ID   INS_HUMAN               Reviewed;         110 AA.
AC   P01308; Q5EEX2;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   25-NOV-2008, entry version 124.
DE   RecName: Full=Insulin;
DE   Contains:
DE     RecName: Full=Insulin B chain;
DE   Contains:
DE     RecName: Full=Insulin A chain;
DE   Flags: Precursor;
GN   Name=INS;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=80120725; PubMed=6243748; DOI=10.1038/284026a0;
RA   Bell G.I., Pictet R.L., Rutter W.J., Cordell B., Tischer E.,
RA   Goodman H.M.;
RT   "Sequence of the human insulin gene.";
RL   Nature 284:26-32(1980).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=80236313; PubMed=6248962;
RA   Ullrich A., Dull T.J., Gray A., Brosius J., Sures I.;
RT   "Genetic variation in the human insulin gene.";
RL   Science 209:612-615(1980).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=80054779; PubMed=503234; DOI=10.1038/282525a0;
RA   Bell G.I., Swain W.F., Pictet R.L., Cordell B., Goodman H.M.,
RA   Rutter W.J.;
RT   "Nucleotide sequence of a cDNA clone encoding human preproinsulin.";
RL   Nature 282:525-527(1979).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=80147417; PubMed=6927840;
RA   Sures I., Goeddel D.V., Gray A., Ullrich A.;
RT   "Nucleotide sequence of human preproinsulin complementary DNA.";
RL   Science 208:57-59(1980).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=93364428; PubMed=8358440; DOI=10.1038/ng0793-305;
RA   Lucassen A.M., Julier C., Beressi J.-P., Boitard C., Froguel P.,
RA   Lathrop M., Bell J.I.;
RT   "Susceptibility to insulin dependent diabetes mellitus maps to a 4.1
RT   kb segment of DNA spanning the insulin gene and associated VNTR.";
RL   Nat. Genet. 4:305-310(1993).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=15070567; DOI=10.1016/S0140-6736(04)15438-X;
RA   Minn A.H., Kayton M., Lorang D., Hoffmann S.C., Harlan D.M.,
RA   Libutti S.K., Shalev A.;
RT   "Insulinomas and expression of an insulin splice variant.";
RL   Lancet 363:363-367(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=22833521; PubMed=12952878; DOI=10.1101/gr.948003;
RA   Stead J.D.H., Hurles M.E., Jeffreys A.J.;
RT   "Global haplotype diversity in the human insulin gene region.";
RL   Genome Res. 13:2101-2111(2003).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT   vector.";
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-59.
RC   TISSUE=Blood;
RA   Fajardy I.I., Weill J.J., Stuckens C.C., Danze P.M.P.;
RT   "Description of a novel RFLP diallelic polymorphism (-127 BsgI C/G)
RT   within the 5' region of insulin gene.";
RL   Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN   [12]
RP   PROTEIN SEQUENCE OF 25-54 AND 90-110.
RX   PubMed=14426955;
RA   Nicol D.S.H.W., Smith L.F.;
RT   "Amino-acid sequence of human insulin.";
RL   Nature 187:483-485(1960).
RN   [13]
RP   PROTEIN SEQUENCE OF 57-87.
RX   MEDLINE=71116410; PubMed=5101771;
RA   Oyer P.E., Cho S., Peterson J.D., Steiner D.F.;
RT   "Studies on human proinsulin. Isolation and amino acid sequence of the
RT   human pancreatic C-peptide.";
RL   J. Biol. Chem. 246:1375-1386(1971).
RN   [14]
RP   PROTEIN SEQUENCE OF 57-87.
RX   MEDLINE=71257722; PubMed=5560404;
RA   Ko A., Smyth D.G., Markussen J., Sundby F.;
RT   "The amino acid sequence of the C-peptide of human proinsulin.";
RL   Eur. J. Biochem. 20:190-199(1971).
RN   [15]
RP   SYNTHESIS.
RX   MEDLINE=75077277; PubMed=4443293; DOI=10.1002/hlca.19740570839;
RA   Sieber P., Kamber B., Hartmann A., Joehl A., Riniker B., Rittel W.;
RT   "Total synthesis of human insulin under directed formation of the
RT   disulfide bonds.";
RL   Helv. Chim. Acta 57:2617-2621(1974).
RN   [16]
RP   SYNTHESIS OF 57-87.
RX   MEDLINE=75040007; PubMed=4803504;
RA   Naithani V.K.;
RT   "Studies on polypeptides, IV. The synthesis of C-peptide of human
RT   proinsulin.";
RL   Hoppe-Seyler's Z. Physiol. Chem. 354:659-672(1973).
RN   [17]
RP   SYNTHESIS OF 65-69 AND 70-73.
RX   MEDLINE=73161263; PubMed=4698555;
RA   Geiger R., Volk A.;
RT   "Synthesis of peptides with the properties of human proinsulin C
RT   peptides (hC peptide). 3. Synthesis of the sequences 14-17 and 9-13 of
RT   human proinsulin C peptides.";
RL   Chem. Ber. 106:199-205(1973).
RN   [18]
RP   SYNTHESIS OF 84-87.
RX   MEDLINE=73161261; PubMed=4698553;
RA   Geiger R., Jaeger G., Keonig W., Treuth G.;
RT   "Synthesis of peptides with the properties of human proinsulin C
RT   peptides (hC peptide). I. Scheme for the synthesis and preparation of
RT   the sequence 28-31 of human proinsulin C peptide.";
RL   Chem. Ber. 106:188-192(1973).
RN   [19]
RP   VARIANT LOS ANGELES SER-48.
RX   MEDLINE=84016053; PubMed=6312455;
RA   Haneda M., Chan S.J., Kwok S.C.M., Rubenstein A.H., Steiner D.F.;
RT   "Studies on mutant human insulin genes: identification and sequence
RT   analysis of a gene encoding [SerB24]insulin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:6366-6370(1983).
RN   [20]
RP   VARIANTS LOS ANGELES SER-48 AND CHICAGO LEU-49.
RX   MEDLINE=84170233; PubMed=6424111;
RA   Shoelson S., Fickova M., Haneda M., Nahum A., Musso G., Kaiser E.T.,
RA   Rubenstein A.H., Tager H.;
RT   "Identification of a mutant human insulin predicted to contain a
RT   serine-for-phenylalanine substitution.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:7390-7394(1983).
RN   [21]
RP   VARIANT PROVIDENCE ASP-34.
RX   MEDLINE=87175640; PubMed=3470784;
RA   Chan S.J., Seino S., Gruppuso P.A., Schwartz R., Steiner D.F.;
RT   "A mutation in the B chain coding region is associated with impaired
RT   proinsulin conversion in a family with hyperproinsulinemia.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:2194-2197(1987).
RN   [22]
RP   VARIANT WAKAYAMA LEU-92.
RX   MEDLINE=87058122; PubMed=3537011;
RA   Sakura H., Iwamoto Y., Sakamoto Y., Kuzuya T., Hirata H.;
RT   "Structurally abnormal insulin in a diabetic patient. Characterization
RT   of the mutant insulin A3 (Val-->Leu) isolated from the pancreas.";
RL   J. Clin. Invest. 78:1666-1672(1986).
RN   [23]
RP   VARIANT HIS-89.
RX   MEDLINE=90317021; PubMed=2196279;
RA   Barbetti F., Raben N., Kadowaki T., Cama A., Accili D., Gabbay K.H.,
RA   Merenich J.A., Taylor S.I., Roth J.;
RT   "Two unrelated patients with familial hyperproinsulinemia due to a
RT   mutation substituting histidine for arginine at position 65 in the
RT   proinsulin molecule: identification of the mutation by direct
RT   sequencing of genomic deoxyribonucleic acid amplified by polymerase
RT   chain reaction.";
RL   J. Clin. Endocrinol. Metab. 71:164-169(1990).
RN   [24]
RP   VARIANT HIS-89.
RX   MEDLINE=85261996; PubMed=4019786;
RA   Shibasaki Y., Kawakami T., Kanazawa Y., Akanuma Y., Takaku F.;
RT   "Posttranslational cleavage of proinsulin is blocked by a point
RT   mutation in familial hyperproinsulinemia.";
RL   J. Clin. Invest. 76:378-380(1985).
RN   [25]
RP   VARIANT KYOTO LEU-89.
RX   MEDLINE=92291307; PubMed=1601997;
RA   Yano H., Kitano N., Morimoto M., Polonsky K.S., Imura H., Seino Y.;
RT   "A novel point mutation in the human insulin gene giving rise to
RT   hyperproinsulinemia (proinsulin Kyoto).";
RL   J. Clin. Invest. 89:1902-1907(1992).
RN   [26]
RP   STRUCTURE BY NMR.
RX   MEDLINE=91104966; PubMed=2271664; DOI=10.1021/bi00498a018;
RA   Hua Q.-X., Weiss M.A.;
RT   "Toward the solution structure of human insulin: sequential 2D 1H NMR
RT   assignment of a des-pentapeptide analogue and comparison with crystal
RT   structure.";
RL   Biochemistry 29:10545-10555(1990).
RN   [27]
RP   STRUCTURE BY NMR.
RX   MEDLINE=91242467; PubMed=2036420; DOI=10.1021/bi00236a025;
RA   Hua Q.-X., Weiss M.A.;
RT   "Comparative 2D NMR studies of human insulin and des-pentapeptide
RT   insulin: sequential resonance assignment and implications for protein
RT   dynamics and receptor recognition.";
RL   Biochemistry 30:5505-5515(1991).
RN   [28]
RP   STRUCTURE BY NMR.
RX   MEDLINE=91265527; PubMed=1646635; DOI=10.1016/0167-4838(91)90098-K;
RA   Hua Q.-X., Weiss M.A.;
RT   "Two-dimensional NMR studies of Des-(B26-B30)-insulin: sequence-
RT   specific resonance assignments and effects of solvent composition.";
RL   Biochim. Biophys. Acta 1078:101-110(1991).
RN   [29]
RP   STRUCTURE BY NMR.
RX   MEDLINE=93059366; PubMed=1433291; DOI=10.1016/0022-2836(92)90527-Q;
RA   Joergensen A.M.M., Kristensen S.M., Led J.J., Balschmidt P.;
RT   "Three-dimensional solution structure of an insulin dimer. A study of
RT   the B9(Asp) mutant of human insulin using nuclear magnetic resonance,
RT   distance geometry and restrained molecular dynamics.";
RL   J. Mol. Biol. 227:1146-1163(1992).
RN   [30]
RP   STRUCTURE BY NMR OF VARIANT LOS-ANGELES SER-48.
RX   MEDLINE=93133832; PubMed=8421693;
RA   Hua Q.-X., Shoelson S.E., Inouye K., Weiss M.A.;
RT   "Paradoxical structure and function in a mutant human insulin
RT   associated with diabetes mellitus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:582-586(1993).
RN   [31]
RP   STRUCTURE BY NMR.
RX   MEDLINE=97383146; PubMed=9235985; DOI=10.1021/bi9631069;
RA   Chang X., Joergensen A.M., Bardrum P., Led J.J.;
RT   "Solution structures of the R6 human insulin hexamer.";
RL   Biochemistry 36:9409-9422(1997).
CC   -!- FUNCTION: Insulin decreases blood glucose concentration. It
CC       increases cell permeability to monosaccharides, amino acids and
CC       fatty acids. It accelerates glycolysis, the pentose phosphate
CC       cycle, and glycogen synthesis in liver.
CC   -!- SUBUNIT: Heterodimer of a B chain and an A chain linked by two
CC       disulfide bonds.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- DISEASE: Defects in INS are the cause of familial
CC       hyperproinsulinemia [MIM:176730].
CC   -!- PHARMACEUTICAL: Available under the names Humulin or Humalog (Eli
CC       Lilly) and Novolin (Novo Nordisk). Used in the treatment of
CC       diabetes. Humalog is an insulin analog with 52-Lys-Pro-53 instead
CC       of 52-Pro-Lys-53.
CC   -!- SIMILARITY: Belongs to the insulin family.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA59179.1; Type=Erroneous gene model prediction;
CC   -!- WEB RESOURCE: Name=Insulin at Eli Lilly; Note=Clinical information
CC       on Eli Lilly insulin products;
CC       URL="http://www.lillyDiabetes.com/Products/PatientInfo.cfm";
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Protein of the 20th
CC       century - Issue 9 of April 2001;
CC       URL="http://www.expasy.org/spotlight/back_issues/sptlt009.shtml";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Insulin entry;
CC       URL="http://en.wikipedia.org/wiki/Insulin";
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DR   EMBL; V00565; CAA23828.1; -; Genomic_DNA.
DR   EMBL; M10039; AAA59173.1; -; Genomic_DNA.
DR   EMBL; J00265; AAA59172.1; -; Genomic_DNA.
DR   EMBL; X70508; CAA49913.1; -; mRNA.
DR   EMBL; L15440; AAA59179.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AY899304; AAW83741.1; -; mRNA.
DR   EMBL; AY138590; AAN39451.1; -; Genomic_DNA.
DR   EMBL; BT006808; AAP35454.1; -; mRNA.
DR   EMBL; CH471158; EAX02488.1; -; Genomic_DNA.
DR   EMBL; BC005255; AAH05255.1; -; mRNA.
DR   EMBL; AJ009655; CAA08766.1; -; Genomic_DNA.
DR   PIR; A93222; IPHU.
DR   RefSeq; NP_000198.1; -.
DR   UniGene; Hs.654579; -.
DR   PDB; 1A7F; NMR; -; A=90-110, B=25-53.
DR   PDB; 1AI0; NMR; -; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 1AIY; NMR; -; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 1B9E; X-ray; 2.50 A; A/C=90-110, B/D=25-54.
DR   PDB; 1BEN; X-ray; 1.40 A; A/C=90-110, B/D=25-54.
DR   PDB; 1EFE; NMR; -; A=25-60.
DR   PDB; 1EV3; X-ray; 1.78 A; A/C=90-110, B/D=25-54.
DR   PDB; 1EV6; X-ray; 1.90 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 1EVR; X-ray; 1.90 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 1FU2; X-ray; 3.24 A; A/C/E/G=90-110, B/D/F/H=25-54.
DR   PDB; 1FUB; X-ray; 3.09 A; A/C=90-110, B/D=25-54.
DR   PDB; 1G7A; X-ray; 1.20 A; A/C/E/G=90-110, B/D/F/H=25-54.
DR   PDB; 1G7B; X-ray; 1.30 A; A/C/E/G=90-110, B/D/F/H=25-54.
DR   PDB; 1GUJ; X-ray; 1.62 A; A/C=90-110, B/D=25-54.
DR   PDB; 1HIQ; NMR; -; A=90-110, B=25-54.
DR   PDB; 1HIS; NMR; -; A=90-110, B=25-49.
DR   PDB; 1HIT; NMR; -; A=90-110, B=25-54.
DR   PDB; 1HLS; NMR; -; A=90-110, B=25-54.
DR   PDB; 1HTV; X-ray; 1.90 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-51.
DR   PDB; 1HUI; NMR; -; A=90-110, B=26-53.
DR   PDB; 1IOG; NMR; -; A=90-110, B=26-53.
DR   PDB; 1IOH; NMR; -; A=90-110, B=26-53.
DR   PDB; 1J73; X-ray; 2.00 A; A/C=90-110, B/D=25-54.
DR   PDB; 1JCA; X-ray; 2.50 A; A/C=90-110, B/D=25-54.
DR   PDB; 1JCO; NMR; -; A=90-110, B=25-54.
DR   PDB; 1K3M; NMR; -; A=90-110, B=25-54.
DR   PDB; 1KMF; NMR; -; A=90-110, B=25-54.
DR   PDB; 1LKQ; NMR; -; A=90-110, B=25-54.
DR   PDB; 1LPH; X-ray; 2.30 A; A/C=90-110, B/D=25-54.
DR   PDB; 1MHI; NMR; -; A=90-110, B=25-54.
DR   PDB; 1MHJ; NMR; -; A=90-110, B=25-48.
DR   PDB; 1MSO; X-ray; 1.00 A; A/C=90-110, B/D=25-54.
DR   PDB; 1OS3; X-ray; 1.95 A; A/C=90-110, B/D=25-54.
DR   PDB; 1OS4; X-ray; 2.25 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 1QIY; X-ray; 2.30 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 1QIZ; X-ray; 2.00 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 1QJ0; X-ray; 2.40 A; A/C=90-110, B/D=25-54.
DR   PDB; 1RWE; X-ray; 1.80 A; A/C=90-110, B/D=25-54.
DR   PDB; 1SF1; NMR; -; A=90-110, B=25-54.
DR   PDB; 1SJT; NMR; -; A=90-110, B=25-53.
DR   PDB; 1SJU; NMR; -; A=25-53.
DR   PDB; 1T0C; NMR; -; A=57-87.
DR   PDB; 1T1K; NMR; -; A=90-110, B=25-54.
DR   PDB; 1T1P; NMR; -; A=90-110, B=25-54.
DR   PDB; 1T1Q; NMR; -; A=90-110, B=25-54.
DR   PDB; 1TRZ; X-ray; 1.60 A; A/C=90-110, B/D=25-54.
DR   PDB; 1TYL; X-ray; 1.90 A; A/C=90-110, B/D=25-54.
DR   PDB; 1TYM; X-ray; 1.90 A; A/C=90-110, B/D=25-54.
DR   PDB; 1UZ9; X-ray; 1.60 A; A=90-110, B=25-53.
DR   PDB; 1VKT; NMR; -; A=90-110, B=25-54.
DR   PDB; 1W8P; X-ray; 2.08 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 1XDA; X-ray; 1.80 A; A/C/E/G=90-110, B/D/F/H=25-53.
DR   PDB; 1XGL; NMR; -; A=90-110, B=25-54.
DR   PDB; 1XW7; X-ray; 2.30 A; A/C=90-110, B/D=25-54.
DR   PDB; 1ZEG; X-ray; 1.60 A; A/C=90-110, B/D=25-54.
DR   PDB; 1ZEH; X-ray; 1.50 A; A/C=90-110, B/D=25-54.
DR   PDB; 1ZNJ; X-ray; 2.00 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 2AIY; NMR; -; B/D/F/H/J/L=25-54.
DR   PDB; 2C8Q; X-ray; 1.95 A; A=90-110, B=25-53.
DR   PDB; 2C8R; X-ray; 1.50 A; A=90-110, B=25-53.
DR   PDB; 2CEU; X-ray; 1.80 A; A/C=90-110, B/D=25-49.
DR   PDB; 2H67; NMR; -; A=90-110, B=25-54.
DR   PDB; 2HH4; NMR; -; A=90-110.
DR   PDB; 2HHO; NMR; -; A=90-110, B=25-54.
DR   PDB; 2HIU; NMR; -; A=90-110, B=25-54.
DR   PDB; 2JMN; NMR; -; A=90-110, B=25-54.
DR   PDB; 2JV1; NMR; -; A=90-110, B=25-54.
DR   PDB; 2JZQ; NMR; -; A=25-54, A=90-110.
DR   PDB; 2OLY; X-ray; 1.70 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 2OLZ; X-ray; 1.70 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 2OM0; X-ray; 2.05 A; 1/3/A/C/E/G/I/K/Q/S/U/X/a/c/e/g/i/k=90-110, 2/4/B/D/F/H/J/L/R/T/V/Y/b/d/f/h/j/l=25-54.
DR   PDB; 2OM1; X-ray; 1.97 A; 1/3/A/C/E/G/I/K/Q/S/U/X/a/c/e/g/i/k=90-110, 2/4/B/D/F/H/J/L/R/T/V/Y/b/d/f/h/j/l=25-54.
DR   PDB; 2OMG; X-ray; 1.52 A; A/C/E=90-110, B/D/F=25-54.
DR   PDB; 2OMH; X-ray; 1.36 A; A/C/E=90-110, B/D/F=25-54.
DR   PDB; 2OMI; X-ray; 2.24 A; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 2QIU; X-ray; 2.00 A; A/C=89-110, B/D=25-54.
DR   PDB; 2R34; X-ray; 2.25 A; A/C=89-110, B/D=25-54.
DR   PDB; 2R35; X-ray; 2.08 A; A/C=89-110, B/D=25-54.
DR   PDB; 2R36; X-ray; 2.00 A; A/C=89-110, B/D=25-54.
DR   PDB; 2VJZ; X-ray; 1.80 A; A/C=90-110, B/D=25-54.
DR   PDB; 2VK0; X-ray; 2.20 A; A/C=90-110, B/D=25-54.
DR   PDB; 3AIY; NMR; -; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 4AIY; NMR; -; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDB; 5AIY; NMR; -; A/C/E/G/I/K=90-110, B/D/F/H/J/L=25-54.
DR   PDBsum; 1A7F; -.
DR   PDBsum; 1AI0; -.
DR   PDBsum; 1AIY; -.
DR   PDBsum; 1B9E; -.
DR   PDBsum; 1BEN; -.
DR   PDBsum; 1EFE; -.
DR   PDBsum; 1EV3; -.
DR   PDBsum; 1EV6; -.
DR   PDBsum; 1EVR; -.
DR   PDBsum; 1FU2; -.
DR   PDBsum; 1FUB; -.
DR   PDBsum; 1G7A; -.
DR   PDBsum; 1G7B; -.
DR   PDBsum; 1GUJ; -.
DR   PDBsum; 1HIQ; -.
DR   PDBsum; 1HIS; -.
DR   PDBsum; 1HIT; -.
DR   PDBsum; 1HLS; -.
DR   PDBsum; 1HTV; -.
DR   PDBsum; 1HUI; -.
DR   PDBsum; 1IOG; -.
DR   PDBsum; 1IOH; -.
DR   PDBsum; 1J73; -.
DR   PDBsum; 1JCA; -.
DR   PDBsum; 1JCO; -.
DR   PDBsum; 1K3M; -.
DR   PDBsum; 1KMF; -.
DR   PDBsum; 1LKQ; -.
DR   PDBsum; 1LPH; -.
DR   PDBsum; 1MHI; -.
DR   PDBsum; 1MHJ; -.
DR   PDBsum; 1MSO; -.
DR   PDBsum; 1OS3; -.
DR   PDBsum; 1OS4; -.
DR   PDBsum; 1QIY; -.
DR   PDBsum; 1QIZ; -.
DR   PDBsum; 1QJ0; -.
DR   PDBsum; 1RWE; -.
DR   PDBsum; 1SF1; -.
DR   PDBsum; 1SJT; -.
DR   PDBsum; 1SJU; -.
DR   PDBsum; 1T0C; -.
DR   PDBsum; 1T1K; -.
DR   PDBsum; 1T1P; -.
DR   PDBsum; 1T1Q; -.
DR   PDBsum; 1TRZ; -.
DR   PDBsum; 1TYL; -.
DR   PDBsum; 1TYM; -.
DR   PDBsum; 1UZ9; -.
DR   PDBsum; 1VKT; -.
DR   PDBsum; 1W8P; -.
DR   PDBsum; 1XDA; -.
DR   PDBsum; 1XGL; -.
DR   PDBsum; 1XW7; -.
DR   PDBsum; 1ZEG; -.
DR   PDBsum; 1ZEH; -.
DR   PDBsum; 1ZNJ; -.
DR   PDBsum; 2AIY; -.
DR   PDBsum; 2C8Q; -.
DR   PDBsum; 2C8R; -.
DR   PDBsum; 2CEU; -.
DR   PDBsum; 2H67; -.
DR   PDBsum; 2HH4; -.
DR   PDBsum; 2HHO; -.
DR   PDBsum; 2HIU; -.
DR   PDBsum; 2JMN; -.
DR   PDBsum; 2JV1; -.
DR   PDBsum; 2JZQ; -.
DR   PDBsum; 2OLY; -.
DR   PDBsum; 2OLZ; -.
DR   PDBsum; 2OM0; -.
DR   PDBsum; 2OM1; -.
DR   PDBsum; 2OMG; -.
DR   PDBsum; 2OMH; -.
DR   PDBsum; 2OMI; -.
DR   PDBsum; 2QIU; -.
DR   PDBsum; 2R34; -.
DR   PDBsum; 2R35; -.
DR   PDBsum; 2R36; -.
DR   PDBsum; 2VJZ; -.
DR   PDBsum; 2VK0; -.
DR   PDBsum; 3AIY; -.
DR   PDBsum; 4AIY; -.
DR   PDBsum; 5AIY; -.
DR   SMR; P01308; 25-84.
DR   DIP; DIP:6024N; -.
DR   PeptideAtlas; P01308; -.
DR   Ensembl; ENSG00000129965; Homo sapiens.
DR   GeneID; 3630; -.
DR   KEGG; hsa:3630; -.
DR   HGNC; HGNC:6081; INS.
DR   HPA; CAB000048; -.
DR   HPA; CAB012098; -.
DR   HPA; HPA004932; -.
DR   MIM; 176730; gene+phenotype.
DR   PharmGKB; PA201; -.
DR   HOGENOM; P01308; -.
DR   HOVERGEN; P01308; -.
DR   Reactome; REACT_1355; Insulin degradation.
DR   Reactome; REACT_498; Signaling by insulin receptor.
DR   Reactome; REACT_508; Signal attenuation.
DR   LinkHub; P01308; -.
DR   NextBio; 14203; -.
DR   ArrayExpress; P01308; -.
DR   GermOnline; ENSG00000129965; Homo sapiens.
DR   GO; GO:0005813; C:centrosome; IDA:HPA.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0005179; F:hormone activity; NAS:UniProtKB.
DR   GO; GO:0005158; F:insulin receptor binding; IDA:UniProtKB.
DR   GO; GO:0005520; F:insulin-like growth factor binding; IPI:UniProtKB.
DR   GO; GO:0005159; F:insulin-like growth factor receptor binding; IPI:UniProtKB.
DR   GO; GO:0006953; P:acute-phase response; IDA:UniProtKB.
DR   GO; GO:0046631; P:alpha-beta T cell activation; IDA:UniProtKB.
DR   GO; GO:0008219; P:cell death; NAS:UniProtKB.
DR   GO; GO:0007267; P:cell-cell signaling; IC:UniProtKB.
DR   GO; GO:0055089; P:fatty acid homeostasis; IMP:UniProtKB.
DR   GO; GO:0007186; P:G-protein coupled receptor protein signalin...; IDA:UniProtKB.
DR   GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR   GO; GO:0045922; P:negative regulation of fatty acid metabolic...; IMP:UniProtKB.
DR   GO; GO:0045818; P:negative regulation of glycogen catabolic p...; IMP:UniProtKB.
DR   GO; GO:0033861; P:negative regulation of NAD(P)H oxidase acti...; IDA:UniProtKB.
DR   GO; GO:0042177; P:negative regulation of protein catabolic pr...; IDA:UniProtKB.
DR   GO; GO:0050709; P:negative regulation of protein secretion; IDA:UniProtKB.
DR   GO; GO:0045861; P:negative regulation of proteolysis; IMP:UniProtKB.
DR   GO; GO:0060266; P:negative regulation of respiratory burst du...; IDA:UniProtKB.
DR   GO; GO:0045908; P:negative regulation of vasodilation; NAS:UniProtKB.
DR   GO; GO:0014065; P:phosphoinositide 3-kinase cascade; IDA:UniProtKB.
DR   GO; GO:0032270; P:positive regulation of cellular protein met...; IMP:UniProtKB.
DR   GO; GO:0050715; P:positive regulation of cytokine secretion; IDA:UniProtKB.
DR   GO; GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB.
DR   GO; GO:0046326; P:positive regulation of glucose import; IDA:UniProtKB.
DR   GO; GO:0045821; P:positive regulation of glycolysis; IDA:UniProtKB.
DR   GO; GO:0046628; P:positive regulation of insulin receptor sig...; IDA:UniProtKB.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynt...; NAS:UniProtKB.
DR   GO; GO:0051000; P:positive regulation of nitric-oxide synthas...; NAS:UniProtKB.
DR   GO; GO:0060267; P:positive regulation of respiratory burst; NAS:UniProtKB.
DR   GO; GO:0045909; P:positive regulation of vasodilation; NAS:UniProtKB.
DR   GO; GO:0006521; P:regulation of amino acid metabolic process; IMP:UniProtKB.
DR   GO; GO:0032583; P:regulation of gene-specific transcription; NAS:UniProtKB.
DR   GO; GO:0022898; P:regulation of transmembrane transporter act...; IDA:UniProtKB.
DR   GO; GO:0042060; P:wound healing; IDA:UniProtKB.
DR   InterPro; IPR004825; Ins/IGF/relaxin.
DR   Gene3D; G3DSA:1.10.100.10; Ins/IGF/relaxin; 1.
DR   Pfam; PF00049; Insulin; 1.
DR   PRINTS; PR00276; INSULINA.
DR   PRINTS; PR00277; INSULINB.
DR   ProDom; PD015667; Mollusc_ins; 1.
DR   SMART; SM00078; IlGF; 1.
DR   PROSITE; PS00262; INSULIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Carbohydrate metabolism;
KW   Cleavage on pair of basic residues; Diabetes mellitus;
KW   Direct protein sequencing; Disease mutation; Glucose metabolism;
KW   Hormone; Pharmaceutical; Secreted; Signal.
FT   SIGNAL        1     24
FT   PEPTIDE      25     54       Insulin B chain.
FT                                /FTId=PRO_0000015819.
FT   PROPEP       57     87       C peptide.
FT                                /FTId=PRO_0000015820.
FT   PEPTIDE      90    110       Insulin A chain.
FT                                /FTId=PRO_0000015821.
FT   DISULFID     31     96       Interchain (between B and A chains).
FT   DISULFID     43    109       Interchain (between B and A chains).
FT   DISULFID     95    100
FT   VARIANT      34     34       H -> D (in familial hyperproinsulinemia;
FT                                Providence).
FT                                /FTId=VAR_003971.
FT   VARIANT      48     48       F -> S (associated with diabetes mellitus
FT                                type-II; Los-Angeles).
FT                                /FTId=VAR_003972.
FT   VARIANT      49     49       F -> L (in Chicago).
FT                                /FTId=VAR_003973.
FT   VARIANT      89     89       R -> H (in familial hyperproinsulinemia;
FT                                impairs posttranslational cleavage).
FT                                /FTId=VAR_003974.
FT   VARIANT      89     89       R -> L (in familial hyperproinsulinemia;
FT                                Kyoto).
FT                                /FTId=VAR_003975.
FT   VARIANT      92     92       V -> L (in Wakayama).
FT                                /FTId=VAR_003976.
FT   HELIX        33     43
FT   HELIX        44     46
FT   STRAND       48     50
FT   TURN         59     66
FT   STRAND       74     76
FT   HELIX        79     81
FT   TURN         84     86
FT   HELIX        91     95
FT   HELIX       102    105
FT   HELIX       106    108
SQ   SEQUENCE   110 AA;  11981 MW;  C2C3B23B85E520E5 CRC64;
     MALWMRLLPL LALLALWGPD PAAAFVNQHL CGSHLVEALY LVCGERGFFY TPKTRREAED
     LQVGQVELGG GPGAGSLQPL ALEGSLQKRG IVEQCCTSIC SLYQLENYCN
//