IGFBP4

Protein identityUniProt · HPA

UniProt accession

P22692

Gene

IGFBP4

Ensembl

ENSG00000141753

Chromosome

17

Canonical length

258 aa

Protein class

Plasma proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein binds both insulin-like growth factors (IGFs) I and II and circulates in the plasma in both glycosylated and non-glycosylated forms. Binding of this protein prolongs the half-life of the IGFs and alters their interaction with cell surface receptors. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

258 residues, UniProt reviewed canonical sequence.

>P22692|IGFBP4
     1  MLPLCLVAAL LLAAGPGPSL GDEAIHCPPC SEEKLARCRP PVGCEELVRE PGCGCCATCA
    61  LGLGMPCGVY TPRCGSGLRC YPPRGVEKPL HTLMHGQGVC MELAEIEAIQ ESLQPSDKDE
   121  GDHPNNSFSP CSAHDRRCLQ KHFAKIRDRS TSGGKMKVNG APREDARPVP QGSCQSELHR
   181  ALERLAASQS RTHEDLYIIP IPNCDRNGNF HPKQCHPALD GQRGKCWCVD RKTGVKLPGG
   241  LEPKGELDCH QLADSFRE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IGFBP4 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)

0.46

Highest tissue expression

1,406 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IGFBP4.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 38 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Abnormal brain morphology

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)

0.98

gnomAD pLI

0.02

gnomAD missense Z

0.85

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• MAPK cascade
• negative regulation of canonical Wnt signaling pathway
• positive regulation of insulin-like growth factor receptor signaling pathway
• positive regulation of MAPK cascade
• regulation of cell growth
• regulation of glucose metabolic process
• regulation of insulin-like growth factor receptor signaling pathway
• signal transduction
• type B pancreatic cell proliferation

Molecular functions

• insulin-like growth factor I binding
• insulin-like growth factor II binding
• signaling receptor binding

Cellular components

• endoplasmic reticulum lumen
• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Thyroglobulin type-1
• Insulin-like growth factor-binding protein, IGFBP
• Growth factor receptor cysteine-rich domain superfamily
• Insulin-like growth factor binding protein, N-terminal, Cys-rich conserved site
• Insulin-like growth factor-binding protein family 1-6, chordata
• Thyroglobulin type-1 superfamily
• Thyroglobulin type-1 repeat
• Insulin-like growth factor binding protein
• Insulin-like growth factor-binding protein 4

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Growth factor binding
• Phosphoprotein
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of IGFBP4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• IGF1