CCN5_HUMAN
ID CCN5_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 03-AUG-2022, entry version 177.
DE RecName: 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 AltName: Full=WNT1-inducible-signaling pathway protein 2;
DE Short=WISP-2;
DE Flags: Precursor;
GN Name=CCN5 {ECO:0000312|HGNC:HGNC:12770}; Synonyms=CT58, CTGFL, WISP2;
GN ORFNames=UNQ228/PRO261;
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 [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., Votta B.J.,
RA James I.E., Rieman D.J., Gowen M., Lee J.C.;
RT "Identification and cloning of a connective tissue growth factor-like cDNA
RT 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 that
RT are up-regulated in wnt-1-transformed cells and aberrantly expressed in
RT 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., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT 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., 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).
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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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., 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 (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 project:
RT 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 verified
RT 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 of
CC fibrinogen to integrin receptors. In addition, inhibits osteocalcin
CC production.
CC -!- INTERACTION:
CC O76076; P49639: HOXA1; NbExp=3; IntAct=EBI-2850068, EBI-740785;
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 -!- 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 and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/WISP2ID42814ch20q12.html";
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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 AlphaFoldDB; O76076; -.
DR SMR; O76076; -.
DR BioGRID; 114366; 11.
DR IntAct; O76076; 7.
DR STRING; 9606.ENSP00000361959; -.
DR BioMuta; WISP2; -.
DR jPOST; O76076; -.
DR MassIVE; O76076; -.
DR PaxDb; O76076; -.
DR PeptideAtlas; O76076; -.
DR PRIDE; O76076; -.
DR ProteomicsDB; 50380; -. [O76076-1]
DR ProteomicsDB; 67077; -.
DR Antibodypedia; 27443; 314 antibodies from 29 providers.
DR DNASU; 8839; -.
DR Ensembl; ENST00000190983.5; ENSP00000190983.4; ENSG00000064205.11. [O76076-1]
DR Ensembl; ENST00000372865.4; ENSP00000361956.4; ENSG00000064205.11. [O76076-2]
DR Ensembl; ENST00000372868.6; ENSP00000361959.2; ENSG00000064205.11. [O76076-1]
DR GeneID; 8839; -.
DR KEGG; hsa:8839; -.
DR MANE-Select; ENST00000190983.5; ENSP00000190983.4; NM_003881.4; NP_003872.1.
DR UCSC; uc002xmp.4; human. [O76076-1]
DR CTD; 8839; -.
DR DisGeNET; 8839; -.
DR GeneCards; CCN5; -.
DR HGNC; HGNC:12770; CCN5.
DR HPA; ENSG00000064205; Tissue enhanced (adipose tissue, cervix).
DR MIM; 603399; gene.
DR neXtProt; NX_O76076; -.
DR OpenTargets; ENSG00000064205; -.
DR PharmGKB; PA37373; -.
DR VEuPathDB; HostDB:ENSG00000064205; -.
DR eggNOG; ENOG502RXIT; Eukaryota.
DR GeneTree; ENSGT00940000160207; -.
DR HOGENOM; CLU_063247_1_1_1; -.
DR InParanoid; O76076; -.
DR OMA; EWICERQ; -.
DR OrthoDB; 999958at2759; -.
DR PhylomeDB; O76076; -.
DR TreeFam; TF326070; -.
DR PathwayCommons; O76076; -.
DR SignaLink; O76076; -.
DR BioGRID-ORCS; 8839; 8 hits in 1072 CRISPR screens.
DR GeneWiki; WNT1-inducible-signaling_pathway_protein_2; -.
DR GenomeRNAi; 8839; -.
DR Pharos; O76076; Tbio.
DR PRO; PR:O76076; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; O76076; protein.
DR Bgee; ENSG00000064205; Expressed in popliteal artery and 130 other tissues.
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:0005634; C:nucleus; IDA:UniProtKB.
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:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 2.20.100.10; -; 1.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR000867; IGFBP-like.
DR InterPro; IPR017891; Insulin_GF-bd_Cys-rich_CS.
DR InterPro; IPR043973; TSP1_CCN.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR InterPro; IPR001007; VWF_dom.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF19035; TSP1_CCN; 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; Direct protein sequencing;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 24..250
FT /note="CCN family member 5"
FT /id="PRO_0000014409"
FT DOMAIN 24..94
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 98..164
FT /note="VWFC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 194..238
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT VAR_SEQ 93..218
FT /note="LAEDDSSCEVNGRLYREGETFQPHCSIRCRCEDGGFTCVPLCSEDVRLPSWD
FT CPHPRRVEVLGKCCPEWVCGQGGGLGTQPLPAQGPQFSGLVSSLPPGVPCPEWSTAWGP
FT CSTTCGLGMATRVSN -> CKQDPSFLALSLPCPLVSPAQNGARPGDPARPPVGWAWPP
FT GCPTRTASADWRPSAACACPGPAHPPGVAVHKTVPSRAGLGMGTRCPPSPAGGPVPGPW
FT ADGRWSVPRPLAAGNTLAWVHHAEHQY (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056298"
FT VAR_SEQ 219..250
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056299"
FT VARIANT 59
FT /note="R -> Q (in dbSNP:rs33932543)"
FT /id="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
