IAPP_HUMAN
ID IAPP_HUMAN Reviewed; 89 AA.
AC P10997; Q0ZD87; Q14598;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Islet amyloid polypeptide;
DE AltName: Full=Amylin;
DE AltName: Full=Diabetes-associated peptide;
DE Short=DAP;
DE AltName: Full=Insulinoma amyloid peptide;
DE Flags: Precursor;
GN Name=IAPP;
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 [GENOMIC DNA / MRNA], AND AMIDATION AT TYR-70.
RX PubMed=2651160; DOI=10.1016/0014-5793(89)81260-8;
RA Mosselman S., Hoeppener J.W.M., Lips C.J.M., Jansz H.S.;
RT "The complete islet amyloid polypeptide precursor is encoded by two
RT exons.";
RL FEBS Lett. 247:154-158(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2608057; DOI=10.1210/mend-3-11-1775;
RA Nishi M., Sanke T., Seino S., Eddy R.L., Fan Y.-S., Byers M.G., Shows T.B.,
RA Bell G.I., Steiner D.F.;
RT "Human islet amyloid polypeptide gene: complete nucleotide sequence,
RT chromosomal localization, and evolutionary history.";
RL Mol. Endocrinol. 3:1775-1781(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=3053705; DOI=10.1016/s0021-9258(19)77825-9;
RA Sanke T., Bell G.I., Sample C., Rubenstein A.H., Steiner D.F.;
RT "An islet amyloid peptide is derived from an 89-amino acid precursor by
RT proteolytic processing.";
RL J. Biol. Chem. 263:17243-17246(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2365085; DOI=10.1016/0014-5793(90)80314-9;
RA Christmanson L., Rorsman F., Stenman G., Westermark P., Betsholtz C.;
RT "The human islet amyloid polypeptide (IAPP) gene. Organization, chromosomal
RT localization and functional identification of a promoter region.";
RL FEBS Lett. 267:160-166(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2223885; DOI=10.1016/0167-4781(90)90210-s;
RA van Mansfeld A.D.M., Mosselman S., Hoeppener J.W.M., Zandberg J.,
RA van Teeffelen H.A.A.M., Baas P.D., Lips C.J.M., Jansz H.S.;
RT "Islet amyloid polypeptide: structure and upstream sequences of the IAPP
RT gene in rat and man.";
RL Biochim. Biophys. Acta 1087:235-240(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1282806; DOI=10.1016/0006-291x(92)90255-j;
RA Hoeppener J.W.M., Oosterwijk C., Visser-Vernooy H.J., Lips C.J.M.,
RA Jansz H.S.;
RT "Characterization of the human islet amyloid polypeptide/amylin gene
RT transcripts: identification of a new polyadenylation site.";
RL Biochem. Biophys. Res. Commun. 189:1569-1577(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, DOMAIN, AND MASS
RP SPECTROMETRY.
RC TISSUE=Fetal pancreas;
RX PubMed=17374526; DOI=10.1016/j.bbrc.2007.03.016;
RA Bhattacharya S., Naveena Lavanya Latha J., Kumresan R., Singh S.;
RT "Cloning and expression of human islet amyloid polypeptide in cultured
RT cells.";
RL Biochem. Biophys. Res. Commun. 356:622-628(2007).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 28-89.
RX PubMed=3181427; DOI=10.1016/0014-5793(88)80922-0;
RA Mosselman S., Hoeppener J.W.M., Zandberg J., van Mansfeld A.D.M.,
RA Geurts van Kessel A.H.M., Lips C.J.M., Jansz H.S.;
RT "Islet amyloid polypeptide: identification and chromosomal localization of
RT the human gene.";
RL FEBS Lett. 239:227-232(1988).
RN [10]
RP PROTEIN SEQUENCE OF 34-70, AND DISULFIDE BOND.
RX PubMed=3317417; DOI=10.1073/pnas.84.23.8628;
RA Cooper G.J., Willis A.C., Clark A., Turner R.C., Sim R.B., Reid K.B.;
RT "Purification and characterization of a peptide from amyloid-rich
RT pancreases of type 2 diabetic patients.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8628-8632(1987).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 34-70, AND SYNTHESIS OF 53-62.
RX PubMed=2666169; DOI=10.1016/0014-5793(89)81467-x;
RA Betsholtz C., Christmansson L., Engstroem U., Rorsman F., Svensson V.,
RA Johnson K.H., Westermark P.;
RT "Sequence divergence in a specific region of islet amyloid polypeptide
RT (IAPP) explains differences in islet amyloid formation between species.";
RL FEBS Lett. 251:261-264(1989).
RN [12]
RP PROTEIN SEQUENCE OF 34-70.
RX PubMed=2091067; DOI=10.1016/0167-0115(90)90004-g;
RA Nakazato M., Asai J., Miyazato M., Matsukura S., Kangawa K., Matsuo H.;
RT "Isolation and identification of islet amyloid polypeptide in normal human
RT pancreas.";
RL Regul. Pept. 31:179-186(1990).
RN [13]
RP PROTEIN SEQUENCE OF 34-52.
RX PubMed=3535798; DOI=10.1016/0006-291x(86)90708-4;
RA Westermark P., Wernstedt C., Wilander E., Sletten K.;
RT "A novel peptide in the calcitonin gene related peptide family as an
RT amyloid fibril protein in the endocrine pancreas.";
RL Biochem. Biophys. Res. Commun. 140:827-831(1986).
RN [14]
RP PROTEIN SEQUENCE OF 34-70.
RX PubMed=3035556; DOI=10.1073/pnas.84.11.3881;
RA Westermark P., Wernstedt C., Wilander E., Hayden D.W., O'Brien T.D.,
RA Johnson K.H.;
RT "Amyloid fibrils in human insulinoma and islets of Langerhans of the
RT diabetic cat are derived from a neuropeptide-like protein also present in
RT normal islet cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:3881-3885(1987).
RN [15]
RP PROTEIN SEQUENCE OF 30-89.
RX PubMed=2690069; DOI=10.1073/pnas.86.24.9662;
RA Roberts A.N., Leighton B., Todd J.A., Cockburn D., Schofield P.N.,
RA Sutton R., Holt S., Boyd Y., Day A.J., Foot E.A., Willis A.C., Reid K.B.M.,
RA Cooper G.J.S.;
RT "Molecular and functional characterization of amylin, a peptide associated
RT with type 2 diabetes mellitus.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:9662-9666(1989).
RN [16]
RP STRUCTURE BY NMR OF IAPP.
RX PubMed=2039456; DOI=10.1042/bj2750785;
RA Hubbard J.A.M., Martin S.R., Chaplin L.C., Bose C., Kelly S.M., Price N.C.;
RT "Solution structures of calcitonin-gene-related-peptide analogues of
RT calcitonin-gene-related peptide and amylin.";
RL Biochem. J. 275:785-788(1991).
RN [17]
RP STRUCTURE BY NMR OF 53-62 IN DETERGENT MICELLES.
RX PubMed=12717720; DOI=10.1002/bip.10305;
RA Mascioni A., Porcelli F., Ilangovan U., Ramamoorthy A., Veglia G.;
RT "Conformational preferences of the amylin nucleation site in SDS micelles:
RT an NMR study.";
RL Biopolymers 69:29-41(2003).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-70 IN COMPLEX WITH IDE, AND
RP INTERACTION WITH IDE.
RX PubMed=17051221; DOI=10.1038/nature05143;
RA Shen Y., Joachimiak A., Rosner M.R., Tang W.-J.;
RT "Structures of human insulin-degrading enzyme reveal a new substrate
RT recognition mechanism.";
RL Nature 443:870-874(2006).
RN [19]
RP STRUCTURE BY NMR OF 34-70 IN DETERGENT MICELLES, DOMAIN, AND DISULFIDE
RP BOND.
RX PubMed=19244249; DOI=10.1074/jbc.m809085200;
RA Patil S.M., Xu S., Sheftic S.R., Alexandrescu A.T.;
RT "Dynamic alpha-helix structure of micelle-bound human amylin.";
RL J. Biol. Chem. 284:11982-11991(2009).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEX WITH INS, DISULFIDE BOND,
RP MUTAGENESIS OF PHE-48, AND DOMAIN.
RX PubMed=19475663; DOI=10.1002/pro.145;
RA Wiltzius J.J., Sievers S.A., Sawaya M.R., Eisenberg D.;
RT "Atomic structures of IAPP (amylin) fusions suggest a mechanism for
RT fibrillation and the role of insulin in the process.";
RL Protein Sci. 18:1521-1530(2009).
RN [21]
RP VARIANT GLY-53.
RX PubMed=8772735; DOI=10.2337/diab.45.9.1279;
RA Sakagashira S., Sanke T., Hanabusa T., Shimomura H., Ohagi S.,
RA Kumagaye K.Y., Nakajima K., Nanjo K.;
RT "Missense mutation of amylin gene (S20G) in Japanese NIDDM patients.";
RL Diabetes 45:1279-1281(1996).
RN [22]
RP VARIANT GLY-53.
RX PubMed=9794116; DOI=10.1007/s001250051060;
RA Chuang L.M., Lee K.C., Huang C.N., Wu H.P., Tai T.Y., Lin B.J.;
RT "Role of S20G mutation of amylin gene in insulin secretion, insulin
RT sensitivity, and type II diabetes mellitus in Taiwanese patients.";
RL Diabetologia 41:1250-1251(1998).
CC -!- FUNCTION: Selectively inhibits insulin-stimulated glucose utilization
CC and glycogen deposition in muscle, while not affecting adipocyte
CC glucose metabolism.
CC -!- SUBUNIT: Interacts with IDE and INS. Can form homodimers. Interaction
CC with INS inhibits homodimerization and fibril formation.
CC {ECO:0000269|PubMed:17051221, ECO:0000269|PubMed:19475663}.
CC -!- INTERACTION:
CC P10997; P56817: BACE1; NbExp=2; IntAct=EBI-8526679, EBI-2433139;
CC P10997; Q9Y5Z0: BACE2; NbExp=3; IntAct=EBI-8526679, EBI-11282723;
CC P10997; P10997: IAPP; NbExp=14; IntAct=EBI-8526679, EBI-8526679;
CC P10997; P14735-1: IDE; NbExp=3; IntAct=EBI-8526679, EBI-15607031;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17374526}.
CC -!- DOMAIN: The mature protein is largely unstructured in the absence of a
CC cognate ligand, and has a strong tendency to form fibrillar aggregates.
CC Homodimerization may be the first step of amyloid formation.
CC {ECO:0000269|PubMed:17374526, ECO:0000269|PubMed:19244249,
CC ECO:0000269|PubMed:19475663}.
CC -!- PTM: Amyloid fibrils are degraded by IDE.
CC -!- MASS SPECTROMETRY: Mass=3936; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17374526};
CC -!- MISCELLANEOUS: IAPP is the peptide subunit of amyloid found in
CC pancreatic islets of type 2 diabetic patients and in insulinomas.
CC -!- SIMILARITY: Belongs to the calcitonin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Amylin entry;
CC URL="https://en.wikipedia.org/wiki/Amylin";
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DR EMBL; M27503; AAA35524.1; -; Genomic_DNA.
DR EMBL; X14904; CAA33032.1; -; mRNA.
DR EMBL; X14905; CAA33033.1; -; mRNA.
DR EMBL; X14902; CAA33031.1; -; Genomic_DNA.
DR EMBL; X14903; CAB57804.1; -; Genomic_DNA.
DR EMBL; X13859; CAB57803.1; -; Genomic_DNA.
DR EMBL; J04422; AAA52281.1; -; mRNA.
DR EMBL; M21785; AAA51728.1; -; Genomic_DNA.
DR EMBL; M26650; AAA35983.1; -; Genomic_DNA.
DR EMBL; X52818; CAA37002.1; -; Genomic_DNA.
DR EMBL; X52819; CAA37002.1; JOINED; Genomic_DNA.
DR EMBL; X56030; CAA39504.1; -; Genomic_DNA.
DR EMBL; X55634; CAA39504.1; JOINED; Genomic_DNA.
DR EMBL; X68830; CAA48724.1; -; Genomic_DNA.
DR EMBL; DQ516082; ABG27010.1; -; mRNA.
DR EMBL; CH471094; EAW96426.1; -; Genomic_DNA.
DR CCDS; CCDS8688.1; -.
DR PIR; S04016; TCHUIA.
DR RefSeq; NP_000406.1; NM_000415.2.
DR RefSeq; NP_001316130.1; NM_001329201.1.
DR PDB; 1KUW; NMR; -; A=53-62.
DR PDB; 2G48; X-ray; 2.60 A; C/D=34-70.
DR PDB; 2KB8; NMR; -; A=34-70.
DR PDB; 2L86; NMR; -; A=34-70.
DR PDB; 3DG1; X-ray; 1.66 A; A=61-66.
DR PDB; 3FPO; X-ray; 1.50 A; A=51-56.
DR PDB; 3FR1; X-ray; 1.85 A; A=47-52.
DR PDB; 3FTH; X-ray; 1.84 A; A/B=47-53.
DR PDB; 3FTK; X-ray; 1.50 A; A=64-70.
DR PDB; 3FTL; X-ray; 1.60 A; A/B=64-70.
DR PDB; 3FTR; X-ray; 1.61 A; A=61-66.
DR PDB; 3G7V; X-ray; 1.86 A; A/B/C/D=34-69.
DR PDB; 3G7W; X-ray; 1.75 A; A=34-55.
DR PDB; 3HGZ; X-ray; 2.91 A; D/E=34-70.
DR PDB; 5K5G; NMR; -; A=34-70.
DR PDB; 5KNZ; EM; 1.90 A; A=52-62.
DR PDB; 5KO0; EM; 1.40 A; A/B=48-58.
DR PDB; 5MGQ; NMR; -; A=34-69.
DR PDB; 6UCJ; NMR; -; A=23-89.
DR PDB; 6UCK; NMR; -; A=23-89.
DR PDB; 6VW2; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J=34-70.
DR PDB; 6Y1A; EM; 4.20 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=34-70.
DR PDB; 6ZRF; EM; 3.60 A; A/B/C/D/E/F/G/H/I/J/K/L=34-70.
DR PDB; 6ZRQ; EM; 3.90 A; A/B/C/D/E/F/G/H/I/J/K/L=34-70.
DR PDB; 6ZRR; EM; 4.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=34-70.
DR PDB; 7BG0; X-ray; 2.89 A; A/B/D/E=34-70.
DR PDB; 7M61; EM; 3.80 A; A/B/C/D/E/F/G/H/I/J=34-70.
DR PDB; 7M62; EM; 3.90 A; A/B/C/D/E/F/G/H/I/J=34-70.
DR PDB; 7M64; EM; 4.00 A; A/B/C/D/E/F/G/H/I/J=34-70.
DR PDB; 7M65; EM; 4.10 A; A/B/C/D/E/F/G/H/I/J=34-70.
DR PDBsum; 1KUW; -.
DR PDBsum; 2G48; -.
DR PDBsum; 2KB8; -.
DR PDBsum; 2L86; -.
DR PDBsum; 3DG1; -.
DR PDBsum; 3FPO; -.
DR PDBsum; 3FR1; -.
DR PDBsum; 3FTH; -.
DR PDBsum; 3FTK; -.
DR PDBsum; 3FTL; -.
DR PDBsum; 3FTR; -.
DR PDBsum; 3G7V; -.
DR PDBsum; 3G7W; -.
DR PDBsum; 3HGZ; -.
DR PDBsum; 5K5G; -.
DR PDBsum; 5KNZ; -.
DR PDBsum; 5KO0; -.
DR PDBsum; 5MGQ; -.
DR PDBsum; 6UCJ; -.
DR PDBsum; 6UCK; -.
DR PDBsum; 6VW2; -.
DR PDBsum; 6Y1A; -.
DR PDBsum; 6ZRF; -.
DR PDBsum; 6ZRQ; -.
DR PDBsum; 6ZRR; -.
DR PDBsum; 7BG0; -.
DR PDBsum; 7M61; -.
DR PDBsum; 7M62; -.
DR PDBsum; 7M64; -.
DR PDBsum; 7M65; -.
DR AlphaFoldDB; P10997; -.
DR BMRB; P10997; -.
DR SMR; P10997; -.
DR BioGRID; 109604; 14.
DR DIP; DIP-29913N; -.
DR IntAct; P10997; 3.
DR MINT; P10997; -.
DR STRING; 9606.ENSP00000240652; -.
DR ChEMBL; CHEMBL1914266; -.
DR DrugBank; DB09130; Copper.
DR iPTMnet; P10997; -.
DR PhosphoSitePlus; P10997; -.
DR BioMuta; IAPP; -.
DR DMDM; 124006; -.
DR MassIVE; P10997; -.
DR PaxDb; P10997; -.
DR PeptideAtlas; P10997; -.
DR PRIDE; P10997; -.
DR ProteomicsDB; 52687; -.
DR ABCD; P10997; 20 sequenced antibodies.
DR Antibodypedia; 4370; 428 antibodies from 35 providers.
DR DNASU; 3375; -.
DR Ensembl; ENST00000240652.8; ENSP00000240652.3; ENSG00000121351.8.
DR Ensembl; ENST00000539393.5; ENSP00000437357.1; ENSG00000121351.8.
DR GeneID; 3375; -.
DR KEGG; hsa:3375; -.
DR MANE-Select; ENST00000240652.8; ENSP00000240652.3; NM_000415.3; NP_000406.1.
DR UCSC; uc001rev.4; human.
DR CTD; 3375; -.
DR DisGeNET; 3375; -.
DR GeneCards; IAPP; -.
DR HGNC; HGNC:5329; IAPP.
DR HPA; ENSG00000121351; Tissue enriched (pancreas).
DR MIM; 147940; gene.
DR neXtProt; NX_P10997; -.
DR OpenTargets; ENSG00000121351; -.
DR PharmGKB; PA29579; -.
DR VEuPathDB; HostDB:ENSG00000121351; -.
DR eggNOG; ENOG502S4AQ; Eukaryota.
DR GeneTree; ENSGT00510000048671; -.
DR InParanoid; P10997; -.
DR OMA; CATQRLT; -.
DR OrthoDB; 1454612at2759; -.
DR PhylomeDB; P10997; -.
DR TreeFam; TF330783; -.
DR PathwayCommons; P10997; -.
DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-419812; Calcitonin-like ligand receptors.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P10997; -.
DR SIGNOR; P10997; -.
DR BioGRID-ORCS; 3375; 6 hits in 1065 CRISPR screens.
DR ChiTaRS; IAPP; human.
DR EvolutionaryTrace; P10997; -.
DR GeneWiki; Amylin; -.
DR GenomeRNAi; 3375; -.
DR Pharos; P10997; Tbio.
DR PRO; PR:P10997; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P10997; protein.
DR Bgee; ENSG00000121351; Expressed in islet of Langerhans and 59 other tissues.
DR ExpressionAtlas; P10997; baseline and differential.
DR Genevisible; P10997; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016234; C:inclusion body; IDA:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; TAS:ARUK-UCL.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0097647; P:amylin receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:1990000; P:amyloid fibril formation; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0042755; P:eating behavior; IEA:Ensembl.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; TAS:ARUK-UCL.
DR GO; GO:0045779; P:negative regulation of bone resorption; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0010823; P:negative regulation of mitochondrion organization; TAS:ARUK-UCL.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; TAS:ARUK-UCL.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:ARUK-UCL.
DR GO; GO:1905665; P:positive regulation of calcium ion import across plasma membrane; IGI:ARUK-UCL.
DR GO; GO:0010942; P:positive regulation of cell death; IGI:ARUK-UCL.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; NAS:ARUK-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IGI:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:ARUK-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; NAS:ARUK-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:ARUK-UCL.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; IGI:ARUK-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:ARUK-UCL.
DR GO; GO:0031648; P:protein destabilization; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR021117; Calcitonin-like.
DR InterPro; IPR021116; Calcitonin/adrenomedullin.
DR InterPro; IPR018360; Calcitonin_CS.
DR InterPro; IPR001693; Calcitonin_peptide-like.
DR InterPro; IPR000443; IAPP.
DR PANTHER; PTHR10505; PTHR10505; 2.
DR PANTHER; PTHR10505:SF4; PTHR10505:SF4; 2.
DR Pfam; PF00214; Calc_CGRP_IAPP; 1.
DR PRINTS; PR00818; ISLETAMYLOID.
DR SMART; SM00113; CALCITONIN; 1.
DR PROSITE; PS00258; CALCITONIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Amyloid; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Hormone; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..31
FT /id="PRO_0000004105"
FT PEPTIDE 34..70
FT /note="Islet amyloid polypeptide"
FT /id="PRO_0000004106"
FT PROPEP 74..89
FT /id="PRO_0000004107"
FT MOD_RES 70
FT /note="Tyrosine amide"
FT /evidence="ECO:0000269|PubMed:2651160,
FT ECO:0000269|PubMed:3053705"
FT DISULFID 35..40
FT /evidence="ECO:0000269|PubMed:19244249,
FT ECO:0000269|PubMed:19475663, ECO:0000269|PubMed:3317417"
FT VARIANT 53
FT /note="S -> G (in dbSNP:rs1800203)"
FT /evidence="ECO:0000269|PubMed:8772735,
FT ECO:0000269|PubMed:9794116"
FT /id="VAR_012080"
FT MUTAGEN 48
FT /note="F->A,D,S: Promotes formation of fibrillar
FT aggregates."
FT /evidence="ECO:0000269|PubMed:19475663"
FT CONFLICT 53
FT /note="S -> C (in Ref. 4; CAA39504)"
FT /evidence="ECO:0000305"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:2G48"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:5K5G"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:5KO0"
FT STRAND 59..66
FT /evidence="ECO:0007829|PDB:6VW2"
FT HELIX 73..81
FT /evidence="ECO:0007829|PDB:6UCJ"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:6UCJ"
SQ SEQUENCE 89 AA; 9806 MW; AA8B1F7FD9FCB4BD CRC64;
MGILKLQVFL IVLSVALNHL KATPIESHQV EKRKCNTATC ATQRLANFLV HSSNNFGAIL
SSTNVGSNTY GKRNAVEVLK REPLNYLPL
