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P10997 (IAPP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Islet amyloid polypeptide
Alternative name(s):
Amylin
Diabetes-associated peptide
Short name=DAP
Insulinoma amyloid peptide
Gene names
Name:IAPP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length89 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself3EBI-8526679,EBI-8526679

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Propeptide23 – 319
PRO_0000004105
Peptide34 – 7037Islet amyloid polypeptide Ref.10 Ref.12 Ref.14
PRO_0000004106
Propeptide74 – 8916
PRO_0000004107

Amino acid modifications

Modified residue701Tyrosine amide Ref.3
Disulfide bond35 ↔ 40 Ref.10 Ref.19 Ref.20

Natural variations

Natural variant531S → G. Ref.21 Ref.22
Corresponds to variant rs1800203 [ dbSNP | Ensembl ].
VAR_012080

Experimental info

Mutagenesis481F → A, D or S: Promotes formation of fibrillar aggregates. Ref.20
Sequence conflict531S → C in CAA39504. Ref.4

Secondary structure

......... 89
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P10997 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: AA8B1F7FD9FCB4BD

FASTA899,806
        10         20         30         40         50         60 
MGILKLQVFL IVLSVALNHL KATPIESHQV EKRKCNTATC ATQRLANFLV HSSNNFGAIL 

        70         80 
SSTNVGSNTY GKRNAVEVLK REPLNYLPL 

« Hide

References

« Hide '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. expand/collapse author list , 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.
PIRTCHUIA. S04016.
RefSeqNP_000406.1. NM_000415.2.
UniGeneHs.46835.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KUWNMR-A53-62[»]
2G48X-ray2.60C/D34-70[»]
2KB8NMR-A34-70[»]
2L86NMR-A34-70[»]
3FPOX-ray1.50A51-56[»]
3FR1X-ray1.85A47-52[»]
3FTHX-ray1.84A/B47-53[»]
3FTKX-ray1.50A64-70[»]
3FTLX-ray1.60A/B64-70[»]
3FTRX-ray1.61A61-66[»]
3G7VX-ray1.86A/B/C/D34-69[»]
3G7WX-ray1.75A34-55[»]
3HGZX-ray2.91D/E34-70[»]
ProteinModelPortalP10997.
SMRP10997. Positions 34-70.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-29913N.
MINTMINT-8074874.
STRING9606.ENSP00000240652.

Chemistry

ChEMBLCHEMBL1914266.
DrugBankDB00790. Perindopril.

PTM databases

PhosphoSiteP10997.

Polymorphism databases

DMDM124006.

Proteomic databases

PaxDbP10997.
PRIDEP10997.

Protocols and materials databases

DNASU3375.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000240652; ENSP00000240652; ENSG00000121351.
ENST00000539393; ENSP00000437357; ENSG00000121351.
GeneID3375.
KEGGhsa:3375.
UCSCuc001rev.3. human.

Organism-specific databases

CTD3375.
GeneCardsGC12P021507.
HGNCHGNC:5329. IAPP.
HPACAB000352.
HPA053194.
MIM147940. gene.
neXtProtNX_P10997.
PharmGKBPA29579.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG38926.
HOGENOMHOG000038203.
HOVERGENHBG096065.
InParanoidP10997.
KOK08039.
OMASHQMEKR.
OrthoDBEOG7TMZVK.
PhylomeDBP10997.
TreeFamTF330783.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

ArrayExpressP10997.
BgeeP10997.
CleanExHS_IAPP.
GenevestigatorP10997.

Family and domain databases

InterProIPR018360. Calcitonin_CS.
IPR001693. Calcitonin_peptide-like.
IPR000443. Pro-islet_amyloid_polypep.
IPR021117. Procalcitonin-like.
IPR021116. Procalcitonin/adrenomedullin.
[Graphical view]
PANTHERPTHR10505. PTHR10505. 1 hit.
PfamPF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view]
PRINTSPR00818. ISLETAMYLOID.
SMARTSM00113. CALCITONIN. 1 hit.
[Graphical view]
PROSITEPS00258. CALCITONIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP10997.
GeneWikiAmylin.
GenomeRNAi3375.
NextBio13352.
PMAP-CutDBP10997.
PROP10997.
SOURCESearch...

Entry information

Entry nameIAPP_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM