Reviewed,
UniProtKB/Swiss-Prot P01308 (INS_HUMAN)
Last modified
September 2, 2008.
Version 121.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Insulin Cleaved into the following 2 chains: 1- Recommended name: Insulin B chain 2- Recommended name: Insulin A chain | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 110 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. |
| Subunit structure | Heterodimer of a B chain and an A chain linked by two disulfide bonds. |
| Subcellular location | |
| Involvement in disease | Defects in INS are the cause of familial hyperproinsulinemia [MIM:176730]. |
| Pharmaceutical use | Available under the names Humulin or Humalog (Eli Lilly) and Novolin (Novo Nordisk). Used in the treatment of diabetes. Humalog is an insulin analog with 52-Lys-Pro-53 instead of 52-Pro-Lys-53. |
| Sequence similarities | Belongs to the insulin family. |
| Sequence caution | The sequence AAA59179.1 differs from that shown. Reason: Erroneous gene model prediction. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | ||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 24 | 24 | ||||||||||||||||||||||||
| Peptide | 25 – 54 | 30 | Insulin B chain | |||||||||||||||||||||||
| Propeptide | 57 – 87 | 31 | C peptide | |||||||||||||||||||||||
| Peptide | 90 – 110 | 21 | Insulin A chain | |||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||
| Disulfide bond | 31 ↔ 96 | Interchain (between B and A chains) | ||||||||||||||||||||||||
| Disulfide bond | 43 ↔ 109 | Interchain (between B and A chains) | ||||||||||||||||||||||||
| Disulfide bond | 95 ↔ 100 | |||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||
| Natural variant | 34 | 1 | H → D in familial hyperproinsulinemia; Providence. | |||||||||||||||||||||||
| Natural variant | 48 | 1 | F → S Associated with diabetes mellitus type-II; Los-Angeles. | |||||||||||||||||||||||
| Natural variant | 49 | 1 | F → L in Chicago. | |||||||||||||||||||||||
| Natural variant | 89 | 1 | R → H in familial hyperproinsulinemia; impairs posttranslational cleavage. | |||||||||||||||||||||||
| Natural variant | 89 | 1 | R → L in familial hyperproinsulinemia; Kyoto. | |||||||||||||||||||||||
| Natural variant | 92 | 1 | V → L in Wakayama. | |||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||
| Helix | 33 – 43 | 11 | ||||||||||||||||||||||||
| Helix | 44 – 46 | 3 | ||||||||||||||||||||||||
| Beta strand | 48 – 50 | 3 | ||||||||||||||||||||||||
| Turn | 61 – 66 | 6 | ||||||||||||||||||||||||
| Beta strand | 74 – 76 | 3 | ||||||||||||||||||||||||
| Helix | 79 – 81 | 3 | ||||||||||||||||||||||||
| Turn | 84 – 86 | 3 | ||||||||||||||||||||||||
| Helix | 91 – 95 | 5 | ||||||||||||||||||||||||
| Helix | 102 – 105 | 4 | ||||||||||||||||||||||||
| Helix | 106 – 108 | 3 | ||||||||||||||||||||||||
Sequences
References
| « Hide 'large scale' references | |
| [1] | "Sequence of the human insulin gene." Bell G.I., Pictet R.L., Rutter W.J., Cordell B., Tischer E., Goodman H.M. Nature 284:26-32(1980) [PubMed: 6243748] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [2] | "Genetic variation in the human insulin gene." Ullrich A., Dull T.J., Gray A., Brosius J., Sures I. Science 209:612-615(1980) [PubMed: 6248962] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "Nucleotide sequence of a cDNA clone encoding human preproinsulin." Bell G.I., Swain W.F., Pictet R.L., Cordell B., Goodman H.M., Rutter W.J. Nature 282:525-527(1979) [PubMed: 503234] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [4] | "Nucleotide sequence of human preproinsulin complementary DNA." Sures I., Goeddel D.V., Gray A., Ullrich A. Science 208:57-59(1980) [PubMed: 6927840] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [5] | "Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR." Lucassen A.M., Julier C., Beressi J.-P., Boitard C., Froguel P., Lathrop M., Bell J.I. Nat. Genet. 4:305-310(1993) [PubMed: 8358440] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [6] | "Insulinomas and expression of an insulin splice variant." Minn A.H., Kayton M., Lorang D., Hoffmann S.C., Harlan D.M., Libutti S.K., Shalev A. Lancet 363:363-367(2004) [PubMed: 15070567] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [7] | "Global haplotype diversity in the human insulin gene region." Stead J.D.H., Hurles M.E., Jeffreys A.J. Genome Res. 13:2101-2111(2003) [PubMed: 12952878] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [8] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [9] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [10] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas. |
| [11] | "Description of a novel RFLP diallelic polymorphism (-127 BsgI C/G) within the 5' region of insulin gene." Fajardy I.I., Weill J.J., Stuckens C.C., Danze P.M.P. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-59. Tissue: Blood. |
| [12] | "Amino-acid sequence of human insulin." Nicol D.S.H.W., Smith L.F. Nature 187:483-485(1960) [PubMed: 14426955] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-54 AND 90-110. |
| [13] | "Studies on human proinsulin. Isolation and amino acid sequence of the human pancreatic C-peptide." Oyer P.E., Cho S., Peterson J.D., Steiner D.F. J. Biol. Chem. 246:1375-1386(1971) [PubMed: 5101771] [Abstract] Cited for: PROTEIN SEQUENCE OF 57-87. |
| [14] | "The amino acid sequence of the C-peptide of human proinsulin." Ko A., Smyth D.G., Markussen J., Sundby F. Eur. J. Biochem. 20:190-199(1971) [PubMed: 5560404] [Abstract] Cited for: PROTEIN SEQUENCE OF 57-87. |
| [15] | "Total synthesis of human insulin under directed formation of the disulfide bonds." Sieber P., Kamber B., Hartmann A., Joehl A., Riniker B., Rittel W. Helv. Chim. Acta 57:2617-2621(1974) [PubMed: 4443293] [Abstract] Cited for: SYNTHESIS. |
| [16] | "Studies on polypeptides, IV. The synthesis of C-peptide of human proinsulin." Naithani V.K. Hoppe-Seyler's Z. Physiol. Chem. 354:659-672(1973) [PubMed: 4803504] [Abstract] Cited for: SYNTHESIS OF 57-87. |
| [17] | "Synthesis of peptides with the properties of human proinsulin C peptides (hC peptide). 3. Synthesis of the sequences 14-17 and 9-13 of human proinsulin C peptides." Geiger R., Volk A. Chem. Ber. 106:199-205(1973) [PubMed: 4698555] [Abstract] Cited for: SYNTHESIS OF 65-69 AND 70-73. |
| [18] | "Synthesis of peptides with the properties of human proinsulin C peptides (hC peptide). I. Scheme for the synthesis and preparation of the sequence 28-31 of human proinsulin C peptide." Geiger R., Jaeger G., Keonig W., Treuth G. Chem. Ber. 106:188-192(1973) [PubMed: 4698553] [Abstract] Cited for: SYNTHESIS OF 84-87. |
| [19] | "Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding [SerB24]insulin." Haneda M., Chan S.J., Kwok S.C.M., Rubenstein A.H., Steiner D.F. Proc. Natl. Acad. Sci. U.S.A. 80:6366-6370(1983) [PubMed: 6312455] [Abstract] Cited for: VARIANT LOS ANGELES SER-48. |
| [20] | "Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution." Shoelson S., Fickova M., Haneda M., Nahum A., Musso G., Kaiser E.T., Rubenstein A.H., Tager H. Proc. Natl. Acad. Sci. U.S.A. 80:7390-7394(1983) [PubMed: 6424111] [Abstract] Cited for: VARIANTS LOS ANGELES SER-48 AND CHICAGO LEU-49. |
| [21] | "A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia." Chan S.J., Seino S., Gruppuso P.A., Schwartz R., Steiner D.F. Proc. Natl. Acad. Sci. U.S.A. 84:2194-2197(1987) [PubMed: 3470784] [Abstract] Cited for: VARIANT PROVIDENCE ASP-34. |
| [22] | "Structurally abnormal insulin in a diabetic patient. Characterization of the mutant insulin A3 (Val-->Leu) isolated from the pancreas." Sakura H., Iwamoto Y., Sakamoto Y., Kuzuya T., Hirata H. J. Clin. Invest. 78:1666-1672(1986) [PubMed: 3537011] [Abstract] Cited for: VARIANT WAKAYAMA LEU-92. |
| [23] | "Two unrelated patients with familial hyperproinsulinemia due to a mutation substituting histidine for arginine at position 65 in the proinsulin molecule: identification of the mutation by direct sequencing of genomic deoxyribonucleic acid amplified by polymerase chain reaction." Barbetti F., Raben N., Kadowaki T., Cama A., Accili D., Gabbay K.H., Merenich J.A., Taylor S.I., Roth J. J. Clin. Endocrinol. Metab. 71:164-169(1990) [PubMed: 2196279] [Abstract] Cited for: VARIANT HIS-89. |
| [24] | "Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia." Shibasaki Y., Kawakami T., Kanazawa Y., Akanuma Y., Takaku F. J. Clin. Invest. 76:378-380(1985) [PubMed: 4019786] [Abstract] Cited for: VARIANT HIS-89. |
| [25] | "A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto)." Yano H., Kitano N., Morimoto M., Polonsky K.S., Imura H., Seino Y. J. Clin. Invest. 89:1902-1907(1992) [PubMed: 1601997] [Abstract] Cited for: VARIANT KYOTO LEU-89. |
| [26] | "Toward the solution structure of human insulin: sequential 2D 1H NMR assignment of a des-pentapeptide analogue and comparison with crystal structure." Hua Q.-X., Weiss M.A. Biochemistry 29:10545-10555(1990) [PubMed: 2271664] [Abstract] Cited for: STRUCTURE BY NMR. |
| [27] | "Comparative 2D NMR studies of human insulin and des-pentapeptide insulin: sequential resonance assignment and implications for protein dynamics and receptor recognition." Hua Q.-X., Weiss M.A. Biochemistry 30:5505-5515(1991) [PubMed: 2036420] [Abstract] Cited for: STRUCTURE BY NMR. |
| [28] | "Two-dimensional NMR studies of Des-(B26-B30)-insulin: sequence-specific resonance assignments and effects of solvent composition." Hua Q.-X., Weiss M.A. Biochim. Biophys. Acta 1078:101-110(1991) [PubMed: 1646635] [Abstract] Cited for: STRUCTURE BY NMR. |
| [29] | "Three-dimensional solution structure of an insulin dimer. A study of the B9(Asp) mutant of human insulin using nuclear magnetic resonance, distance geometry and restrained molecular dynamics." Joergensen A.M.M., Kristensen S.M., Led J.J., Balschmidt P. J. Mol. Biol. 227:1146-1163(1992) [PubMed: 1433291] [Abstract] Cited for: STRUCTURE BY NMR. |
| [30] | "Paradoxical structure and function in a mutant human insulin associated with diabetes mellitus." Hua Q.-X., Shoelson S.E., Inouye K., Weiss M.A. Proc. Natl. Acad. Sci. U.S.A. 90:582-586(1993) [PubMed: 8421693] [Abstract] Cited for: STRUCTURE BY NMR OF VARIANT LOS-ANGELES SER-48. |
| [31] | "Solution structures of the R6 human insulin hexamer." Chang X., Joergensen A.M., Bardrum P., Led J.J. Biochemistry 36:9409-9422(1997) [PubMed: 9235985] [Abstract] Cited for: STRUCTURE BY NMR. |
| + | Additional computationally mapped references. |
Web resources
| Insulin at Eli Lilly Clinical information on Eli Lilly insulin products |
| Protein Spotlight Protein of the 20th century - Issue 9 of April 2001 |
| Wikipedia Insulin entry |
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| V00565 Genomic DNA. Translation: CAA23828.1. M10039 Genomic DNA. Translation: AAA59173.1. J00265 Genomic DNA. Translation: AAA59172.1. X70508 mRNA. Translation: CAA49913.1. L15440 Genomic DNA. Translation: AAA59179.1. Sequence problems. AY899304 mRNA. Translation: AAW83741.1. AY138590 Genomic DNA. Translation: AAN39451.1. BT006808 mRNA. Translation: AAP35454.1. CH471158 Genomic DNA. Translation: EAX02488.1. BC005255 mRNA. Translation: AAH05255.1. AJ009655 Genomic DNA. Translation: CAA08766.1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PIR | IPHU. A93222. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RefSeq | NP_000198.1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UniGene | Hs.654579 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clusters with