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 27-NOV-2024, entry version 223. 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, AND INTERACTION WITH ITGA5. RX PubMed=16569642; DOI=10.1074/jbc.m513686200; RA Wang G.K., Hu L., Fuller G.N., Zhang W.; RT "An interaction between insulin-like growth factor-binding protein 2 RT (IGFBP2) and integrin alpha5 is essential for IGFBP2-induced cell RT mobility."; RL J. Biol. Chem. 281:14085-14091(2006). RN [12] RP FUNCTION, INTERACTION WITH IGF1, DOMAIN, AND MUTAGENESIS OF RP 216-LYS--ARG-219 AND 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 [13] RP FUNCTION, INTERACTION WITH IGF2, AND CLEAVAGE BY MMP9. RX PubMed=18563800; DOI=10.1002/glia.20719; RA Rorive S., Berton A., D'haene N., Takacs C.N., Debeir O., Decaestecker C., RA Salmon I.; RT "Matrix metalloproteinase-9 interplays with the IGFBP2-IGFII complex to RT promote cell growth and motility in astrocytomas."; RL Glia 56:1679-1690(2008). RN [14] RP FUNCTION, INTERACTION WITH PTPRB, AND SUBCELLULAR LOCATION. RX PubMed=22869525; DOI=10.1128/mcb.01011-12; RA Shen X., Xi G., Maile L.A., Wai C., Rosen C.J., Clemmons D.R.; RT "Insulin-like growth factor (IGF) binding protein 2 functions coordinately RT with receptor protein tyrosine phosphatase beta and the IGF-I receptor to RT regulate IGF-I-stimulated signaling."; RL Mol. Cell. Biol. 32:4116-4130(2012). RN [15] 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 [16] RP FUNCTION, INTERACTION WITH ITGA5 AND ITGB1, AND MUTAGENESIS OF ASP-303. RX PubMed=26076738; DOI=10.1007/s12031-015-0589-3; RA Feng N., Zhang Z., Wang Z., Zheng H., Qu F., He X., Wang C.; RT "Insulin-Like Growth Factor Binding Protein-2 Promotes Adhesion of RT Endothelial Progenitor Cells to Endothelial Cells via Integrin RT alpha5beta1."; RL J. Mol. Neurosci. 57:426-434(2015). RN [17] RP SUBCELLULAR LOCATION. RX PubMed=34035374; DOI=10.1038/s41598-021-90333-0; RA Guiot J., Njock M.S., Andre B., Gester F., Henket M., de Seny D., RA Moermans C., Malaise M.G., Louis R.; RT "Serum IGFBP-2 in systemic sclerosis as a prognostic factor of lung RT dysfunction."; RL Sci. Rep. 11:10882-10882(2021). RN [18] RP FUNCTION, INTERACTION WITH ITGA5, AND SUBCELLULAR LOCATION. RX PubMed=38796567; DOI=10.1007/s10495-024-01974-1; RA Wang X., Zhang Y., Chi K., Ji Y., Zhang K., Li P., Fu Z., Wang X., Cui S., RA Shen W., Cai G., Chen X., Zhu H., Hong Q.; RT "IGFBP2 induces podocyte apoptosis promoted by mitochondrial damage via RT integrin alpha5/FAK in diabetic kidney disease."; RL Apoptosis 0:0-0(2024). RN [19] 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: 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 (PubMed:18563800, PubMed:38796567). Functions CC coordinately with receptor protein tyrosine phosphatase beta/PTPRB and CC the IGF1 receptor to regulate IGF1-mediated signaling by stimulating CC the phosphorylation of PTEN leading to its inactivation and AKT1 CC activation (PubMed:22869525). Plays a positive role in cell migration CC via interaction with integrin alpha5/ITGA5 through an RGD motif CC (PubMed:16569642). Additionally, interaction with ITGA5/ITGB1 enhances CC the adhesion of endothelial progenitor cells to endothelial cells CC (PubMed:26076738). Upon mitochondrial damage, facilitates apoptosis CC with ITGA5 of podocytes, and then activates the phosphorylation of CC focal adhesion kinase (FAK)-mediated mitochondrial injury CC (PubMed:38796567). {ECO:0000269|PubMed:16569642, CC ECO:0000269|PubMed:18563800, ECO:0000269|PubMed:19081843, CC ECO:0000269|PubMed:22869525, ECO:0000269|PubMed:26076738, CC ECO:0000269|PubMed:38796567}. CC -!- SUBUNIT: Interacts with IGF1 (PubMed:19081843). Interacts with IGF2 CC (PubMed:1726837, PubMed:18563800). Interacts (via RGD motif) with CC integrin alpha5/ITGA5; this interaction induces cell migration, CC adhesion or apoptosis according to the context (PubMed:16569642, CC PubMed:26076738, PubMed:38796567). Interacts with PTPRB; this CC interaction leads to PTPRB dimerization and inactivation CC (PubMed:22869525). {ECO:0000269|PubMed:16569642, CC ECO:0000269|PubMed:1726837, ECO:0000269|PubMed:18563800, CC ECO:0000269|PubMed:19081843, ECO:0000269|PubMed:22869525, CC ECO:0000269|PubMed:26076738, ECO:0000269|PubMed:38796567}. CC -!- INTERACTION: CC P18065; Q9C086: INO80B; NbExp=4; IntAct=EBI-2504392, EBI-715611; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22869525, CC ECO:0000269|PubMed:34035374, ECO:0000269|PubMed:38796567}. CC -!- DOMAIN: The C-terminus is required for IGF-binding and growth CC inhibition. {ECO:0000269|PubMed:19081843}. 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:0000269|PubMed:18563800}. CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:1726837}. 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; 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; 20. DR CORUM; P18065; -. DR IntAct; P18065; 8. DR STRING; 9606.ENSP00000233809; -. DR BindingDB; P18065; -. DR ChEMBL; CHEMBL3088; -. DR DrugBank; DB01277; Mecasermin. DR MEROPS; I31.953; -. DR GlyCosmos; P18065; 1 site, 1 glycan. DR GlyGen; P18065; 2 sites, 2 O-linked glycans (2 sites). DR iPTMnet; P18065; -. DR PhosphoSitePlus; P18065; -. DR BioMuta; IGFBP2; -. DR DMDM; 290457647; -. DR jPOST; P18065; -. DR MassIVE; P18065; -. DR PaxDb; 9606-ENSP00000233809; -. DR PeptideAtlas; P18065; -. DR ProteomicsDB; 53541; -. DR Pumba; P18065; -. DR Antibodypedia; 11351; 462 antibodies from 36 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 AGR; HGNC:5471; -. 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; DPECHLY; -. DR OrthoDB; 5394492at2759; -. 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; 15 hits in 1152 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 173 other cell types or tissues. DR ExpressionAtlas; P18065; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; 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:0004864; F:protein phosphatase inhibitor activity; IDA:UniProt. DR GO; GO:0141069; F:receptor ligand inhibitor activity; IDA:UniProt. DR GO; GO:0005102; F:signaling receptor binding; TAS:ParkinsonsUK-UCL. DR GO; GO:0030547; F:signaling receptor inhibitor activity; IDA:UniProt. 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:0001649; P:osteoblast differentiation; IDA:UniProt. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:BHF-UCL. 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: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 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 3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein; KW Growth factor binding; Growth regulation; Proteomics identification; KW Reference proteome; Secreted; 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 42..84 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 45..86 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 53..87 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 75..90 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 98..111 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 105..131 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" 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 Loss of endothelial progenitor cells-endothelial adhesion FT activity." FT /evidence="ECO:0000269|PubMed:19081843, FT ECO:0000269|PubMed:26076738" FT CONFLICT 15 FT /note="P -> PPLL (in Ref. 1; CAA34373, 3; AAA36048, 4; FT AAA03246, 5; AAB22308, 7; AAQ87876 and 9; FT AAH04312/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 //