ID VWDE_HUMAN Reviewed; 1590 AA. AC Q8N2E2; B7ZM77; Q96SQ3; DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 05-APR-2011, sequence version 4. DT 27-NOV-2024, entry version 145. DE RecName: Full=von Willebrand factor D and EGF domain-containing protein; DE Flags: Precursor; GN Name=VWDE; 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 GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS PHE-607; RP ASN-964 AND MET-1032. 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-342 (ISOFORM 1). RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 639-1590 (ISOFORM 1), AND RP VARIANTS LYS-1256 AND CYS-1485. RC TISSUE=Teratocarcinoma; 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). CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8N2E2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N2E2-3; Sequence=VSP_055465; CC -!- SEQUENCE CAUTION: CC Sequence=AAI44320.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAB55237.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAC11671.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; CC Sequence=EAW93644.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; 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; AC007321; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC013470; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471073; EAW93644.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC144319; AAI44320.1; ALT_FRAME; mRNA. DR EMBL; AK075525; BAC11671.1; ALT_SEQ; mRNA. DR EMBL; AK027618; BAB55237.1; ALT_INIT; mRNA. DR CCDS; CCDS47544.1; -. [Q8N2E2-1] DR RefSeq; NP_001129396.1; NM_001135924.2. [Q8N2E2-1] DR RefSeq; XP_005249698.1; XM_005249641.1. DR AlphaFoldDB; Q8N2E2; -. DR SMR; Q8N2E2; -. DR BioGRID; 128755; 139. DR IntAct; Q8N2E2; 62. DR STRING; 9606.ENSP00000275358; -. DR GlyCosmos; Q8N2E2; 3 sites, No reported glycans. DR GlyGen; Q8N2E2; 3 sites. DR iPTMnet; Q8N2E2; -. DR PhosphoSitePlus; Q8N2E2; -. DR BioMuta; VWDE; -. DR DMDM; 327478608; -. DR MassIVE; Q8N2E2; -. DR PaxDb; 9606-ENSP00000275358; -. DR PeptideAtlas; Q8N2E2; -. DR ProteomicsDB; 71685; -. [Q8N2E2-1] DR Pumba; Q8N2E2; -. DR Antibodypedia; 66337; 10 antibodies from 5 providers. DR DNASU; 221806; -. DR Ensembl; ENST00000275358.8; ENSP00000275358.3; ENSG00000146530.15. [Q8N2E2-1] DR GeneID; 221806; -. DR KEGG; hsa:221806; -. DR MANE-Select; ENST00000275358.8; ENSP00000275358.3; NM_001135924.3; NP_001129396.1. DR UCSC; uc003ssj.3; human. [Q8N2E2-1] DR AGR; HGNC:21897; -. DR CTD; 221806; -. DR DisGeNET; 221806; -. DR GeneCards; VWDE; -. DR HGNC; HGNC:21897; VWDE. DR HPA; ENSG00000146530; Tissue enhanced (epididymis, salivary gland, thyroid gland). DR neXtProt; NX_Q8N2E2; -. DR OpenTargets; ENSG00000146530; -. DR VEuPathDB; HostDB:ENSG00000146530; -. DR eggNOG; KOG1217; Eukaryota. DR GeneTree; ENSGT00940000160835; -. DR HOGENOM; CLU_002130_0_0_1; -. DR InParanoid; Q8N2E2; -. DR OMA; GNLCTCA; -. DR OrthoDB; 2906846at2759; -. DR PhylomeDB; Q8N2E2; -. DR TreeFam; TF351702; -. DR PathwayCommons; Q8N2E2; -. DR SignaLink; Q8N2E2; -. DR BioGRID-ORCS; 221806; 12 hits in 1152 CRISPR screens. DR ChiTaRS; VWDE; human. DR GenomeRNAi; 221806; -. DR Pharos; Q8N2E2; Tdark. DR PRO; PR:Q8N2E2; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q8N2E2; protein. DR Bgee; ENSG00000146530; Expressed in pituitary gland and 109 other cell types or tissues. DR ExpressionAtlas; Q8N2E2; baseline and differential. DR GO; GO:0009986; C:cell surface; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; IBA:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central. DR FunFam; 2.10.25.10:FF:000499; Predicted protein; 1. DR FunFam; 2.10.25.10:FF:000490; von Willebrand factor D and EGF domain-containing protein; 1. DR FunFam; 2.10.25.10:FF:000595; von Willebrand factor D and EGF domain-containing protein; 1. DR FunFam; 2.60.120.260:FF:000100; von Willebrand factor D and EGF domain-containing protein; 1. DR FunFam; 2.10.25.10:FF:000865; von Willebrand factor D and EGF domains; 1. DR FunFam; 2.10.25.10:FF:001218; von Willebrand factor D and EGF domains; 1. DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1. DR Gene3D; 2.10.25.10; Laminin; 6. DR InterPro; IPR050969; Dev_Signal_Modulators. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR001846; VWF_type-D. DR PANTHER; PTHR14949:SF50; 3-PHYTASE; 1. DR PANTHER; PTHR14949; EGF-LIKE-DOMAIN, MULTIPLE 7, 8; 1. DR Pfam; PF00094; VWD; 1. DR SMART; SM00181; EGF; 12. DR SMART; SM00216; VWD; 1. DR SUPFAM; SSF57196; EGF/Laminin; 2. DR PROSITE; PS00022; EGF_1; 9. DR PROSITE; PS01186; EGF_2; 6. DR PROSITE; PS50026; EGF_3; 7. DR PROSITE; PS51233; VWFD; 1. 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..20 FT /evidence="ECO:0000255" FT CHAIN 21..1590 FT /note="von Willebrand factor D and EGF domain-containing FT protein" FT /id="PRO_0000329441" FT DOMAIN 423..606 FT /note="VWFD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DOMAIN 1177..1216 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1294..1326 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1358..1390 FT /note="EGF-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1422..1454 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1455..1486 FT /note="EGF-like 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1518..1550 FT /note="EGF-like 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1551..1582 FT /note="EGF-like 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 1268..1288 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1268..1284 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 367 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 703 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 968 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 425..565 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 468..477 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 1181..1189 FT /evidence="ECO:0000250" FT DISULFID 1183..1204 FT /evidence="ECO:0000250" FT DISULFID 1206..1215 FT /evidence="ECO:0000250" FT DISULFID 1298..1308 FT /evidence="ECO:0000250" FT DISULFID 1302..1314 FT /evidence="ECO:0000250" FT DISULFID 1316..1325 FT /evidence="ECO:0000250" FT DISULFID 1362..1372 FT /evidence="ECO:0000250" FT DISULFID 1366..1378 FT /evidence="ECO:0000250" FT DISULFID 1380..1389 FT /evidence="ECO:0000250" FT DISULFID 1426..1436 FT /evidence="ECO:0000250" FT DISULFID 1430..1442 FT /evidence="ECO:0000250" FT DISULFID 1444..1453 FT /evidence="ECO:0000250" FT DISULFID 1458..1468 FT /evidence="ECO:0000250" FT DISULFID 1462..1474 FT /evidence="ECO:0000250" FT DISULFID 1522..1532 FT /evidence="ECO:0000250" FT DISULFID 1526..1538 FT /evidence="ECO:0000250" FT DISULFID 1540..1549 FT /evidence="ECO:0000250" FT DISULFID 1554..1564 FT /evidence="ECO:0000250" FT DISULFID 1558..1570 FT /evidence="ECO:0000250" FT DISULFID 1572..1581 FT /evidence="ECO:0000250" FT VAR_SEQ 1..546 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_055465" FT VARIANT 607 FT /note="S -> F (in dbSNP:rs963323)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_071061" FT VARIANT 964 FT /note="K -> N (in dbSNP:rs6460939)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_047871" FT VARIANT 1032 FT /note="T -> M (in dbSNP:rs2053380)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_047872" FT VARIANT 1256 FT /note="Q -> K (in dbSNP:rs6967385)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_047873" FT VARIANT 1485 FT /note="F -> C (in dbSNP:rs2192828)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_047874" FT CONFLICT 1078 FT /note="C -> F (in Ref. 3; AAI44320)" FT /evidence="ECO:0000305" FT CONFLICT 1106 FT /note="Q -> L (in Ref. 5; BAB55237)" FT /evidence="ECO:0000305" FT CONFLICT 1371 FT /note="T -> I (in Ref. 5; BAB55237)" FT /evidence="ECO:0000305" SQ SEQUENCE 1590 AA; 176780 MW; 58BAB222EE4D3F04 CRC64; MPGGACVLVI ALMFLAWGEA QECSPGGHQF LRSPYRSVRF DSWHLQQSAV QDLICDHSLS PGWYRFLILD RPAEMPTKCV EMNHCGTQAP IWLSLRDSET LPSPGEIKQL TACATWQFLF STTKDCCLFQ IPVSVRNCGN FSVYLLQPTQ GCMGYCAEAI SDARLHPCGS DETETGGDCV RQLAASLPPP PAGRPEVLVE LIESRLFCRC SFDVPATKNS VGFHIAWSRL SSQEVKEELT QETTVQAFSL LELDGINLRL GDRIFCSASV FFLENPHVQS VAIESQEFFA GFKLQPELST ISEDGKEYYL RIESTVPIIC SEFSELDQEC KISLKLKTIG QGREHLGLNL ALSSCHVDLL QTSSCANGTC SHTFVYYTAV TDFSRDGDRV SNIVVQPIVN EDFLWNNYIP DSIQIKVKDV PTAYCYTFTD PHIITFDGRV YDNFKTGTFV LYKSMSRDFE VHVRQWDCRS LHYPVSCNCG FVAQEGGDIV TFDMCNGQLR ESQPYLFIKS QDVTRNIKIS ESYLGRKVTI WFSSGAFIRA DLGEWGMSLT IRAPSVDYRN TLGLCGTFDE NPENDFHDKN GMQIDQNFNN YVAFINEWRI LPGKSMSDTL PVSMTSPGKP SYCSCSLDTA AYPSSEDLDS VSRSEIALGC KDLNHVSLSS LIPELDVTSE YINSDTLVRE INKHTSPEEY NLNLFLQEKK HINLTKLGLN VQKHPGNEKE DSLQYLANKK YTQGRGSHSQ EMRYNRQNRW KRQNFHEFPP LFAFPSLSQT DLEELTYFFP EDHAEDVQQE FFPSWPTPSG LTEYSTLTLC QETLANSSIG RLCLAFLGKR LDSVIEMCVK DVLLKDDLSW AEAGVALLEN ECEKRIVEEG KYNTEEYGTS IEDILSVLKC PNLCSGNGQC MEWGCACSPS FSSYDCSDSY DKAPEITELG NAGFCDVQKY NCMMVRVFGK GFKELPSIKC EVTKLQYNSS EWMPGEPIYT QTVFHNSRAV DCQLPTDVQQ FDTMDLVGGK PTGKWQLKVS NDGYKFSNPK ITVIYDGACQ VCGLYKNDSC TIKENVCIID GLCYVEGDKN PTSPCLICRP KISRFTWSFL ENNQPPVIQA LQDKLQTFYG ENFEYQFVAF DPEGSDIHFT LDSGPEGASV SSAGLFMWKT DLLTTQQITV RLNDDCDAET RVTIEVTVKS CDCLNGGSCV SDRNFSPGSG VYLCVCLPGF HGSLCEVDIS GCQSNPCGLG SYISGFHSYS CDCPPELKVE TQFVNQFTTQ TVVLTRSDKS VNKEEDDKNA QGRKRHVKPT SGNAFTICKY PCGKSRECVA PNICKCKPGY IGSNCQTALC DPDCKNHGKC IKPNICQCLP GHGGATCDEE HCNPPCQHGG TCLAGNLCTC PYGFVGPRCE TMVCNRHCEN GGQCLTPDIC QCKPGWYGPT CSTALCDPVC LNGGSCNKPN TCLCPNGFFG EHCQNAFCHP PCKNGGHCMR NNVCVCREGY TGRRFQKSIC DPTCMNGGKC VGPSTCSCPS GWSGKRCNTP ICLQKCKNGG ECIAPSICHC PSSWEGVRCQ IPICNPKCLY GGRCIFPNVC SCRTEYSGVK CEKKIQIRRH //