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IGFBP4

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From Wikipedia, the free encyclopedia

Protein-coding gene in the species Homo sapiens

IGFBP4

Available structures

PDB

Ortholog search:PDBe RCSB

List of PDB id codes
1WQJ,2DSP,2DSQ,2DSR

Identifiers

Aliases

IGFBP4, BP-4, HT29-IGFBP, IBP4, IGFBP-4, insulin like growth factor binding protein 4

External IDs

OMIM:146733;MGI:96439;HomoloGene:1192;GeneCards:IGFBP4;OMA:IGFBP4 - orthologs

Gene location (Human)

Chr.	Chromosome 17 (human)^[1]

Band	17q21.2	Start	40,443,450bp^[1]
Band	17q21.2	End	40,457,725bp^[1]

Gene location (Mouse)

Chr.	Chromosome 11 (mouse)^[2]

Band	11\|11 D	Start	98,932,070bp^[2]
Band	11\|11 D	End	98,945,218bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

stromal cell of endometrium

decidua

right ovary

left ovary

left uterine tube

right lobe of liver

right lobe of thyroid gland

canal of the cervix

body of uterus

smooth muscle tissue

Top expressed in

external carotid artery

internal carotid artery

Gonadal ridge

calvaria

aortic valve

ascending aorta

vestibular sensory epithelium

molar

atrium

tunica adventitia of aorta

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

Species

Human

Mouse

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 Mb

Chr 11: 98.93 – 98.95 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Insulin-like growth factor-binding protein 4 is aprotein that in humans is encoded by theIGFBP4gene.^[5]^[6]^[7]

Function

[edit]

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

[edit]

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

[edit]

IGFBP4 has been shown tointeract withInsulin-like growth factor 1 and2.^[10]^[11]

References

[edit]

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000141753 –Ensembl, May 2017
^^a ^b ^cGRCm38: Ensembl release 89: ENSMUSG00000017493 –Ensembl, May 2017
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.
^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.
^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.
^"Entrez Gene: IGFBP4 insulin-like growth factor binding protein 4".
^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.
^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.
^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.

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 PDB gallery
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 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

PDB gallery

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
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

v t e Proteins:carrier proteins
Fatty acid	FABP1 FABP2 FABP3 FABP4 FABP5 FABP6 FABP7
Hormone	peptide hormone:Follistatin Growth hormone binding protein Insulin-like growth factor binding protein IGFBP1 IGFBP2 IGFBP3 IGFBP4 IGFBP5 IGFBP6 IGFBP7 Neurophysins Neurophysin I II steroid hormone:Sex hormone binding globulin/Androgen binding protein Transcortin Thyroxine-binding globulin Transthyretin
Metal/element	calcium Calcium-binding protein Calmodulin-binding proteins copper Ceruloplasmin iron Iron-binding proteins Transferrin receptor
Vitamin	Retinol binding protein 1 2 3 4 Transcobalamin
Pigment	Plant Light-Harvesting Complex Orange Carotenoid Protein Phycobiliprotein Photosynthetic Reaction Centers Phytochrome Rhodopsin
Other	Acyl carrier protein Adaptor protein Cholesterylester transfer protein F-box protein GTP-binding protein Latent TGF-beta binding protein Major urinary proteins Membrane transport protein Odorant binding protein

Growth factor receptor modulators

Angiopoietin

Agonists:Angiopoietin 1
Angiopoietin 4

Antagonists:Angiopoietin 2
Angiopoietin 3

Kinase inhibitors:Altiratinib
CE-245677
Rebastinib

Antibodies:Evinacumab (against angiopoietin 3)
Nesvacumab (against angiopoietin 2)

CNTF

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists:Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors:Afatinib Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies:Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab
ErbB2/HER2	Agonists:Unknown/none Antibodies:Ertumaxomab Pertuzumab Trastuzumab Trastuzumab deruxtecan Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors:Afatinib Lapatinib Mubritinib Neratinib Tucatinib
ErbB3/HER3	Agonists:Neuregulins (heregulins) (1,2,6 (neuroglycan C)) Antibodies:Duligotumab Patritumab Seribantumab
ErbB4/HER4	Agonists:Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1,2,3,4,5 (tomoregulin, TMEFF))

FGF

FGFR1	Agonists:Ersofermin FGF (1,2 (bFGF),3,4,5,6,8,10 (KGF2),20) Repifermin Selpercatinib Trafermin Velafermin
FGFR2	Agonists:Ersofermin FGF (1,2 (bFGF),3,4,5,6,7 (KGF),8,9,10 (KGF2),17,18,22) Palifermin Repifermin Selpercatinib Sprifermin Trafermin Antibodies:Aprutumab Aprutumab ixadotin Kinase inhibitors:Infigratinib
FGFR3	Agonists:Ersofermin FGF (1,2 (bFGF),4,8,9,18,23) Selpercatinib Sprifermin Trafermin Antibodies:Burosumab (against FGF23)
FGFR4	Agonists:Ersofermin FGF (1,2 (bFGF),4,6,8,9,19) Trafermin
Unsorted	Agonists:FGF15/19

HGF (c-Met)

Agonists:Fosgonimeton
Hepatocyte growth factor

Potentiators:Dihexa (PNB-0408)

IGF

IGF-1	Agonists:des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors:BMS-754807 Linsitinib NVP-ADW742 NVP-AEW541 OSl-906 Antibodies:AVE-1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab (against IGF-1 and IGF-2)
IGF-2	Agonists:Insulin-like growth factor-2 (somatomedin A) Antibodies:Dusigitumab Xentuzumab (against IGF-1 and IGF-2)
Others	Binding proteins:IGFBP (1,2,3,4,5,6,7) Cleavage products/derivatives with unknown target:Glypromate (GPE, (1-3)IGF-1) Trofinetide

LNGF (p75^NTR)

Antibodies:Against NGF:ABT-110 (PG110)
ASP-6294
Fasinumab
Frunevetmab
Fulranumab
MEDI-578
Ranevetmab
Tanezumab

Aptamers:Against NGF:RBM-004

Decoy receptors:LEVI-04 (p75^NTR-Fc)

PDGF

Agonists:Becaplermin
Platelet-derived growth factor (A,B,C,D)

RET (GFL)

GFRα1	Agonists:Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors:Vandetanib
GFRα2	Agonists:Neurturin (NRTN) Kinase inhibitors:Vandetanib
GFRα3	Agonists:Artemin (ARTN) Kinase inhibitors:Vandetanib
GFRα4	Agonists:Persephin (PSPN) Kinase inhibitors:Vandetanib
Unsorted	Kinase inhibitors:Agerafenib

SCF (c-Kit)

Agonists:Ancestim
Stem cell factor

TGFβ

Seehere instead.

Trk

TrkA	Agonists:Amitriptyline BNN-20 BNN-27 Cenegermin DHEA DHEA-S Gambogic amide NGF Tavilermide Antagonists:ALE-0540 Dexamethasone FX007 Testosterone Positive allosteric modulators:ACD856 ACD857 Ponazuril (ACD855) Toltrazuril Negative allosteric modulators:VM-902A Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib Milciclib ONO-4474 ONO-5390556 PLX-7486 Rebastinib SNA-120 (pegylated K252a)) Antibodies:Against TrkA:GBR-900;Against NGF:ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers:Against NGF:RBM-004 Decoy receptors:ReN-1820 (TrkAd5)
TrkB	Agonists:3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline Braegen-02 BDNF BNN-20 Deoxygedunin Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 (BrAD-R13, Braegen-01) TDP6 Antagonists:ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Ligands:DHEA Positive allosteric modulators:ACD856 ACD857 Ponazuril (ACD855) Toltrazuril Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486
TrkC	Agonists:BNN-20 DHEA NT-3 Positive allosteric modulators:ACD856 Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486