CCN2 (cellular communication network factor 2)

Gene

• Entrez ID: 1490
• Gene name: Cellular communication network factor 2
• Gene symbol: CCN2
• Synonyms: CTGF, HCS24, IGFBP8, NOV2
• Chromosome: 6
• Chromosome location: 6q23.2
• Summary: The protein encoded by this gene is a mitogen that is secreted by vascular endothelial cells. The encoded protein plays a role in chondrocyte proliferation and differentiation, cell adhesion in many cell types, and is related to platelet-derived growth factor. Certain polymorphisms in this gene have been linked with a higher incidence of systemic sclerosis. [provided by RefSeq, Nov 2009]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT002604	hsa-miR-124-3p	Microarray	15685193
MIRT002604	hsa-miR-124-3p	Luciferase reporter assay	22085528
MIRT002604	hsa-miR-124-3p	Microarray	18668037
MIRT004174	hsa-miR-18a-5p	Western blot, Microarray, Northern blot, Luciferase reporter assay	16331254
MIRT004174	hsa-miR-18a-5p	Luciferase reporter assay	19233176
MIRT004174	hsa-miR-18a-5p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	27421245
MIRT004338	hsa-miR-26a-5p	Western blot	18713946
MIRT004338	hsa-miR-26a-5p	Microarray, qRT-PCR	26063197
MIRT006936	hsa-miR-205-5p	Western blot	23056551
MIRT007247	hsa-miR-145-5p	Luciferase reporter assay	23390502
MIRT019692	hsa-miR-375	Microarray	20215506
MIRT053207	hsa-miR-18b-5p	Luciferase reporter assay, Western blot	23681229
MIRT438303	hsa-miR-133b	Luciferase reporter assay	24065814
MIRT438303	hsa-miR-133b	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	25451078
MIRT438303	hsa-miR-133b	Immunofluorescence, Immunohistochemistry, In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	26945106
MIRT538277	hsa-miR-1277-5p	PAR-CLIP	22012620
MIRT538277	hsa-miR-1277-5p	HITS-CLIP	23824327
MIRT538277	hsa-miR-1277-5p	HITS-CLIP	21572407
MIRT538277	hsa-miR-1277-5p	HITS-CLIP	27418678
MIRT538278	hsa-miR-190a-3p	PAR-CLIP	22012620
MIRT538278	hsa-miR-190a-3p	HITS-CLIP	23824327
MIRT538278	hsa-miR-190a-3p	HITS-CLIP	21572407
MIRT538278	hsa-miR-190a-3p	HITS-CLIP	27418678
MIRT538279	hsa-miR-493-5p	PAR-CLIP	22012620
MIRT538279	hsa-miR-493-5p	HITS-CLIP	21572407
MIRT538280	hsa-miR-4789-5p	PAR-CLIP	22012620
MIRT538280	hsa-miR-4789-5p	HITS-CLIP	23824327
MIRT538280	hsa-miR-4789-5p	HITS-CLIP	21572407
MIRT538280	hsa-miR-4789-5p	HITS-CLIP	27418678
MIRT538281	hsa-miR-3941	PAR-CLIP	22012620
MIRT538281	hsa-miR-3941	HITS-CLIP	23824327
MIRT538281	hsa-miR-3941	HITS-CLIP	21572407
MIRT538281	hsa-miR-3941	HITS-CLIP	27418678
MIRT538282	hsa-miR-5011-5p	PAR-CLIP	22012620
MIRT538282	hsa-miR-5011-5p	HITS-CLIP	23824327
MIRT538282	hsa-miR-5011-5p	HITS-CLIP	21572407
MIRT538282	hsa-miR-5011-5p	HITS-CLIP	27418678
MIRT538283	hsa-miR-577	PAR-CLIP	22012620
MIRT538284	hsa-miR-5580-3p	PAR-CLIP	22012620
MIRT538284	hsa-miR-5580-3p	HITS-CLIP	21572407
MIRT538285	hsa-miR-603	PAR-CLIP	22012620
MIRT538285	hsa-miR-603	HITS-CLIP	23824327
MIRT538285	hsa-miR-603	HITS-CLIP	21572407
MIRT538285	hsa-miR-603	HITS-CLIP	27418678
MIRT538286	hsa-miR-362-3p	PAR-CLIP	22012620
MIRT538286	hsa-miR-362-3p	HITS-CLIP	23824327
MIRT538286	hsa-miR-362-3p	HITS-CLIP	21572407
MIRT538286	hsa-miR-362-3p	HITS-CLIP	27418678
MIRT538287	hsa-miR-329-3p	PAR-CLIP	22012620
MIRT538287	hsa-miR-329-3p	HITS-CLIP	23824327
MIRT538287	hsa-miR-329-3p	HITS-CLIP	21572407
MIRT538287	hsa-miR-329-3p	HITS-CLIP	27418678
MIRT538288	hsa-miR-8485	PAR-CLIP	22012620
MIRT538288	hsa-miR-8485	HITS-CLIP	23824327
MIRT538288	hsa-miR-8485	HITS-CLIP	21572407
MIRT538288	hsa-miR-8485	HITS-CLIP	27418678
MIRT610644	hsa-miR-195-3p	HITS-CLIP	23824327
MIRT610644	hsa-miR-195-3p	HITS-CLIP	27418678
MIRT610645	hsa-miR-16-2-3p	HITS-CLIP	23824327
MIRT610645	hsa-miR-16-2-3p	HITS-CLIP	27418678
MIRT610646	hsa-miR-4699-3p	HITS-CLIP	23824327
MIRT610646	hsa-miR-4699-3p	HITS-CLIP	27418678
MIRT610647	hsa-miR-338-5p	HITS-CLIP	23824327
MIRT610647	hsa-miR-338-5p	HITS-CLIP	27418678
MIRT731589	hsa-miR-143-3p	Luciferase reporter assay	27075467
MIRT731589	hsa-miR-143-3p	Luciferase reporter assay, qRT-PCR, Western blot	27398154
MIRT731945	hsa-miR-26b-5p	Luciferase reporter assay, qRT-PCR, Western blot	28079129
MIRT732490	hsa-miR-133a-3p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	25451078
MIRT732585	hsa-miR-199a-5p	qRT-PCR	27062921
MIRT734856	hsa-miR-483-3p	Luciferase reporter assay	27923814
MIRT735520	hsa-miR-30c-5p	Immunocytochemistry, Immunohistochemistry, In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	26775556

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001502	Process	Cartilage condensation	IEA
GO:0001503	Process	Ossification	IEA
GO:0001525	Process	Angiogenesis	IEA
GO:0001894	Process	Tissue homeostasis	IEA
GO:0001934	Process	Positive regulation of protein phosphorylation	IEA
GO:0001968	Function	Fibronectin binding	IEA
GO:0005178	Function	Integrin binding	IBA	21873635
GO:0005515	Function	Protein binding	IPI	16457822, 21629692, 30232710
GO:0005520	Function	Insulin-like growth factor binding	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IEA
GO:0005801	Component	Cis-Golgi network	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005886	Component	Plasma membrane	TAS	10809757
GO:0005938	Component	Cell cortex	IEA
GO:0006367	Process	Transcription initiation from RNA polymerase II promoter	TAS
GO:0007155	Process	Cell adhesion	IBA	21873635
GO:0007160	Process	Cell-matrix adhesion	IEA
GO:0007165	Process	Signal transduction	IBA	21873635
GO:0007229	Process	Integrin-mediated signaling pathway	IEA
GO:0007568	Process	Aging	IEA
GO:0008022	Function	Protein C-terminus binding	IPI	9927660
GO:0008083	Function	Growth factor activity	IEA
GO:0008201	Function	Heparin binding	IBA	21873635
GO:0008284	Process	Positive regulation of cell population proliferation	IEA
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IEA
GO:0008544	Process	Epidermis development	TAS	10809757
GO:0009611	Process	Response to wounding	TAS	10809757
GO:0009749	Process	Response to glucose	IEA
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0010629	Process	Negative regulation of gene expression	IEA
GO:0010942	Process	Positive regulation of cell death	IEA
GO:0016477	Process	Cell migration	IEA
GO:0030154	Process	Cell differentiation	IEA
GO:0030324	Process	Lung development	IEA
GO:0031012	Component	Extracellular matrix	IBA	21873635
GO:0032330	Process	Regulation of chondrocyte differentiation	IEA
GO:0032355	Process	Response to estradiol	IEA
GO:0032967	Process	Positive regulation of collagen biosynthetic process	IEA
GO:0034059	Process	Response to anoxia	IEA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0035988	Process	Chondrocyte proliferation	IEA
GO:0043200	Process	Response to amino acid	IEA
GO:0043280	Process	Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IEA
GO:0043434	Process	Response to peptide hormone	IEA
GO:0045597	Process	Positive regulation of cell differentiation	IDA	20008146
GO:0046330	Process	Positive regulation of JNK cascade	IDA	20008146
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0050867	Process	Positive regulation of cell activation	IEA
GO:0051385	Process	Response to mineralocorticoid	IEA
GO:0051496	Process	Positive regulation of stress fiber assembly	IDA	20008146
GO:0060401	Process	Cytosolic calcium ion transport	IEA
GO:0060452	Process	Positive regulation of cardiac muscle contraction	IEA
GO:0060548	Process	Negative regulation of cell death	IBA	21873635
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	28327460
GO:0070278	Process	Extracellular matrix constituent secretion	IEA
GO:0070318	Process	Positive regulation of G0 to G1 transition	IEA
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IDA	20008146
GO:0070542	Process	Response to fatty acid	IEA
GO:0071897	Process	DNA biosynthetic process	IEA
GO:0072593	Process	Reactive oxygen species metabolic process	IEA

Other IDs

• MIM: 121009
• HGNC: 2500
• e!Ensembl: ENSG00000118523

Protein

• UniProt ID: P29279
• Protein name: CCN family member 2 (Cellular communication network factor 2) (Connective tissue growth factor) (Hypertrophic chondrocyte-specific protein 24) (Insulin-like growth factor-binding protein 8) (IBP-8) (IGF-binding protein 8) (IGFBP-8)
• Protein function: Major connective tissue mitoattractant secreted by vascular endothelial cells. Promotes proliferation and differentiation of chondrocytes. Mediates heparin- and divalent cation-dependent cell adhesion in many cell types including fibroblasts, myofibroblasts, endothelial and epithelial cells. Enhances fibroblast growth factor-induced DNA synthesis.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00219	IGFBP	27 → 82	Insulin-like growth factor binding protein	Domain
  PF00093	VWC	103 → 166	von Willebrand factor type C domain	Family
  PF19035	TSP1_CCN	199 → 242	CCN3 Nov like TSP1 domain	Domain
  PF00007	Cys_knot	253 → 346	Cystine-knot domain	Domain

• Sequence:

  MTAASMGPVRVAFVVLLALCSRPAVGQNCSGPCRCPDEPAPRCPAGVSLVLDGCGCCRVC
  AKQLGELCTERDPCDPHKGLFCHFGSPANRKIGVCTAKDGAPCIFGGTVYRSGESFQSSC
  KYQCTCLDGAVGCMPLCSMDVRLPSPDCPFPRRVKLPGKCCEEWVCDEPKDQTVVGPALA
  AYRLEDTFGPDPTMIRANCLVQTTEWSACSKTCGMGISTRVTNDNASCRLEKQSRLCMVR
  PCEADLEENIKKGKKCIRTPKISKPIKFELSGCTSMKTYRAKFCGVCTDGRCCTPHRTTT
  LPVEFKCPDGEVMKKNMMFIKTCACHYNCPGDNDIFESLYYRKMYGDMA

• Sequence length: 349

Pathways

KEGG:

Apelin signaling pathway
Hippo signaling pathway

Reactome:

YAP1- and WWTR1 (TAZ)-stimulated gene expression
RUNX3 regulates YAP1-mediated transcription

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Rheumatoid arthritis	Rheumatoid Arthritis	rs3766379, rs3792876, rs2071592, rs3087456, rs587776843, rs1566328963	19192274
Congenital diaphragmatic hernia	Congenital diaphragmatic hernia	rs121908602, rs121908604, rs864309713, rs780263938, rs756636036, rs775394591	21258935, 20939759
Carcinoma	Carcinoma, Cribriform, Carcinoma, Granular Cell	rs121912654, rs555607708, rs786202962, rs1564055259	21552421
Lymphoblastic leukemia	Precursor B-Cell Lymphoblastic Leukemia-Lymphoma	rs387906351, rs104894562, rs398122513, rs398122840, rs398123063, rs1057524466, rs1064796115, rs1064795660, rs1064793129, rs1064796227, rs1567887558, rs-1, rs1161194345, rs1597558200, rs1406320425, rs1597566470, rs1597566699, rs1597567692, rs1597567985, rs1438890364, rs1288977950, rs1597552140, rs1597566356, rs1597566726, rs1597568117, rs2069719445, rs2069729948, rs2070018439, rs745708044, rs1169577591	24154679
Myocardial infarction	Myocardial Failure	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	17229371
Cholestasis	Cholestasis, Extrahepatic	rs121909103, rs751511532, rs376368459, rs762702807, rs1578490102, rs1578499691, rs1578504946, rs1317656688, rs199791850, rs1452792080, rs1578491039	28789951
Pulmonary fibrosis	Pulmonary Fibrosis	rs121918666, rs199422300, rs121917737, rs121917834, rs199422294, rs201159197, rs199422297, rs199422305, rs751381953, rs876661305, rs878853260, rs863223336, rs786205702, rs1555811762, rs1060502990, rs1555903332, rs1554038539, rs1554042899, rs938938578	26817844, 25815693, 15677772, 15298857
Hypertension	Hypertensive disease	rs13306026	16685210
Pulmonary arterial hypertension	Pulmonary arterial hypertension, Idiopathic pulmonary arterial hypertension	rs121909288, rs137852741, rs137852742, rs137852743, rs137852744, rs137852745, rs137852746, rs137852748, rs137852749, rs137852750, rs137852751, rs137852753, rs863223423, rs863223426, rs863223424, rs863223408, rs869025366, rs876657748, rs886039506, rs886041324, rs1060502576, rs1060502581, rs1060502584, rs1085307149, rs1085307154, rs1085307157, rs1085307163, rs1085307169, rs1085307177, rs1085307180, rs1085307184, rs1085307188, rs1085307191, rs1085307203, rs1085307222, rs1085307223, rs1085307225, rs1085307229, rs1085307234, rs1085307246, rs1085307261, rs1085307267, rs576091247, rs200948870, rs1085307278, rs1085307282, rs1085307285, rs1085307290, rs1085307301, rs1085307306, rs1085307307, rs1085307308, rs1085307315, rs1085307316, rs1553509997, rs1085307324, rs1085307340, rs1085307349, rs1085307352, rs765887545, rs1085307183, rs1555208696, rs1592224412, rs-1, rs1574415785, rs1574415799, rs1574462520, rs1085307197, rs1574464060, rs749485755, rs1574464121, rs1574464150, rs1574464160, rs1085307214, rs1574485996, rs1574486497, rs1574486566, rs1574488314, rs1574488346, rs1574488353, rs1574488357, rs1574488412, rs1414031345, rs1574488484, rs1574488490, rs863223419, rs1574489046, rs1574494632, rs1574494655, rs1574500018, rs1574505253, rs1574505321, rs371174955, rs1574506729, rs1574506732, rs1574506781, rs1574506790, rs1574506799, rs1574506914, rs1574506976, rs1574507076, rs1574507124, rs1574507215, rs1574507268, rs1574507272, rs1574507276, rs1574507290, rs1574507331, rs398123042, rs374644720, rs1588573831, rs1592222308, rs1592223392, rs756315327, rs1603248167, rs1397811125, rs1603255267, rs1603255327, rs1603255336, rs1603255339, rs754897911, rs1603256095, rs1085307155, rs1085307156, rs1574464226, rs1085307226, rs1574486038, rs1553508321, rs1574488277, rs1574488501, rs1574493841, rs1574499954
Lung cancer	Malignant neoplasm of lung	rs121913530, rs121913529, rs878855122, rs1057519784, rs770315135	21552421
Adenocarcinoma	Adenocarcinoma, Adenocarcinoma, Basal Cell, Adenocarcinoma, Oxyphilic, Adenocarcinoma, Tubular	rs121913530, rs886039394, rs121913474, rs-1	21552421
Dermatitis	Contact Dermatitis	rs61816761, rs150597413, rs138726443, rs201356558, rs149484917, rs372754256, rs747301529, rs567795279, rs745915174	25724174
Arthritis	Arthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470
Renal insufficiency	Renal Insufficiency	rs1596536873

Unknown
Disease name	Disease term	dbSNP ID	References
Heart failure	Heart failure, Left-Sided Heart Failure, Heart Failure, Right-Sided	rs121918074, rs142027794, rs148791216, rs72648927, rs71578935, rs142416150, rs199830512, rs755445214, rs150102469, rs779568205, rs907992794, rs1202130741	17229371
Congestive heart failure	Congestive heart failure	rs2301610, rs3833910, rs12301951, rs201674674, rs186741807, rs150140412, rs786205727, rs757840030, rs552050895, rs759465783, rs201978086, rs572757800, rs1572143354, rs749160569	17229371
Alveolitis	Alveolitis, Fibrosing		26817844, 15677772, 15298857, 25815693
Aortic valve insufficiency	Aortic Valve Insufficiency		21216836
Posterolateral diaphragmatic hernia	Congenital hernia of foramen of Bochdalek		21258935, 20939759
Morgagni diaphragmatic hernia	Congenital hernia of foramen of Morgagni		20939759, 21258935
Crest syndrome	CREST Syndrome
Diffuse cutaneous systemic sclerosis	Diffuse cutaneous systemic sclerosis
Dysphagia	Deglutition Disorders
Gastroesophageal reflux disease	Gastroesophageal reflux disease
Glomerular hyalinosis	Hyalinosis, Segmental Glomerular		17121042
Glomerulosclerosis	Focal glomerulosclerosis		17121042
Limited systemic sclerosis	Limited cutaneous systemic sclerosis
Liver cirrhosis	Liver Cirrhosis		17657819, 26396155, 16652398
Liver fibrosis	Fibrosis, Liver		26396155, 16652398, 17657819
Lung neoplasms	Lung Neoplasms		21552421
Lung diseases	Lung diseases		20939759, 21258935
Malabsorption syndrome	Malabsorption Syndrome
Scleroderma	Systemic Scleroderma, Scleroderma, Limited, Diffuse Scleroderma		24706986
Subfertility	Subfertility, Female		21868453