ID WISP3_HUMAN Reviewed; 354 AA. AC O95389; Q3KR29; Q5H8W4; Q6UXH6; DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 13-FEB-2019, entry version 149. DE RecName: Full=WNT1-inducible-signaling pathway protein 3; DE Short=WISP-3; DE AltName: Full=CCN family member 6; DE Flags: Precursor; GN Name=WISP3; Synonyms=CCN6; ORFNames=UNQ462/PRO790/PRO956; 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=Bone marrow, and Fetal kidney; 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 [LARGE SCALE MRNA] (ISOFORM 2). 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [6] RP VARIANT PPAC ARG-78, AND VARIANT HIS-56. RX PubMed=10471507; DOI=10.1038/12699; RA Hurvitz J.R., Suwairi W.M., Van Hul W., El-Shanti H., RA Superti-Furga A., Roudier J., Holderbaum D., Pauli R.M., Herd J.K., RA Van Hul E.V., Rezai-Delui H., Legius E., Le Merrer M., Al-Alami J., RA Bahabri S.A., Warman M.L.; RT "Mutations in the CCN gene family member WISP3 cause progressive RT pseudorheumatoid dysplasia."; RL Nat. Genet. 23:94-98(1999). CC -!- FUNCTION: Appears to be required for normal postnatal skeletal CC growth and cartilage homeostasis. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O95389-1; Sequence=Displayed; CC Name=2; CC IsoId=O95389-2; Sequence=VSP_037803; CC -!- TISSUE SPECIFICITY: Predominant expression in adult kidney and CC testis and fetal kidney. Weaker expression found in placenta, CC ovary, prostate and small intestine. Also expressed in skeletally- CC derived cells such as synoviocytes and articular cartilage CC chondrocytes. CC -!- DISEASE: Progressive pseudorheumatoid arthropathy of childhood CC (PPAC) [MIM:208230]: Autosomal recessive disorder characterized by CC stiffness and swelling of joints, motor weakness and joint CC contractures. Signs and symptoms of the disease develop typically CC between three and eight years of age. This progressive disease is CC a primary disorder of articular cartilage with continued cartilage CC loss and destructive bone changes with aging. CC {ECO:0000269|PubMed:10471507}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. 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/WISP3ID469ch6q22.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; AF100781; AAC96323.1; -; mRNA. DR EMBL; AY358349; AAQ88715.1; -; mRNA. DR EMBL; AY358350; AAQ88716.1; -; mRNA. DR EMBL; Z99289; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL512299; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48273.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48275.1; -; Genomic_DNA. DR EMBL; BC105941; AAI05942.1; -; mRNA. DR CCDS; CCDS5097.1; -. [O95389-2] DR CCDS; CCDS5098.1; -. [O95389-1] DR RefSeq; NP_003871.1; NM_003880.3. [O95389-1] DR RefSeq; NP_937882.1; NM_198239.1. [O95389-2] DR RefSeq; XP_011534522.1; XM_011536220.1. [O95389-1] DR UniGene; Hs.558428; -. DR ProteinModelPortal; O95389; -. DR SMR; O95389; -. DR BioGrid; 114365; 6. DR STRING; 9606.ENSP00000354734; -. DR iPTMnet; O95389; -. DR PhosphoSitePlus; O95389; -. DR BioMuta; WISP3; -. DR PaxDb; O95389; -. DR PeptideAtlas; O95389; -. DR PRIDE; O95389; -. DR ProteomicsDB; 50840; -. DR ProteomicsDB; 50841; -. [O95389-2] DR Ensembl; ENST00000230529; ENSP00000230529; ENSG00000112761. [O95389-1] DR Ensembl; ENST00000361714; ENSP00000354734; ENSG00000112761. [O95389-1] DR Ensembl; ENST00000368666; ENSP00000357655; ENSG00000112761. [O95389-2] DR Ensembl; ENST00000604763; ENSP00000473777; ENSG00000112761. [O95389-1] DR GeneID; 8838; -. DR KEGG; hsa:8838; -. DR UCSC; uc003pvm.4; human. [O95389-1] DR CTD; 8838; -. DR DisGeNET; 8838; -. DR EuPathDB; HostDB:ENSG00000112761.18; -. DR GeneCards; WISP3; -. DR GeneReviews; WISP3; -. DR HGNC; HGNC:12771; WISP3. DR HPA; HPA062438; -. DR HPA; HPA078340; -. DR MalaCards; WISP3; -. DR MIM; 208230; phenotype. DR MIM; 603400; gene. DR neXtProt; NX_O95389; -. DR OpenTargets; ENSG00000112761; -. DR Orphanet; 1159; Progressive pseudorheumatoid arthropathy of childhood. DR PharmGKB; PA37374; -. DR eggNOG; ENOG410IJZE; Eukaryota. DR eggNOG; ENOG4110BH0; LUCA. DR GeneTree; ENSGT00940000160119; -. DR HOGENOM; HOG000231462; -. DR HOVERGEN; HBG000635; -. DR InParanoid; O95389; -. DR OMA; CQRNCRD; -. DR OrthoDB; 825025at2759; -. DR PhylomeDB; O95389; -. DR TreeFam; TF326070; -. DR GeneWiki; WNT1-inducible-signaling_pathway_protein_3; -. DR GenomeRNAi; 8838; -. DR PRO; PR:O95389; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000112761; Expressed in 90 organ(s), highest expression level in tibia. DR ExpressionAtlas; O95389; baseline and differential. DR Genevisible; O95389; HS. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; NAS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. 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 Gene3D; 2.20.100.10; -; 1. DR InterPro; IPR006207; Cys_knot_C. DR InterPro; IPR006208; Glyco_hormone_CN. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. 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; IPR036383; TSP1_rpt_sf. DR Pfam; PF00007; Cys_knot; 1. DR Pfam; PF00219; IGFBP; 1. DR PIRSF; PIRSF036495; IGFBP_rP_CNN; 1. DR SMART; SM00041; CT; 1. DR SMART; SM00121; IB; 1. DR SMART; SM00209; TSP1; 1. DR SUPFAM; SSF57184; SSF57184; 1. DR SUPFAM; SSF82895; SSF82895; 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. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Disease mutation; KW Disulfide bond; Glycoprotein; Growth factor; Polymorphism; KW Reference proteome; Secreted; Signal. FT SIGNAL 1 23 {ECO:0000255}. FT CHAIN 24 354 WNT1-inducible-signaling pathway protein FT 3. FT /FTId=PRO_0000014412. FT DOMAIN 44 117 IGFBP N-terminal. {ECO:0000255|PROSITE- FT ProRule:PRU00653}. FT DOMAIN 208 253 TSP type-1. {ECO:0000255|PROSITE- FT ProRule:PRU00210}. FT DOMAIN 268 342 CTCK. {ECO:0000255|PROSITE- FT ProRule:PRU00039}. FT CARBOHYD 178 178 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 308 308 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 268 305 {ECO:0000250}. FT DISULFID 285 319 {ECO:0000250}. FT DISULFID 296 335 {ECO:0000250}. FT DISULFID 299 337 {ECO:0000250}. FT DISULFID 304 341 {ECO:0000250}. FT VAR_SEQ 1 1 M -> MNKRRLLYPSGWLHGPSDM (in isoform 2). FT {ECO:0000303|PubMed:12975309, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_037803. FT VARIANT 56 56 Q -> H (common polymorphism; FT dbSNP:rs1230345). FT {ECO:0000269|PubMed:10471507}. FT /FTId=VAR_016224. FT VARIANT 60 60 R -> C (in dbSNP:rs17073260). FT /FTId=VAR_049567. FT VARIANT 78 78 C -> R (in PPAC; dbSNP:rs121908902). FT {ECO:0000269|PubMed:10471507}. FT /FTId=VAR_016225. FT CONFLICT 200 200 N -> D (in Ref. 2; AAQ88715). FT {ECO:0000305}. SQ SEQUENCE 354 AA; 39293 MW; 67F48D0D5C2F5EE3 CRC64; MQGLLFSTLL LAGLAQFCCR VQGTGPLDTT PEGRPGEVSD APQRKQFCHW PCKCPQQKPR CPPGVSLVRD GCGCCKICAK QPGEICNEAD LCDPHKGLYC DYSVDRPRYE TGVCAYLVAV GCEFNQVHYH NGQVFQPNPL FSCLCVSGAI GCTPLFIPKL AGSHCSGAKG GKKSDQSNCS LEPLLQQLST SYKTMPAYRN LPLIWKKKCL VQATKWTPCS RTCGMGISNR VTNENSNCEM RKEKRLCYIQ PCDSNILKTI KIPKGKTCQP TFQLSKAEKF VFSGCSSTQS YKPTFCGICL DKRCCIPNKS KMITIQFDCP NEGSFKWKML WITSCVCQRN CREPGDIFSE LKIL //