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   27-MAR-2024, entry version 211.
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   PDB; 7YKW; EM; 3.60 A; A/B/C/D/E/F/G/H=34-70.
DR   PDB; 7YL0; EM; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=34-70.
DR   PDB; 7YL3; EM; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=34-70.
DR   PDB; 7YL7; EM; 3.30 A; A/B/C/D/E/F/G/H/I/J/K/L=34-70.
DR   PDB; 8F0J; EM; 2.00 A; P=34-70.
DR   PDB; 8F0K; EM; 1.90 A; P=34-70.
DR   PDB; 8F2A; EM; 2.20 A; P=34-70.
DR   PDB; 8F2B; EM; 2.00 A; P=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   PDBsum; 7YKW; -.
DR   PDBsum; 7YL0; -.
DR   PDBsum; 7YL3; -.
DR   PDBsum; 7YL7; -.
DR   PDBsum; 8F0J; -.
DR   PDBsum; 8F0K; -.
DR   PDBsum; 8F2A; -.
DR   PDBsum; 8F2B; -.
DR   AlphaFoldDB; P10997; -.
DR   BMRB; P10997; -.
DR   EMDB; EMD-10669; -.
DR   EMDB; EMD-11380; -.
DR   EMDB; EMD-11382; -.
DR   EMDB; EMD-11383; -.
DR   EMDB; EMD-21410; -.
DR   EMDB; EMD-23686; -.
DR   EMDB; EMD-23687; -.
DR   EMDB; EMD-23688; -.
DR   EMDB; EMD-23689; -.
DR   SMR; P10997; -.
DR   BioGRID; 109604; 14.
DR   DIP; DIP-29913N; -.
DR   IntAct; P10997; 3.
DR   MINT; P10997; -.
DR   STRING; 9606.ENSP00000240652; -.
DR   BindingDB; P10997; -.
DR   ChEMBL; CHEMBL1914266; -.
DR   DrugBank; DB09130; Copper.
DR   iPTMnet; P10997; -.
DR   PhosphoSitePlus; P10997; -.
DR   BioMuta; IAPP; -.
DR   DMDM; 124006; -.
DR   MassIVE; P10997; -.
DR   PaxDb; 9606-ENSP00000240652; -.
DR   PeptideAtlas; P10997; -.
DR   ProteomicsDB; 52687; -.
DR   ABCD; P10997; 20 sequenced antibodies.
DR   Antibodypedia; 4370; 469 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   AGR; HGNC:5329; -.
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; 3910643at2759; -.
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-977225; Amyloid fiber formation.
DR   SignaLink; P10997; -.
DR   SIGNOR; P10997; -.
DR   BioGRID-ORCS; 3375; 7 hits in 1139 CRISPR screens.
DR   ChiTaRS; IAPP; human.
DR   EvolutionaryTrace; P10997; -.
DR   GeneWiki; Amylin; -.
DR   GenomeRNAi; 3375; -.
DR   Pharos; P10997; Tchem.
DR   PRO; PR:P10997; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; P10997; Protein.
DR   Bgee; ENSG00000121351; Expressed in islet of Langerhans and 59 other cell types or tissues.
DR   ExpressionAtlas; P10997; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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; IPI:IntAct.
DR   GO; GO:0008289; F:lipid binding; EXP:DisProt.
DR   GO; GO:0048018; F:receptor ligand activity; IDA:ARUK-UCL.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL.
DR   GO; GO:0097647; P:amylin receptor signaling pathway; ISS:ARUK-UCL.
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: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:0050850; P:positive regulation of calcium-mediated signaling; IGI:ARUK-UCL.
DR   GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IDA:ARUK-UCL.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; NAS:ARUK-UCL.
DR   GO; GO:0010739; P:positive regulation of protein kinase A signaling; IGI:ARUK-UCL.
DR   GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   Gene3D; 6.10.250.2190; -; 1.
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; CALCITONIN-RELATED; 1.
DR   PANTHER; PTHR10505:SF4; ISLET AMYLOID POLYPEPTIDE; 1.
DR   Pfam; PF00214; Calc_CGRP_IAPP; 1.
DR   PRINTS; PR00818; ISLETAMYLOID.
DR   SMART; SM00113; CALCITONIN; 1.
DR   PROSITE; PS00258; CALCITONIN; 1.
DR   Genevisible; P10997; HS.
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
//