IGFBP4 insulin-like growth factor binding protein 4 [Homo sapiens] - Gene

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Summary

Official Symbol: IGFBP4provided by HGNC
Official Full Name: insulin-like growth factor binding protein 4provided by HGNC
Primary source: HGNC:5473
See related: Ensembl:ENSG00000141753; HPRD:00900; MIM:146733; Vega:OTTHUMG00000133326
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: BP-4; IBP4; IGFBP-4; HT29-IGFBP
Summary: 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]

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Genomic context

Location :: 17q12-q21.1

Sequence :: Chromosome: 17; NC_000017.10 (38599676..38613982)

See IGFBP4 in Epigenomics, MapViewer

Chromosome 17 - NC_000017.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

IGF1 haplotypes are associated with genetic susceptibility to high myopia in Chinese adults, whereas IGFBP3 and IGFBP4 are unlikely to be important in the genetic predisposition to high myopia
Title: Association of IGF1 gene haplotypes with high myopia in Chinese adults.
The resistance of VEGF-stimulated angiogenesis to IGFBP-4 inhibition appears to depend on sustained activation of p38 MAPK as blocking its activity restored the anti-angiogenic effects of IGFBP-4 on VEGF-induced blood vessel growth in vivo
Title: Insulin-like growth factor binding protein-4 differentially inhibits growth factor-induced angiogenesis.
This study demonistrated that IGFBP4 was significantly decreased in skeletal muscel in patient with amyotrophic lateral sclerosis.
Title: Impaired expression of insulin-like growth factor-1 system in skeletal muscle of amyotrophic lateral sclerosis patients.
circulating IGFBP-4 levels are not influenced by secondary hyperparathyroidism in vitamin D deficiency rickets
Title: Circulating insulin-like growth factor binding protein-4 (IGFBP-4) is not regulated by parathyroid hormone and vitamin D in vivo: evidence from children with rickets.
This is a first report documenting that IGFBP-4 expression in RCC activates cell growth, metastasis, Wnt/beta-catenin signaling and may be involved in RCC metastasis.
Title: IGFBP-4 activates the Wnt/beta-catenin signaling pathway and induces M-CAM expression in human renal cell carcinoma.
These findings suggest that the expression of IGFBP-4 in adenocarcinoma cells in vivo is downregulated by epigenetic silencing in association with tumor differentiation, resulting in disruption of the mechanism of IGFBP-4-mediated growth inhibition.
Title: Insulin-like growth factor binding protein-4 gene silencing in lung adenocarcinomas.
Meta-analysis of gene-disease association. (HuGE Navigator)
Title: Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium.
Revealed is a dose-dependent stimulating effect of the IGFBP2 and IGFBP4 on the migration of CD34-/CD133+ hematopoietic stem and progenitor cells.
Title: Insulin-like growth factor binding proteins-2 and -4 enhance the migration of human CD34-/CD133+ hematopoietic stem and progenitor cells.
IGFBP4, which can inhibit IGF action, also increased during in-vitro decidualization of cultured human ESCs.
Title: The IGF system in in-vitro human decidualization.
conclusion: decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma; data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma
Title: Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients.

Submit: New GeneRIF Correction See all (27)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Using a yeast two-hybrid system, HIV-1 Tat has been shown to bind the human insulin-like growth factor binding protein 4, suggesting a role for this protein in mediating the biological activity of Tat during HIV-1 replication	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_001543.1	NP_000180.2	HK2	BIND	PubMed	HKII interacts with IGFBP-4. This interaction was modeled on a demonstrated interaction between rat HKII and human IGFBP-4.
NP_001543.1	NP_002106.1	HK3	BIND	PubMed	HKIII interacts with IGFBP-4. This interaction was modeled on a demonstrated interaction between rat HKIII and human IGFBP-4.
NP_001543.1	NP_000609.1	IGF1	BIND	PubMed	IGF-I interacts with IGFBP-4.
NP_001543.1	NP_000603.1	IGF2	BIND	PubMed	IGF-II interacts with IGFBP-4.
P22692	P07339	CTSD	HPRD	PubMed
P22692	P52790	HK3	HPRD	PubMed
P22692	P05019	IGF1	HPRD	PubMed
P22692	P01344	IGF2	HPRD	PubMed
P22692	Q13219	PAPPA	HPRD	PubMed
P22692	P02787	TF	HPRD	PubMed
BioGRID:109708	BioGRID:109348	HK3	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:109708	BioGRID:109700	IGF1	BioGRID	PubMed	Reconstituted Complex
BioGRID:109708	BioGRID:109702	IGF2	BioGRID	PubMed	Reconstituted Complex

Function	Evidence Code	Pubs
insulin-like growth factor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
DNA metabolic process	TAS Traceable Author Statement more info	PubMed
cell proliferation	TAS Traceable Author Statement more info	PubMed
inflammatory response	IEA Inferred from Electronic Annotation more info
positive regulation of MAPK cascade	IEA Inferred from Electronic Annotation more info
positive regulation of insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
regulation of cell growth	IEA Inferred from Electronic Annotation more info
regulation of glucose metabolic process	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed
skeletal system development	TAS Traceable Author Statement more info	PubMed
type B pancreatic cell proliferation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
extracellular region	TAS Traceable Author Statement more info
extracellular space	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: insulin-like growth factor-binding protein 4

Names: insulin-like growth factor-binding protein 4; IBP-4; IGF-binding protein 4

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NCBI Reference Sequences (RefSeq)

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.

mRNA and Protein(s)

NM_001552.2 → NP_001543.2 insulin-like growth factor-binding protein 4 precursor

Status: REVIEWED

Source sequence(s)

AC018629, BC016041, BU683435, CN431519

Consensus CDS

CCDS11367.1

UniProtKB/Swiss-Prot

P22692

Related

ENSP00000269593, OTTHUMP00000164451, ENST00000269593, OTTHUMT00000257134

Conserved Domains (2) summary

cd00191
Location:173 – 249
Blast Score: 140

TY; Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases

cl02472
Location:25 – 101
Blast Score: 185

IGFBP; Insulin-like growth factor binding protein

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000017.10 Reference GRCh37.p5 Primary Assembly

Range

38599676..38613982

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000149.1 Alternate HuRef

Range

34392540..34406855

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC018629.12 (98489..112795)	None
genomic	AY442346.1	AAR05443.1
genomic	CH471152.1	EAW60664.1
		EAW60665.1
genomic	U20982.1	AAA62670.1
genomic	Y12508.1	CAA73110.1
mRNA	AK290810.1	BAF83499.1
mRNA	AK304572.1	BAG65363.1
mRNA	BC016041.1	AAH16041.1
mRNA	BT019891.1	AAV38694.1
mRNA	BT019892.1	AAV38695.1
mRNA	BU683435.1	None
mRNA	CN431519.1	None
mRNA	M38177.1	None
mRNA	M62403.1	AAB06189.1