IGFBP3

Protein identityUniProt · HPA

UniProt accession

P17936

Gene

IGFBP3

Ensembl

ENSG00000146674

Chromosome

7

Canonical length

291 aa

Protein class

Cancer-related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Vesicles

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 forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

291 residues, UniProt reviewed canonical sequence.

>P17936|IGFBP3
     1  MQRARPTLWA AALTLLVLLR GPPVARAGAS SAGLGPVVRC EPCDARALAQ CAPPPAVCAE
    61  LVREPGCGCC LTCALSEGQP CGIYTERCGS GLRCQPSPDE ARPLQALLDG RGLCVNASAV
   121  SRLRAYLLPA PPAPGNASES EEDRSAGSVE SPSVSSTHRV SDPKFHPLHS KIIIIKKGHA
   181  KDSQRYKVDY ESQSTDTQNF SSESKRETEY GPCRREMEDT LNHLKFLNVL SPRGVHIPNC
   241  DKKGFYKKKQ CRPSKGRKRG FCWCVDKYGQ PLPGYTTKGK EDVHCYSMQS K

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IGFBP3 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)

0.53

Highest tissue expression

1,749 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IGFBP3.

Disease | ImmuneIEDB

Conditions an epitope on IGFBP3 was assayed in.

• intrahepatic cholangiocarcinoma T cell
• bile duct adenocarcinoma T cell

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)

0.39

gnomAD pLI

0.91

gnomAD missense Z

0.79

DepMap mean gene effect

-0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• MAPK cascade
• negative regulation of cell population proliferation
• negative regulation of protein phosphorylation
• negative regulation of signal transduction
• negative regulation of smooth muscle cell migration
• negative regulation of smooth muscle cell proliferation
• osteoblast differentiation
• positive regulation of apoptotic process
• positive regulation of insulin-like growth factor receptor signaling pathway
• positive regulation of MAPK cascade
• positive regulation of myoblast differentiation
• protein phosphorylation
• regulation of cell growth
• regulation of glucose metabolic process
• regulation of insulin-like growth factor receptor signaling pathway
• type B pancreatic cell proliferation

Molecular functions

• fibronectin binding
• insulin-like growth factor binding
• insulin-like growth factor I binding
• insulin-like growth factor II binding
• metal ion binding
• protein tyrosine phosphatase activator activity

Cellular components

• endoplasmic reticulum lumen
• extracellular region
• extracellular space
• insulin-like growth factor binding protein complex
• insulin-like growth factor ternary complex
• nucleus

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 3

KeywordsUniProt

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

InteractionsUniProt · HPA

Protein binding partners of IGFBP3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LRP1
• RXRA
• TMEM219
• XLKD1
• LYVE1