Back to PBIL home pageID INS_HUMAN STANDARD; PRT; 110 AA.
AC P01308;
DT 21-JUL-1986 (Rel. 01, Created)
DT 21-JUL-1986 (Rel. 01, Last sequence update)
DT 20-AUG-2001 (Rel. 40, Last annotation update)
DE INSULIN PRECURSOR.
GN INS.
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP SEQUENCE FROM N.A.
RX MEDLINE=80120725; PubMed=6243748;
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 SEQUENCE FROM N.A.
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 SEQUENCE FROM N.A.
RX MEDLINE=80054779; PubMed=503234;
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 SEQUENCE FROM N.A.
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 SEQUENCE FROM N.A.
RX MEDLINE=93364428; PubMed=8358440;
RA Lucassen A.M., Bell J.I., Julier C., Lathrop M.;
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 SEQUENCE FROM N.A.
RC TISSUE=PANCREAS;
RA Strausberg R.;
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP SEQUENCE OF 1-59 FROM N.A.
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 [8]
RP SEQUENCE OF 25-54 AND 90-110.
RA Nicol D.S.H.W., Smith L.F.;
RT "Amino-acid sequence of human insulin.";
RL Nature 187:483-485(1960).
RN [9]
RP 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 [10]
RP 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 [11]
RP SYNTHESIS.
RX MEDLINE=75077277; PubMed=4443293;
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 [12]
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 [13]
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 [14]
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 [15]
RP VARIANT LOS ANGELES.
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 [16]
RP VARIANTS LOS ANGELES AND CHICAGO.
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 [17]
RP VARIANT PROVIDENCE.
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 [18]
RP VARIANT WAKAKYAMA.
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 [19]
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 [20]
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 [21]
RP VARIANT KYOTO.
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 [22]
RP STRUCTURE BY NMR.
RX MEDLINE=91104966; PubMed=2271664;
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 [23]
RP STRUCTURE BY NMR.
RX MEDLINE=91242467; PubMed=2036420;
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 [24]
RP STRUCTURE BY NMR.
RX MEDLINE=91265527; PubMed=1646635;
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 [25]
RP STRUCTURE BY NMR.
RX MEDLINE=93059366; PubMed=1433291;
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 [26]
RP STRUCTURE BY NMR OF VARIANT LOS-ANGELES.
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 [27]
RP STRUCTURE BY NMR.
RX MEDLINE=97383146; PubMed=9235985;
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 OF INSULIN ARE THE CAUSE OF HYPERPROINSULINEMIA
CC AND OF TYPE-II DIABETES MELLITUS.
CC -!- PHARMACEUTICAL: AVAILABLE UNDER THE NAMES HUMULIN OR HUMALOG
CC (ELI 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/IGF/RELAXIN FAMILY.
CC -!- DATABASE: NAME=Insulin at Eli Lilly;
CC NOTE=Clinical information on Eli Lilly insulin products;
CC WWW="http://diabetes.lilly.com/02-products/insulin.shtml".
CC -!- DATABASE: NAME=Protein Spotlight;
CC NOTE=Issue 9 of April 2001;
CC WWW="http://www.expasy.org/spotlight/articles/sptlt009.html".
CC --------------------------------------------------------------------------
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CC between the Swiss Institute of Bioinformatics and the EMBL outstation -
CC the European Bioinformatics Institute. There are no restrictions on its
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DR EMBL; V00565; CAA23828.1; -.
DR EMBL; M10039; AAA59173.1; -.
DR EMBL; J00265; AAA59172.1; -.
DR EMBL; X70508; CAA49913.1; -.
DR EMBL; L15440; AAA59179.1; ALT_SEQ.
DR EMBL; BC005255; AAH05255.1; -.
DR EMBL; AJ009655; CAA08766.1; -.
DR PIR; A01579; IPHU.
DR PDB; 1HIQ; 31-JAN-94.
DR PDB; 1HIS; 31-JAN-94.
DR PDB; 1HIT; 31-JAN-94.
DR PDB; 2HIU; 01-APR-97.
DR PDB; 1TYL; 30-SEP-94.
DR PDB; 1TYM; 30-SEP-94.
DR PDB; 1TRZ; 31-JAN-94.
DR PDB; 1HLS; 15-SEP-95.
DR PDB; 1HUI; 12-MAR-97.
DR PDB; 1BEN; 11-JUL-96.
DR PDB; 1AI0; 12-NOV-97.
DR PDB; 1AIY; 12-NOV-97.
DR PDB; 1LPH; 20-JUN-96.
DR PDB; 1XDA; 07-JUL-97.
DR PDB; 1XGL; 01-APR-97.
DR PDB; 1MHI; 15-OCT-95.
DR PDB; 1MHJ; 15-OCT-95.
DR PDB; 1SJT; 18-MAR-98.
DR PDB; 1SJU; 18-MAR-98.
DR PDB; 1VKS; 01-APR-97.
DR PDB; 1VKT; 01-APR-97.
DR PDB; 1A7F; 15-JUL-98.
DR PDB; 1ZEG; 15-JUL-98.
DR PDB; 1ZEH; 13-JAN-99.
DR MIM; 176730; -.
DR InterPro; IPR000739; Insulin_IGF_relaxin.
DR Pfam; PF00049; Insulin; 1.
DR PRINTS; PR00276; INSULINA.
DR PRINTS; PR00277; INSULINB.
DR SMART; SM00078; IlGF; 1.
DR PROSITE; PS00262; INSULIN; 1.
DR PRODOM; P01308.
DR SWISS-2DPAGE; P01308.
KW Insulin family; Hormone; Glucose metabolism; Signal; Disease mutation;
KW Diabetes; Pharmaceutical; 3D-structure.
FT SIGNAL 1 24
FT CHAIN 25 54 INSULIN B CHAIN.
FT PROPEP 57 87 C PEPTIDE.
FT CHAIN 90 110 INSULIN A CHAIN.
FT DISULFID 31 96 INTERCHAIN.
FT DISULFID 43 109 INTERCHAIN.
FT DISULFID 95 100
FT VARIANT 34 34 H -> D (IN PROVIDENCE; FAMILIAL
FT HYPERPROINSULINEMIA).
FT /FTID=VAR_003971.
FT VARIANT 48 48 F -> S (IN LOS-ANGELES; TYPE-II DIABETES
FT MELLITUS).
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 KYOTO; FAMILIAL
FT HYPERPROINSULINEMIA).
FT /FTID=VAR_003975.
FT VARIANT 92 92 V -> L (IN WAKAYAMA).
FT /FTID=VAR_003976.
FT TURN 32 32
FT HELIX 33 46
FT STRAND 48 50
FT HELIX 91 95
FT TURN 96 97
FT HELIX 102 108
FT STRAND 109 109
SQ SEQUENCE 110 AA; 11981 MW; C2C3B23B85E520E5 CRC64;
MALWMRLLPL LALLALWGPD PAAAFVNQHL CGSHLVEALY LVCGERGFFY TPKTRREAED
LQVGQVELGG GPGAGSLQPL ALEGSLQKRG IVEQCCTSIC SLYQLENYCN
//
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