Reviewed, UniProtKB/Swiss-Prot P12969 (IAPP_RAT)

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)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › 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 Direct protein sequencing
Gene Ontology (GO)
Biological process	glucose metabolic process Traceable author statement. Source: RGD
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell secretory granule Ref.1 Traceable author statement. Source: RGD
Molecular function	hormone activity Inferred from electronic annotation. Source: UniProtKB-KW
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

55 – 58

4

Sequences

	Sequence		Length	Mass (Da)
	P12969-1 [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: 2668946] [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: 2654937] [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: 2223885] [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: 2679555] [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: 2357234] [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: 2666169] [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: 19360098] [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: 19456151] [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.

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

P12969.

Genome annotation databases

Ensembl

ENSRNOT00000016614; ENSRNOP00000016614; ENSRNOG00000012417; Rattus norvegicus. [Genome view]

GeneID

24476.

KEGG

rno:24476.

UCSC

NM_012586. rat.

Organism-specific databases

CTD

24476.

RGD

2854. Iapp.

Phylogenomic databases

eggNOG

roNOG17456.

HOVERGEN

P12969.

InParanoid

P12969.

OMA

VEKRKCN.

OrthoDB

EOG9F4VX1.

PhylomeDB

P12969.

Gene expression databases

ArrayExpress

P12969.

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. Calcitonin-like. 1 hit.
PTHR10505:SF4. Pro-islet_amyloid_polypep. 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 Resources

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:	February 9, 2010
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)