P01308 (INS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin

Cleaved into the following 2 chains:

1. Insulin B chain
2. Insulin A chain

Gene names

Name:

INS

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	Secreted.
Involvement in disease	Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:176730]. Ref.21 Ref.23 Ref.24 Ref.25 Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:125852]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Ref.34 Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:606176]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy. Ref.32 Ref.33 Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:613370]. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. Ref.33 Ref.34 Ref.35
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

Keywords
Biological process	Carbohydrate metabolism Glucose metabolism
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Signal
Molecular function	Hormone
PTM	Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor signaling pathway Inferred from direct assay. Source: BHF-UCL MAPKKK cascade Inferred from direct assay. Source: BHF-UCL activation of protein kinase B activity Inferred from direct assay. Source: BHF-UCL acute-phase response Inferred from direct assay. Source: BHF-UCL alpha-beta T cell activation Inferred from direct assay. Source: UniProtKB cell-cell signaling Inferred by curator. Source: UniProtKB endocrine pancreas development Traceable author statement. Source: Reactome energy reserve metabolic process Traceable author statement. Source: Reactome fatty acid homeostasis Inferred from mutant phenotype. Source: BHF-UCL fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome glucose homeostasis Inferred from mutant phenotype. Source: BHF-UCL glucose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW glucose transport Inferred from direct assay. Source: UniProtKB insulin receptor signaling pathway Traceable author statement. Source: Reactome negative regulation of NAD(P)H oxidase activity Inferred from direct assay. Source: BHF-UCL negative regulation of acute inflammatory response Inferred from direct assay. Source: BHF-UCL negative regulation of apoptotic process Non-traceable author statement. Source: BHF-UCL negative regulation of fatty acid metabolic process Inferred from mutant phenotype. Source: BHF-UCL negative regulation of feeding behavior Inferred from direct assay. Source: DFLAT negative regulation of gluconeogenesis Non-traceable author statement. Source: BHF-UCL negative regulation of glycogen catabolic process Inferred from mutant phenotype. Source: BHF-UCL negative regulation of lipid catabolic process Non-traceable author statement. Source: BHF-UCL negative regulation of protein catabolic process Inferred from direct assay. Source: UniProtKB negative regulation of protein secretion Inferred from direct assay. Source: BHF-UCL negative regulation of proteolysis Inferred from mutant phenotype. Source: BHF-UCL negative regulation of respiratory burst involved in inflammatory response Inferred from direct assay. Source: BHF-UCL negative regulation of vasodilation Non-traceable author statement. Source: UniProtKB positive regulation of DNA replication Inferred from direct assay. Source: BHF-UCL positive regulation of MAPKKK cascade Inferred from direct assay. Source: BHF-UCL positive regulation of NF-kappaB transcription factor activity Inferred from direct assay. Source: BHF-UCL positive regulation of cell differentiation Non-traceable author statement. Source: BHF-UCL positive regulation of cell growth Non-traceable author statement. Source: BHF-UCL positive regulation of cell migration Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell proliferation Inferred from direct assay. Source: BHF-UCL positive regulation of cytokine secretion Inferred from direct assay. Source: UniProtKB positive regulation of glucose import Inferred from direct assay. Source: BHF-UCL positive regulation of glycogen biosynthetic process Inferred from direct assay. Source: BHF-UCL positive regulation of glycolysis Inferred from direct assay. Source: BHF-UCL positive regulation of insulin receptor signaling pathway Inferred from direct assay. Source: BHF-UCL positive regulation of lipid biosynthetic process Non-traceable author statement. Source: BHF-UCL positive regulation of mitosis Inferred from direct assay. Source: UniProtKB positive regulation of nitric oxide biosynthetic process Non-traceable author statement. Source: UniProtKB positive regulation of nitric-oxide synthase activity Non-traceable author statement. Source: UniProtKB positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Inferred from direct assay. Source: BHF-UCL positive regulation of protein autophosphorylation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of protein kinase B signaling cascade Inferred from direct assay. Source: BHF-UCL positive regulation of respiratory burst Inferred from direct assay. Source: BHF-UCL positive regulation of vasodilation Non-traceable author statement. Source: UniProtKB regulation of cellular amino acid metabolic process Inferred from mutant phenotype. Source: BHF-UCL regulation of insulin secretion Traceable author statement. Source: Reactome regulation of transmembrane transporter activity Inferred from direct assay. Source: BHF-UCL wound healing Inferred from direct assay. Source: BHF-UCL
Cellular component	Golgi lumen Traceable author statement. Source: Reactome endoplasmic reticulum lumen Traceable author statement. Source: Reactome endosome lumen Traceable author statement. Source: Reactome extracellular space Inferred from direct assay. Source: BHF-UCL secretory granule Traceable author statement. Source: Reactome
Molecular function	hormone activity Non-traceable author statement. Source: UniProtKB insulin receptor binding Inferred from direct assay. Source: UniProtKB insulin-like growth factor receptor binding Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Ref.12

Peptide

25 – 54

30

Insulin B chain Ref.12

PRO_0000015819

Propeptide

57 – 87

31

C peptide Ref.13 Ref.14

PRO_0000015820

Peptide

90 – 110

21

Insulin A chain

PRO_0000015821

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

Ref.13

Natural variations

Natural variant

6

1

R → C in MODY10. [dbSNP:rs121908278] Ref.33

VAR_063721

Natural variant

6

1

R → H in MODY10. [dbSNP:rs121908259] Ref.35

VAR_063722

Natural variant

24

1

A → D in PNDM. [dbSNP:rs80356663] Ref.32 Ref.33

VAR_063723

Natural variant

29

1

H → D in PNDM. [dbSNP:rs121908272] Ref.33

VAR_063724

Natural variant

32

1

G → R in PNDM. [dbSNP:rs80356664] Ref.32 Ref.33

VAR_063725

Natural variant

32

1

G → S in PNDM. [dbSNP:rs80356664] Ref.32 Ref.33

VAR_063726

Natural variant

34

1

H → D in FHPRI; Providence. Ref.21

VAR_003971

Natural variant

35

1

L → P in PNDM. [dbSNP:rs121908273] Ref.33

VAR_063727

Natural variant

43

1

C → G in PNDM. [dbSNP:rs80356666] Ref.32 Ref.33

VAR_063728

Natural variant

46

1

R → Q in MODY10. [dbSNP:rs121908260] Ref.34 Ref.35

VAR_063729

Natural variant

47

1

G → V in PNDM. [dbSNP:rs80356667] Ref.32 Ref.33

VAR_063730

Natural variant

48

1

F → C in PNDM. [dbSNP:rs80356668] Ref.32 Ref.33

VAR_063731

Natural variant

48

1

F → S Associated with diabetes mellitus type-II; Los-Angeles. Ref.19 Ref.20 Ref.30

VAR_003972

Natural variant

49

1

F → L in Chicago. Ref.20

VAR_003973

Natural variant

55

1

R → C in IDDM2. [dbSNP:rs121908261] Ref.34

VAR_063732

Natural variant

68

1

L → M. [dbSNP:rs121908279] Ref.33

VAR_063733

Natural variant

84

1

G → R in PNDM; uncertain pathological significance. [dbSNP:rs121908274] Ref.33

VAR_063734

Natural variant

89

1

R → C in PNDM. [dbSNP:rs80356669] Ref.32 Ref.33

VAR_063735

Natural variant

89

1

R → H in FHPRI; impairs posttranslational cleavage. [dbSNP:rs28933985] Ref.23 Ref.24

VAR_003974

Natural variant

89

1

R → L in FHPRI; Kyoto. Ref.25

VAR_003975

Natural variant

90

1

G → C in PNDM. [dbSNP:rs80356670] Ref.32 Ref.33

VAR_063736

Natural variant

92

1

V → L in Wakayama. Ref.22

VAR_003976

Natural variant

96

1

C → S in PNDM. [dbSNP:rs80356671] Ref.33

VAR_063737

Natural variant

96

1

C → Y in PNDM. [dbSNP:rs80356671] Ref.32 Ref.33

VAR_063738

Natural variant

101

1

S → C in PNDM. [dbSNP:rs121908276] Ref.33

VAR_063739

Natural variant

103

1

Y → C in PNDM. [dbSNP:rs121908277] Ref.33

VAR_063740

Natural variant

108

1

Y → C in PNDM. [dbSNP:rs80356672] Ref.32 Ref.33

VAR_063741

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

110

Helix Strand Turn

Details...

Helix

33 – 43

11

Helix

44 – 46

3

Beta strand

48 – 50

3

Turn

59 – 66

8

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

	Sequence		Length	Mass (Da)
	P01308 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: C2C3B23B85E520E5	FASTA	110	11,981
	10 20 30 40 50 60 MALWMRLLPL LALLALWGPD PAAAFVNQHL CGSHLVEALY LVCGERGFFY TPKTRREAED 70 80 90 100 110 LQVGQVELGG GPGAGSLQPL ALEGSLQKRG IVEQCCTSIC SLYQLENYCN

References

	« Hide 'large scale' referencesShow '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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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 FHPRI 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 FHPRI 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 FHPRI 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 FHPRI 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.
[32]	"Insulin gene mutations as a cause of permanent neonatal diabetes." Stoy J., Edghill E.L., Flanagan S.E., Ye H., Paz V.P., Pluzhnikov A., Below J.E., Hayes M.G., Cox N.J., Lipkind G.M., Lipton R.B., Greeley S.A., Patch A.M., Ellard S., Steiner D.F., Hattersley A.T., Philipson L.H., Bell G.I. Proc. Natl. Acad. Sci. U.S.A. 104:15040-15044(2007) [PubMed: 17855560] [Abstract] Cited for: VARIANTS PNDM ASP-24; ARG-32; SER-32; GLY-43; VAL-47; CYS-48; CYS-89; CYS-90; TYR-96 AND CYS-108.
[33]	"Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood." Edghill E.L., Flanagan S.E., Patch A.M., Boustred C., Parrish A., Shields B., Shepherd M.H., Hussain K., Kapoor R.R., Malecki M., MacDonald M.J., Stoy J., Steiner D.F., Philipson L.H., Bell G.I., Hattersley A.T., Ellard S. Diabetes 57:1034-1042(2008) [PubMed: 18162506] [Abstract] Cited for: VARIANTS PNDM ASP-24; ASP-29; ARG-32; SER-32; PRO-35; GLY-43; VAL-47; CYS-48; ARG-84; CYS-89; CYS-90; SER-96; TYR-96; CYS-101; CYS-103 AND CYS-108, VARIANT MODY10 CYS-6, VARIANT MET-68.
[34]	"Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes." Molven A., Ringdal M., Nordbo A.M., Raeder H., Stoy J., Lipkind G.M., Steiner D.F., Philipson L.H., Bergmann I., Aarskog D., Undlien D.E., Joner G., Sovik O., Bell G.I., Njolstad P.R. Diabetes 57:1131-1135(2008) [PubMed: 18192540] [Abstract] Cited for: VARIANT MODY10 GLN-46, VARIANT IDDM2 CYS-55.
[35]	"Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY)." Boesgaard T.W., Pruhova S., Andersson E.A., Cinek O., Obermannova B., Lauenborg J., Damm P., Bergholdt R., Pociot F., Pisinger C., Barbetti F., Lebl J., Pedersen O., Hansen T. BMC Med. Genet. 11:42-42(2010) [PubMed: 20226046] [Abstract] Cited for: VARIANTS MODY10 HIS-6 AND GLN-46.
+	Additional computationally mapped references.

Web resources

GeneReviews

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

EMBL
GenBank
DDBJ

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.

IPI

IPI00001508.

PIR

IPHU. A93222.

RefSeq

NP_000198.1. NM_000207.2.
NP_001172026.1. NM_001185097.1.
NP_001172027.1. NM_001185098.1.

UniGene

Hs.272259.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A7F	NMR	-	A	90-110	[»]
			B	25-53	[»]
1AI0	NMR	-	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
1AIY	NMR	-	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
1B9E	X-ray	2.50	A/C	90-110	[»]
			B/D	25-54	[»]
1BEN	X-ray	1.40	A/C	90-110	[»]
			B/D	25-54	[»]
1EFE	NMR	-	A	25-110	[»]
1EV3	X-ray	1.78	A/C	90-110	[»]
			B/D	25-54	[»]
1EV6	X-ray	1.90	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
1EVR	X-ray	1.90	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
1FU2	X-ray	3.24	A/C/E/G	90-110	[»]
			B/D/F/H	25-54	[»]
1FUB	X-ray	3.09	A/C	90-110	[»]
			B/D	25-54	[»]
1G7A	X-ray	1.20	A/C/E/G	90-110	[»]
			B/D/F/H	25-54	[»]
1G7B	X-ray	1.30	A/C/E/G	90-110	[»]
			B/D/F/H	25-54	[»]
1GUJ	X-ray	1.62	A/C	90-110	[»]
			B/D	25-54	[»]
1HIQ	NMR	-	A	90-110	[»]
			B	25-54	[»]
1HIS	NMR	-	A	90-110	[»]
			B	25-49	[»]
1HIT	NMR	-	A	90-110	[»]
			B	25-54	[»]
1HLS	NMR	-	A	90-110	[»]
			B	25-54	[»]
1HTV	X-ray	1.90	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-51	[»]
1HUI	NMR	-	A	90-110	[»]
			B	26-53	[»]
1IOG	NMR	-	A	90-110	[»]
			B	26-53	[»]
1IOH	NMR	-	A	90-110	[»]
			B	26-53	[»]
1J73	X-ray	2.00	A/C	90-110	[»]
			B/D	25-54	[»]
1JCA	X-ray	2.50	A/C	90-110	[»]
			B/D	25-54	[»]
1JCO	NMR	-	A	90-110	[»]
			B	25-54	[»]
1K3M	NMR	-	A	90-110	[»]
			B	25-54	[»]
1KMF	NMR	-	A	90-110	[»]
			B	25-54	[»]
1LKQ	NMR	-	A	90-110	[»]
			B	25-54	[»]
1LPH	X-ray	2.30	A/C	90-110	[»]
			B/D	25-54	[»]
1MHI	NMR	-	A	90-110	[»]
			B	25-54	[»]
1MHJ	NMR	-	A	90-110	[»]
			B	25-48	[»]
1MSO	X-ray	1.00	A/C	90-110	[»]
			B/D	25-54	[»]
1OS3	X-ray	1.95	A/C	90-110	[»]
			B/D	25-54	[»]
1OS4	X-ray	2.25	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
1Q4V	X-ray	2.00	A/C	90-110	[»]
			B/D	25-54	[»]
1QIY	X-ray	2.30	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
1QIZ	X-ray	2.00	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
1QJ0	X-ray	2.40	A/C	90-110	[»]
			B/D	25-54	[»]
1RWE	X-ray	1.80	A/C	90-110	[»]
			B/D	25-54	[»]
1SF1	NMR	-	A	90-110	[»]
			B	25-54	[»]
1SJT	NMR	-	A	90-110	[»]
			B	25-53	[»]
1SJU	NMR	-	A	25-53	[»]
			A	90-110	[»]
1T0C	NMR	-	A	57-87	[»]
1T1K	NMR	-	A	90-110	[»]
			B	25-54	[»]
1T1P	NMR	-	A	90-110	[»]
			B	25-54	[»]
1T1Q	NMR	-	A	90-110	[»]
			B	25-54	[»]
1TRZ	X-ray	1.60	A/C	90-110	[»]
			B/D	25-54	[»]
1TYL	X-ray	1.90	A/C	90-110	[»]
			B/D	25-54	[»]
1TYM	X-ray	1.90	A/C	90-110	[»]
			B/D	25-54	[»]
1UZ9	X-ray	1.60	A	90-110	[»]
			B	25-53	[»]
1VKT	NMR	-	A	90-110	[»]
			B	25-54	[»]
1W8P	X-ray	2.08	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
1XDA	X-ray	1.80	A/C/E/G	90-110	[»]
			B/D/F/H	25-53	[»]
1XGL	NMR	-	A	90-110	[»]
			B	25-54	[»]
1XW7	X-ray	2.30	A/C	90-110	[»]
			B/D	25-54	[»]
1ZEG	X-ray	1.60	A/C	90-110	[»]
			B/D	25-54	[»]
1ZEH	X-ray	1.50	A/C	90-110	[»]
			B/D	25-54	[»]
1ZNJ	X-ray	2.00	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
2AIY	NMR	-	B/D/F/H/J/L	25-54	[»]
2C8Q	X-ray	1.95	A	90-110	[»]
			B	25-53	[»]
2C8R	X-ray	1.50	A	90-110	[»]
			B	25-53	[»]
2CEU	X-ray	1.80	A/C	90-110	[»]
			B/D	25-49	[»]
2G54	X-ray	2.25	C/D	25-54	[»]
2G56	X-ray	2.20	C/D	25-54	[»]
2H67	NMR	-	A	90-110	[»]
			B	25-54	[»]
2HH4	NMR	-	A	90-110	[»]
2HHO	NMR	-	A	90-110	[»]
			B	25-54	[»]
2HIU	NMR	-	A	90-110	[»]
			B	25-54	[»]
2JMN	NMR	-	A	90-110	[»]
			B	25-54	[»]
2JUM	NMR	-	A	90-110	[»]
			B	25-51	[»]
2JUU	NMR	-	A	90-110	[»]
			B	25-51	[»]
2JUV	NMR	-	A	90-110	[»]
			B	25-51	[»]
2JV1	NMR	-	A	90-110	[»]
			B	25-54	[»]
2JZQ	NMR	-	A	25-54	[»]
			A	90-110	[»]
2K91	NMR	-	A	90-110	[»]
			B	25-51	[»]
2K9R	NMR	-	A	90-110	[»]
			B	25-51	[»]
2KJJ	NMR	-	A	90-110	[»]
			B	25-51	[»]
2KJU	NMR	-	A	90-110	[»]
			B	25-51	[»]
2KQP	NMR	-	A	25-110	[»]
2KQQ	NMR	-	A	90-110	[»]
			B	25-51	[»]
2KXK	NMR	-	A	90-110	[»]
			B	25-54	[»]
2L1Y	NMR	-	A	90-110	[»]
			B	25-51	[»]
2L1Z	NMR	-	A	93-110	[»]
			B	25-51	[»]
2OLY	X-ray	1.70	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
2OLZ	X-ray	1.70	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
2OM0	X-ray	2.05	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	[»]
2OM1	X-ray	1.97	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	[»]
2OMG	X-ray	1.52	A/C/E	90-110	[»]
			B/D/F	25-54	[»]
2OMH	X-ray	1.36	A/C/E	90-110	[»]
			B/D/F	25-54	[»]
2OMI	X-ray	2.24	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
2QIU	X-ray	2.00	A/C	89-110	[»]
			B/D	25-54	[»]
2R34	X-ray	2.25	A/C	89-110	[»]
			B/D	25-54	[»]
2R35	X-ray	2.08	A/C	89-110	[»]
			B/D	25-54	[»]
2R36	X-ray	2.00	A/C	89-110	[»]
			B/D	25-54	[»]
2RN5	NMR	-	A	90-110	[»]
			B	25-56	[»]
2VJZ	X-ray	1.80	A/C	90-110	[»]
			B/D	25-54	[»]
2VK0	X-ray	2.20	A/C	90-110	[»]
			B/D	25-54	[»]
2W44	X-ray	2.00	A/C/E	94-110	[»]
			B/D/F	25-53	[»]
2WBY	X-ray	2.60	C/E	90-109	[»]
			D/F	25-43	[»]
2WC0	X-ray	2.80	C/E	90-110	[»]
			D/F	25-54	[»]
2WRU	X-ray	1.57	A	90-110	[»]
			B	25-49	[»]
2WRV	X-ray	2.15	A	90-110	[»]
			B	25-49	[»]
2WRW	X-ray	2.41	A	90-110	[»]
			B	25-49	[»]
2WRX	X-ray	1.50	A/C	90-110	[»]
			B/D	25-54	[»]
2WS0	X-ray	2.10	A	90-110	[»]
			B	25-54	[»]
2WS1	X-ray	1.60	A	90-110	[»]
			B	25-54	[»]
2WS4	X-ray	1.90	A	90-110	[»]
			B	25-49	[»]
2WS6	X-ray	1.50	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
2WS7	X-ray	2.59	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-49	[»]
3AIY	NMR	-	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
3BRR	X-ray	1.70	A/C	90-110	[»]
			B/D	25-53	[»]
3BXQ	X-ray	1.30	A/C	90-110	[»]
			B/D	25-54	[»]
3E7Y	X-ray	1.60	A/C	90-110	[»]
			B/D	25-53	[»]
3E7Z	X-ray	1.70	A/C	90-110	[»]
			B/D	25-53	[»]
3EXX	X-ray	1.35	A/C	90-110	[»]
			B/D	25-54	[»]
3FQ9	X-ray	1.35	A/C	91-110	[»]
			B/D	25-54	[»]
3HYD	X-ray	1.00	A	35-41	[»]
3I3Z	X-ray	1.60	A	90-110	[»]
			B	25-53	[»]
3I40	X-ray	1.85	A	90-110	[»]
			B	25-53	[»]
3ILG	X-ray	1.90	A/C	90-110	[»]
			B/D	25-54	[»]
3INC	X-ray	1.85	A/C	90-110	[»]
			B/D	25-54	[»]
3IR0	X-ray	2.20	A/C/E/G/I/K/M/O/R/T/V/X	90-110	[»]
			B/D/F/H/J/L/N/P/S/U/W/Y	25-54	[»]
3JSD	X-ray	2.50	A/C	90-110	[»]
			B/D	25-54	[»]
3KQ6	X-ray	1.90	A/C	90-110	[»]
			B/D	25-54	[»]
3P2X	X-ray	2.00	A/C	90-110	[»]
			B/D	25-54	[»]
3P33	X-ray	2.30	A/C/E/G	90-110	[»]
			B/D/F/H	25-54	[»]
3Q6E	X-ray	2.05	A/C	90-110	[»]
			B/D	25-54	[»]
3TT8	X-ray	1.12	A/C	90-110	[»]
			B/D	25-54	[»]
3ZQR	X-ray	1.90	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
3ZS2	X-ray	1.97	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-48	[»]
3ZU1	X-ray	1.60	A/C	90-110	[»]
			B/D	25-54	[»]
4AIY	NMR	-	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]
5AIY	NMR	-	A/C/E/G/I/K	90-110	[»]
			B/D/F/H/J/L	25-54	[»]

ProteinModelPortal

P01308.

SMR

P01308. Positions 25-110.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6024N.

MINT

MINT-106847.

STRING

P01308.

Protein family/group databases

Allergome

2121. Hom s Insulin.

Polymorphism databases

DMDM

124617.

Proteomic databases

PeptideAtlas

P01308.

PRIDE

P01308.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000250971; ENSP00000250971; ENSG00000129965.
ENST00000381330; ENSP00000370731; ENSG00000129965.
ENST00000397262; ENSP00000380432; ENSG00000129965.

GeneID

3630.

KEGG

hsa:3630.

UCSC

uc001lvn.1. human.

Organism-specific databases

CTD

3630.

GeneCards

GC11M002181.

HGNC

HGNC:6081. INS.

HPA

CAB000048.
CAB012098.
HPA004932.

MIM

125852. phenotype.
176730. gene+phenotype.
606176. phenotype.
613370. phenotype.

neXtProt

NX_P01308.

Orphanet

552. MODY syndrome.
99885. Permanent neonatal diabetes mellitus.

PharmGKB

PA201.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG21311.

GeneTree

ENSGT00390000015440.

HOVERGEN

HBG006137.

OMA

PAPAFVN.

PhylomeDB

P01308.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-16190.

Pathway_Interaction_DB

arf6_traffickingpathway. Arf6 trafficking events.
hnf3apathway. FOXA1 transcription factor network.
hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
insulin_pathway. Insulin Pathway.
insulin_glucose_pathway. Insulin-mediated glucose transport.
mtor_4pathway. mTOR signaling pathway.
ptp1bpathway. Signaling events mediated by PTP1B.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_15380. Diabetes pathways.
REACT_75925. Amyloids.

Gene expression databases

ArrayExpress

P01308.

Bgee

P01308.

Genevestigator

P01308.

GermOnline

ENSG00000129965. Homo sapiens.

Family and domain databases

InterPro

IPR004825. Insulin.
IPR016179. Insulin-like.
IPR022353. Insulin_CS.
IPR022352. Insulin_family.
[Graphical view]

Gene3D

G3DSA:1.10.100.10. Ins/IGF/relaxin. 1 hit.

KO

K04526.

Pfam

PF00049. Insulin. 1 hit.
[Graphical view]

PRINTS

PR00277. INSULIN.
PR00276. INSULINFAMLY.

SMART

SM00078. IlGF. 1 hit.
[Graphical view]

SUPFAM

SSF56994. Insulin-like. 1 hit.

PROSITE

PS00262. INSULIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

14203.

PMAP-CutDB

P01308.

SOURCE

Search...

Entry information

Entry name

INS_HUMAN

Accession

Primary (citable) accession number: P01308
Secondary accession number(s): Q5EEX2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	January 25, 2012
This is version 166 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.