IGF1_HUMAN
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 03-AUG-2022, entry version 243.
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] (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 initiatiating 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 {ECO:0000250|UniProtKB:P05017, 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; AAI48267.1; -; 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 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 AlphaFoldDB; P05019; -.
DR BMRB; P05019; -.
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.ENSP00000302665; -.
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; P05019; -.
DR PeptideAtlas; P05019; -.
DR PRIDE; P05019; -.
DR ProteomicsDB; 19553; -.
DR ProteomicsDB; 51765; -. [P05019-1]
DR ProteomicsDB; 51766; -. [P05019-2]
DR ProteomicsDB; 51767; -. [P05019-3]
DR ABCD; P05019; 7 sequenced antibodies.
DR Antibodypedia; 18040; 1447 antibodies from 41 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 CTD; 3479; -.
DR DisGeNET; 3479; -.
DR GeneCards; IGF1; -.
DR HGNC; HGNC:5464; IGF1.
DR HPA; ENSG00000017427; Tissue enhanced (adipose tissue, 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; FFYLALC; -.
DR OrthoDB; 1644517at2759; -.
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; 10 hits in 1086 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 188 other tissues.
DR ExpressionAtlas; P05019; baseline and differential.
DR Genevisible; P05019; HS.
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:0070371; P:ERK1 and ERK2 cascade; IMP:AgBase.
DR GO; GO:0009441; P:glycolate metabolic process; TAS:ProtInc.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:UniProtKB.
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:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:AgBase.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IDA: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: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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; 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:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
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:0043491; P:protein kinase B signaling; IMP:AgBase.
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:0040014; P:regulation of multicellular organism growth; IEP:BHF-UCL.
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 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 Pfam; PF00049; Insulin; 1.
DR PRINTS; PR02002; INSLNLIKEGF.
DR PRINTS; PR02005; INSLNLIKEGF1.
DR PRINTS; PR00276; INSULINFAMLY.
DR SMART; SM00078; IlGF; 1.
DR SUPFAM; SSF56994; SSF56994; 1.
DR PROSITE; PS00262; INSULIN; 1.
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 unknown pathological 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 IGFR1-
FT binding, defective in integrin-binding and the formation of
FT ternary complex with integrins and IGFR1, defective in
FT inducing IGF1 signaling and cell proliferation, and
FT suppresses activation of IGF1R by insulin and tumorigenesis
FT in vivo; when associated with 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 IGFR1-
FT binding, defective in integrin-binding and the formation of
FT ternary complex with integrins and IGFR1, defective in
FT inducing IGF1 signaling and cell proliferation, and
FT suppresses activation of IGF1R by insulin and tumorigenesis
FT in vivo; when associated with 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
