreted protein-2 (CCSP-2), a novel candidate serological
RT marker of colon neoplasia.";
RL Oncogene 24:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS THR-9 AND
RP GLY-131.
RC TISSUE=Brain, and Tongue;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 VARIANT [LARGE SCALE ANALYSIS] ARG-137.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- SUBUNIT: Forms monomers and multimers. {ECO:0000250}.
CC -!- INTERACTION:
CC Q5GFL6; Q12933: TRAF2; NbExp=3; IntAct=EBI-10243723, EBI-355744;
CC Q5GFL6-3; P26045: PTPN3; NbExp=3; IntAct=EBI-13451145, EBI-1047946;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5GFL6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5GFL6-2; Sequence=VSP_028739;
CC Name=3;
CC IsoId=Q5GFL6-3; Sequence=VSP_028737, VSP_028738, VSP_028739;
CC -!- TISSUE SPECIFICITY: Expression is generally absent in normal colon and
CC other normal body tissues, but it is induced an average of 78-fold in
CC Stage II, III, and IV colon cancers, as well as in colon adenomas and
CC colon cancer cell lines. {ECO:0000269|PubMed:15580307}.
CC -!- PTM: A 55 kDa form is produced by proteolytic cleavage.
CC {ECO:0000269|PubMed:15580307}.
CC -!- MISCELLANEOUS: May be used as a serological marker for colon neoplasia.
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; AJ616914; CAE83814.1; -; mRNA.
DR EMBL; AJ536328; CAD60276.1; -; mRNA.
DR EMBL; AY572972; AAT77225.1; -; mRNA.
DR EMBL; AY572973; AAT77226.1; -; Genomic_DNA.
DR EMBL; AK122716; BAC85505.1; -; mRNA.
DR EMBL; AK127756; BAC87116.1; -; mRNA.
DR EMBL; AC005383; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022023; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC128588; AAI28589.1; -; mRNA.
DR CCDS; CCDS7589.2; -. [Q5GFL6-1]
DR RefSeq; NP_001258975.1; NM_001272046.1. [Q5GFL6-1]
DR RefSeq; NP_001307733.1; NM_001320804.1. [Q5GFL6-1]
DR RefSeq; XP_011538059.1; XM_011539757.2.
DR AlphaFoldDB; Q5GFL6; -.
DR SMR; Q5GFL6; -.
DR BioGRID; 131091; 44.
DR IntAct; Q5GFL6; 8.
DR STRING; 9606.ENSP00000376708; -.
DR GlyGen; Q5GFL6; 1 site.
DR iPTMnet; Q5GFL6; -.
DR PhosphoSitePlus; Q5GFL6; -.
DR BioMuta; VWA2; -.
DR DMDM; 74722595; -.
DR jPOST; Q5GFL6; -.
DR MassIVE; Q5GFL6; -.
DR PaxDb; Q5GFL6; -.
DR PeptideAtlas; Q5GFL6; -.
DR PRIDE; Q5GFL6; -.
DR ProteomicsDB; 62826; -. [Q5GFL6-1]
DR ProteomicsDB; 62827; -. [Q5GFL6-2]
DR ProteomicsDB; 62828; -. [Q5GFL6-3]
DR Antibodypedia; 46200; 103 antibodies from 22 providers.
DR DNASU; 340706; -.
DR Ensembl; ENST00000392982.8; ENSP00000376708.3; ENSG00000165816.13. [Q5GFL6-1]
DR Ensembl; ENST00000603594.2; ENSP00000473752.2; ENSG00000165816.13. [Q5GFL6-3]
DR GeneID; 340706; -.
DR KEGG; hsa:340706; -.
DR MANE-Select; ENST00000392982.8; ENSP00000376708.3; NM_001272046.2; NP_001258975.1.
DR UCSC; uc001lbl.3; human. [Q5GFL6-1]
DR CTD; 340706; -.
DR DisGeNET; 340706; -.
DR GeneCards; VWA2; -.
DR HGNC; HGNC:24709; VWA2.
DR HPA; ENSG00000165816; Tissue enhanced (stomach).
DR MIM; 618281; gene.
DR neXtProt; NX_Q5GFL6; -.
DR OpenTargets; ENSG00000165816; -.
DR PharmGKB; PA142670613; -.
DR VEuPathDB; HostDB:ENSG00000165816; -.
DR eggNOG; KOG3544; Eukaryota.
DR GeneTree; ENSGT00940000159040; -.
DR HOGENOM; CLU_008905_7_3_1; -.
DR InParanoid; Q5GFL6; -.
DR OMA; CWRGSRQ; -.
DR OrthoDB; 350336at2759; -.
DR PhylomeDB; Q5GFL6; -.
DR TreeFam; TF318242; -.
DR PathwayCommons; Q5GFL6; -.
DR SignaLink; Q5GFL6; -.
DR BioGRID-ORCS; 340706; 7 hits in 1057 CRISPR screens.
DR ChiTaRS; VWA2; human.
DR GeneWiki; VWA2; -.
DR GenomeRNAi; 340706; -.
DR Pharos; Q5GFL6; Tbio.
DR PRO; PR:Q5GFL6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q5GFL6; protein.
DR Bgee; ENSG00000165816; Expressed in thymus and 93 other tissues.
DR GO; GO:0005604; C:basement membrane; IBA:GO_Central.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0007161; P:calcium-independent cell-matrix adhesion; IBA:GO_Central.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IMP:UniProtKB.
DR Gene3D; 3.40.50.410; -; 3.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR030755; VWA2.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR PANTHER; PTHR24020:SF37; PTHR24020:SF37; 1.
DR Pfam; PF00008; EGF; 2.
DR Pfam; PF00092; VWA; 3.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00327; VWA; 3.
DR SUPFAM; SSF53300; SSF53300; 3.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS50234; VWFA; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; EGF-like domain; Glycoprotein;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..755
FT /note="von Willebrand factor A domain-containing protein 2"
FT /id="PRO_0000307362"
FT DOMAIN 51..222
FT /note="VWFA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 296..333
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 343..517
FT /note="VWFA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 531..705
FT /note="VWFA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 712..748
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT SITE 267..268
FT /note="Cleavage"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 299..310
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 304..320
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 322..332
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 716..727
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 721..736
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 738..747
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 1..304
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028737"
FT VAR_SEQ 305..332
FT /note="QNGGTCVPEGLDGYQCLCPLAFGGEANC -> MEAHVFQKDWTATSASARWP
FT LEGRLTVV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028738"
FT VAR_SEQ 708..755
FT /note="EAKQPVNLCKPSPCMNEGSCVLQNGSYRCKCRDGWEGPHCENRFLRRP ->
FT GEWGNPHPQGCPHGRPSA (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_028739"
FT VARIANT 9
FT /note="A -> T (in dbSNP:rs9664945)"
FT /evidence="ECO:0000269|PubMed:14506275,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_035418"
FT VARIANT 131
FT /note="E -> G (in dbSNP:rs597371)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_035419"
FT VARIANT 137
FT /note="L -> R (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036641"
FT CONFLICT 76
FT /note="T -> A (in Ref. 3; BAC87116)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="Q -> R (in Ref. 1; CAD60276)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 755 AA; 82012 MW; E02B99335BE28BEC CRC64;
MPPFLLLEAV CVFLFSRVPP SLPLQEVHVS KETIGKISAA SKMMWCSAAV DIMFLLDGSN
SVGKGSFERS KHFAITVCDG LDISPERVRV GAFQFSSTPH LEFPLDSFST QQEVKARIKR
MVFKGGRTET ELALKYLLHR GLPGGRNASV PQILIIVTDG KSQGDVALPS KQLKERGVTV
FAVGVRFPRW EELHALASEP RGQHVLLAEQ VEDATNGLFS TLSSSAICSS ATPDCRVEAH
PCEHRTLEMV REFAGNAPCW RGSRRTLAVL AAHCPFYSWK RVFLTHPATC YRTTCPGPCD
SQPCQNGGTC VPEGLDGYQC LCPLAFGGEA NCALKLSLEC RVDLLFLLDS SAGTTLDGFL
RAKVFVKRFV RAVLSEDSRA RVGVATYSRE LLVAVPVGEY QDVPDLVWSL DGIPFRGGPT
LTGSALRQAA ERGFGSATRT GQDRPRRVVV LLTESHSEDE VAGPARHARA RELLLLGVGS
EAVRAELEEI TGSPKHVMVY SDPQDLFNQI PELQGKLCSR QRPGCRTQAL DLVFMLDTSA
SVGPENFAQM QSFVRSCALQ FEVNPDVTQV GLVVYGSQVQ TAFGLDTKPT RAAMLRAISQ
APYLGGVGSA GTALLHIYDK VMTVQRGARP GVPKAVVVLT GGRGAEDAAV PAQKLRNNGI
SVLVVGVGPV LSEGLRRLAG PRDSLIHVAA YADLRYHQDV LIEWLCGEAK QPVNLCKPSP
CMNEGSCVLQ NGSYRCKCRD GWEGPHCENR FLRRP
