IGFBP4

Protein-coding gene in the species Homo sapiens
IGFBP4
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1WQJ, 2DSP, 2DSQ, 2DSR

Identifiers
AliasesIGFBP4, BP-4, HT29-IGFBP, IBP4, IGFBP-4, insulin like growth factor binding protein 4
External IDsOMIM: 146733 MGI: 96439 HomoloGene: 1192 GeneCards: IGFBP4
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for IGFBP4
Genomic location for IGFBP4
Band17q21.2Start40,443,450 bp[1]
End40,457,725 bp[1]
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)[2]
Chromosome 11 (mouse)
Genomic location for IGFBP4
Genomic location for IGFBP4
Band11|11 DStart98,932,070 bp[2]
End98,945,218 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • stromal cell of endometrium

  • left uterine tube

  • right lobe of liver

  • right lobe of thyroid gland

  • canal of the cervix

  • smooth muscle tissue

  • gallbladder

  • left lobe of thyroid gland

  • pericardium

  • gastric mucosa
Top expressed in
  • external carotid artery

  • internal carotid artery

  • calvaria

  • aortic valve

  • ascending aorta

  • molar

  • atrium

  • left lobe of liver

  • carotid body

  • vas deferens
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • insulin-like growth factor I binding
  • insulin-like growth factor II binding
  • signaling receptor binding
  • insulin-like growth factor binding
  • growth factor binding
  • protein binding
Cellular component
  • extracellular region
  • extracellular space
  • endoplasmic reticulum lumen
Biological process
  • skeletal system development
  • regulation of growth
  • DNA metabolic process
  • regulation of insulin-like growth factor receptor signaling pathway
  • regulation of glucose metabolic process
  • cell population proliferation
  • inflammatory response
  • positive regulation of insulin-like growth factor receptor signaling pathway
  • type B pancreatic cell proliferation
  • negative regulation of canonical Wnt signaling pathway
  • regulation of cell growth
  • signal transduction
  • positive regulation of MAPK cascade
  • post-translational protein modification
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

3487

16010

Ensembl

ENSG00000141753

ENSMUSG00000017493

UniProt

P22692

P47879

RefSeq (mRNA)

NM_001552

NM_010517

RefSeq (protein)

NP_001543

NP_034647

Location (UCSC)Chr 17: 40.44 – 40.46 MbChr 11: 98.93 – 98.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Insulin-like growth factor-binding protein 4 is a protein that in humans is encoded by the IGFBP4 gene.[5][6][7]

Function

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.[8] IGFBP-4 is a unique protein and it consistently inhibits several cancer cells in vivo and in vitro. Its inhibitory action has been shown in vivo in prostate and colon. It is secreted by all colon cancer cells.

Clinical significance

The protein itself does not prevent the formation of cancer.[9] However it may reduce the growth of cancer and act as an apoptotic factor.

Interactions

IGFBP4 has been shown to interact with Insulin-like growth factor 1 and 2.[10][11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000141753 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000017493 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ LaTour D, Mohan S, Linkhart TA, Baylink DJ, Strong DD (May 1991). "Inhibitory insulin-like growth factor-binding protein: cloning, complete sequence, and physiological regulation". Mol Endocrinol. 4 (12): 1806–14. doi:10.1210/mend-4-12-1806. PMID 1707125. S2CID 26393652.
  6. ^ Shimasaki S, Uchiyama F, Shimonaka M, Ling N (Mar 1991). "Molecular cloning of the cDNAs encoding a novel insulin-like growth factor-binding protein from rat and human". Mol Endocrinol. 4 (10): 1451–8. doi:10.1210/mend-4-10-1451. PMID 1704481.
  7. ^ Zazzi H, Nikoshkov A, Hall K, Luthman H (1998). "Structure and transcription regulation of the human insulin-like growth factor binding protein 4 gene (IGFBP4)". Genomics. 49 (3): 401–10. doi:10.1006/geno.1998.5283. PMID 9615225.
  8. ^ "Entrez Gene: IGFBP4 insulin-like growth factor binding protein 4".
  9. ^ Durai R, Yang SY, Seifalian AM, Goldspink G, Winslet MC (2007). "Role of insulin-like growth factor binding protein-4 in prevention of colon cancer". World J Surg Oncol. 5: 128. doi:10.1186/1477-7819-5-128. PMC 2203999. PMID 17988381.
  10. ^ Bach LA, Hsieh S, Sakano K, Fujiwara H, Perdue JF, Rechler MM (May 1993). "Binding of mutants of human insulin-like growth factor II to insulin-like growth factor binding proteins 1-6". J. Biol. Chem. 268 (13): 9246–54. doi:10.1016/S0021-9258(18)98342-0. PMID 7683646.
  11. ^ Qin X, Strong DD, Baylink DJ, Mohan S (Sep 1998). "Structure-function analysis of the human insulin-like growth factor binding protein-4". J. Biol. Chem. 273 (36): 23509–16. doi:10.1074/jbc.273.36.23509. PMID 9722589.

Further reading

  • Rajaram S, Baylink DJ, Mohan S (1998). "Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions". Endocr. Rev. 18 (6): 801–31. doi:10.1210/edrv.18.6.0321. PMID 9408744.
  • Zhou R, Diehl D, Hoeflich A, Lahm H, Wolf E (2003). "IGF-binding protein-4: biochemical characteristics and functional consequences". J. Endocrinol. 178 (2): 177–93. doi:10.1677/joe.0.1780177. PMID 12904166.
  • Durai R, Davies M, Yang W, Yang SY, Seifalian A, Goldspink G, Winslet M (2006). "Biology of insulin-like growth factor binding protein-4 and its role in cancer (review)". Int. J. Oncol. 28 (6): 1317–25. doi:10.3892/ijo.28.6.1317. PMID 16685432.
  • Giudice LC, Dsupin BA, Irwin JC, Eckert RL (1992). "Identification of insulin-like growth factor binding proteins in human oviduct". Fertil. Steril. 57 (2): 294–301. doi:10.1016/S0015-0282(16)54833-X. PMID 1370941.
  • Bajalica S, Allander SV, Ehrenborg E, Brøndum-Nielsen K, Luthman H, Larsson C (1992). "Localization of the human insulin-like growth-factor-binding protein 4 gene to chromosomal region 17q12-21.1". Hum. Genet. 89 (2): 234–6. doi:10.1007/BF00217129. PMID 1375185. S2CID 22341448.
  • Kiefer MC, Schmid C, Waldvogel M, Schläpfer I, Futo E, Masiarz FR, Green K, Barr PJ, Zapf J (1992). "Characterization of recombinant human insulin-like growth factor binding proteins 4, 5, and 6 produced in yeast". J. Biol. Chem. 267 (18): 12692–9. doi:10.1016/S0021-9258(18)42332-0. PMID 1377672.
  • Zhou J, Bondy C (1992). "Insulin-like growth factor-II and its binding proteins in placental development". Endocrinology. 131 (3): 1230–40. doi:10.1210/en.131.3.1230. PMID 1380437.
  • Kiefer MC, Masiarz FR, Bauer DM, Zapf J (1991). "Identification and molecular cloning of two new 30-kDa insulin-like growth factor binding proteins isolated from adult human serum". J. Biol. Chem. 266 (14): 9043–9. doi:10.1016/S0021-9258(18)31549-7. PMID 1709161.
  • Culouscou JM, Shoyab M (1991). "Purification of a colon cancer cell growth inhibitor and its identification as an insulin-like growth factor binding protein". Cancer Res. 51 (11): 2813–9. PMID 1709585.
  • Tonin P, Ehrenborg E, Lenoir G, Feunteun J, Lynch H, Morgan K, Zazzi H, Vivier A, Pollak M, Huynh H (1994). "The human insulin-like growth factor-binding protein 4 gene maps to chromosome region 17q12-q21.1 and is close to the gene for hereditary breast-ovarian cancer". Genomics. 18 (2): 414–7. doi:10.1006/geno.1993.1487. PMID 7507078.
  • Ilvesmäki V, Blum WF, Voutilainen R (1994). "Insulin-like growth factor binding proteins in the human adrenal gland". Mol. Cell. Endocrinol. 97 (1–2): 71–9. doi:10.1016/0303-7207(93)90212-3. PMID 7511544. S2CID 22503525.
  • Zhou J, Bondy C (1993). "Anatomy of the human ovarian insulin-like growth factor system". Biol. Reprod. 48 (3): 467–82. doi:10.1095/biolreprod48.3.467. PMID 7680905.
  • Conover CA, Clarkson JT, Bale LK (1993). "Phorbol ester tumor promoters regulate insulin-like growth factor-binding protein-4 proteolysis". Endocrinology. 133 (3): 1347–51. doi:10.1210/endo.133.3.7689953. PMID 7689953.
  • Fridell RA, Harding LS, Bogerd HP, Cullen BR (1995). "Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins". Virology. 209 (2): 347–57. doi:10.1006/viro.1995.1266. PMID 7778269.
  • Batch JA, Mercuri FA, Werther GA (1996). "Identification and localization of insulin-like growth factor-binding protein (IGFBP) messenger RNAs in human hair follicle dermal papilla". J. Invest. Dermatol. 106 (3): 471–5. doi:10.1111/1523-1747.ep12343649. PMID 8648179.
  • Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
  • Han VK, Matsell DG, Delhanty PJ, Hill DJ, Shimasaki S, Nygard K (1996). "IGF-binding protein mRNAs in the human fetus: tissue and cellular distribution of developmental expression". Horm. Res. 45 (3–5): 160–6. doi:10.1159/000184780. PMID 8964576.
  • Di Battista JA, Doré S, Morin N, He Y, Pelletier JP, Martel-Pelletier J (1997). "Prostaglandin E2 stimulates insulin-like growth factor binding protein-4 expression and synthesis in cultured human articular chondrocytes: possible mediation by Ca(++)-calmodulin regulated processes". J. Cell. Biochem. 65 (3): 408–19. doi:10.1002/(SICI)1097-4644(19970601)65:3<408::AID-JCB10>3.0.CO;2-B. PMID 9138096. S2CID 9142234.
  • v
  • t
  • e
  • 1wqj: Structural Basis for the Regulation of Insulin-Like Growth Factors (IGFs) by IGF Binding Proteins (IGFBPs)
    1wqj: Structural Basis for the Regulation of Insulin-Like Growth Factors (IGFs) by IGF Binding Proteins (IGFBPs)
  • 2dsp: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins
    2dsp: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins
  • 2dsq: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins
    2dsq: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins
  • 2dsr: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins
    2dsr: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins
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