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 27-NOV-2024, entry version 153. 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 RefSeq; XP_016871669.1; XM_017016180.1. [Q5GFL6-3] DR AlphaFoldDB; Q5GFL6; -. DR SMR; Q5GFL6; -. DR BioGRID; 131091; 44. DR IntAct; Q5GFL6; 32. DR STRING; 9606.ENSP00000376708; -. DR GlyCosmos; Q5GFL6; 1 site, No reported glycans. DR GlyGen; Q5GFL6; 1 site, 9 N-linked glycans (1 site). DR iPTMnet; Q5GFL6; -. DR PhosphoSitePlus; Q5GFL6; -. DR BioMuta; VWA2; -. DR DMDM; 74722595; -. DR jPOST; Q5GFL6; -. DR MassIVE; Q5GFL6; -. DR PaxDb; 9606-ENSP00000376708; -. DR PeptideAtlas; Q5GFL6; -. DR ProteomicsDB; 62826; -. [Q5GFL6-1] DR ProteomicsDB; 62827; -. [Q5GFL6-2] DR ProteomicsDB; 62828; -. [Q5GFL6-3] DR Antibodypedia; 46200; 103 antibodies from 21 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 AGR; HGNC:24709; -. 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; MWCSAAM; -. DR OrthoDB; 5299728at2759; -. DR PhylomeDB; Q5GFL6; -. DR TreeFam; TF318242; -. DR PathwayCommons; Q5GFL6; -. DR SignaLink; Q5GFL6; -. DR BioGRID-ORCS; 340706; 7 hits in 1135 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 94 other cell types or tissues. DR GO; GO:0005604; C:basement membrane; 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 CDD; cd00053; EGF; 1. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd01472; vWA_collagen; 1. DR FunFam; 2.10.25.10:FF:000066; FAT atypical cadherin 4; 1. DR FunFam; 2.10.25.10:FF:000336; von Willebrand factor A domain containing 2; 1. DR FunFam; 3.40.50.410:FF:000047; von Willebrand factor A domain containing 2; 1. DR FunFam; 3.40.50.410:FF:000054; von Willebrand factor A domain containing 2; 1. DR FunFam; 3.40.50.410:FF:000058; von Willebrand factor A domain containing 2; 1. DR Gene3D; 2.10.25.10; Laminin; 2. DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 3. DR InterPro; IPR050525; ECM_Assembly_Org. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR002035; VWF_A. DR InterPro; IPR036465; vWFA_dom_sf. DR PANTHER; PTHR24020; COLLAGEN ALPHA; 1. DR PANTHER; PTHR24020:SF70; PH DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF00008; EGF; 2. DR Pfam; PF00092; VWA; 3. DR PRINTS; PR00453; VWFADOMAIN. DR SMART; SM00181; EGF; 2. DR SMART; SM00179; EGF_CA; 2. DR SMART; SM00327; VWA; 3. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF53300; vWA-like; 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 Proteomics identification; 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 //