Full text data of IGFBP5
IGFBP5
(IBP5)
[Confidence: low (only semi-automatic identification from reviews)]
Insulin-like growth factor-binding protein 5; IBP-5; IGF-binding protein 5; IGFBP-5; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Insulin-like growth factor-binding protein 5; IBP-5; IGF-binding protein 5; IGFBP-5; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P24593
ID IBP5_HUMAN Reviewed; 272 AA.
AC P24593; Q5U0A3;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-1992, sequence version 1.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Insulin-like growth factor-binding protein 5;
DE Short=IBP-5;
DE Short=IGF-binding protein 5;
DE Short=IGFBP-5;
DE Flags: Precursor;
GN Name=IGFBP5; Synonyms=IBP5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Osteosarcoma;
RX PubMed=1850258; DOI=10.1016/0006-291X(91)90912-Q;
RA Kiefer M.C., Ioh R.S., Bauer D.M., Zapf J.;
RT "Molecular cloning of a new human insulin-like growth factor binding
RT protein.";
RL Biochem. Biophys. Res. Commun. 176:219-225(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=1709938;
RA Shimasaki S., Shimonaka M., Zhang H.-P., Ling N.;
RT "Identification of five different insulin-like growth factor binding
RT proteins (IGFBPs) from adult rat serum and molecular cloning of a
RT novel IGFBP-5 in rat and human.";
RL J. Biol. Chem. 266:10646-10653(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7511611;
RA Allander S.V., Larsson C., Ehrenborg E., Suwanichkul A., Weber G.,
RA Morris S.L., Bajalica S., Kiefer M.C., Luthman H., Powell D.R.;
RT "Characterization of the chromosomal gene and promoter for human
RT insulin-like growth factor binding protein-5.";
RL J. Biol. Chem. 269:10891-10898(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Yu W., Gibbs R.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TRP-138.
RG NIEHS SNPs program;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 24-43.
RX PubMed=1850257; DOI=10.1016/0006-291X(91)90911-P;
RA Andress D.L., Birnbaum R.S.;
RT "A novel human insulin-like growth factor binding protein secreted by
RT osteoblast-like cells.";
RL Biochem. Biophys. Res. Commun. 176:213-218(1991).
RN [9]
RP PROTEIN SEQUENCE OF 141-178 AND 209-223, AND GLYCOSYLATION AT THR-172.
RC TISSUE=Plasma;
RX PubMed=9883900; DOI=10.1016/S0014-5793(98)01497-5;
RA Standker L., Wobst P., Mark S., Forssmann W.-G.;
RT "Isolation and characterization of circulating 13-kDa C-terminal
RT fragments of human insulin-like growth factor binding protein-5.";
RL FEBS Lett. 441:281-286(1998).
RN [10]
RP DISULFIDE BONDS, AND MASS SPECTROMETRY.
RX PubMed=22117064; DOI=10.1074/jbc.M111.285528;
RA Nili M., Mukherjee A., Shinde U., David L., Rotwein P.;
RT "Defining the disulfide bonds of insulin-like growth factor-binding
RT protein-5 by tandem mass spectrometry with electron transfer
RT dissociation and collision-induced dissociation.";
RL J. Biol. Chem. 287:1510-1519(2012).
RN [11]
RP STRUCTURE BY NMR OF 60-106.
RX PubMed=9822601; DOI=10.1093/emboj/17.22.6558;
RA Kalus W., Zweckstetter M., Renner C., Sanchez Y., Georgescu J.,
RA Grol M., Demuth D., Schumacher R., Dony C., Lang K., Holak T.A.;
RT "Structure of the IGF-binding domain of the insulin-like growth
RT factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I
RT receptor interactions.";
RL EMBO J. 17:6558-6572(1998).
CC -!- FUNCTION: IGF-binding proteins prolong the half-life of the IGFs
CC and have been shown to either inhibit or stimulate the growth
CC promoting effects of the IGFs on cell culture. They alter the
CC interaction of IGFs with their cell surface receptors.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Osteosarcoma, and at lower levels in liver,
CC kidney and brain.
CC -!- SIMILARITY: Contains 1 IGFBP N-terminal domain.
CC -!- SIMILARITY: Contains 1 thyroglobulin type-1 domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/igfbp5/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M65062; AAD04730.1; -; mRNA.
DR EMBL; M62782; AAA53505.1; -; mRNA.
DR EMBL; L27559; AAA72051.1; -; Genomic_DNA.
DR EMBL; L27556; AAA72051.1; JOINED; Genomic_DNA.
DR EMBL; L27557; AAA72051.1; JOINED; Genomic_DNA.
DR EMBL; L27558; AAA72051.1; JOINED; Genomic_DNA.
DR EMBL; AF055033; AAC09368.1; -; mRNA.
DR EMBL; BT019706; AAV38512.1; -; mRNA.
DR EMBL; BT019707; AAV38513.1; -; mRNA.
DR EMBL; AY534685; AAS16353.1; -; Genomic_DNA.
DR EMBL; BC011453; AAH11453.1; -; mRNA.
DR PIR; A53748; A53748.
DR RefSeq; NP_000590.1; NM_000599.3.
DR UniGene; Hs.607212; -.
DR PDB; 1BOE; NMR; -; A=60-106.
DR PDB; 1H59; X-ray; 2.10 A; B=60-112.
DR PDBsum; 1BOE; -.
DR PDBsum; 1H59; -.
DR ProteinModelPortal; P24593; -.
DR SMR; P24593; 25-105, 190-268.
DR DIP; DIP-48433N; -.
DR IntAct; P24593; 3.
DR MINT; MINT-1378863; -.
DR STRING; 9606.ENSP00000233813; -.
DR BindingDB; P24593; -.
DR ChEMBL; CHEMBL2665; -.
DR MEROPS; I31.952; -.
DR PhosphoSite; P24593; -.
DR DMDM; 124069; -.
DR PaxDb; P24593; -.
DR PeptideAtlas; P24593; -.
DR PRIDE; P24593; -.
DR DNASU; 3488; -.
DR Ensembl; ENST00000233813; ENSP00000233813; ENSG00000115461.
DR GeneID; 3488; -.
DR KEGG; hsa:3488; -.
DR UCSC; uc002vgj.4; human.
DR CTD; 3488; -.
DR GeneCards; GC02M217504; -.
DR HGNC; HGNC:5474; IGFBP5.
DR HPA; CAB009216; -.
DR MIM; 146734; gene.
DR neXtProt; NX_P24593; -.
DR PharmGKB; PA29707; -.
DR eggNOG; NOG42882; -.
DR HOGENOM; HOG000253012; -.
DR HOVERGEN; HBG002631; -.
DR InParanoid; P24593; -.
DR OMA; YREQAKI; -.
DR OrthoDB; EOG74N5HG; -.
DR PhylomeDB; P24593; -.
DR BioCyc; MetaCyc:ENSG00000115461-MONOMER; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; IGFBP5; human.
DR EvolutionaryTrace; P24593; -.
DR GeneWiki; IGFBP5; -.
DR GenomeRNAi; 3488; -.
DR NextBio; 13718; -.
DR PMAP-CutDB; P24593; -.
DR PRO; PR:P24593; -.
DR ArrayExpress; P24593; -.
DR Bgee; P24593; -.
DR CleanEx; HS_IGFBP5; -.
DR Genevestigator; P24593; -.
DR GO; GO:0016942; C:insulin-like growth factor binding protein complex; IC:BHF-UCL.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR GO; GO:0060056; P:mammary gland involution; IEA:Ensembl.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IDA:BHF-UCL.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0017148; P:negative regulation of translation; IDA:BHF-UCL.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Ensembl.
DR GO; GO:0001558; P:regulation of cell growth; IEA:Ensembl.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0048630; P:skeletal muscle tissue growth; IEA:Ensembl.
DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; IEA:Ensembl.
DR Gene3D; 4.10.40.20; -; 1.
DR Gene3D; 4.10.800.10; -; 1.
DR InterPro; IPR009030; Growth_fac_rcpt_N_dom.
DR InterPro; IPR012213; IGFBP-5.
DR InterPro; IPR000867; IGFBP-like.
DR InterPro; IPR009168; IGFBP1-6.
DR InterPro; IPR022321; IGFBP_1-6_chordata.
DR InterPro; IPR017891; Insulin_GF-bd_Cys-rich_CS.
DR InterPro; IPR000716; Thyroglobulin_1.
DR PANTHER; PTHR11551; PTHR11551; 1.
DR PANTHER; PTHR11551:SF4; PTHR11551:SF4; 1.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF00086; Thyroglobulin_1; 1.
DR PRINTS; PR01976; IGFBPFAMILY.
DR PRINTS; PR01981; IGFBPFAMILY5.
DR SMART; SM00121; IB; 1.
DR SMART; SM00211; TY; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF57610; SSF57610; 1.
DR PROSITE; PS00222; IGFBP_N_1; 1.
DR PROSITE; PS51323; IGFBP_N_2; 1.
DR PROSITE; PS00484; THYROGLOBULIN_1_1; 1.
DR PROSITE; PS51162; THYROGLOBULIN_1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Growth factor binding; Polymorphism;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1 20 Potential.
FT CHAIN 21 272 Insulin-like growth factor-binding
FT protein 5.
FT /FTId=PRO_0000014385.
FT DOMAIN 23 103 IGFBP N-terminal.
FT DOMAIN 189 263 Thyroglobulin type-1.
FT CARBOHYD 172 172 O-linked (HexNAc...).
FT DISULFID 45 59
FT DISULFID 67 80
FT DISULFID 192 219
FT DISULFID 230 241
FT DISULFID 243 263
FT VARIANT 138 138 R -> W (in dbSNP:rs11575194).
FT /FTId=VAR_019284.
FT STRAND 79 81
FT TURN 84 86
FT HELIX 89 94
FT STRAND 98 101
SQ SEQUENCE 272 AA; 30570 MW; 0A7AD37C6EEA3A81 CRC64;
MVLLTAVLLL LAAYAGPAQS LGSFVHCEPC DEKALSMCPP SPLGCELVKE PGCGCCMTCA
LAEGQSCGVY TERCAQGLRC LPRQDEEKPL HALLHGRGVC LNEKSYREQV KIERDSREHE
EPTTSEMAEE TYSPKIFRPK HTRISELKAE AVKKDRRKKL TQSKFVGGAE NTAHPRIISA
PEMRQESEQG PCRRHMEASL QELKASPRMV PRAVYLPNCD RKGFYKRKQC KPSRGRKRGI
CWCVDKYGMK LPGMEYVDGD FQCHTFDSSN VE
//
ID IBP5_HUMAN Reviewed; 272 AA.
AC P24593; Q5U0A3;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-1992, sequence version 1.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Insulin-like growth factor-binding protein 5;
DE Short=IBP-5;
DE Short=IGF-binding protein 5;
DE Short=IGFBP-5;
DE Flags: Precursor;
GN Name=IGFBP5; Synonyms=IBP5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Osteosarcoma;
RX PubMed=1850258; DOI=10.1016/0006-291X(91)90912-Q;
RA Kiefer M.C., Ioh R.S., Bauer D.M., Zapf J.;
RT "Molecular cloning of a new human insulin-like growth factor binding
RT protein.";
RL Biochem. Biophys. Res. Commun. 176:219-225(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=1709938;
RA Shimasaki S., Shimonaka M., Zhang H.-P., Ling N.;
RT "Identification of five different insulin-like growth factor binding
RT proteins (IGFBPs) from adult rat serum and molecular cloning of a
RT novel IGFBP-5 in rat and human.";
RL J. Biol. Chem. 266:10646-10653(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7511611;
RA Allander S.V., Larsson C., Ehrenborg E., Suwanichkul A., Weber G.,
RA Morris S.L., Bajalica S., Kiefer M.C., Luthman H., Powell D.R.;
RT "Characterization of the chromosomal gene and promoter for human
RT insulin-like growth factor binding protein-5.";
RL J. Biol. Chem. 269:10891-10898(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Yu W., Gibbs R.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TRP-138.
RG NIEHS SNPs program;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 24-43.
RX PubMed=1850257; DOI=10.1016/0006-291X(91)90911-P;
RA Andress D.L., Birnbaum R.S.;
RT "A novel human insulin-like growth factor binding protein secreted by
RT osteoblast-like cells.";
RL Biochem. Biophys. Res. Commun. 176:213-218(1991).
RN [9]
RP PROTEIN SEQUENCE OF 141-178 AND 209-223, AND GLYCOSYLATION AT THR-172.
RC TISSUE=Plasma;
RX PubMed=9883900; DOI=10.1016/S0014-5793(98)01497-5;
RA Standker L., Wobst P., Mark S., Forssmann W.-G.;
RT "Isolation and characterization of circulating 13-kDa C-terminal
RT fragments of human insulin-like growth factor binding protein-5.";
RL FEBS Lett. 441:281-286(1998).
RN [10]
RP DISULFIDE BONDS, AND MASS SPECTROMETRY.
RX PubMed=22117064; DOI=10.1074/jbc.M111.285528;
RA Nili M., Mukherjee A., Shinde U., David L., Rotwein P.;
RT "Defining the disulfide bonds of insulin-like growth factor-binding
RT protein-5 by tandem mass spectrometry with electron transfer
RT dissociation and collision-induced dissociation.";
RL J. Biol. Chem. 287:1510-1519(2012).
RN [11]
RP STRUCTURE BY NMR OF 60-106.
RX PubMed=9822601; DOI=10.1093/emboj/17.22.6558;
RA Kalus W., Zweckstetter M., Renner C., Sanchez Y., Georgescu J.,
RA Grol M., Demuth D., Schumacher R., Dony C., Lang K., Holak T.A.;
RT "Structure of the IGF-binding domain of the insulin-like growth
RT factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I
RT receptor interactions.";
RL EMBO J. 17:6558-6572(1998).
CC -!- FUNCTION: IGF-binding proteins prolong the half-life of the IGFs
CC and have been shown to either inhibit or stimulate the growth
CC promoting effects of the IGFs on cell culture. They alter the
CC interaction of IGFs with their cell surface receptors.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Osteosarcoma, and at lower levels in liver,
CC kidney and brain.
CC -!- SIMILARITY: Contains 1 IGFBP N-terminal domain.
CC -!- SIMILARITY: Contains 1 thyroglobulin type-1 domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/igfbp5/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M65062; AAD04730.1; -; mRNA.
DR EMBL; M62782; AAA53505.1; -; mRNA.
DR EMBL; L27559; AAA72051.1; -; Genomic_DNA.
DR EMBL; L27556; AAA72051.1; JOINED; Genomic_DNA.
DR EMBL; L27557; AAA72051.1; JOINED; Genomic_DNA.
DR EMBL; L27558; AAA72051.1; JOINED; Genomic_DNA.
DR EMBL; AF055033; AAC09368.1; -; mRNA.
DR EMBL; BT019706; AAV38512.1; -; mRNA.
DR EMBL; BT019707; AAV38513.1; -; mRNA.
DR EMBL; AY534685; AAS16353.1; -; Genomic_DNA.
DR EMBL; BC011453; AAH11453.1; -; mRNA.
DR PIR; A53748; A53748.
DR RefSeq; NP_000590.1; NM_000599.3.
DR UniGene; Hs.607212; -.
DR PDB; 1BOE; NMR; -; A=60-106.
DR PDB; 1H59; X-ray; 2.10 A; B=60-112.
DR PDBsum; 1BOE; -.
DR PDBsum; 1H59; -.
DR ProteinModelPortal; P24593; -.
DR SMR; P24593; 25-105, 190-268.
DR DIP; DIP-48433N; -.
DR IntAct; P24593; 3.
DR MINT; MINT-1378863; -.
DR STRING; 9606.ENSP00000233813; -.
DR BindingDB; P24593; -.
DR ChEMBL; CHEMBL2665; -.
DR MEROPS; I31.952; -.
DR PhosphoSite; P24593; -.
DR DMDM; 124069; -.
DR PaxDb; P24593; -.
DR PeptideAtlas; P24593; -.
DR PRIDE; P24593; -.
DR DNASU; 3488; -.
DR Ensembl; ENST00000233813; ENSP00000233813; ENSG00000115461.
DR GeneID; 3488; -.
DR KEGG; hsa:3488; -.
DR UCSC; uc002vgj.4; human.
DR CTD; 3488; -.
DR GeneCards; GC02M217504; -.
DR HGNC; HGNC:5474; IGFBP5.
DR HPA; CAB009216; -.
DR MIM; 146734; gene.
DR neXtProt; NX_P24593; -.
DR PharmGKB; PA29707; -.
DR eggNOG; NOG42882; -.
DR HOGENOM; HOG000253012; -.
DR HOVERGEN; HBG002631; -.
DR InParanoid; P24593; -.
DR OMA; YREQAKI; -.
DR OrthoDB; EOG74N5HG; -.
DR PhylomeDB; P24593; -.
DR BioCyc; MetaCyc:ENSG00000115461-MONOMER; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; IGFBP5; human.
DR EvolutionaryTrace; P24593; -.
DR GeneWiki; IGFBP5; -.
DR GenomeRNAi; 3488; -.
DR NextBio; 13718; -.
DR PMAP-CutDB; P24593; -.
DR PRO; PR:P24593; -.
DR ArrayExpress; P24593; -.
DR Bgee; P24593; -.
DR CleanEx; HS_IGFBP5; -.
DR Genevestigator; P24593; -.
DR GO; GO:0016942; C:insulin-like growth factor binding protein complex; IC:BHF-UCL.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR GO; GO:0060056; P:mammary gland involution; IEA:Ensembl.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IDA:BHF-UCL.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0017148; P:negative regulation of translation; IDA:BHF-UCL.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Ensembl.
DR GO; GO:0001558; P:regulation of cell growth; IEA:Ensembl.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0048630; P:skeletal muscle tissue growth; IEA:Ensembl.
DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; IEA:Ensembl.
DR Gene3D; 4.10.40.20; -; 1.
DR Gene3D; 4.10.800.10; -; 1.
DR InterPro; IPR009030; Growth_fac_rcpt_N_dom.
DR InterPro; IPR012213; IGFBP-5.
DR InterPro; IPR000867; IGFBP-like.
DR InterPro; IPR009168; IGFBP1-6.
DR InterPro; IPR022321; IGFBP_1-6_chordata.
DR InterPro; IPR017891; Insulin_GF-bd_Cys-rich_CS.
DR InterPro; IPR000716; Thyroglobulin_1.
DR PANTHER; PTHR11551; PTHR11551; 1.
DR PANTHER; PTHR11551:SF4; PTHR11551:SF4; 1.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF00086; Thyroglobulin_1; 1.
DR PRINTS; PR01976; IGFBPFAMILY.
DR PRINTS; PR01981; IGFBPFAMILY5.
DR SMART; SM00121; IB; 1.
DR SMART; SM00211; TY; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF57610; SSF57610; 1.
DR PROSITE; PS00222; IGFBP_N_1; 1.
DR PROSITE; PS51323; IGFBP_N_2; 1.
DR PROSITE; PS00484; THYROGLOBULIN_1_1; 1.
DR PROSITE; PS51162; THYROGLOBULIN_1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Growth factor binding; Polymorphism;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1 20 Potential.
FT CHAIN 21 272 Insulin-like growth factor-binding
FT protein 5.
FT /FTId=PRO_0000014385.
FT DOMAIN 23 103 IGFBP N-terminal.
FT DOMAIN 189 263 Thyroglobulin type-1.
FT CARBOHYD 172 172 O-linked (HexNAc...).
FT DISULFID 45 59
FT DISULFID 67 80
FT DISULFID 192 219
FT DISULFID 230 241
FT DISULFID 243 263
FT VARIANT 138 138 R -> W (in dbSNP:rs11575194).
FT /FTId=VAR_019284.
FT STRAND 79 81
FT TURN 84 86
FT HELIX 89 94
FT STRAND 98 101
SQ SEQUENCE 272 AA; 30570 MW; 0A7AD37C6EEA3A81 CRC64;
MVLLTAVLLL LAAYAGPAQS LGSFVHCEPC DEKALSMCPP SPLGCELVKE PGCGCCMTCA
LAEGQSCGVY TERCAQGLRC LPRQDEEKPL HALLHGRGVC LNEKSYREQV KIERDSREHE
EPTTSEMAEE TYSPKIFRPK HTRISELKAE AVKKDRRKKL TQSKFVGGAE NTAHPRIISA
PEMRQESEQG PCRRHMEASL QELKASPRMV PRAVYLPNCD RKGFYKRKQC KPSRGRKRGI
CWCVDKYGMK LPGMEYVDGD FQCHTFDSSN VE
//
MIM
146734
*RECORD*
*FIELD* NO
146734
*FIELD* TI
*146734 INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN 5; IGFBP5
;;IBP5
*FIELD* TX
For background information on the IGFBP gene family, see IGFBP4
read more(146733).
CLONING
Allander et al. (1994) cloned the IGFBP5 gene from a human genomic
library.
GENE FUNCTION
Sato et al. (2002) overexpressed a constitutively active form of Six5
(600963) in murine P19 embryonal carcinoma cells. Using expression
profiling in cDNA arrays, they identified 21 potential target genes
whose expression level increased by the treatment. One of these genes
was Igfbp5, which was also decreased in Six5-deficient mouse
fibroblasts. The response of human IGFBP5 to MyoD (159970)-induced
muscle conversion was altered in cells of myotonic dystrophy-1 (DM1;
160900) patients. The authors concluded that Six5 is an activator that
directs Igfbp5 expression, and hypothesized that reduced SIX5 expression
in DM1 may contribute to the DM1 phenotype.
Using a yeast 2-hybrid screen, Amaar et al. (2002) found strong and
specific interaction between IGFBP5 and FHL2 (602633). Western blot
analysis of nuclear extracts from calvaria and rib osteoblasts and
immunofluorescence microscopy of osteosarcoma cell lines indicated
interaction between FHL2 and IGFBP5 in vivo. Purified FHL2 did not
interact with any other IGFBP tested.
Butt et al. (2003) found that expression of IGFBP5 by stable
transfection and adenovirus-mediated infection was inhibitory to growth
in 2 human breast cancer cell lines. IGFBP5 expression led to G2/M cell
cycle arrest and apoptosis. Apoptosis was associated with increased
expression of the proapoptotic regulator BAX (600040) and a decrease in
the antiapoptotic BCL2 (151430), and it was abrogated by a
broad-spectrum caspase inhibitor. Stable expression of IGFBP5 in the
breast cancer cell lines also inhibited the formation and growth of
tumors following injection in athymic mice. The authors concluded that
IGFBP5 is a growth inhibitor and proapoptotic agent in breast cancer
cells.
GENE STRUCTURE
Allander et al. (1994) showed that the IGFBP5 gene is divided into 4
exons and spans about 33 kb, primarily due to a first intron of
approximately 25 kb. Primer extension studies identified the IGFBP5 mRNA
cap site 772 bp 5-prime to the first nucleotide of the translation start
codon. A potential TATA element beginning 33 bp 5-prime to the mRNA cap
site was identified. When a DNA fragment containing this cap site and
461 bp of upstream sequence was placed 5-prime to the chloramphenicol
acetyltransferase (CAT) reporter gene and transfected into human breast
cancer cells, it directed CAT expression in an orientation-specific
manner, suggesting that this region contains elements essential for
IGFBP5 promoter activity.
MAPPING
By PCR amplification of DNA from somatic human/rodent cell hybrids, by
fluorescence in situ hybridization, and by hybridization to pulsed field
gel electrophoresis fragments, Allander et al. (1994) mapped the IGFBP5
gene to chromosome 2q33-q34. Southern analysis identified a single copy
of the IGFBP5 gene in the haploid human genome. The IGFBP2 gene (146731)
and the IGFBP5 gene are transcribed convergently and are separated by
approximately 20 to 40 kb of DNA.
Kou et al. (1994) demonstrated that, in the mouse, Igfbp2 and Igfbp5
colocalize to a proximal region of chromosome 1 that is syntenic with
human chromosome 2q33-q36 and that the 2 genes are 5 kb apart in a
tail-to-tail orientation. This suggests that the human IGFBP5 gene is
located on 2q33-q36. Kou et al. (1994) also used interspecific backcross
mapping and gene cloning to demonstrate that the Igfbp1 and Igfbp3 are
located in the proximal part of chromosome 11. In the human genome,
these 2 loci map within 20 kb of one another on 7p14-p12, and the genes
are organized in a tail-to-tail configuration. The results suggested to
Kou et al. (1994) an evolutionary scheme in which a primordial IGFBP
gene duplicated to form a cluster that was later replicated to create a
second linkage group.
ANIMAL MODEL
The insulin-like growth factors IGF1 (147440) and IGF2 (147470) are
essential for development; bioavailable IGF is tightly regulated by 6
related IGFBPs. IGFBP5 is the most conserved and is developmentally
upregulated in key lineages and pathologies; in vitro studies suggest
that it functions independently of IGF interaction (Butt et al., 2003).
Genetic ablation of individual Igfbps yields limited phenotypes because
of substantial compensation by remaining family members. Therefore, to
reveal Igfbp5 actions in vivo, Salih et al. (2004) generated lines of
transgenic mice that ubiquitously overexpressed Igfbp5 from early
development. Significantly increased neonatal mortality, reduced female
fertility, whole-body growth inhibition, and retarded muscle development
were observed in Igfbp5-overexpressing mice. Despite only modest changes
in Igf and Igfbp concentrations, the Igfbp5-overexpressing mice
displayed a phenotype more extreme than that observed for other Igfbp
genetic models. Although growth retardation was obvious prenatally,
maximal inhibition occurred postnatally before the onset of growth
hormone-dependent growth, regardless of Igfbp5 expression level,
revealing a period of sensitivity to Igfbp5 during this important stage
of tissue programming.
*FIELD* RF
1. Allander, S. V.; Larsson, C.; Ehrenborg, E.; Suwanichkul, A.; Weber,
G.; Morris, S. L.; Bajalica, S.; Kiefer, M. C.; Luthman, H.; Powell,
D. R.: Characterization of the chromosomal gene and promoter for
human insulin-like growth factor binding protein-5. J. Biol. Chem. 269:
10891-10898, 1994.
2. Amaar, Y. G.; Thompson, G. R.; Linkhart, T. A.; Chen, S.-T.; Baylink,
D. J.; Mohan, S.: Insulin-like growth factor-binding protein 5 (IGFBP-5)
interacts with a four and a half LIM protein 2 (FHL2). J. Biol. Chem. 277:
12053-12060, 2002.
3. Butt, A. J.; Dickson, K. A.; McDougall, F.; Baxter, R. C.: Insulin-like
growth factor-binding protein-5 inhibits the growth of human breast
cancer cells in vitro and in vivo. J. Biol. Chem. 278: 29676-29685,
2003.
4. Kou, K.; James, P. L.; Clemmons, D. R.; Copeland, N. G.; Gilbert,
D. J.; Jenkins, N. A.; Rotwein, P.: Identification of two clusters
of mouse insulin-like growth factor binding protein genes on chromosomes
1 and 11. Genomics 21: 653-655, 1994.
5. Salih, D. A. M.; Tripathi, G.; Holding, C.; Szestak, T. A. M.;
Ivelisse Gonzalez, M.; Carter, E. J.; Cobb, L. J.; Eisemann, J. E.;
Pell, J. M.: Insulin-like growth factor-binding protein 5 (Igfbp5)
compromises survival, growth, muscle development, and fertility in
mice. Proc. Nat. Acad. Sci. 101: 4314-4319, 2004.
6. Sato, S.; Nakamura, M.; Cho, D. H.; Tapscott, S. J.; Ozaki, H.;
Kawakami, K.: Identification of transcriptional targets for Six5:
implication for the pathogenesis of myotonic dystrophy type 1. Hum.
Molec. Genet. 11: 1045-1058, 2002.
*FIELD* CN
Victor A. McKusick - updated: 4/28/2004
Patricia A. Hartz - updated: 10/10/2003
Patricia A. Hartz - updated: 1/16/2003
George E. Tiller - updated: 12/13/2002
*FIELD* CD
Victor A. McKusick: 8/27/1992
*FIELD* ED
tkritzer: 05/06/2004
terry: 4/28/2004
mgross: 10/10/2003
cwells: 4/11/2003
terry: 1/16/2003
cwells: 12/13/2002
alopez: 7/21/1998
dkim: 7/2/1998
mark: 11/7/1996
jason: 7/1/1994
carol: 8/27/1992
*RECORD*
*FIELD* NO
146734
*FIELD* TI
*146734 INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN 5; IGFBP5
;;IBP5
*FIELD* TX
For background information on the IGFBP gene family, see IGFBP4
read more(146733).
CLONING
Allander et al. (1994) cloned the IGFBP5 gene from a human genomic
library.
GENE FUNCTION
Sato et al. (2002) overexpressed a constitutively active form of Six5
(600963) in murine P19 embryonal carcinoma cells. Using expression
profiling in cDNA arrays, they identified 21 potential target genes
whose expression level increased by the treatment. One of these genes
was Igfbp5, which was also decreased in Six5-deficient mouse
fibroblasts. The response of human IGFBP5 to MyoD (159970)-induced
muscle conversion was altered in cells of myotonic dystrophy-1 (DM1;
160900) patients. The authors concluded that Six5 is an activator that
directs Igfbp5 expression, and hypothesized that reduced SIX5 expression
in DM1 may contribute to the DM1 phenotype.
Using a yeast 2-hybrid screen, Amaar et al. (2002) found strong and
specific interaction between IGFBP5 and FHL2 (602633). Western blot
analysis of nuclear extracts from calvaria and rib osteoblasts and
immunofluorescence microscopy of osteosarcoma cell lines indicated
interaction between FHL2 and IGFBP5 in vivo. Purified FHL2 did not
interact with any other IGFBP tested.
Butt et al. (2003) found that expression of IGFBP5 by stable
transfection and adenovirus-mediated infection was inhibitory to growth
in 2 human breast cancer cell lines. IGFBP5 expression led to G2/M cell
cycle arrest and apoptosis. Apoptosis was associated with increased
expression of the proapoptotic regulator BAX (600040) and a decrease in
the antiapoptotic BCL2 (151430), and it was abrogated by a
broad-spectrum caspase inhibitor. Stable expression of IGFBP5 in the
breast cancer cell lines also inhibited the formation and growth of
tumors following injection in athymic mice. The authors concluded that
IGFBP5 is a growth inhibitor and proapoptotic agent in breast cancer
cells.
GENE STRUCTURE
Allander et al. (1994) showed that the IGFBP5 gene is divided into 4
exons and spans about 33 kb, primarily due to a first intron of
approximately 25 kb. Primer extension studies identified the IGFBP5 mRNA
cap site 772 bp 5-prime to the first nucleotide of the translation start
codon. A potential TATA element beginning 33 bp 5-prime to the mRNA cap
site was identified. When a DNA fragment containing this cap site and
461 bp of upstream sequence was placed 5-prime to the chloramphenicol
acetyltransferase (CAT) reporter gene and transfected into human breast
cancer cells, it directed CAT expression in an orientation-specific
manner, suggesting that this region contains elements essential for
IGFBP5 promoter activity.
MAPPING
By PCR amplification of DNA from somatic human/rodent cell hybrids, by
fluorescence in situ hybridization, and by hybridization to pulsed field
gel electrophoresis fragments, Allander et al. (1994) mapped the IGFBP5
gene to chromosome 2q33-q34. Southern analysis identified a single copy
of the IGFBP5 gene in the haploid human genome. The IGFBP2 gene (146731)
and the IGFBP5 gene are transcribed convergently and are separated by
approximately 20 to 40 kb of DNA.
Kou et al. (1994) demonstrated that, in the mouse, Igfbp2 and Igfbp5
colocalize to a proximal region of chromosome 1 that is syntenic with
human chromosome 2q33-q36 and that the 2 genes are 5 kb apart in a
tail-to-tail orientation. This suggests that the human IGFBP5 gene is
located on 2q33-q36. Kou et al. (1994) also used interspecific backcross
mapping and gene cloning to demonstrate that the Igfbp1 and Igfbp3 are
located in the proximal part of chromosome 11. In the human genome,
these 2 loci map within 20 kb of one another on 7p14-p12, and the genes
are organized in a tail-to-tail configuration. The results suggested to
Kou et al. (1994) an evolutionary scheme in which a primordial IGFBP
gene duplicated to form a cluster that was later replicated to create a
second linkage group.
ANIMAL MODEL
The insulin-like growth factors IGF1 (147440) and IGF2 (147470) are
essential for development; bioavailable IGF is tightly regulated by 6
related IGFBPs. IGFBP5 is the most conserved and is developmentally
upregulated in key lineages and pathologies; in vitro studies suggest
that it functions independently of IGF interaction (Butt et al., 2003).
Genetic ablation of individual Igfbps yields limited phenotypes because
of substantial compensation by remaining family members. Therefore, to
reveal Igfbp5 actions in vivo, Salih et al. (2004) generated lines of
transgenic mice that ubiquitously overexpressed Igfbp5 from early
development. Significantly increased neonatal mortality, reduced female
fertility, whole-body growth inhibition, and retarded muscle development
were observed in Igfbp5-overexpressing mice. Despite only modest changes
in Igf and Igfbp concentrations, the Igfbp5-overexpressing mice
displayed a phenotype more extreme than that observed for other Igfbp
genetic models. Although growth retardation was obvious prenatally,
maximal inhibition occurred postnatally before the onset of growth
hormone-dependent growth, regardless of Igfbp5 expression level,
revealing a period of sensitivity to Igfbp5 during this important stage
of tissue programming.
*FIELD* RF
1. Allander, S. V.; Larsson, C.; Ehrenborg, E.; Suwanichkul, A.; Weber,
G.; Morris, S. L.; Bajalica, S.; Kiefer, M. C.; Luthman, H.; Powell,
D. R.: Characterization of the chromosomal gene and promoter for
human insulin-like growth factor binding protein-5. J. Biol. Chem. 269:
10891-10898, 1994.
2. Amaar, Y. G.; Thompson, G. R.; Linkhart, T. A.; Chen, S.-T.; Baylink,
D. J.; Mohan, S.: Insulin-like growth factor-binding protein 5 (IGFBP-5)
interacts with a four and a half LIM protein 2 (FHL2). J. Biol. Chem. 277:
12053-12060, 2002.
3. Butt, A. J.; Dickson, K. A.; McDougall, F.; Baxter, R. C.: Insulin-like
growth factor-binding protein-5 inhibits the growth of human breast
cancer cells in vitro and in vivo. J. Biol. Chem. 278: 29676-29685,
2003.
4. Kou, K.; James, P. L.; Clemmons, D. R.; Copeland, N. G.; Gilbert,
D. J.; Jenkins, N. A.; Rotwein, P.: Identification of two clusters
of mouse insulin-like growth factor binding protein genes on chromosomes
1 and 11. Genomics 21: 653-655, 1994.
5. Salih, D. A. M.; Tripathi, G.; Holding, C.; Szestak, T. A. M.;
Ivelisse Gonzalez, M.; Carter, E. J.; Cobb, L. J.; Eisemann, J. E.;
Pell, J. M.: Insulin-like growth factor-binding protein 5 (Igfbp5)
compromises survival, growth, muscle development, and fertility in
mice. Proc. Nat. Acad. Sci. 101: 4314-4319, 2004.
6. Sato, S.; Nakamura, M.; Cho, D. H.; Tapscott, S. J.; Ozaki, H.;
Kawakami, K.: Identification of transcriptional targets for Six5:
implication for the pathogenesis of myotonic dystrophy type 1. Hum.
Molec. Genet. 11: 1045-1058, 2002.
*FIELD* CN
Victor A. McKusick - updated: 4/28/2004
Patricia A. Hartz - updated: 10/10/2003
Patricia A. Hartz - updated: 1/16/2003
George E. Tiller - updated: 12/13/2002
*FIELD* CD
Victor A. McKusick: 8/27/1992
*FIELD* ED
tkritzer: 05/06/2004
terry: 4/28/2004
mgross: 10/10/2003
cwells: 4/11/2003
terry: 1/16/2003
cwells: 12/13/2002
alopez: 7/21/1998
dkim: 7/2/1998
mark: 11/7/1996
jason: 7/1/1994
carol: 8/27/1992