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-MAR-2024, entry version 141.
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};
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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; 7.
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   EPD; Q8N2E2; -.
DR   MassIVE; Q8N2E2; -.
DR   MaxQB; Q8N2E2; -.
DR   PaxDb; 9606-ENSP00000275358; -.
DR   PeptideAtlas; Q8N2E2; -.
DR   ProteomicsDB; 71685; -. [Q8N2E2-1]
DR   Pumba; Q8N2E2; -.
DR   Antibodypedia; 66337; 9 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   GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR   Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR   Gene3D; 2.10.25.10; Laminin; 6.
DR   InterPro; IPR013032; EGF-like_CS.
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; PF12661; hEGF; 3.
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.
DR   Genevisible; Q8N2E2; HS.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Disulfide bond; EGF-like domain; Glycoprotein;
KW   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
//