CCN4 cellular communication network factor 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CCN4provided by HGNC
Official Full Name: cellular communication network factor 4provided by HGNC
Primary source: HGNC:HGNC:12769
See related: Ensembl:ENSG00000104415 MIM:603398; AllianceGenome:HGNC:12769
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: WISP1; WISP1c; WISP1i; WISP1tc; WISP1-OT1; WISP1-UT1
Summary: This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like domain. This gene may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. It is expressed at a high level in fibroblast cells, and overexpressed in colon tumors. The encoded protein binds to decorin and biglycan, two members of a family of small leucine-rich proteoglycans present in the extracellular matrix of connective tissue, and possibly prevents the inhibitory activity of decorin and biglycan in tumor cell proliferation. It also attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase. It is 83% identical to the mouse protein at the amino acid level. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2011]
Expression: Broad expression in endometrium (RPKM 7.1), adrenal (RPKM 6.0) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8q24.22

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (133191039..133231690)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (134314374..134355795)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (134203282..134243933)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Silencing of METTL3 prevents the proliferation, migration, epithelial-mesenchymal transition, and renal fibrosis of high glucose-induced HK2 cells by mediating WISP1 in m6A-dependent manner.
Title: Silencing of METTL3 prevents the proliferation, migration, epithelial-mesenchymal transition, and renal fibrosis of high glucose-induced HK2 cells by mediating WISP1 in m6A-dependent manner.
WISP1 induces the expression of macrophage migration inhibitory factor in human lung fibroblasts through Src kinases and EGFR-activated signaling pathways.
Title: WISP1 induces the expression of macrophage migration inhibitory factor in human lung fibroblasts through Src kinases and EGFR-activated signaling pathways.
Effect of WISP1 on paraquat-induced EMT.
Title: Effect of WISP1 on paraquat-induced EMT.
CCN4/WISP1 Promotes Migration of Human Primary Osteoarthritic Chondrocytes.
Title: CCN4/WISP1 Promotes Migration of Human Primary Osteoarthritic Chondrocytes.
The ADAM9/WISP-1 axis cooperates with osteoblasts to stimulate primary prostate tumor growth and metastasis.
Title: The ADAM9/WISP-1 axis cooperates with osteoblasts to stimulate primary prostate tumor growth and metastasis.
WNT1 Inducible Signaling Pathway Protein 1 Is a Stroma-Specific Secreting Protein Inducing a Fibroblast Contraction and Carcinoma Cell Growth in the Human Prostate.
Title: WNT1 Inducible Signaling Pathway Protein 1 Is a Stroma-Specific Secreting Protein Inducing a Fibroblast Contraction and Carcinoma Cell Growth in the Human Prostate.
WISP1 induces ovarian cancer via the IGF1/alphavbeta3/Wnt axis.
Title: WISP1 induces ovarian cancer via the IGF1/αvβ3/Wnt axis.
Circulating levels of WISP-1 (Wnt1-inducible signaling pathway protein 1) and other selected adipokines in children with inflammatory bowel disease.
Title: Circulating levels of WISP-1 (Wnt1-inducible signaling pathway protein 1) and other selected adipokines in children with inflammatory bowel disease.
Increased Serum WISP1 Levels are Associated with Lower Extremity Atherosclerotic Disease in Patients with Type 2 Diabetes Mellitus.
Title: Increased Serum WISP1 Levels are Associated with Lower Extremity Atherosclerotic Disease in Patients with Type 2 Diabetes Mellitus.
Matricellular Protein WISP2 Is an Endogenous Inhibitor of Collagen Linearization and Cancer Metastasis.
Title: Matricellular Protein WISP2 Is an Endogenous Inhibitor of Collagen Linearization and Cancer Metastasis.

Submit: New GeneRIF Correction See all GeneRIFs (114)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India. EBI GWAS Catalog EBI GWAS CatalogPubMed
Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:482064

NoName (e-PCR)
- UniSTS:481399

RH76344 (e-PCR)
- UniSTS:92556

RH102883 (e-PCR)
- UniSTS:97217

NoName (e-PCR)
- UniSTS:486382

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables heparin binding	IBA Inferred from Biological aspect of Ancestor more info
enables integrin binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in bone development	IEA Inferred from Electronic Annotation more info
involved_in cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in glucose homeostasis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of fat cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in osteoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in osteoclast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of smooth muscle cell migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of smooth muscle cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of wound healing	IEA Inferred from Electronic Annotation more info
involved_in regulation of cytokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
is_active_in extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: CCN family member 4

Names: WISP1 3'UTR-associated RNA 1; WISP1 overlapping transcript 1 (non-protein coding); WNT1 induced secreted protein 1; WNT1 inducible signaling pathway protein 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029529.2 RefSeqGene

Range

5002..45653

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001204869.2 → NP_001191798.1 CCN family member 4 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two consecutive exons in the coding region, as compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus, as compared to isoform 1.

Source sequence(s)

AB034725, AF192304, AI347990, AY196488, BX476382

Consensus CDS

CCDS56555.1

UniProtKB/Swiss-Prot

O95388

Related

ENSP00000427744.1, ENST00000517423.5

Conserved Domains (1) summary

pfam00219
Location:49 → 101

IGFBP; Insulin-like growth factor binding protein
NM_001204870.2 → NP_001191799.1 CCN family member 4 isoform 4 precursor

See identical proteins and their annotated locations for NP_001191799.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks three internal exons in the coding region, as compared to variant 1. The resulting isoform (4) has a shorter and distinct C-terminus, as compared to isoform 1.

Source sequence(s)

AF192304, AI347990, AY196486, BX476382

Consensus CDS

CCDS56556.1

UniProtKB/Swiss-Prot

O95388

Related

ENSP00000429185.1, ENST00000519433.1

Conserved Domains (1) summary

cl21545
Location:35 → 117

GHB_like; Glycoprotein hormone beta chain homologues
NM_003882.4 → NP_003873.1 CCN family member 4 isoform 1 precursor

See identical proteins and their annotated locations for NP_003873.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the full length protein (isoform 1).

Source sequence(s)

AF192304, AI347990, AK293031

Consensus CDS

CCDS6371.1

UniProtKB/Swiss-Prot

A8KAG6, E7EMM5, O95388, Q5JBS6, Q5JBS7, Q5JBS8, Q9HCS3

UniProtKB/TrEMBL

B0AZN1

Related

ENSP00000250160.5, ENST00000250160.11

Conserved Domains (3) summary

smart00209
Location:220 → 260

TSP1; Thrombospondin type 1 repeats

smart00214
Location:123 → 181

VWC; von Willebrand factor (vWF) type C domain

pfam00219
Location:49 → 101

IGFBP; Insulin-like growth factor binding protein
NM_080838.3 → NP_543028.1 CCN family member 4 isoform 2 precursor

See identical proteins and their annotated locations for NP_543028.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, as compared to variant 1. Isoform 2 encoded by this variant thus lacks a von Willbrand type C module that is thought to participate in protein complex formation. This variant is overexpressed in scirrhous carcinomas.

Source sequence(s)

AB034725, AF192304, AI347990, BX476382, DN997366

Consensus CDS

CCDS6372.1

UniProtKB/Swiss-Prot

O95388

Related

ENSP00000220856.6, ENST00000220856.6

Conserved Domains (2) summary

smart00209
Location:133 → 173

TSP1; Thrombospondin type 1 repeats

pfam00219
Location:49 → 101

IGFBP; Insulin-like growth factor binding protein

RNA

NR_037944.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks internal two exons, resulting in an immature translation termination, as compared to variant 1. The transcript is a nonsense-mediated mRNA decay candidate.

Source sequence(s)

AF192304, AI347990, AK301508

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

133191039..133231690

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024447319.2 → XP_024303087.1 CCN family member 4 isoform X1

Conserved Domains (2) summary

smart00209
Location:142 → 182

TSP1; Thrombospondin type 1 repeats

smart00214
Location:45 → 103

VWC; von Willebrand factor (vWF) type C domain
XM_047422392.1 → XP_047278348.1 CCN family member 4 isoform X2
XM_024447321.2 → XP_024303089.1 CCN family member 4 isoform X3

Conserved Domains (2) summary

smart00209
Location:37 → 77

TSP1; Thrombospondin type 1 repeats

cl21545
Location:97 → 179

GHB_like; Glycoprotein hormone beta chain homologues