P10997 (IAPP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Islet amyloid polypeptide

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

Gene names

Name:

IAPP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	89 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.
Subunit structure	Interacts with IDE and INS. Can form homodimers. Interaction with INS inhibits homodimerization and fibril formation. Ref.18
Subcellular location	Secreted Ref.7.
Domain	The mature protein is largely unstructured in the absence of a cognate ligand, and has a strong tendency to form fibrillar aggregates. Homodimerization may be the first step of amyloid formation. Ref.7 Ref.19 Ref.20
Post-translational modification	Amyloid fibrils are degraded by IDE.
Miscellaneous	IAPP is the peptide subunit of amyloid found in pancreatic islets of type 2 diabetic patients and in insulinomas.
Sequence similarities	Belongs to the calcitonin family.
Mass spectrometry	Molecular mass is 3936 Da from positions 34 - 70. Determined by MALDI. Ref.7

Ontologies

Keywords
Cellular component	Amyloid Secreted
Coding sequence diversity	Polymorphism
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	apoptotic process Traceable author statement PubMed 8152488. Source: ProtInc cell-cell signaling Traceable author statement Ref.2. Source: ProtInc endocrine pancreas development Traceable author statement. Source: Reactome 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 signal transduction Traceable author statement PubMed 10342886. Source: ProtInc
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara
Molecular_function	receptor binding Traceable author statement PubMed 10342886Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Propeptide

23 – 31

9

PRO_0000004105

Peptide

34 – 70

37

Islet amyloid polypeptide Ref.10 Ref.12 Ref.14

PRO_0000004106

Propeptide

74 – 89

16

PRO_0000004107

Amino acid modifications

Modified residue

70

1

Tyrosine amide Ref.3

Disulfide bond

35 ↔ 40

Ref.10 Ref.19 Ref.20

Natural variations

Natural variant

53

1

S → G. Ref.21 Ref.22
Corresponds to variant rs1800203 [ dbSNP | Ensembl ].

VAR_012080

Experimental info

Mutagenesis

48

1

F → A, D or S: Promotes formation of fibrillar aggregates. Ref.20

Sequence conflict

53

1

S → C in CAA39504. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

89

Helix Strand Turn

Details...

Helix

36 – 38

3

Helix

43 – 49

7

Helix

53 – 60

8

Turn

63 – 69

7

Sequences

	Sequence		Length	Mass (Da)
	P10997 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: AA8B1F7FD9FCB4BD	FASTA	89	9,806
	10 20 30 40 50 60 MGILKLQVFL IVLSVALNHL KATPIESHQV EKRKCNTATC ATQRLANFLV HSSNNFGAIL 70 80 SSTNVGSNTY GKRNAVEVLK REPLNYLPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete islet amyloid polypeptide precursor is encoded by two exons." Mosselman S., Hoeppener J.W.M., Lips C.J.M., Jansz H.S. FEBS Lett. 247:154-158(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"Human islet amyloid polypeptide gene: complete nucleotide sequence, chromosomal localization, and evolutionary history." Nishi M., Sanke T., Seino S., Eddy R.L., Fan Y.-S., Byers M.G., Shows T.B., Bell G.I., Steiner D.F. Mol. Endocrinol. 3:1775-1781(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing." Sanke T., Bell G.I., Sample C., Rubenstein A.H., Steiner D.F. J. Biol. Chem. 263:17243-17246(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[4]	"The human islet amyloid polypeptide (IAPP) gene. Organization, chromosomal localization and functional identification of a promoter region." Christmanson L., Rorsman F., Stenman G., Westermark P., Betsholtz C. FEBS Lett. 267:160-166(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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].
[6]	"Characterization of the human islet amyloid polypeptide/amylin gene transcripts: identification of a new polyadenylation site." Hoeppener J.W.M., Oosterwijk C., Visser-Vernooy H.J., Lips C.J.M., Jansz H.S. Biochem. Biophys. Res. Commun. 189:1569-1577(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Cloning and expression of human islet amyloid polypeptide in cultured cells." Bhattacharya S., Naveena Lavanya Latha J., Kumresan R., Singh S. Biochem. Biophys. Res. Commun. 356:622-628(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, DOMAIN, MASS SPECTROMETRY. Tissue: Fetal pancreas.
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"Islet amyloid polypeptide: identification and chromosomal localization of the human gene." Mosselman S., Hoeppener J.W.M., Zandberg J., van Mansfeld A.D.M., Geurts van Kessel A.H.M., Lips C.J.M., Jansz H.S. FEBS Lett. 239:227-232(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 28-89.
[10]	"Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients." Cooper G.J., Willis A.C., Clark A., Turner R.C., Sim R.B., Reid K.B. Proc. Natl. Acad. Sci. U.S.A. 84:8628-8632(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-70, DISULFIDE BOND.
[11]	"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 34-70, SYNTHESIS OF 53-62.
[12]	"Isolation and identification of islet amyloid polypeptide in normal human pancreas." Nakazato M., Asai J., Miyazato M., Matsukura S., Kangawa K., Matsuo H. Regul. Pept. 31:179-186(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-70.
[13]	"A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas." Westermark P., Wernstedt C., Wilander E., Sletten K. Biochem. Biophys. Res. Commun. 140:827-831(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-52.
[14]	"Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells." Westermark P., Wernstedt C., Wilander E., Hayden D.W., O'Brien T.D., Johnson K.H. Proc. Natl. Acad. Sci. U.S.A. 84:3881-3885(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-70.
[15]	"Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus." Roberts A.N., Leighton B., Todd J.A., Cockburn D., Schofield P.N., Sutton R., Holt S., Boyd Y., Day A.J., Foot E.A., Willis A.C., Reid K.B.M., Cooper G.J.S. Proc. Natl. Acad. Sci. U.S.A. 86:9662-9666(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 30-89.
[16]	"Solution structures of calcitonin-gene-related-peptide analogues of calcitonin-gene-related peptide and amylin." Hubbard J.A.M., Martin S.R., Chaplin L.C., Bose C., Kelly S.M., Price N.C. Biochem. J. 275:785-788(1991) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF IAPP.
[17]	"Conformational preferences of the amylin nucleation site in SDS micelles: an NMR study." Mascioni A., Porcelli F., Ilangovan U., Ramamoorthy A., Veglia G. Biopolymers 69:29-41(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 53-62 IN DETERGENT MICELLES.
[18]	"Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism." Shen Y., Joachimiak A., Rosner M.R., Tang W.-J. Nature 443:870-874(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-70 IN COMPLEX WITH IDE, INTERACTION WITH IDE.
[19]	"Dynamic alpha-helix structure of micelle-bound human amylin." Patil S.M., Xu S., Sheftic S.R., Alexandrescu A.T. J. Biol. Chem. 284:11982-11991(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 34-70 IN DETERGENT MICELLES, DOMAIN, DISULFIDE BOND.
[20]	"Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process." Wiltzius J.J., Sievers S.A., Sawaya M.R., Eisenberg D. Protein Sci. 18:1521-1530(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEX WITH INS, DISULFIDE BOND, MUTAGENESIS OF PHE-48, DOMAIN.
[21]	"Missense mutation of amylin gene (S20G) in Japanese NIDDM patients." Sakagashira S., Sanke T., Hanabusa T., Shimomura H., Ohagi S., Kumagaye K.Y., Nakajima K., Nanjo K. Diabetes 45:1279-1281(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLY-53.
[22]	"Role of S20G mutation of amylin gene in insulin secretion, insulin sensitivity, and type II diabetes mellitus in Taiwanese patients." Chuang L.M., Lee K.C., Huang C.N., Wu H.P., Tai T.Y., Lin B.J. Diabetologia 41:1250-1251(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLY-53.
+	Additional computationally mapped references.

Web resources

Wikipedia

Amylin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M27503 Genomic DNA. Translation: AAA35524.1.
X14904 mRNA. Translation: CAA33032.1.
X14905 mRNA. Translation: CAA33033.1.
X14902 Genomic DNA. Translation: CAA33031.1.
X14903 Genomic DNA. Translation: CAB57804.1.
X13859 Genomic DNA. Translation: CAB57803.1.
J04422 mRNA. Translation: AAA52281.1.
M21785 Genomic DNA. Translation: AAA51728.1.
M26650 Genomic DNA. Translation: AAA35983.1.
X52818, X52819 Genomic DNA. Translation: CAA37002.1.
X56030, X55634 Genomic DNA. Translation: CAA39504.1.
X68830 Genomic DNA. Translation: CAA48724.1.
DQ516082 mRNA. Translation: ABG27010.1.
CH471094 Genomic DNA. Translation: EAW96426.1.

IPI

IPI00023679.

PIR

TCHUIA. S04016.

RefSeq

NP_000406.1. NM_000415.2.

UniGene

Hs.46835.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KUW	NMR	-	A	53-62	[»]
2G48	X-ray	2.60	C/D	34-70	[»]
2KB8	NMR	-	A	34-70	[»]
2L86	NMR	-	A	34-70	[»]
3FPO	X-ray	1.50	A	51-56	[»]
3FR1	X-ray	1.85	A	47-52	[»]
3FTH	X-ray	1.84	A/B	47-53	[»]
3FTK	X-ray	1.50	A	64-70	[»]
3FTL	X-ray	1.60	A/B	64-70	[»]
3FTR	X-ray	1.61	A	61-66	[»]
3G7V	X-ray	1.86	A/B/C/D	34-69	[»]
3G7W	X-ray	1.75	A	34-55	[»]
3HGZ	X-ray	2.91	D/E	34-70	[»]

ProteinModelPortal

P10997.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29913N.

STRING

9606.ENSP00000240652.

PTM databases

PhosphoSite

P10997.

Polymorphism databases

DMDM

124006.

Proteomic databases

PaxDb

P10997.

PRIDE

P10997.

Protocols and materials databases

DNASU

3375.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000240652; ENSP00000240652; ENSG00000121351.
ENST00000539393; ENSP00000437357; ENSG00000121351.

GeneID

3375.

KEGG

hsa:3375.

UCSC

uc001rev.3. human.

Organism-specific databases

CTD

3375.

GeneCards

GC12P021507.

HGNC

HGNC:5329. IAPP.

HPA

CAB000352.

MIM

147940. gene.

neXtProt

NX_P10997.

PharmGKB

PA29579.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG38926.

HOGENOM

HOG000038203.

HOVERGEN

HBG096065.

InParanoid

P10997.

KO

K08039.

OMA

SHQMEKR.

OrthoDB

EOG4X0MV3.

PhylomeDB

P10997.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

ArrayExpress

P10997.

Bgee

P10997.

CleanEx

HS_IAPP.

Genevestigator

P10997.

GermOnline

ENSG00000121351. Homo sapiens.

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

ChEMBL

CHEMBL1914266.

DrugBank

DB00790. Perindopril.

EvolutionaryTrace

P10997.

GenomeRNAi

3375.

NextBio

13352.

PMAP-CutDB

P10997.

SOURCE

Search...

Entry information

Entry name

IAPP_HUMAN

Accession

Primary (citable) accession number: P10997
Secondary accession number(s): Q0ZD87, Q14598

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 136 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.