IAPP_RAT
ID IAPP_RAT Reviewed; 93 AA.
AC P12969;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Islet amyloid polypeptide;
DE AltName: Full=Amylin;
DE AltName: Full=Diabetes-associated peptide;
DE Short=DAP;
DE Flags: Precursor;
GN Name=Iapp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2668946; DOI=10.1073/pnas.86.15.5738;
RA Nishi M., Chan S.J., Nagamatsu S., Bell G.I., Steiner D.F.;
RT "Conservation of the sequence of islet amyloid polypeptide in five mammals
RT is consistent with its putative role as an islet hormone.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5738-5742(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2654937; DOI=10.1073/pnas.86.9.3127;
RA Leffert J.D., Newgard C.B., Okamoto H., Milburn J.L., Luskey K.L.;
RT "Rat amylin: cloning and tissue-specific expression in pancreatic islets.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:3127-3130(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=WAP; TISSUE=Liver;
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 [4]
RP PROTEIN SEQUENCE OF 38-74, AND AMIDATION AT TYR-74.
RX PubMed=2679555; DOI=10.1016/0006-291x(89)91733-6;
RA Asai J., Nakazato M., Kangawa K., Matsukura S., Matsuo H.;
RT "Isolation and sequence determination of rat islet amyloid polypeptide.";
RL Biochem. Biophys. Res. Commun. 164:400-405(1989).
RN [5]
RP PROTEIN SEQUENCE OF 38-74.
RX PubMed=2357234; DOI=10.1016/0006-291x(90)90400-h;
RA Asai J., Nakazato M., Miyazato M., Kangawa K., Matsuo H., Matsukura S.;
RT "Regional distribution and molecular forms of rat islet amyloid
RT polypeptide.";
RL Biochem. Biophys. Res. Commun. 169:788-795(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 38-74.
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 [7]
RP DOMAIN.
RX PubMed=19360098; DOI=10.1371/journal.pcbi.1000357;
RA Jiang P., Xu W., Mu Y.;
RT "Amyloidogenesis abolished by proline substitutions but enhanced by lipid
RT binding.";
RL PLoS Comput. Biol. 5:E1000357-E1000357(2009).
RN [8]
RP STRUCTURE BY NMR OF 38-74, AND DISULFIDE BOND.
RX PubMed=19456151; DOI=10.1021/ja9010095;
RA Nanga R.P., Brender J.R., Xu J., Hartman K., Subramanian V.,
RA Ramamoorthy A.;
RT "Three-dimensional structure and orientation of rat islet amyloid
RT polypeptide protein in a membrane environment by solution NMR
RT spectroscopy.";
RL J. Am. Chem. Soc. 131:8252-8261(2009).
CC -!- FUNCTION: Selectively inhibits insulin-stimulated glucose utilization
CC and glycogen deposition in muscle, while not affecting adipocyte
CC glucose metabolism. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with IDE and INS. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Abundant in the islets of Langerhans but is not
CC present in the brain or seven other tissues examined.
CC -!- DOMAIN: The mature protein is largely unstructured in the absence of a
CC cognate ligand, but contrary to the human protein, it does not easily
CC form fibrillar aggregates. {ECO:0000269|PubMed:19360098}.
CC -!- SIMILARITY: Belongs to the calcitonin family. {ECO:0000305}.
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DR EMBL; M25390; AAA41359.1; -; mRNA.
DR EMBL; J04544; AAA40730.1; -; mRNA.
DR EMBL; X52820; CAA37003.1; -; Genomic_DNA.
DR EMBL; X52821; CAA37003.1; JOINED; Genomic_DNA.
DR PIR; S13566; TCRTIA.
DR RefSeq; NP_036718.1; NM_012586.2.
DR RefSeq; XP_006237676.1; XM_006237614.3.
DR PDB; 2KJ7; NMR; -; A=38-74.
DR PDB; 7TYF; EM; 2.20 A; P=38-74.
DR PDB; 7TYI; EM; 3.30 A; P=38-74.
DR PDB; 7TYL; EM; 3.30 A; P=38-74.
DR PDB; 7TYX; EM; 2.55 A; P=38-74.
DR PDB; 7TZF; EM; 2.40 A; P=38-74.
DR PDBsum; 2KJ7; -.
DR PDBsum; 7TYF; -.
DR PDBsum; 7TYI; -.
DR PDBsum; 7TYL; -.
DR PDBsum; 7TYX; -.
DR PDBsum; 7TZF; -.
DR AlphaFoldDB; P12969; -.
DR BMRB; P12969; -.
DR SMR; P12969; -.
DR BioGRID; 246637; 1.
DR STRING; 10116.ENSRNOP00000016614; -.
DR PaxDb; P12969; -.
DR PRIDE; P12969; -.
DR Ensembl; ENSRNOT00000016614; ENSRNOP00000016614; ENSRNOG00000012417.
DR GeneID; 24476; -.
DR KEGG; rno:24476; -.
DR UCSC; RGD:2854; rat.
DR CTD; 3375; -.
DR RGD; 2854; Iapp.
DR eggNOG; ENOG502S4AQ; Eukaryota.
DR GeneTree; ENSGT00510000048671; -.
DR HOGENOM; CLU_189304_0_0_1; -.
DR InParanoid; P12969; -.
DR OMA; CATQRLT; -.
DR OrthoDB; 1454612at2759; -.
DR PhylomeDB; P12969; -.
DR TreeFam; TF330783; -.
DR Reactome; R-RNO-419812; Calcitonin-like ligand receptors.
DR EvolutionaryTrace; P12969; -.
DR PRO; PR:P12969; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000012417; Expressed in pancreas and 7 other tissues.
DR Genevisible; P12969; RN.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0030141; C:secretory granule; TAS:RGD.
DR GO; GO:0005179; F:hormone activity; TAS:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
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:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0042755; P:eating behavior; IMP:RGD.
DR GO; GO:0006006; P:glucose metabolic process; TAS:RGD.
DR GO; GO:0045779; P:negative regulation of bone resorption; ISO:RGD.
DR GO; GO:0045596; P:negative regulation of cell differentiation; ISO:RGD.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
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; 1.
DR PANTHER; PTHR10505:SF4; PTHR10505:SF4; 1.
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..23
FT /evidence="ECO:0000255"
FT PROPEP 24..35
FT /id="PRO_0000004121"
FT PEPTIDE 38..74
FT /note="Islet amyloid polypeptide"
FT /id="PRO_0000004122"
FT PROPEP 78..93
FT /id="PRO_0000004123"
FT MOD_RES 74
FT /note="Tyrosine amide"
FT /evidence="ECO:0000269|PubMed:2679555"
FT DISULFID 39..44
FT /evidence="ECO:0000269|PubMed:19456151"
FT HELIX 42..54
FT /evidence="ECO:0007829|PDB:2KJ7"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:2KJ7"
SQ SEQUENCE 93 AA; 10015 MW; 5A76C92E624DA962 CRC64;
MRCISRLPAV LLILSVALGH LRATPVGSGT NPQVDKRKCN TATCATQRLA NFLVRSSNNL
GPVLPPTNVG SNTYGKRNVA EDPNRESLDF LLL
