ID   IBP2_BOVIN              Reviewed;         317 AA.
AC   P13384; O97599;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 2.
DT   04-NOV-2026, entry version 152.
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;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX   PubMed=1377702; DOI=10.1002/jcb.240480212;
RA   Bourner M.J., Busby W.H. Jr., Siegel N.R., Krivi G.G., McCusker R.H.,
RA   Clemmons D.R.;
RT   "Cloning and sequence determination of bovine insulin-like growth factor
RT   binding protein-2 (IGFBP-2): comparison of its structural and functional
RT   properties with IGFBP-1.";
RL   J. Cell. Biochem. 48:215-226(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 8-317.
RX   PubMed=1697752; DOI=10.1677/jme.0.0050077;
RA   Upton F.Z., Szabo L., Wallace J.C., Ballard F.J.;
RT   "Characterization and cloning of a bovine insulin-like growth factor-
RT   binding protein.";
RL   J. Mol. Endocrinol. 5:77-84(1990).
RN   [3]
RP   PROTEIN SEQUENCE OF 34-86.
RX   PubMed=2450535; DOI=10.1016/0006-291x(88)90580-3;
RA   Szabo L., Mottershead D.G., Ballard F.J., Wallace J.C.;
RT   "The bovine insulin-like growth factor (IGF) binding protein purified from
RT   conditioned medium requires the N-terminal tripeptide in IGF-1 for
RT   binding.";
RL   Biochem. Biophys. Res. Commun. 151:207-214(1988).
CC   -!- FUNCTION: Multifunctional protein that plays a critical role in
CC       regulating the availability of IGFs such as IGF1 and IGF2 to their
CC       receptors and thereby regulates IGF-mediated cellular processes
CC       including proliferation, differentiation, and apoptosis in a cell-type
CC       specific manner. Functions coordinately with receptor protein tyrosine
CC       phosphatase beta/PTPRB and the IGF1 receptor to regulate IGF1-mediated
CC       signaling by stimulating the phosphorylation of PTEN leading to its
CC       inactivation and AKT1 activation. Plays a positive role in cell
CC       migration via interaction with integrin alpha5/ITGA5 through an RGD
CC       motif. Additionally, interaction with ITGA5/ITGB1 enhances the adhesion
CC       of endothelial progenitor cells to endothelial cells. Upon
CC       mitochondrial damage, facilitates apoptosis with ITGA5 of podocytes,
CC       and then activates the phosphorylation of focal adhesion kinase (FAK)-
CC       mediated mitochondrial injury. {ECO:0000250|UniProtKB:P18065}.
CC   -!- SUBUNIT: Interacts with IGF1. Interacts with IGF2. Interacts (via RGD
CC       motif) with integrin alpha5/ITGA5; this interaction induces cell
CC       migration, adhesion or apoptosis according to the context. Interacts
CC       with PTPRB; this interaction leads to PTPRB dimerization and
CC       inactivation. {ECO:0000250|UniProtKB:P18065}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P18065}.
CC   -!- DOMAIN: The C-terminus is required for IGF-binding and growth
CC       inhibition. {ECO:0000250}.
CC   -!- PTM: Cleaved by MMP9 leading to release of free IGF2 from IGFBP2-IGF2
CC       complex, which contributes to enhance the motility and the growth of
CC       astrocytes. {ECO:0000250|UniProtKB:P18065}.
CC   -!- PTM: O-glycosylated. {ECO:0000250|UniProtKB:P18065}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF074854; AAD04862.1; -; mRNA.
DR   PIR; A60967; A60967.
DR   RefSeq; NP_776980.1; NM_174555.1.
DR   AlphaFoldDB; P13384; -.
DR   BMRB; P13384; -.
DR   SMR; P13384; -.
DR   FunCoup; P13384; 163.
DR   STRING; 9913.ENSBTAP00000007349; -.
DR   MEROPS; I31.953; -.
DR   PaxDb; 9913-ENSBTAP00000007349; -.
DR   GeneID; 282260; -.
DR   KEGG; bta:282260; -.
DR   CTD; 3485; -.
DR   VEuPathDB; HostDB:ENSBTAG00000005596; -.
DR   VGNC; VGNC:30084; IGFBP2.
DR   InParanoid; P13384; -.
DR   OMA; AAWMGPK; -.
DR   OrthoDB; 9984807at2759; -.
DR   Reactome; R-BTA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Proteomes; UP000009136; Chromosome 2.
DR   Bgee; ENSBTAG00000005596; Expressed in anterior segment of eyeball and 103 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; IDA:AgBase.
DR   GO; GO:0031994; F:insulin-like growth factor I binding; ISS:UniProtKB.
DR   GO; GO:0031995; F:insulin-like growth factor II binding; ISS:UniProtKB.
DR   GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB.
DR   GO; GO:0043567; P:regulation of insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0032868; P:response to insulin; IDA:AgBase.
DR   CDD; cd00191; TY; 1.
DR   FunFam; 4.10.40.20:FF:000007; Insulin-like growth factor-binding protein 2; 1.
DR   FunFam; 4.10.800.10:FF:000002; Insulin-like growth factor-binding protein 2; 1.
DR   Gene3D; 4.10.40.20; -; 1.
DR   Gene3D; 4.10.800.10; Thyroglobulin type-1; 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   PANTHER; PTHR11551; INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN; 1.
DR   PANTHER; PTHR11551:SF5; INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN 2; 1.
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; Growth factor receptor domain; 1.
DR   SUPFAM; SSF57610; Thyroglobulin type-1 domain; 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   Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Growth factor binding; Growth regulation; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000269|PubMed:2450535"
FT   CHAIN           34..317
FT                   /note="Insulin-like growth factor-binding protein 2"
FT                   /id="PRO_0000014369"
FT   DOMAIN          35..126
FT                   /note="IGFBP N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DOMAIN          216..298
FT                   /note="Thyroglobulin type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT   REGION          126..146
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          190..218
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           293..295
FT                   /note="Cell attachment site"
FT                   /evidence="ECO:0000255"
FT   DISULFID        39..76
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        42..78
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        50..79
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        68..82
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        90..103
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        97..123
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        219..253
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT   DISULFID        264..275
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT   DISULFID        277..298
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT   CONFLICT        32..33
FT                   /note="RA -> AS (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        46
FT                   /note="S -> C (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        60..61
FT                   /note="PA -> AP (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        82
FT                   /note="C -> F (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        114
FT                   /note="R -> H (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        128
FT                   /note="D -> S (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        134
FT                   /note="S -> T (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        313
FT                   /note="T -> N (in Ref. 2)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   317 AA;  34015 MW;  2B552BC61CA7E9CD CRC64;
     MQPRLGGPAL LLLPPLLLLL LLGAGGGDCG ARAEVLFRCP PCTPESLAAC KPPPGAAAGP
     AGDARVPCEL VREPGCGCCS VCARLEGERC GVYTPRCGQG LRCYPNPGSE LPLRALVHGE
     GTCEKHGDAE YSASPEQVAD NGEEHSEGGL VENHVDGNVN LMGGGGGAGR KPLKSGMKEL
     AVFREKVTEQ HRQMGKGGKH HLGLEEPKKL RPPPARTPCQ QELDQVLERI STMRLPDERG
     PLEHLYSLHI PNCDKHGLYN LKQCKMSLNG QRGECWCVNP NTGKLIQGAP TIRGDPECHL
     FYNEQQGARG VHTQRMQ
//