ID IGF1_HUMAN Reviewed; 195 AA. AC P05019; B2RWM7; E9PD02; P01343; Q14620; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 13-AUG-1987, sequence version 1. DT 27-MAR-2024, entry version 252. DE RecName: Full=Insulin-like growth factor I; DE Short=IGF-I; DE AltName: Full=Mechano growth factor; DE Short=MGF; DE AltName: Full=Somatomedin-C; DE Flags: Precursor; GN Name=IGF1; Synonyms=IBP1; 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] (ISOFORM 2). RX PubMed=6358902; DOI=10.1038/306609a0; RA Jansen M., van Schaik F.M.A., Ricker A.T., Bullock B., Woods D.E., RA Gabbay K.H., Nussbaum A.L., Sussenbach J.S., van den Brande J.L.; RT "Sequence of cDNA encoding human insulin-like growth factor I precursor."; RL Nature 306:609-611(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3002851; DOI=10.1016/0014-5793(86)80156-9; RA de Pagter-Holthuizen P., van Schaik F.M.A., Verduijn G.M., RA van Ommen G.J.B., Bouma B.N., Jansen M., Sussenbach J.S.; RT "Organization of the human genes for insulin-like growth factors I and RT II."; RL FEBS Lett. 195:179-184(1986). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=2935423; DOI=10.1016/0014-5793(86)80223-x; RA le Bouc Y., Dreyer D., Jaeger F., Binoux M., Sondermeyer P.; RT "Complete characterization of the human IGF-I nucleotide sequence isolated RT from a newly constructed adult liver cDNA library."; RL FEBS Lett. 196:108-112(1986). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2937782; DOI=10.1016/s0021-9258(19)89179-2; RA Rotwein P., Pollock K.M., Didier D.K., Krivi G.G.; RT "Organization and sequence of the human insulin-like growth factor I gene. RT Alternative RNA processing produces two insulin-like growth factor I RT precursor peptides."; RL J. Biol. Chem. 261:4828-4832(1986). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3455760; DOI=10.1073/pnas.83.1.77; RA Rotwein P.; RT "Two insulin-like growth factor I messenger RNAs are expressed in human RT liver."; RL Proc. Natl. Acad. Sci. U.S.A. 83:77-81(1986). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RX PubMed=2082190; DOI=10.1210/mend-4-12-1914; RA Tobin G., Yee D., Brunner N., Rotwein P.; RT "A novel human insulin-like growth factor I messenger RNA is expressed in RT normal and tumor cells."; RL Mol. Endocrinol. 4:1914-1920(1990). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Liver; RX PubMed=2018498; DOI=10.1016/0006-291x(91)91593-2; RA Steenbergh P.H., Koonen-Reemst A.M.C.B., Cleutjens C.B.J.M., RA Sussenbach J.S.; RT "Complete nucleotide sequence of the high molecular weight human IGF-I RT mRNA."; RL Biochem. Biophys. Res. Commun. 175:507-514(1991). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=1372070; DOI=10.1016/0169-328x(92)90094-r; RA Sandberg-Nordqvist A.-C., Staehlbom P.-A., Lake M., Sara V.R.; RT "Characterization of two cDNAs encoding insulin-like growth factor 1 (IGF- RT 1) in the human fetal brain."; RL Brain Res. Mol. Brain Res. 12:275-277(1992). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=8495408; RA Sandberg-Nordqvist A.-C., Staehlbom P.-A., Reinecke M., Collins V.P., RA von Holst H., Sara V.; RT "Characterization of insulin-like growth factor 1 in human primary brain RT tumors."; RL Cancer Res. 53:2475-2478(1993). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-195 (ISOFORM 1). 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 [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-73. RX PubMed=6382022; DOI=10.1038/310777a0; RA Dull T.J., Gray A., Hayflick J.S., Ullrich A.; RT "Insulin-like growth factor II precursor gene organization in relation to RT insulin gene family."; RL Nature 310:777-781(1984). RN [15] RP PROTEIN SEQUENCE OF 49-118 (ISOFORMS 1 AND 2). RX PubMed=632300; DOI=10.1016/s0021-9258(17)40889-1; RA Rinderknecht E., Humbel R.E.; RT "The amino acid sequence of human insulin-like growth factor I and its RT structural homology with proinsulin."; RL J. Biol. Chem. 253:2769-2776(1978). RN [16] RP DISULFIDE BONDS. RX PubMed=3242681; DOI=10.1002/bms.1200160102; RA Raschdorf F., Dahinden R., Maerki W., Richter W.J., Merryweather J.P.; RT "Location of disulphide bonds in human insulin-like growth factors (IGFs) RT synthesized by recombinant DNA technology."; RL Biomed. Environ. Mass Spectrom. 16:3-8(1988). RN [17] RP FUNCTION, BINDING TO IGF1R AND INTEGRIN, IDENTIFICATION IN A COMPLEX WITH RP INTEGRIN AND IGF1R, AND MUTAGENESIS OF ARG-84 AND ARG-85. RX PubMed=19578119; DOI=10.1074/jbc.m109.013201; RA Saegusa J., Yamaji S., Ieguchi K., Wu C.Y., Lam K.S., Liu F.T., RA Takada Y.K., Takada Y.; RT "The direct binding of insulin-like growth factor-1 (IGF-1) to integrin RT alphavbeta3 is involved in IGF-1 signaling."; RL J. Biol. Chem. 284:24106-24114(2009). RN [18] RP INTERACTION WITH SH2D3C. RX PubMed=20881139; DOI=10.1523/jneurosci.3289-10.2010; RA Wang L., Vervoort V., Wallez Y., Core N., Cremer H., Pasquale E.B.; RT "The SRC homology 2 domain protein Shep1 plays an important role in the RT penetration of olfactory sensory axons into the forebrain."; RL J. Neurosci. 30:13201-13210(2010). RN [19] RP FUNCTION. RX PubMed=21076856; DOI=10.1007/s11010-010-0634-z; RA Zoidis E., Ghirlanda-Keller C., Schmid C.; RT "Stimulation of glucose transport in osteoblastic cells by parathyroid RT hormone and insulin-like growth factor I."; RL Mol. Cell. Biochem. 348:33-42(2011). RN [20] RP FUNCTION, BINDING TO INTEGRIN, IDENTIFICATION IN A COMPLEX WITH INTEGRIN RP AND IGF1R, AND MUTAGENESIS OF ARG-84 AND ARG-85. RX PubMed=22351760; DOI=10.1074/jbc.m111.304170; RA Fujita M., Ieguchi K., Davari P., Yamaji S., Taniguchi Y., Sekiguchi K., RA Takada Y.K., Takada Y.; RT "Cross-talk between integrin alpha6beta4 and insulin-like growth factor-1 RT receptor (IGF1R) through direct alpha6beta4 binding to IGF1 and subsequent RT alpha6beta4-IGF1-IGF1R ternary complex formation in anchorage-independent RT conditions."; RL J. Biol. Chem. 287:12491-12500(2012). RN [21] RP FUNCTION, AND MUTAGENESIS OF ARG-84 AND ARG-85. RX PubMed=23243309; DOI=10.1074/jbc.m112.412536; RA Fujita M., Takada Y.K., Takada Y.; RT "Insulin-like growth factor (IGF) signaling requires alphavbeta3-IGF1-IGF RT type 1 receptor (IGF1R) ternary complex formation in anchorage RT independence, and the complex formation does not require IGF1R and Src RT activation."; RL J. Biol. Chem. 288:3059-3069(2013). RN [22] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH INTEGRIN AND IGF1R, AND RP MUTAGENESIS OF ARG-84 AND ARG-85. RX PubMed=23696648; DOI=10.1074/jbc.m113.470872; RA Fujita M., Ieguchi K., Cedano-Prieto D.M., Fong A., Wilkerson C., RA Chen J.Q., Wu M., Lo S.H., Cheung A.T., Wilson M.D., Cardiff R.D., RA Borowsky A.D., Takada Y.K., Takada Y.; RT "An integrin binding-defective mutant of insulin-like growth factor-1 RT (R36E/R37E IGF1) acts as a dominant-negative antagonist of the IGF1 RT receptor (IGF1R) and suppresses tumorigenesis but still binds to IGF1R."; RL J. Biol. Chem. 288:19593-19603(2013). RN [23] RP FUNCTION IN SYNAPSE FORMATION. RX PubMed=24132240; DOI=10.1038/nature12618; RA Shcheglovitov A., Shcheglovitova O., Yazawa M., Portmann T., Shu R., RA Sebastiano V., Krawisz A., Froehlich W., Bernstein J.A., Hallmayer J.F., RA Dolmetsch R.E.; RT "SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion RT syndrome patients."; RL Nature 503:267-271(2013). RN [24] RP 3D-STRUCTURE MODELING. RX PubMed=6189745; RA Blundell T.L., Bedarkar S., Humbel R.E.; RT "Tertiary structures, receptor binding, and antigenicity of insulinlike RT growth factors."; RL Fed. Proc. 42:2592-2597(1983). RN [25] RP STRUCTURE BY NMR. RX PubMed=2036417; DOI=10.1021/bi00236a022; RA Cooke R.M., Harvey T.S., Campbell I.D.; RT "Solution structure of human insulin-like growth factor 1: a nuclear RT magnetic resonance and restrained molecular dynamics study."; RL Biochemistry 30:5484-5491(1991). RN [26] RP STRUCTURE BY NMR. RX PubMed=1319992; DOI=10.1093/oxfordjournals.jbchem.a123791; RA Sato A., Nishimura S., Ohkubo T., Kyogoku Y., Koyama S., Kobayashi M., RA Yasuda T., Kobayashi Y.; RT "1H-NMR assignment and secondary structure of human insulin-like growth RT factor-I (IGF-I) in solution."; RL J. Biochem. 111:529-536(1992). RN [27] RP INVOLVEMENT IN IGF1 DEFICIENCY. RX PubMed=8857020; DOI=10.1056/nejm199610313351805; RA Woods K.A., Camacho-Hubner C., Savage M.O., Clark A.J.; RT "Intrauterine growth retardation and postnatal growth failure associated RT with deletion of the insulin-like growth factor I gene."; RL N. Engl. J. Med. 335:1363-1367(1996). RN [28] RP VARIANT ASP-187. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions of RT human genes."; RL Nat. Genet. 22:231-238(1999). RN [29] RP ERRATUM OF PUBMED:10391209. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [30] RP VARIANT TRP-98. RX PubMed=24389050; DOI=10.1101/gr.160572.113; RA Shaheen R., Faqeih E., Ansari S., Abdel-Salam G., Al-Hassnan Z.N., RA Al-Shidi T., Alomar R., Sogaty S., Alkuraya F.S.; RT "Genomic analysis of primordial dwarfism reveals novel disease genes."; RL Genome Res. 24:291-299(2014). CC -!- FUNCTION: The insulin-like growth factors, isolated from plasma, are CC structurally and functionally related to insulin but have a much higher CC growth-promoting activity. May be a physiological regulator of [1-14C]- CC 2-deoxy-D-glucose (2DG) transport and glycogen synthesis in CC osteoblasts. Stimulates glucose transport in bone-derived osteoblastic CC (PyMS) cells and is effective at much lower concentrations than CC insulin, not only regarding glycogen and DNA synthesis but also with CC regard to enhancing glucose uptake. May play a role in synapse CC maturation (PubMed:21076856, PubMed:24132240). Ca(2+)-dependent CC exocytosis of IGF1 is required for sensory perception of smell in the CC olfactory bulb (By similarity). Acts as a ligand for IGF1R. Binds to CC the alpha subunit of IGF1R, leading to the activation of the intrinsic CC tyrosine kinase activity which autophosphorylates tyrosine residues in CC the beta subunit thus initiating a cascade of down-stream signaling CC events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK CC pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4. Its binding CC to integrins and subsequent ternary complex formation with integrins CC and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation CC and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1 CC (PubMed:19578119, PubMed:22351760, PubMed:23696648, PubMed:23243309). CC As part of the MAPK/ERK signaling pathway, acts as a negative regulator CC of apoptosis in cardiomyocytes via promotion of STUB1/CHIP-mediated CC ubiquitination and degradation of ICER-type isoforms of CREM (By CC similarity). {ECO:0000250|UniProtKB:P05017, CC ECO:0000250|UniProtKB:P08025, ECO:0000269|PubMed:19578119, CC ECO:0000269|PubMed:21076856, ECO:0000269|PubMed:22351760, CC ECO:0000269|PubMed:23243309, ECO:0000269|PubMed:23696648, CC ECO:0000269|PubMed:24132240}. CC -!- SUBUNIT: Forms a ternary complex with IGFR1 and ITGAV:ITGB3 CC (PubMed:19578119). Forms a ternary complex with IGFR1 and ITGA6:ITGB4 CC (PubMed:22351760, PubMed:23696648). Interacts with SH2D3C isoform 2 CC (PubMed:20881139). {ECO:0000269|PubMed:19578119, CC ECO:0000269|PubMed:20881139, ECO:0000269|PubMed:22351760, CC ECO:0000269|PubMed:23696648}. CC -!- INTERACTION: CC P05019; P08069: IGF1R; NbExp=8; IntAct=EBI-7902275, EBI-475981; CC P05019; P08833: IGFBP1; NbExp=2; IntAct=EBI-7902275, EBI-13646303; CC P05019; P22692: IGFBP4; NbExp=7; IntAct=EBI-7902275, EBI-2831948; CC P05019; P06213: INSR; NbExp=4; IntAct=EBI-7902275, EBI-475899; CC P05019-2; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-12837046, EBI-11524452; CC P05019-2; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-12837046, EBI-744099; CC P05019-2; Q14696: MESD; NbExp=3; IntAct=EBI-12837046, EBI-6165891; CC P05019-2; Q13064: MKRN3; NbExp=3; IntAct=EBI-12837046, EBI-2340269; CC P05019-2; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-12837046, EBI-11955057; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P05017}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=IGF-IB; CC IsoId=P05019-1; Sequence=Displayed; CC Name=2; Synonyms=IGF-IA; CC IsoId=P05019-2; Sequence=VSP_039637; CC Name=3; CC IsoId=P05019-3; Sequence=VSP_043317, VSP_039637; CC Name=4; CC IsoId=P05019-4; Sequence=VSP_047399; CC -!- DISEASE: Insulin-like growth factor I deficiency (IGF1 deficiency) CC [MIM:608747]: Autosomal recessive disorder characterized by growth CC retardation, sensorineural deafness and intellectual disability. CC {ECO:0000269|PubMed:8857020}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: Expressed in liver. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA27250.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/igf1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Insulin-like growth factor 1 entry; CC URL="https://en.wikipedia.org/wiki/Insulin-like_growth_factor_1"; 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; X00173; CAA24998.1; -; mRNA. DR EMBL; X03420; CAA27152.1; -; Genomic_DNA. DR EMBL; X03421; CAA27153.1; -; Genomic_DNA. DR EMBL; X03422; CAA27154.1; -; Genomic_DNA. DR EMBL; M27544; AAA52787.1; -; mRNA. DR EMBL; M14155; AAA52537.1; -; Genomic_DNA. DR EMBL; M12659; AAA52537.1; JOINED; Genomic_DNA. DR EMBL; M14153; AAA52537.1; JOINED; Genomic_DNA. DR EMBL; M14154; AAA52537.1; JOINED; Genomic_DNA. DR EMBL; M14156; AAA52538.1; -; Genomic_DNA. DR EMBL; M12659; AAA52538.1; JOINED; Genomic_DNA. DR EMBL; M14153; AAA52538.1; JOINED; Genomic_DNA. DR EMBL; M14154; AAA52538.1; JOINED; Genomic_DNA. DR EMBL; M11568; AAA52539.1; -; mRNA. DR EMBL; M37484; AAA52789.1; -; mRNA. DR EMBL; X57025; CAA40342.1; -; mRNA. DR EMBL; X56773; CAA40092.1; -; mRNA. DR EMBL; X56774; CAA40093.1; -; mRNA. DR EMBL; AY260957; AAO74829.1; -; Genomic_DNA. DR EMBL; AC010202; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC068648; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW97696.1; -; Genomic_DNA. DR EMBL; CH471054; EAW97697.1; -; Genomic_DNA. DR EMBL; BC148266; AAI48267.2; -; mRNA. DR EMBL; X03563; CAA27250.1; ALT_SEQ; Genomic_DNA. DR CCDS; CCDS44960.1; -. [P05019-3] DR CCDS; CCDS44961.1; -. [P05019-4] DR CCDS; CCDS9091.1; -. [P05019-2] DR PIR; A01611; IGHU1B. DR PIR; A92581; IGHU1. DR RefSeq; NP_000609.1; NM_000618.4. [P05019-2] DR RefSeq; NP_001104754.1; NM_001111284.1. [P05019-3] DR RefSeq; NP_001104755.1; NM_001111285.2. [P05019-1] DR PDB; 1B9G; NMR; -; A=49-118. DR PDB; 1BQT; NMR; -; A=49-118. DR PDB; 1GZR; X-ray; 2.00 A; B=49-118. DR PDB; 1GZY; X-ray; 2.54 A; B=49-118. DR PDB; 1GZZ; X-ray; 2.30 A; B=49-118. DR PDB; 1H02; X-ray; 2.00 A; B=49-118. DR PDB; 1H59; X-ray; 2.10 A; A=49-118. DR PDB; 1IMX; X-ray; 1.82 A; A=49-118. DR PDB; 1PMX; NMR; -; A=49-118. DR PDB; 1TGR; X-ray; 1.42 A; A/B=49-77, A/B=90-110. DR PDB; 1WQJ; X-ray; 1.60 A; I=49-118. DR PDB; 2DSP; X-ray; 2.50 A; I=49-118. DR PDB; 2DSQ; X-ray; 2.80 A; C/I=49-118. DR PDB; 2DSR; X-ray; 2.10 A; I=49-118. DR PDB; 2GF1; NMR; -; A=49-118. DR PDB; 3GF1; NMR; -; A=49-118. DR PDB; 3LRI; NMR; -; A=49-118. DR PDB; 4XSS; X-ray; 3.00 A; B=49-118. DR PDB; 5U8Q; X-ray; 3.27 A; B=49-118. DR PDB; 6FF3; X-ray; 2.57 A; B=49-118. DR PDB; 6PYH; EM; 4.30 A; B=49-118. DR PDB; 6RVA; NMR; -; X=49-118. DR PDB; 7S0Q; EM; 3.70 A; D=49-118. DR PDB; 7WRQ; EM; 3.60 A; C=49-118. DR PDB; 7YRR; EM; 4.30 A; C/D=52-111. DR PDB; 8EYR; EM; 4.00 A; C/D=1-195. DR PDBsum; 1B9G; -. DR PDBsum; 1BQT; -. DR PDBsum; 1GZR; -. DR PDBsum; 1GZY; -. DR PDBsum; 1GZZ; -. DR PDBsum; 1H02; -. DR PDBsum; 1H59; -. DR PDBsum; 1IMX; -. DR PDBsum; 1PMX; -. DR PDBsum; 1TGR; -. DR PDBsum; 1WQJ; -. DR PDBsum; 2DSP; -. DR PDBsum; 2DSQ; -. DR PDBsum; 2DSR; -. DR PDBsum; 2GF1; -. DR PDBsum; 3GF1; -. DR PDBsum; 3LRI; -. DR PDBsum; 4XSS; -. DR PDBsum; 5U8Q; -. DR PDBsum; 6FF3; -. DR PDBsum; 6PYH; -. DR PDBsum; 6RVA; -. DR PDBsum; 7S0Q; -. DR PDBsum; 7WRQ; -. DR PDBsum; 7YRR; -. DR PDBsum; 8EYR; -. DR AlphaFoldDB; P05019; -. DR BMRB; P05019; -. DR EMDB; EMD-20524; -. DR EMDB; EMD-24791; -. DR EMDB; EMD-28693; -. DR EMDB; EMD-32735; -. DR EMDB; EMD-34065; -. DR SMR; P05019; -. DR BioGRID; 109700; 23. DR CORUM; P05019; -. DR DIP; DIP-41933N; -. DR DIP; DIP-6021N; -. DR IntAct; P05019; 11. DR MINT; P05019; -. DR STRING; 9606.ENSP00000376637; -. DR ChEMBL; CHEMBL3217394; -. DR DrugBank; DB01890; N,N-Bis(3-(D-gluconamido)propyl)deoxycholamide. DR DrugBank; DB02643; N-Dodecyl-N,N-Dimethyl-3-Ammonio-1-Propanesulfonate. DR Allergome; 11751; Hom s IGF-1. DR iPTMnet; P05019; -. DR PhosphoSitePlus; P05019; -. DR BioMuta; IGF1; -. DR DMDM; 124263; -. DR CPTAC; non-CPTAC-2677; -. DR MassIVE; P05019; -. DR PaxDb; 9606-ENSP00000302665; -. DR PeptideAtlas; P05019; -. DR ProteomicsDB; 19553; -. DR ProteomicsDB; 51765; -. [P05019-1] DR ProteomicsDB; 51766; -. [P05019-2] DR ProteomicsDB; 51767; -. [P05019-3] DR Pumba; P05019; -. DR ABCD; P05019; 7 sequenced antibodies. DR Antibodypedia; 18040; 1619 antibodies from 42 providers. DR DNASU; 3479; -. DR Ensembl; ENST00000307046.8; ENSP00000302665.8; ENSG00000017427.17. [P05019-1] DR Ensembl; ENST00000337514.11; ENSP00000337612.7; ENSG00000017427.17. [P05019-2] DR Ensembl; ENST00000392904.5; ENSP00000376637.1; ENSG00000017427.17. [P05019-4] DR Ensembl; ENST00000392905.7; ENSP00000376638.3; ENSG00000017427.17. [P05019-4] DR Ensembl; ENST00000424202.6; ENSP00000416811.2; ENSG00000017427.17. [P05019-3] DR Ensembl; ENST00000644491.1; ENSP00000494228.1; ENSG00000017427.17. [P05019-2] DR GeneID; 3479; -. DR KEGG; hsa:3479; -. DR MANE-Select; ENST00000337514.11; ENSP00000337612.7; NM_000618.5; NP_000609.1. [P05019-2] DR UCSC; uc001tjm.2; human. [P05019-1] DR AGR; HGNC:5464; -. DR CTD; 3479; -. DR DisGeNET; 3479; -. DR GeneCards; IGF1; -. DR HGNC; HGNC:5464; IGF1. DR HPA; ENSG00000017427; Tissue enhanced (cervix). DR MalaCards; IGF1; -. DR MIM; 147440; gene. DR MIM; 608747; phenotype. DR neXtProt; NX_P05019; -. DR OpenTargets; ENSG00000017427; -. DR Orphanet; 73272; Growth delay due to insulin-like growth factor type 1 deficiency. DR PharmGKB; PA29697; -. DR VEuPathDB; HostDB:ENSG00000017427; -. DR eggNOG; ENOG502RCAB; Eukaryota. DR GeneTree; ENSGT00940000159081; -. DR HOGENOM; CLU_123939_0_0_1; -. DR InParanoid; P05019; -. DR OMA; NECCFQS; -. DR OrthoDB; 5402912at2759; -. DR PhylomeDB; P05019; -. DR TreeFam; TF332820; -. DR PathwayCommons; P05019; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-2404192; Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R). DR Reactome; R-HSA-2428928; IRS-related events triggered by IGF1R. DR Reactome; R-HSA-2428933; SHC-related events triggered by IGF1R. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin. DR SABIO-RK; P05019; -. DR SignaLink; P05019; -. DR SIGNOR; P05019; -. DR BioGRID-ORCS; 3479; 11 hits in 1173 CRISPR screens. DR ChiTaRS; IGF1; human. DR EvolutionaryTrace; P05019; -. DR GeneWiki; Insulin-like_growth_factor_1; -. DR GenomeRNAi; 3479; -. DR Pharos; P05019; Tbio. DR PRO; PR:P05019; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P05019; Protein. DR Bgee; ENSG00000017427; Expressed in pericardium and 190 other cell types or tissues. DR ExpressionAtlas; P05019; baseline and differential. DR GO; GO:0035867; C:alphav-beta3 integrin-IGF-1-IGF1R complex; IDA:UniProtKB. DR GO; GO:0070382; C:exocytic vesicle; ISS:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:AgBase. DR GO; GO:0016942; C:insulin-like growth factor binding protein complex; IC:BHF-UCL. DR GO; GO:0042567; C:insulin-like growth factor ternary complex; IDA:BHF-UCL. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0005179; F:hormone activity; IDA:BHF-UCL. DR GO; GO:0005158; F:insulin receptor binding; IPI:BHF-UCL. DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IDA:UniProtKB. DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB. DR GO; GO:0032148; P:activation of protein kinase B activity; IMP:UniProtKB. DR GO; GO:0035630; P:bone mineralization involved in bone maturation; IDA:BHF-UCL. DR GO; GO:0001775; P:cell activation; IDA:MGI. DR GO; GO:0008283; P:cell population proliferation; IMP:AgBase. DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL. DR GO; GO:0001837; P:epithelial to mesenchymal transition; NAS:BHF-UCL. DR GO; GO:0009441; P:glycolate metabolic process; TAS:ProtInc. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0014896; P:muscle hypertrophy; IMP:BHF-UCL. DR GO; GO:0007517; P:muscle organ development; TAS:ProtInc. DR GO; GO:0045445; P:myoblast differentiation; IDA:BHF-UCL. DR GO; GO:0051450; P:myoblast proliferation; IDA:BHF-UCL. DR GO; GO:0014904; P:myotube cell development; IDA:BHF-UCL. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IGI:ARUK-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:AgBase. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IGI:ARUK-UCL. DR GO; GO:0150079; P:negative regulation of neuroinflammatory response; IGI:ARUK-UCL. DR GO; GO:0060283; P:negative regulation of oocyte development; IMP:AgBase. DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB. DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IDA:BHF-UCL. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IGI:ARUK-UCL. DR GO; GO:1905460; P:negative regulation of vascular associated smooth muscle cell apoptotic process; IMP:BHF-UCL. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:BHF-UCL. DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IDA:UniProtKB. DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IDA:UniProtKB. DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:AgBase. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IGI:ARUK-UCL. DR GO; GO:0046326; P:positive regulation of glucose import; IDA:UniProtKB. DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; IDA:UniProtKB. DR GO; GO:0045821; P:positive regulation of glycolytic process; IDA:BHF-UCL. DR GO; GO:0010560; P:positive regulation of glycoprotein biosynthetic process; IMP:AgBase. DR GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:UniProtKB. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:BHF-UCL. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:ARUK-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL. DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:AgBase. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IDA:BHF-UCL. DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IDA:BHF-UCL. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; IDA:AgBase. DR GO; GO:1904075; P:positive regulation of trophectodermal cell proliferation; IMP:AgBase. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL. DR GO; GO:0050821; P:protein stabilization; IMP:AgBase. DR GO; GO:0030166; P:proteoglycan biosynthetic process; IDA:BHF-UCL. DR GO; GO:0007265; P:Ras protein signal transduction; TAS:ProtInc. DR GO; GO:0010468; P:regulation of gene expression; IMP:AgBase. DR GO; GO:0001932; P:regulation of protein phosphorylation; IBA:GO_Central. DR GO; GO:0009408; P:response to heat; IDA:AgBase. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0014834; P:skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration; IDA:BHF-UCL. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR GO; GO:0042060; P:wound healing; IDA:BHF-UCL. DR CDD; cd04368; IlGF; 1. DR Gene3D; 1.10.100.10; Insulin-like; 1. DR InterPro; IPR022341; IGF-I. DR InterPro; IPR016179; Insulin-like. DR InterPro; IPR022350; Insulin-like_growth_factor. DR InterPro; IPR036438; Insulin-like_sf. DR InterPro; IPR022353; Insulin_CS. DR InterPro; IPR022352; Insulin_family. DR PANTHER; PTHR46845; INSULIN-LIKE GROWTH FACTOR I; 1. DR PANTHER; PTHR46845:SF1; INSULIN-LIKE GROWTH FACTOR I; 1. DR Pfam; PF00049; Insulin; 1. DR PRINTS; PR02002; INSLNLIKEGF. DR PRINTS; PR02005; INSLNLIKEGF1. DR PRINTS; PR00276; INSULINFAMLY. DR SMART; SM00078; IlGF; 1. DR SUPFAM; SSF56994; Insulin-like; 1. DR PROSITE; PS00262; INSULIN; 1. DR Genevisible; P05019; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Deafness; Direct protein sequencing; KW Disulfide bond; Growth factor; Reference proteome; Secreted; Signal. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT PROPEP 22..48 FT /id="PRO_0000015663" FT CHAIN 49..118 FT /note="Insulin-like growth factor I" FT /id="PRO_0000015664" FT PROPEP 119..195 FT /note="E peptide" FT /id="PRO_0000015665" FT REGION 49..77 FT /note="B" FT REGION 78..89 FT /note="C" FT REGION 90..110 FT /note="A" FT REGION 111..118 FT /note="D" FT REGION 119..195 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 130..146 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 153..195 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT DISULFID 54..96 FT /evidence="ECO:0000269|PubMed:3242681" FT DISULFID 66..109 FT /evidence="ECO:0000269|PubMed:3242681" FT DISULFID 95..100 FT /evidence="ECO:0000269|PubMed:3242681" FT VAR_SEQ 1..21 FT /note="MGKISSLPTQLFKCCFCDFLK -> MITPT (in isoform 3)" FT /evidence="ECO:0000303|PubMed:2082190" FT /id="VSP_043317" FT VAR_SEQ 135..195 FT /note="YQPPSTNKNTKSQRRKGWPKTHPGGEQKEGTEASLQIRGKKKEQRREIGSRN FT AECRGKKGK -> EVHLKNASRGSAGNKNYRM (in isoform 2 and isoform FT 3)" FT /evidence="ECO:0000303|PubMed:1372070, FT ECO:0000303|PubMed:2018498, ECO:0000303|PubMed:2082190, FT ECO:0000303|PubMed:2935423, ECO:0000303|PubMed:6358902" FT /id="VSP_039637" FT VAR_SEQ 152..195 FT /note="WPKTHPGGEQKEGTEASLQIRGKKKEQRREIGSRNAECRGKKGK -> STFE FT ERK (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_047399" FT VARIANT 98 FT /note="R -> W (found in a patient with primordial dwarfism; FT uncertain significance; dbSNP:rs587779350)" FT /evidence="ECO:0000269|PubMed:24389050" FT /id="VAR_075825" FT VARIANT 115 FT /note="A -> T (in dbSNP:rs17884626)" FT /id="VAR_056113" FT VARIANT 187 FT /note="A -> D (in dbSNP:rs6213)" FT /evidence="ECO:0000269|PubMed:10391209" FT /id="VAR_013945" FT MUTAGEN 84 FT /note="R->E: Dominant-negative mutant, no effect on FT IGFR1-binding, defective in integrin-binding and the FT formation of ternary complex with integrins and IGFR1, FT defective in inducing IGF1 signaling and cell FT proliferation, and suppresses activation of IGF1R by FT insulin and tumorigenesis in vivo; when associated with FT E-85." FT /evidence="ECO:0000269|PubMed:19578119, FT ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:23243309, FT ECO:0000269|PubMed:23696648" FT MUTAGEN 85 FT /note="R->E: Dominant-negative mutant, no effect on FT IGFR1-binding, defective in integrin-binding and the FT formation of ternary complex with integrins and IGFR1, FT defective in inducing IGF1 signaling and cell FT proliferation, and suppresses activation of IGF1R by FT insulin and tumorigenesis in vivo; when associated with FT E-84." FT /evidence="ECO:0000269|PubMed:19578119, FT ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:23243309, FT ECO:0000269|PubMed:23696648" FT STRAND 44..46 FT /evidence="ECO:0007829|PDB:3LRI" FT HELIX 52..66 FT /evidence="ECO:0007829|PDB:1TGR" FT HELIX 67..69 FT /evidence="ECO:0007829|PDB:1TGR" FT STRAND 71..73 FT /evidence="ECO:0007829|PDB:1TGR" FT STRAND 79..81 FT /evidence="ECO:0007829|PDB:1H02" FT STRAND 82..85 FT /evidence="ECO:0007829|PDB:3LRI" FT HELIX 90..95 FT /evidence="ECO:0007829|PDB:1TGR" FT STRAND 96..98 FT /evidence="ECO:0007829|PDB:1TGR" FT HELIX 102..108 FT /evidence="ECO:0007829|PDB:1TGR" FT STRAND 109..111 FT /evidence="ECO:0007829|PDB:1BQT" FT STRAND 112..116 FT /evidence="ECO:0007829|PDB:1B9G" SQ SEQUENCE 195 AA; 21841 MW; E88A8CFBD1CD1873 CRC64; MGKISSLPTQ LFKCCFCDFL KVKMHTMSSS HLFYLALCLL TFTSSATAGP ETLCGAELVD ALQFVCGDRG FYFNKPTGYG SSSRRAPQTG IVDECCFRSC DLRRLEMYCA PLKPAKSARS VRAQRHTDMP KTQKYQPPST NKNTKSQRRK GWPKTHPGGE QKEGTEASLQ IRGKKKEQRR EIGSRNAECR GKKGK //