CCN3_RAT
ID CCN3_RAT Reviewed; 351 AA.
AC Q9QZQ5;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=CCN family member 3 {ECO:0000305};
DE AltName: Full=Cellular communication network factor 3 {ECO:0000250|UniProtKB:P48745};
DE AltName: Full=Nephroblastoma-overexpressed gene protein homolog;
DE AltName: Full=Protein NOV homolog;
DE Short=NovH;
DE Flags: Precursor;
GN Name=Ccn3; Synonyms=Nov {ECO:0000312|RGD:621553};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=10570975; DOI=10.1016/s0378-1119(99)00364-9;
RA Liu C., Liu X.J., Crowe P.D., Kelner G.S., Fan J., Barry G., Manu F.,
RA Ling N., De Souza E.B., Maki R.A.;
RT "Nephroblastoma overexpressed gene (NOV) codes for a growth factor that
RT induces protein tyrosine phosphorylation.";
RL Gene 238:471-478(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [3]
RP INTERACTION WITH GJA1.
RX PubMed=15181016; DOI=10.1074/jbc.m404073200;
RA Gellhaus A., Dong X., Propson S., Maass K., Klein-Hitpass L., Kibschull M.,
RA Traub O., Willecke K., Perbal B., Lye S.J., Winterhager E.;
RT "Connexin43 interacts with NOV: a possible mechanism for negative
RT regulation of cell growth in choriocarcinoma cells.";
RL J. Biol. Chem. 279:36931-36942(2004).
RN [4]
RP SUBCELLULAR LOCATION, INTERACTION WITH GJA1, AND TISSUE SPECIFICITY.
RX PubMed=15213231; DOI=10.1074/jbc.m403952200;
RA Fu C.T., Bechberger J.F., Ozog M.A., Perbal B., Naus C.C.;
RT "CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible
RT mechanism of connexin-mediated growth suppression.";
RL J. Biol. Chem. 279:36943-36950(2004).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21871891; DOI=10.1016/j.febslet.2011.08.024;
RA Janune D., Kubota S., Nishida T., Kawaki H., Perbal B., Iida S.,
RA Takigawa M.;
RT "Novel effects of CCN3 that may direct the differentiation of
RT chondrocytes.";
RL FEBS Lett. 585:3033-3040(2011).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY
RP INFLAMMATORY PAIN.
RX PubMed=22353423; DOI=10.1186/1742-2094-9-36;
RA Kular L., Rivat C., Lelongt B., Calmel C., Laurent M., Pohl M., Kitabgi P.,
RA Melik-Parsadaniantz S., Martinerie C.;
RT "NOV/CCN3 attenuates inflammatory pain through regulation of matrix
RT metalloproteinases-2 and -9.";
RL J. Neuroinflamm. 9:36-36(2012).
CC -!- FUNCTION: Immediate-early protein playing a role in various cellular
CC processes including proliferation, adhesion, migration, differentiation
CC and survival. Acts by binding to integrins or membrane receptors such
CC as NOTCH1. Essential regulator of hematopoietic stem and progenitor
CC cell function. Inhibits myogenic differentiation through the activation
CC of Notch-signaling pathway. Inhibits vascular smooth muscle cells
CC proliferation by increasing expression of cell-cycle regulators such as
CC CDKN2B or CDKN1A independently of TGFB1 signaling. Ligand of integrins
CC ITGAV:ITGB3 and ITGA5:ITGB1, acts directly upon endothelial cells to
CC stimulate pro-angiogenic activities and induces angiogenesis. In
CC endothelial cells, supports cell adhesion, induces directed cell
CC migration (chemotaxis) and promotes cell survival. Also plays a role in
CC cutaneous wound healing acting as integrin receptor ligand. Supports
CC skin fibroblast adhesion through ITGA5:ITGB1 and ITGA6:ITGB1 and
CC induces fibroblast chemotaxis through ITGAV:ITGB5. Seems to enhance
CC bFGF-induced DNA synthesis in fibroblasts (By similarity). Involved in
CC bone regeneration as a negative regulator (By similarity). Enhances the
CC articular chondrocytic phenotype, whereas it repressed the one
CC representing endochondral ossification (PubMed:21871891). Impairs
CC pancreatic beta-cell function, inhibits beta-cell proliferation and
CC insulin secretion (By similarity). Plays a role as negative regulator
CC of endothelial pro-inflammatory activation reducing monocyte adhesion,
CC its anti-inflammatory effects occur secondary to the inhibition of NF-
CC kappaB signaling pathway (By similarity). Contributes to the control
CC and coordination of inflammatory processes in atherosclerosis (By
CC similarity). Attenuates inflammatory pain through regulation of
CC IL1B- and TNF-induced MMP9, MMP2 and CCL2 expression. Inhibits MMP9
CC expression through ITGB1 engagement (PubMed:22353423).
CC {ECO:0000250|UniProtKB:P48745, ECO:0000250|UniProtKB:Q64299,
CC ECO:0000269|PubMed:21871891, ECO:0000269|PubMed:22353423}.
CC -!- SUBUNIT: Interacts with FBLN1. Interacts (via CTCK domain) with NOTCH1
CC (via the EGF-like repeat region) (By similarity). Interacts with
CC GJA1/CX43 (PubMed:15181016, PubMed:15213231). Interacts with
CC ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB5 (By similarity). Interacts
CC with ZDHHC22; the interaction may lead to CCN3 palmitoylation (By
CC similarity). {ECO:0000250|UniProtKB:P48745,
CC ECO:0000250|UniProtKB:Q64299, ECO:0000269|PubMed:15181016,
CC ECO:0000269|PubMed:15213231}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15213231}. Cytoplasm
CC {ECO:0000269|PubMed:15213231, ECO:0000269|PubMed:22353423}. Cell
CC junction, gap junction {ECO:0000269|PubMed:15213231}. Note=Localizes at
CC the gap junction in presence of GJA1. {ECO:0000269|PubMed:15213231}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in neurons of
CC dorsal root ganglia and dorsal horn of the spinal cord (at protein
CC level) (PubMed:22353423). Expressed in astrocytes (at protein level)
CC (PubMed:15213231). In cartilage, dominantly expressed in the
CC chondrocyte territorial matrix (PubMed:21871891).
CC {ECO:0000269|PubMed:10570975, ECO:0000269|PubMed:15213231,
CC ECO:0000269|PubMed:21871891, ECO:0000269|PubMed:22353423}.
CC -!- INDUCTION: During persistent inflammatory pain the expression levels
CC are down-regulated. {ECO:0000269|PubMed:22353423}.
CC -!- PTM: May be palmitoylated on Cys-238, which is important for
CC extracellular secretion. {ECO:0000250|UniProtKB:Q64299}.
CC -!- SIMILARITY: Belongs to the CCN family. {ECO:0000305}.
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DR EMBL; AF171936; AAD49371.1; -; mRNA.
DR EMBL; BC072548; AAH72548.1; -; mRNA.
DR RefSeq; NP_110495.1; NM_030868.2.
DR PDB; 5NB8; X-ray; 2.10 A; A/B/C/D=100-195.
DR PDB; 6RK1; X-ray; 1.63 A; A/B=195-249.
DR PDBsum; 5NB8; -.
DR PDBsum; 6RK1; -.
DR AlphaFoldDB; Q9QZQ5; -.
DR SMR; Q9QZQ5; -.
DR STRING; 10116.ENSRNOP00000011904; -.
DR GlyGen; Q9QZQ5; 2 sites.
DR PhosphoSitePlus; Q9QZQ5; -.
DR PaxDb; Q9QZQ5; -.
DR PRIDE; Q9QZQ5; -.
DR Ensembl; ENSRNOT00000011904; ENSRNOP00000011904; ENSRNOG00000008697.
DR GeneID; 81526; -.
DR KEGG; rno:81526; -.
DR UCSC; RGD:621553; rat.
DR CTD; 4856; -.
DR RGD; 621553; Ccn3.
DR eggNOG; ENOG502QR9V; Eukaryota.
DR GeneTree; ENSGT00940000159963; -.
DR HOGENOM; CLU_063247_1_0_1; -.
DR InParanoid; Q9QZQ5; -.
DR OMA; CHTNCPQ; -.
DR OrthoDB; 999958at2759; -.
DR PhylomeDB; Q9QZQ5; -.
DR TreeFam; TF326070; -.
DR PRO; PR:Q9QZQ5; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000008697; Expressed in Ammon's horn and 20 other tissues.
DR Genevisible; Q9QZQ5; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005921; C:gap junction; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0008083; F:growth factor activity; TAS:RGD.
DR GO; GO:0008201; F:heparin binding; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0005112; F:Notch binding; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:1990523; P:bone regeneration; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0033627; P:cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0002062; P:chondrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0035767; P:endothelial cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0071603; P:endothelial cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0010761; P:fibroblast migration; ISS:UniProtKB.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; ISO:RGD.
DR GO; GO:0060548; P:negative regulation of cell death; IBA:GO_Central.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:1902731; P:negative regulation of chondrocyte proliferation; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0090027; P:negative regulation of monocyte chemotaxis; ISS:UniProtKB.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISS:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:1904057; P:negative regulation of sensory perception of pain; IMP:UniProtKB.
DR GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0014909; P:smooth muscle cell migration; ISS:UniProtKB.
DR GO; GO:0048659; P:smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; ISS:UniProtKB.
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 1: Evidence at protein level;
KW 3D-structure; Cell junction; Cytoplasm; Disulfide bond; Gap junction;
KW Glycoprotein; Growth factor; Lipoprotein; Palmitate; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..351
FT /note="CCN family member 3"
FT /id="PRO_0000014417"
FT DOMAIN 25..99
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 102..168
FT /note="VWFC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 199..244
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 258..332
FT /note="CTCK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT LIPID 238
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q64299"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 258..295
FT /evidence="ECO:0000250"
FT DISULFID 275..309
FT /evidence="ECO:0000250"
FT DISULFID 286..325
FT /evidence="ECO:0000250"
FT DISULFID 289..327
FT /evidence="ECO:0000250"
FT DISULFID 294..331
FT /evidence="ECO:0000250"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:5NB8"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:5NB8"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:5NB8"
FT STRAND 131..138
FT /evidence="ECO:0007829|PDB:5NB8"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:5NB8"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:5NB8"
FT STRAND 213..223
FT /evidence="ECO:0007829|PDB:6RK1"
FT STRAND 232..241
FT /evidence="ECO:0007829|PDB:6RK1"
SQ SEQUENCE 351 AA; 38510 MW; 02619707DE7C1BFB CRC64;
MSVFLRKQCL CLGFLLLHLL NQVSATLRCP SRCPSQCPSI SPTCAPGVRS VLDGCSCCPV
CARQRGESCS EMRPCDQSSG LYCDRSADPN NETGICMVPE GDNCVFDGVI YRNGEKFEPN
CQYHCTCRDG QIGCVPRCQL DVLLPGPDCP APKKVAVPGE CCEKWTCGSE EKGTLGGLAL
PAYRPEATVG VELSDSSINC IEQTTEWSAC SKSCGMGLST RVTNRNLQCE MVKQTRLCMV
RPCEQEPGEA TDMKGKKCLR TKKSLKSIHL QFKNCTSLYT YKPRFCGICS DGRCCTPFNT
KTIQVEFQCL PGQIIKKPVM VIGTCTCHSN CPQNNEAFLQ ELELKTSRGE M
