IBP2_HUMAN
ID IBP2_HUMAN Reviewed; 325 AA.
AC P18065; Q14619; Q9UCL3;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Insulin-like growth factor-binding protein 2;
DE Short=IBP-2;
DE Short=IGF-binding protein 2;
DE Short=IGFBP-2;
DE Flags: Precursor;
GN Name=IGFBP2; Synonyms=BP2, IBP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal liver;
RX PubMed=2479552; DOI=10.1002/j.1460-2075.1989.tb08386.x;
RA Binkert C., Landwehr J., Mary J.L., Schwander J., Heinrich G.;
RT "Cloning, sequence analysis and expression of a cDNA encoding a novel
RT insulin-like growth factor binding protein (IGFBP-2).";
RL EMBO J. 8:2497-2502(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 37-74.
RX PubMed=1697583; DOI=10.1016/s0021-9258(18)77200-1;
RA Zapf J., Kiefer M., Merryweather J., Musiarz F., Bauer D., Born W.,
RA Fischer J.A., Froesch E.R.;
RT "Isolation from adult human serum of four insulin-like growth factor (IGF)
RT binding proteins and molecular cloning of one of them that is increased by
RT IGF I administration and in extrapancreatic tumor hypoglycemia.";
RL J. Biol. Chem. 265:14892-14898(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=1710112; DOI=10.1016/0006-291x(91)90420-c;
RA Ehrenborg E., Vilhelmsdotter S., Bajalica S., Larsson C., Sterm I.,
RA Koch J., Brondum-Nielsen K., Luthman H.;
RT "Structure and localization of the human insulin-like growth factor-binding
RT protein 2 gene.";
RL Biochem. Biophys. Res. Commun. 176:1250-1255(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Retina;
RX PubMed=1712312; DOI=10.1016/0014-4835(91)90056-k;
RA Agarwal N., Hsieh C.L., Sills D., Swaroop M., Desai B., Francke U.,
RA Swaroop A.;
RT "Sequence analysis, expression and chromosomal localization of a gene,
RT isolated from a subtracted human retina cDNA library, that encodes an
RT insulin-like growth factor binding protein (IGFBP2).";
RL Exp. Eye Res. 52:549-561(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=1376411; DOI=10.1210/mend.6.5.1376411;
RA Binkert C., Margot J.B., Landwehr J., Heinrich G., Schwander J.;
RT "Structure of the human insulin-like growth factor binding protein-2
RT gene.";
RL Mol. Endocrinol. 6:826-836(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-137.
RG NIEHS SNPs program;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Ovary, and Uterus;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 40-58, INTERACTION WITH IGF2, AND GLYCOSYLATION.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=1726837;
RA Roghani M., Segovia B., Whitechurch O., Binoux M.;
RT "Purification from human cerebrospinal fluid of insulin-like growth factor
RT binding proteins (IGFBPs). Isolation of IGFBP-2, an altered form of IGFBP-3
RT and a new IGFBP species.";
RL Growth Regul. 1:125-130(1991).
RN [11]
RP FUNCTION, IGF1-BINDING, DOMAIN, AND MUTAGENESIS OF 216-LYS--ARG-219 AND
RP ASP-303.
RX PubMed=19081843; DOI=10.1371/journal.pone.0003926;
RA Zhou J., Li W., Kamei H., Duan C.;
RT "Duplication of the IGFBP-2 gene in teleost fish: protein structure and
RT functionality conservation and gene expression divergence.";
RL PLoS ONE 3:E3926-E3926(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP STRUCTURE BY NMR OF 220-325, AND DISULFIDE BONDS.
RX PubMed=17020769; DOI=10.1016/j.jmb.2006.09.006;
RA Kuang Z., Yao S., Keizer D.W., Wang C.C., Bach L.A., Forbes B.E.,
RA Wallace J.C., Norton R.S.;
RT "Structure, dynamics and heparin binding of the C-terminal domain of
RT insulin-like growth factor-binding protein-2 (IGFBP-2).";
RL J. Mol. Biol. 364:690-704(2006).
CC -!- FUNCTION: Inhibits IGF-mediated growth and developmental rates. IGF-
CC binding proteins prolong the half-life of the IGFs and have been shown
CC to either inhibit or stimulate the growth promoting effects of the IGFs
CC on cell culture. They alter the interaction of IGFs with their cell
CC surface receptors. {ECO:0000269|PubMed:19081843}.
CC -!- SUBUNIT: Binds IGF2 more than IGF1.
CC -!- INTERACTION:
CC P18065; Q9C086: INO80B; NbExp=4; IntAct=EBI-2504392, EBI-715611;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DOMAIN: The C-terminus is required for IGF-binding and growth
CC inhibition. {ECO:0000269|PubMed:19081843}.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:1726837}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/igfbp2/";
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DR EMBL; X16302; CAA34373.1; -; mRNA.
DR EMBL; M69241; AAA36048.1; -; Genomic_DNA.
DR EMBL; M69237; AAA36048.1; JOINED; Genomic_DNA.
DR EMBL; M69239; AAA36048.1; JOINED; Genomic_DNA.
DR EMBL; M69240; AAA36048.1; JOINED; Genomic_DNA.
DR EMBL; M35410; AAA03246.1; -; mRNA.
DR EMBL; S37730; AAB22308.1; -; Genomic_DNA.
DR EMBL; S37712; AAB22308.1; JOINED; Genomic_DNA.
DR EMBL; S37722; AAB22308.1; JOINED; Genomic_DNA.
DR EMBL; S37726; AAB22308.1; JOINED; Genomic_DNA.
DR EMBL; CR610845; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY398667; AAQ87876.1; -; Genomic_DNA.
DR EMBL; AC073321; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007563; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004312; AAH04312.1; -; mRNA.
DR EMBL; BC009902; AAH09902.1; -; mRNA.
DR EMBL; BC012769; AAH12769.1; -; mRNA.
DR EMBL; BC071967; AAH71967.1; -; mRNA.
DR CCDS; CCDS42815.1; -.
DR PIR; A41927; A41927.
DR RefSeq; NP_000588.2; NM_000597.2.
DR RefSeq; NP_001300919.1; NM_001313990.1.
DR RefSeq; NP_001300921.1; NM_001313992.1.
DR RefSeq; NP_001300922.1; NM_001313993.1.
DR PDB; 2H7T; NMR; -; A=220-325.
DR PDBsum; 2H7T; -.
DR AlphaFoldDB; P18065; -.
DR BMRB; P18065; -.
DR SMR; P18065; -.
DR BioGRID; 109706; 17.
DR CORUM; P18065; -.
DR IntAct; P18065; 4.
DR STRING; 9606.ENSP00000233809; -.
DR BindingDB; P18065; -.
DR ChEMBL; CHEMBL3088; -.
DR DrugBank; DB01277; Mecasermin.
DR MEROPS; I31.953; -.
DR GlyGen; P18065; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P18065; -.
DR PhosphoSitePlus; P18065; -.
DR BioMuta; IGFBP2; -.
DR DMDM; 290457647; -.
DR EPD; P18065; -.
DR jPOST; P18065; -.
DR MassIVE; P18065; -.
DR PaxDb; P18065; -.
DR PeptideAtlas; P18065; -.
DR PRIDE; P18065; -.
DR ProteomicsDB; 53541; -.
DR Antibodypedia; 11351; 465 antibodies from 37 providers.
DR DNASU; 3485; -.
DR Ensembl; ENST00000233809.9; ENSP00000233809.4; ENSG00000115457.10.
DR GeneID; 3485; -.
DR KEGG; hsa:3485; -.
DR MANE-Select; ENST00000233809.9; ENSP00000233809.4; NM_000597.3; NP_000588.3.
DR UCSC; uc061sgd.1; human.
DR CTD; 3485; -.
DR DisGeNET; 3485; -.
DR GeneCards; IGFBP2; -.
DR HGNC; HGNC:5471; IGFBP2.
DR HPA; ENSG00000115457; Tissue enhanced (pancreas).
DR MIM; 146731; gene.
DR neXtProt; NX_P18065; -.
DR OpenTargets; ENSG00000115457; -.
DR PharmGKB; PA29704; -.
DR VEuPathDB; HostDB:ENSG00000115457; -.
DR eggNOG; ENOG502QRWQ; Eukaryota.
DR GeneTree; ENSGT00940000158542; -.
DR HOGENOM; CLU_070833_3_0_1; -.
DR InParanoid; P18065; -.
DR OMA; AEPCAEM; -.
DR OrthoDB; 979270at2759; -.
DR PhylomeDB; P18065; -.
DR TreeFam; TF331211; -.
DR PathwayCommons; P18065; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR SignaLink; P18065; -.
DR SIGNOR; P18065; -.
DR BioGRID-ORCS; 3485; 14 hits in 1074 CRISPR screens.
DR ChiTaRS; IGFBP2; human.
DR EvolutionaryTrace; P18065; -.
DR GeneWiki; IGFBP2; -.
DR GenomeRNAi; 3485; -.
DR Pharos; P18065; Tchem.
DR PRO; PR:P18065; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P18065; protein.
DR Bgee; ENSG00000115457; Expressed in descending thoracic aorta and 171 other tissues.
DR ExpressionAtlas; P18065; baseline and differential.
DR Genevisible; P18065; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0031994; F:insulin-like growth factor I binding; IDA:UniProtKB.
DR GO; GO:0031995; F:insulin-like growth factor II binding; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; TAS:ParkinsonsUK-UCL.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:BHF-UCL.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0043567; P:regulation of insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0010226; P:response to lithium ion; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IEA:Ensembl.
DR CDD; cd00191; TY; 1.
DR Gene3D; 4.10.800.10; -; 1.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR012210; IGFBP-2.
DR InterPro; IPR000867; IGFBP-like.
DR InterPro; IPR022321; IGFBP_1-6_chordata.
DR InterPro; IPR017891; Insulin_GF-bd_Cys-rich_CS.
DR InterPro; IPR000716; Thyroglobulin_1.
DR InterPro; IPR036857; Thyroglobulin_1_sf.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF00086; Thyroglobulin_1; 1.
DR PRINTS; PR01976; IGFBPFAMILY.
DR PRINTS; PR01978; IGFBPFAMILY2.
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; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Growth factor binding; Growth regulation; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..35
FT CHAIN 36..325
FT /note="Insulin-like growth factor-binding protein 2"
FT /id="PRO_0000014370"
FT DOMAIN 38..134
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 224..306
FT /note="Thyroglobulin type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT REGION 198..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 301..303
FT /note="Cell attachment site"
FT COMPBIAS 198..220
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 227..261
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500,
FT ECO:0000269|PubMed:17020769"
FT DISULFID 272..283
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500,
FT ECO:0000269|PubMed:17020769"
FT DISULFID 285..306
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500,
FT ECO:0000269|PubMed:17020769"
FT VARIANT 137
FT /note="A -> D (in dbSNP:rs9341096)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_018871"
FT MUTAGEN 216..219
FT /note="KKLR->NNLA: Does not disrupt growth-inhibiting
FT activity."
FT /evidence="ECO:0000269|PubMed:19081843"
FT MUTAGEN 303
FT /note="D->E: Does not disrupt growth-inhibiting activity."
FT /evidence="ECO:0000269|PubMed:19081843"
FT CONFLICT 15
FT /note="P -> PPLL (in Ref. 1; CAA34373, 3; AAA36048, 4;
FT AAA03246, 5; AAB22308, 7; AAQ87876 and 9; AAH04312/
FT AAH09902/AAH12769/AAH71967)"
FT /evidence="ECO:0000305"
FT CONFLICT 57
FT /note="P -> R (in Ref. 3; AAA36048)"
FT /evidence="ECO:0000305"
FT CONFLICT 317
FT /note="R -> C (in Ref. 1; CAA34373)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="H -> D (in Ref. 3; AAA36048)"
FT /evidence="ECO:0000305"
FT HELIX 226..240
FT /evidence="ECO:0007829|PDB:2H7T"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:2H7T"
FT STRAND 269..276
FT /evidence="ECO:0007829|PDB:2H7T"
FT TURN 277..279
FT /evidence="ECO:0007829|PDB:2H7T"
FT STRAND 282..285
FT /evidence="ECO:0007829|PDB:2H7T"
SQ SEQUENCE 325 AA; 34814 MW; 9E1436DBCCC6EA2A CRC64;
MLPRVGCPAL PLPPPPLLPL LLLLLGASGG GGGARAEVLF RCPPCTPERL AACGPPPVAP
PAAVAAVAGG ARMPCAELVR EPGCGCCSVC ARLEGEACGV YTPRCGQGLR CYPHPGSELP
LQALVMGEGT CEKRRDAEYG ASPEQVADNG DDHSEGGLVE NHVDSTMNML GGGGSAGRKP
LKSGMKELAV FREKVTEQHR QMGKGGKHHL GLEEPKKLRP PPARTPCQQE LDQVLERIST
MRLPDERGPL EHLYSLHIPN CDKHGLYNLK QCKMSLNGQR GECWCVNPNT GKLIQGAPTI
RGDPECHLFY NEQQEARGVH TQRMQ
