Seroatlas · Human Serome Atlas

CCN4

CCN family member 4

Also known as: CCN4_HUMAN, WISP-1, WISP1, WISP1-OT1, WISP1-UT1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
O95388
Gene
CCN4
Ensembl
ENSG00000104415
Chromosome
8
Canonical length
367 aa
Protein class
Cancer-related genes, Predicted secreted proteins
Subcellular location
Cytosol
Secretome location
Secreted to extracellular matrix

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

367 residues, UniProt reviewed canonical sequence.

>O95388|CCN4
     1  MRWFLPWTLA AVTAAAASTV LATALSPAPT TMDFTPAPLE DTSSRPQFCK WPCECPPSPP
    61  RCPLGVSLIT DGCECCKMCA QQLGDNCTEA AICDPHRGLY CDYSGDRPRY AIGVCAQVVG
   121  VGCVLDGVRY NNGQSFQPNC KYNCTCIDGA VGCTPLCLRV RPPRLWCPHP RRVSIPGHCC
   181  EQWVCEDDAK RPRKTAPRDT GAFDAVGEVE AWHRNCIAYT SPWSPCSTSC GLGVSTRISN
   241  VNAQCWPEQE SRLCNLRPCD VDIHTLIKAG KKCLAVYQPE ASMNFTLAGC ISTRSYQPKY
   301  CGVCMDNRCC IPYKSKTIDV SFQCPDGLGF SRQVLWINAC FCNLSCRNPN DIFADLESYP
   361  DFSEIAN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CCN4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Secreted
Secreted
Yes
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.44
Highest tissue expression
19 nTPM

Expression across tissuesHPA

Tissue

  • ovary: 19 nTPM
  • smooth muscle: 13 nTPM
  • endometrium: 12 nTPM
  • cervix: 12 nTPM
  • adrenal gland: 11 nTPM
  • kidney: 11 nTPM

Single-cell type

  • hepatic stellate cells: 39 nCPM
  • fibroblasts: 36 nCPM
  • pericytes: 23 nCPM
  • epicardial cells: 18 nCPM
  • mesothelial cells: 15 nCPM
  • vascular smooth muscle cells: 13 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • cerebral cortex: 5.2 nTPM
  • basal ganglia: 3.2 nTPM
  • thalamus: 1.8 nTPM
  • choroid plexus: 1.6 nTPM
  • white matter: 1.6 nTPM
  • amygdala: 1.5 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
1.13
gnomAD pLI
0
DepMap mean gene effect
0.1
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CCN4 as an antibody target. Whether an autoantibody or antibody against CCN4 could matter depends on whether native CCN4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CCN4 is annotated as secreted, so native CCN4 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label CCN4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/CCN4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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