ID WISP1_HUMAN Reviewed; 367 AA. AC O95388; A8KAG6; E7EMM5; Q5JBS6; Q5JBS7; Q5JBS8; Q9HCS3; DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 11-NOV-2015, entry version 136. DE RecName: Full=WNT1-inducible-signaling pathway protein 1; DE Short=WISP-1; DE AltName: Full=CCN family member 4; DE AltName: Full=Wnt-1-induced secreted protein; DE Flags: Precursor; GN Name=WISP1; Synonyms=CCN4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal kidney, and Lung; RX PubMed=9843955; DOI=10.1073/pnas.95.25.14717; RA Pennica D., Swanson T.A., Welsh J.W., Roy M.A., Lawrence D.A., Lee J., RA Brush J., Taneyhill L.A., Deuel B., Lew M., Watanabe C., Cohen R.L., RA Melham M.F., Finley G.G., Quirke P., Goddard A.D., Hillan K.J., RA Gurney A.L., Botstein D., Levine A.J.; RT "WISP genes are members of the connective tissue growth factor family RT that are up-regulated in wnt-1-transformed cells and aberrantly RT expressed in human colon tumors."; RL Proc. Natl. Acad. Sci. U.S.A. 95:14717-14722(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Gastric carcinoma; RX PubMed=11571650; DOI=10.1038/sj.onc.1204723; RA Tanaka S., Sugimachi K., Saeki H., Kinoshita J., Ohga T., Shimada M., RA Maehara Y., Sugimachi K.; RT "A novel variant of WISP1 lacking a Von Willebrand type C module RT overexpressed in scirrhous gastric carcinoma."; RL Oncogene 20:5525-5532(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5). RA Li Z., Chiao P.J., Evans D.B.; RT "Multiple alternatively spliced variants of WISP1 are overexpressed in RT pancreatic cancer."; RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5). RC TISSUE=Synovium, and Uterus; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T., RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., RA Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION IN WNT1 SIGNALING. RX PubMed=10716946; RA Xu L., Corcoran R.B., Welsh J.W., Pennica D., Levine A.J.; RT "WISP-1 is a Wnt-1- and beta-catenin-responsive oncogene."; RL Genes Dev. 14:585-595(2000). RN [9] RP FUNCTION IN TP53-MEDIATED APOPTOSIS. RX PubMed=11782444; DOI=10.1101/gad.942902; RA Su F., Overholtzer M., Besser D., Levine A.J.; RT "WISP-1 attenuates p53-mediated apoptosis in response to DNA damage RT through activation of the Akt kinase."; RL Genes Dev. 16:46-57(2002). RN [10] RP INTERACTION WITH DECORIN AND BIGLYCAN. RX PubMed=11598131; DOI=10.1074/jbc.M108339200; RA Desnoyers L., Arnott D., Pennica D.; RT "WISP-1 binds to decorin and biglycan."; RL J. Biol. Chem. 276:47599-47607(2001). CC -!- FUNCTION: Downstream regulator in the Wnt/Frizzled-signaling CC pathway. Associated with cell survival. Attenuates p53-mediated CC apoptosis in response to DNA damage through activation of AKT CC kinase. Up-regulates the anti-apoptotic Bcl-X(L) protein. Adheres CC to skin and melanoma fibroblasts. In vitro binding to skin CC fibroblasts occurs through the proteoglycans, decorin and CC biglycan. {ECO:0000269|PubMed:10716946, CC ECO:0000269|PubMed:11782444}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=O95388-1; Sequence=Displayed; CC Name=2; Synonyms=WISP1v; CC IsoId=O95388-2; Sequence=VSP_008008, VSP_008009; CC Name=3; CC IsoId=O95388-3; Sequence=VSP_042010; CC Name=4; CC IsoId=O95388-4; Sequence=VSP_045958, VSP_045959; CC Note=Ref.3 (AAP43926) sequence is in conflict in position: CC 155:Q->QQVLHPLQV. {ECO:0000305}; CC Name=5; CC IsoId=O95388-5; Sequence=VSP_047706, VSP_047707; CC -!- TISSUE SPECIFICITY: Expressed in heart, kidney, lung, pancreas, CC placenta, ovary, small intestine and spleen. Isoform 2 is CC expressed predominantly in scirrhous gastric carcinoma and, weakly CC in placenta. Overexpression is associated with several cancers CC including breast cancer and colon tumors. Isoform 2 is CC overexpressed in scirrhous gastric carcinoma. CC -!- SIMILARITY: Belongs to the CCN family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 CTCK (C-terminal cystine knot-like) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00039}. CC -!- SIMILARITY: Contains 1 IGFBP N-terminal domain. CC {ECO:0000255|PROSITE-ProRule:PRU00653}. CC -!- SIMILARITY: Contains 1 TSP type-1 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00210}. CC -!- SIMILARITY: Contains 1 VWFC domain. {ECO:0000255|PROSITE- CC ProRule:PRU00220}. 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; AF100779; AAC96321.1; -; mRNA. DR EMBL; AB034725; BAB17849.1; -; mRNA. DR EMBL; AY196486; AAP43924.1; -; mRNA. DR EMBL; AY196487; AAP43925.1; -; mRNA. DR EMBL; AY196488; AAP43926.1; -; mRNA. DR EMBL; AK293031; BAF85720.1; -; mRNA. DR EMBL; AK301508; BAG63017.1; -; mRNA. DR EMBL; AF192304; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471060; EAW92162.1; -; Genomic_DNA. DR EMBL; BC074840; AAH74840.1; -; mRNA. DR EMBL; BC074841; AAH74841.1; -; mRNA. DR CCDS; CCDS56555.1; -. [O95388-4] DR CCDS; CCDS56556.1; -. [O95388-3] DR CCDS; CCDS6371.1; -. [O95388-1] DR CCDS; CCDS6372.1; -. [O95388-2] DR RefSeq; NP_001191798.1; NM_001204869.1. [O95388-4] DR RefSeq; NP_001191799.1; NM_001204870.1. [O95388-3] DR RefSeq; NP_003873.1; NM_003882.3. [O95388-1] DR RefSeq; NP_543028.1; NM_080838.2. [O95388-2] DR UniGene; Hs.492974; -. DR ProteinModelPortal; O95388; -. DR SMR; O95388; 283-346. DR BioGrid; 114367; 1. DR STRING; 9606.ENSP00000250160; -. DR PhosphoSite; O95388; -. DR BioMuta; WISP1; -. DR PaxDb; O95388; -. DR PRIDE; O95388; -. DR DNASU; 8840; -. DR Ensembl; ENST00000220856; ENSP00000220856; ENSG00000104415. [O95388-2] DR Ensembl; ENST00000250160; ENSP00000250160; ENSG00000104415. [O95388-1] DR Ensembl; ENST00000517423; ENSP00000427744; ENSG00000104415. [O95388-4] DR Ensembl; ENST00000519433; ENSP00000429185; ENSG00000104415. [O95388-3] DR GeneID; 8840; -. DR KEGG; hsa:8840; -. DR UCSC; uc003yub.3; human. [O95388-1] DR UCSC; uc003yuc.3; human. [O95388-2] DR UCSC; uc010meb.3; human. DR UCSC; uc010med.3; human. [O95388-3] DR CTD; 8840; -. DR GeneCards; WISP1; -. DR HGNC; HGNC:12769; WISP1. DR HPA; CAB012205; -. DR HPA; HPA007121; -. DR MIM; 603398; gene. DR neXtProt; NX_O95388; -. DR PharmGKB; PA37372; -. DR eggNOG; ENOG410IH8M; Eukaryota. DR eggNOG; ENOG410ZWR5; LUCA. DR GeneTree; ENSGT00760000119225; -. DR HOGENOM; HOG000231462; -. DR HOVERGEN; HBG000635; -. DR InParanoid; O95388; -. DR OMA; VDITKHI; -. DR PhylomeDB; O95388; -. DR TreeFam; TF326070; -. DR ChiTaRS; WISP1; human. DR GeneWiki; WNT1-inducible-signaling_pathway_protein_1; -. DR GenomeRNAi; 8840; -. DR NextBio; 33184; -. DR PRO; PR:O95388; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; O95388; -. DR CleanEx; HS_WISP1; -. DR ExpressionAtlas; O95388; baseline and differential. DR Genevisible; O95388; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005615; C:extracellular space; NAS:UniProtKB. DR GO; GO:0005578; C:proteinaceous extracellular matrix; IBA:GO_Central. DR GO; GO:0008201; F:heparin binding; IBA:GO_Central. DR GO; GO:0005178; F:integrin binding; IBA:GO_Central. DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0060548; P:negative regulation of cell death; IBA:GO_Central. DR GO; GO:0001558; P:regulation of cell growth; IEA:InterPro. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR InterPro; IPR006207; Cys_knot_C. DR InterPro; IPR006208; Glyco_hormone_CN. DR InterPro; IPR009030; Growth_fac_rcpt_N_dom. DR InterPro; IPR000867; IGFBP-like. DR InterPro; IPR012395; IGFBP_CNN. DR InterPro; IPR017891; Insulin_GF-bd_Cys-rich_CS. DR InterPro; IPR000884; TSP1_rpt. DR InterPro; IPR001007; VWF_dom. DR Pfam; PF00007; Cys_knot; 1. DR Pfam; PF00219; IGFBP; 1. DR Pfam; PF00090; TSP_1; 1. DR Pfam; PF00093; VWC; 1. DR PIRSF; PIRSF036495; IGFBP_rP_CNN; 1. DR SMART; SM00041; CT; 1. DR SMART; SM00121; IB; 1. DR SMART; SM00209; TSP1; 1. DR SMART; SM00214; VWC; 1. DR SUPFAM; SSF57184; SSF57184; 1. DR SUPFAM; SSF82895; SSF82895; 1. DR PROSITE; PS01185; CTCK_1; 1. DR PROSITE; PS01225; CTCK_2; 1. DR PROSITE; PS00222; IGFBP_N_1; 1. DR PROSITE; PS51323; IGFBP_N_2; 1. DR PROSITE; PS50092; TSP1; 1. DR PROSITE; PS01208; VWFC_1; 1. DR PROSITE; PS50184; VWFC_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell adhesion; Complete proteome; KW Disulfide bond; Glycoprotein; Polymorphism; Proto-oncogene; KW Reference proteome; Secreted; Signal; Wnt signaling pathway. FT SIGNAL 1 22 {ECO:0000255}. FT CHAIN 23 367 WNT1-inducible-signaling pathway protein FT 1. FT /FTId=PRO_0000014406. FT DOMAIN 40 118 IGFBP N-terminal. {ECO:0000255|PROSITE- FT ProRule:PRU00653}. FT DOMAIN 121 186 VWFC. {ECO:0000255|PROSITE- FT ProRule:PRU00220}. FT DOMAIN 215 260 TSP type-1. {ECO:0000255|PROSITE- FT ProRule:PRU00210}. FT DOMAIN 273 347 CTCK. {ECO:0000255|PROSITE- FT ProRule:PRU00039}. FT CARBOHYD 86 86 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 143 143 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 284 284 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 343 343 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 273 310 {ECO:0000250}. FT DISULFID 290 324 {ECO:0000250}. FT DISULFID 301 340 {ECO:0000250}. FT DISULFID 304 342 {ECO:0000250}. FT DISULFID 309 346 {ECO:0000250}. FT VAR_SEQ 1 31 MRWFLPWTLAAVTAAAASTVLATALSPAPTT -> MPVPLT FT SRHEVVPALDAGSSDSSSRQHRPGH (in isoform 5). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|Ref.3}. FT /FTId=VSP_047706. FT VAR_SEQ 24 268 Missing (in isoform 3). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_042010. FT VAR_SEQ 32 203 Missing (in isoform 5). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|Ref.3}. FT /FTId=VSP_047707. FT VAR_SEQ 117 155 QVVGVGCVLDGVRYNNGQSFQPNCKYNCTCIDGAVGCTP FT -> RREEVSGCVPARGIHELHTCGLHQHTLLSTQVLWSLHG FT Q (in isoform 4). {ECO:0000303|Ref.3}. FT /FTId=VSP_045958. FT VAR_SEQ 117 117 Q -> H (in isoform 2). FT {ECO:0000303|PubMed:11571650}. FT /FTId=VSP_008008. FT VAR_SEQ 118 204 Missing (in isoform 2). FT {ECO:0000303|PubMed:11571650}. FT /FTId=VSP_008009. FT VAR_SEQ 156 367 Missing (in isoform 4). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_045959. FT VARIANT 205 205 A -> S (in dbSNP:rs35513885). FT /FTId=VAR_061265. FT CONFLICT 91 91 A -> V (in Ref. 3; AAP43926). FT {ECO:0000305}. SQ SEQUENCE 367 AA; 40331 MW; 9F29CA94D69C0502 CRC64; MRWFLPWTLA AVTAAAASTV LATALSPAPT TMDFTPAPLE DTSSRPQFCK WPCECPPSPP RCPLGVSLIT DGCECCKMCA QQLGDNCTEA AICDPHRGLY CDYSGDRPRY AIGVCAQVVG VGCVLDGVRY NNGQSFQPNC KYNCTCIDGA VGCTPLCLRV RPPRLWCPHP RRVSIPGHCC EQWVCEDDAK RPRKTAPRDT GAFDAVGEVE AWHRNCIAYT SPWSPCSTSC GLGVSTRISN VNAQCWPEQE SRLCNLRPCD VDIHTLIKAG KKCLAVYQPE ASMNFTLAGC ISTRSYQPKY CGVCMDNRCC IPYKSKTIDV SFQCPDGLGF SRQVLWINAC FCNLSCRNPN DIFADLESYP DFSEIAN //