ID   WISP2_HUMAN             Reviewed;         250 AA.
AC   O76076; B2R9N4; E1P612; Q6PEG3;
DT   19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   13-FEB-2019, entry version 158.
DE   RecName: Full=WNT1-inducible-signaling pathway protein 2;
DE            Short=WISP-2;
DE   AltName: Full=CCN family member 5;
DE   AltName: Full=Connective tissue growth factor-like protein;
DE            Short=CTGF-L;
DE   AltName: Full=Connective tissue growth factor-related protein 58;
DE   Flags: Precursor;
GN   Name=WISP2; Synonyms=CCN5, CT58, CTGFL; ORFNames=UNQ228/PRO261;
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).
RX   PubMed=10358067; DOI=10.1074/jbc.274.24.17123;
RA   Kumar S., Hand A.T., Connor J.R., Dodds R.A., Ryan P.J., Trill J.J.,
RA   Fisher S.M., Nuttall M.E., Lipshutz D.B., Zou C., Hwang S.M.,
RA   Votta B.J., James I.E., Rieman D.J., Gowen M., Lee J.C.;
RT   "Identification and cloning of a connective tissue growth factor-like
RT   cDNA from human osteoblasts encoding a novel regulator of osteoblast
RT   functions.";
RL   J. Biol. Chem. 274:17123-17131(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Rowles J., Gendler S.;
RT   "CT58, a new member of the connective tissue growth factor family,
RT   interacts with the breast cancer associated mucin MUC1.";
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Skeletal muscle;
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [7]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain, Lung, and Ovary;
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   [9]
RP   PROTEIN SEQUENCE OF 24-38.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally
RT   verified cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
CC   -!- FUNCTION: May play an important role in modulating bone turnover.
CC       Promotes the adhesion of osteoblast cells and inhibits the binding
CC       of fibrinogen to integrin receptors. In addition, inhibits
CC       osteocalcin production.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O76076-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O76076-2; Sequence=VSP_056298, VSP_056299;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Expressed in primary osteoblasts, fibroblasts,
CC       ovary, testes, and heart.
CC   -!- SIMILARITY: Belongs to the CCN family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/WISP2ID42814ch20q12.html";
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; AF083500; AAC70350.1; -; mRNA.
DR   EMBL; AF074604; AAC26794.1; -; mRNA.
DR   EMBL; AF100780; AAC96322.1; -; mRNA.
DR   EMBL; AY358915; AAQ89274.1; -; mRNA.
DR   EMBL; AK313853; BAG36581.1; -; mRNA.
DR   EMBL; AL139352; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471077; EAW75902.1; -; Genomic_DNA.
DR   EMBL; CH471077; EAW75903.1; -; Genomic_DNA.
DR   EMBL; BC017782; AAH17782.1; -; mRNA.
DR   EMBL; BC058074; AAH58074.1; -; mRNA.
DR   EMBL; BC064379; AAH64379.1; -; mRNA.
DR   CCDS; CCDS13336.1; -. [O76076-1]
DR   CCDS; CCDS82619.1; -. [O76076-2]
DR   RefSeq; NP_001310298.1; NM_001323369.1. [O76076-2]
DR   RefSeq; NP_001310299.1; NM_001323370.1. [O76076-1]
DR   RefSeq; NP_003872.1; NM_003881.3. [O76076-1]
DR   UniGene; Hs.592145; -.
DR   ProteinModelPortal; O76076; -.
DR   SMR; O76076; -.
DR   BioGrid; 114366; 9.
DR   IntAct; O76076; 4.
DR   STRING; 9606.ENSP00000190983; -.
DR   BioMuta; WISP2; -.
DR   jPOST; O76076; -.
DR   PaxDb; O76076; -.
DR   PeptideAtlas; O76076; -.
DR   PRIDE; O76076; -.
DR   ProteomicsDB; 50380; -.
DR   DNASU; 8839; -.
DR   Ensembl; ENST00000190983; ENSP00000190983; ENSG00000064205. [O76076-1]
DR   Ensembl; ENST00000372865; ENSP00000361956; ENSG00000064205. [O76076-2]
DR   Ensembl; ENST00000372868; ENSP00000361959; ENSG00000064205. [O76076-1]
DR   GeneID; 8839; -.
DR   KEGG; hsa:8839; -.
DR   UCSC; uc002xmp.4; human. [O76076-1]
DR   CTD; 8839; -.
DR   DisGeNET; 8839; -.
DR   EuPathDB; HostDB:ENSG00000064205.10; -.
DR   GeneCards; WISP2; -.
DR   HGNC; HGNC:12770; WISP2.
DR   HPA; CAB019273; -.
DR   MIM; 603399; gene.
DR   neXtProt; NX_O76076; -.
DR   OpenTargets; ENSG00000064205; -.
DR   PharmGKB; PA37373; -.
DR   eggNOG; ENOG410IWPW; Eukaryota.
DR   eggNOG; ENOG410YSW1; LUCA.
DR   GeneTree; ENSGT00940000160207; -.
DR   HOGENOM; HOG000231462; -.
DR   HOVERGEN; HBG000635; -.
DR   InParanoid; O76076; -.
DR   OMA; SNQNRFC; -.
DR   OrthoDB; 999958at2759; -.
DR   PhylomeDB; O76076; -.
DR   TreeFam; TF326070; -.
DR   SignaLink; O76076; -.
DR   GeneWiki; WNT1-inducible-signaling_pathway_protein_2; -.
DR   GenomeRNAi; 8839; -.
DR   PRO; PR:O76076; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   Bgee; ENSG00000064205; Expressed in 136 organ(s), highest expression level in lower esophagus.
DR   Genevisible; O76076; HS.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0008201; F:heparin binding; IBA:GO_Central.
DR   GO; GO:0005520; F:insulin-like growth factor binding; IEA:InterPro.
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:0007165; P:signal transduction; TAS:ProtInc.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR000867; IGFBP-like.
DR   InterPro; IPR017891; Insulin_GF-bd_Cys-rich_CS.
DR   InterPro; IPR000884; TSP1_rpt.
DR   InterPro; IPR036383; TSP1_rpt_sf.
DR   InterPro; IPR001007; VWF_dom.
DR   Pfam; PF00219; IGFBP; 1.
DR   Pfam; PF00093; VWC; 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; 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   Direct protein sequencing; Polymorphism; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL        1     23       {ECO:0000269|PubMed:15340161}.
FT   CHAIN        24    250       WNT1-inducible-signaling pathway protein
FT                                2.
FT                                /FTId=PRO_0000014409.
FT   DOMAIN       24     94       IGFBP N-terminal. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00653}.
FT   DOMAIN       98    164       VWFC. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00220}.
FT   DOMAIN      194    238       TSP type-1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   VAR_SEQ      93    218       LAEDDSSCEVNGRLYREGETFQPHCSIRCRCEDGGFTCVPL
FT                                CSEDVRLPSWDCPHPRRVEVLGKCCPEWVCGQGGGLGTQPL
FT                                PAQGPQFSGLVSSLPPGVPCPEWSTAWGPCSTTCGLGMATR
FT                                VSN -> CKQDPSFLALSLPCPLVSPAQNGARPGDPARPPV
FT                                GWAWPPGCPTRTASADWRPSAACACPGPAHPPGVAVHKTVP
FT                                SRAGLGMGTRCPPSPAGGPVPGPWADGRWSVPRPLAAGNTL
FT                                AWVHHAEHQY (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_056298.
FT   VAR_SEQ     219    250       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_056299.
FT   VARIANT      59     59       R -> Q (in dbSNP:rs33932543).
FT                                /FTId=VAR_049566.
SQ   SEQUENCE   250 AA;  26825 MW;  C499837EF42FEEAC CRC64;
     MRGTPKTHLL AFSLLCLLSK VRTQLCPTPC TCPWPPPRCP LGVPLVLDGC GCCRVCARRL
     GEPCDQLHVC DASQGLVCQP GAGPGGRGAL CLLAEDDSSC EVNGRLYREG ETFQPHCSIR
     CRCEDGGFTC VPLCSEDVRL PSWDCPHPRR VEVLGKCCPE WVCGQGGGLG TQPLPAQGPQ
     FSGLVSSLPP GVPCPEWSTA WGPCSTTCGL GMATRVSNQN RFCRLETQRR LCLSRPCPPS
     RGRSPQNSAF
//