P12969 (IAPP_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Islet amyloid polypeptide

Alternative name(s):
Amylin
Diabetes-associated peptide
Short name=DAP

Gene names

Name:

Iapp

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	93 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	Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism By similarity.
Subunit structure	Interacts with IDE and INS By similarity.
Subcellular location	Secreted.
Tissue specificity	Abundant in the islets of Langerhans but is not present in the brain or seven other tissues examined.
Domain	The mature protein is largely unstructured in the absence of a cognate ligand, but contrary to the human protein, it does not easily form fibrillar aggregates. Ref.7
Sequence similarities	Belongs to the calcitonin family.

Ontologies

Keywords
Cellular component	Amyloid Secreted
Domain	Signal
Molecular function	Hormone
PTM	Amidation Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	eating behavior Inferred from mutant phenotype PubMed 15130879. Source: RGD glucose metabolic process Traceable author statement PubMed 17123962. Source: RGD negative regulation of bone resorption Inferred from electronic annotation. Source: Compara negative regulation of cell differentiation Inferred from electronic annotation. Source: Compara sensory perception of pain Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara secretory granule Traceable author statement Ref.1. Source: RGD
Molecular_function	hormone activity Traceable author statement PubMed 15130879. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Propeptide

24 – 35

12

PRO_0000004121

Peptide

38 – 74

37

Islet amyloid polypeptide Ref.4 Ref.5

PRO_0000004122

Propeptide

78 – 93

16

PRO_0000004123

Amino acid modifications

Modified residue

74

1

Tyrosine amide Ref.4

Disulfide bond

39 ↔ 44

Ref.8

Secondary structure

1

.

.

.

.

.

93

Helix Strand Turn

Details...

Helix

42 – 54

13

Helix

57 – 60

4

Sequences

	Sequence		Length	Mass (Da)
	P12969 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: 5A76C92E624DA962	FASTA	93	10,015
	10 20 30 40 50 60 MRCISRLPAV LLILSVALGH LRATPVGSGT NPQVDKRKCN TATCATQRLA NFLVRSSNNL 70 80 90 GPVLPPTNVG SNTYGKRNVA EDPNRESLDF LLL

References

[1]	"Conservation of the sequence of islet amyloid polypeptide in five mammals is consistent with its putative role as an islet hormone." Nishi M., Chan S.J., Nagamatsu S., Bell G.I., Steiner D.F. Proc. Natl. Acad. Sci. U.S.A. 86:5738-5742(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Rat amylin: cloning and tissue-specific expression in pancreatic islets." Leffert J.D., Newgard C.B., Okamoto H., Milburn J.L., Luskey K.L. Proc. Natl. Acad. Sci. U.S.A. 86:3127-3130(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Islet amyloid polypeptide: structure and upstream sequences of the IAPP gene in rat and man." van Mansfeld A.D.M., Mosselman S., Hoeppener J.W.M., Zandberg J., van Teeffelen H.A.A.M., Baas P.D., Lips C.J.M., Jansz H.S. Biochim. Biophys. Acta 1087:235-240(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: WAP. Tissue: Liver.
[4]	"Isolation and sequence determination of rat islet amyloid polypeptide." Asai J., Nakazato M., Kangawa K., Matsukura S., Matsuo H. Biochem. Biophys. Res. Commun. 164:400-405(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 38-74.
[5]	"Regional distribution and molecular forms of rat islet amyloid polypeptide." Asai J., Nakazato M., Miyazato M., Kangawa K., Matsuo H., Matsukura S. Biochem. Biophys. Res. Commun. 169:788-795(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 38-74.
[6]	"Sequence divergence in a specific region of islet amyloid polypeptide (IAPP) explains differences in islet amyloid formation between species." Betsholtz C., Christmansson L., Engstroem U., Rorsman F., Svensson V., Johnson K.H., Westermark P. FEBS Lett. 251:261-264(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 38-74.
[7]	"Amyloidogenesis abolished by proline substitutions but enhanced by lipid binding." Jiang P., Xu W., Mu Y. PLoS Comput. Biol. 5:E1000357-E1000357(2009) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN.
[8]	"Three-dimensional structure and orientation of rat islet amyloid polypeptide protein in a membrane environment by solution NMR spectroscopy." Nanga R.P., Brender J.R., Xu J., Hartman K., Subramanian V., Ramamoorthy A. J. Am. Chem. Soc. 131:8252-8261(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 38-74, DISULFIDE BOND.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M25390 mRNA. Translation: AAA41359.1.
J04544 mRNA. Translation: AAA40730.1.
X52820, X52821 Genomic DNA. Translation: CAA37003.1.

IPI

IPI00202679.

PIR

TCRTIA. S13566.

RefSeq

NP_036718.1. NM_012586.2.

UniGene

Rn.11394.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KJ7	NMR	-	A	38-74	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

10116.ENSRNOP00000016614.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000016614; ENSRNOP00000016614; ENSRNOG00000012417.

GeneID

24476.

KEGG

rno:24476.

UCSC

RGD:2854. rat.

Organism-specific databases

CTD

3375.

RGD

2854. Iapp.

Phylogenomic databases

eggNOG

NOG38926.

GeneTree

ENSGT00510000048671.

HOGENOM

HOG000038203.

HOVERGEN

HBG096065.

InParanoid

P12969.

KO

K08039.

OMA

SHQMEKR.

OrthoDB

EOG4X0MV3.

Gene expression databases

Genevestigator

P12969.

GermOnline

ENSRNOG00000012417. Rattus norvegicus.

Family and domain databases

InterPro

IPR018360. Calcitonin_CS.
IPR001693. Calcitonin_peptide-like.
IPR000443. Pro-islet_amyloid_polypep.
IPR021117. Procalcitonin-like.
IPR021116. Procalcitonin/adrenomedullin.
[Graphical view]

PANTHER

PTHR10505. PTHR10505. 1 hit.

Pfam

PF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view]

PRINTS

PR00818. ISLETAMYLOID.

SMART

SM00113. CALCITONIN. 1 hit.
[Graphical view]

PROSITE

PS00258. CALCITONIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P12969.

NextBio

603429.

Entry information

Entry name

IAPP_RAT

Accession

Primary (citable) accession number: P12969

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	April 3, 2013
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program