CCN4_MOUSE
ID CCN4_MOUSE Reviewed; 367 AA.
AC O54775; Q80ZL1;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=CCN family member 4 {ECO:0000305};
DE AltName: Full=ELM-1;
DE AltName: Full=WNT1-inducible-signaling pathway protein 1;
DE Short=WISP-1;
DE Flags: Precursor;
GN Name=Ccn4; Synonyms=Elm1, Wisp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=HeN;
RX PubMed=9449709; DOI=10.1084/jem.187.3.289;
RA Hashimoto Y., Shindo-Okada N., Tani M., Nagamachi Y., Takeuchi K.,
RA Shiroishi T., Toma H., Yokota J.;
RT "Expression of the Elm1 gene, a novel gene of the CCN (connective tissue
RT growth factor, Cyr61/Cef10, and neuroblastoma overexpressed gene) family,
RT suppresses In vivo tumor growth and metastasis of K-1735 murine melanoma
RT cells.";
RL J. Exp. Med. 187:289-296(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C3H/HeN, and FVB/N; TISSUE=Colon, and Mesenchymal cell;
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).
CC -!- FUNCTION: Downstream regulator in the Wnt/Frizzled-signaling pathway
CC (By similarity). Associated with cell survival. Adheres to skin and
CC melanoma fibroblasts (By similarity). In vitro binding to skin
CC fibroblasts occurs through the proteoglycans, decorin and biglycan (By
CC similarity). Suppresses tumor growth in vivo. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney and lung. Lower levels
CC in heart, brain, spleen, liver, skeletal muscle and testis. Expressed
CC in low metastatic melanoma cells.
CC -!- SIMILARITY: Belongs to the CCN family. {ECO:0000305}.
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DR EMBL; AB004873; BAA24949.1; -; mRNA.
DR EMBL; AF100777; AAC96319.1; -; mRNA.
DR EMBL; BC048791; AAH48791.1; -; mRNA.
DR EMBL; BC052677; AAH52677.1; -; mRNA.
DR CCDS; CCDS27510.1; -.
DR RefSeq; NP_061353.1; NM_018865.2.
DR AlphaFoldDB; O54775; -.
DR SMR; O54775; -.
DR BioGRID; 204561; 1.
DR STRING; 10090.ENSMUSP00000005255; -.
DR GlyGen; O54775; 4 sites.
DR PhosphoSitePlus; O54775; -.
DR PaxDb; O54775; -.
DR PeptideAtlas; O54775; -.
DR PRIDE; O54775; -.
DR ProteomicsDB; 297849; -.
DR Antibodypedia; 1567; 327 antibodies from 35 providers.
DR DNASU; 22402; -.
DR Ensembl; ENSMUST00000005255; ENSMUSP00000005255; ENSMUSG00000005124.
DR GeneID; 22402; -.
DR KEGG; mmu:22402; -.
DR UCSC; uc007wau.1; mouse.
DR CTD; 8840; -.
DR MGI; MGI:1197008; Ccn4.
DR VEuPathDB; HostDB:ENSMUSG00000005124; -.
DR eggNOG; ENOG502QQQQ; Eukaryota.
DR GeneTree; ENSGT00940000158587; -.
DR HOGENOM; CLU_063247_3_1_1; -.
DR InParanoid; O54775; -.
DR OMA; IEVRFEC; -.
DR OrthoDB; 601212at2759; -.
DR PhylomeDB; O54775; -.
DR TreeFam; TF326070; -.
DR BioGRID-ORCS; 22402; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Wisp1; mouse.
DR PRO; PR:O54775; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O54775; protein.
DR Bgee; ENSMUSG00000005124; Expressed in molar tooth and 205 other tissues.
DR ExpressionAtlas; O54775; baseline and differential.
DR Genevisible; O54775; MM.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0008201; F:heparin binding; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0060348; P:bone development; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; IBA:GO_Central.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; IMP:UniProtKB.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; ISO:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISS:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0090303; P:positive regulation of wound healing; IMP:UniProtKB.
DR GO; GO:0001817; P:regulation of cytokine production; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
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; IPR043973; TSP1_CCN.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR InterPro; IPR001007; VWF_dom.
DR Pfam; PF00007; Cys_knot; 1.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF19035; TSP1_CCN; 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 2: Evidence at transcript level;
KW Cell adhesion; Disulfide bond; Glycoprotein; Proto-oncogene;
KW Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..367
FT /note="CCN family member 4"
FT /id="PRO_0000014407"
FT DOMAIN 45..118
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 121..186
FT /note="VWFC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 215..260
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 273..347
FT /note="CTCK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 273..310
FT /evidence="ECO:0000250"
FT DISULFID 290..324
FT /evidence="ECO:0000250"
FT DISULFID 301..340
FT /evidence="ECO:0000250"
FT DISULFID 304..342
FT /evidence="ECO:0000250"
FT DISULFID 309..346
FT /evidence="ECO:0000250"
FT CONFLICT 79
FT /note="C -> R (in Ref. 3; AAH52677)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="D -> G (in Ref. 3; AAH52677)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="K -> R (in Ref. 3; AAH52677)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="E -> G (in Ref. 3; AAH52677)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 367 AA; 40703 MW; 3B7C0569EFAB5E96 CRC64;
MRWLLPWTLA AVAVLRVGNI LATALSPTPT TMTFTPAPLE ETTTRPEFCK WPCECPQSPP
RCPLGVSLIT DGCECCKICA QQLGDNCTEA AICDPHRGLY CDYSGDRPRY AIGVCAQVVG
VGCVLDGVRY TNGESFQPNC RYNCTCIDGT VGCTPLCLSP RPPRLWCRQP RHVRVPGQCC
EQWVCDDDAR RPRQTALLDT RAFAASGAVE QRYENCIAYT SPWSPCSTTC GLGISTRISN
VNARCWPEQE SRLCNLRPCD VDIQLHIKAG KKCLAVYQPE EATNFTLAGC VSTRTYRPKY
CGVCTDNRCC IPYKSKTISV DFQCPEGPGF SRQVLWINAC FCNLSCRNPN DIFADLESYP
DFEEIAN
