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Protein

Islet amyloid polypeptide

Gene

IAPP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism.

Miscellaneous

IAPP is the peptide subunit of amyloid found in pancreatic islets of type 2 diabetic patients and in insulinomas.

GO - Molecular functioni

  • amyloid-beta binding Source: ARUK-UCL
  • hormone activity Source: UniProtKB-KW
  • identical protein binding Source: UniProtKB
  • signaling receptor binding Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionHormone

Enzyme and pathway databases

ReactomeiR-HSA-210745 Regulation of gene expression in beta cells
R-HSA-418555 G alpha (s) signalling events
R-HSA-419812 Calcitonin-like ligand receptors
R-HSA-977225 Amyloid fiber formation

Names & Taxonomyi

Protein namesi
Recommended name:
Islet amyloid polypeptide
Alternative name(s):
Amylin
Diabetes-associated peptide
Short name:
DAP
Insulinoma amyloid peptide
Gene namesi
Name:IAPP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000121351.7
HGNCiHGNC:5329 IAPP
MIMi147940 gene
neXtProtiNX_P10997

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Amyloid, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi48F → A, D or S: Promotes formation of fibrillar aggregates. 1 Publication1

Organism-specific databases

DisGeNETi3375
OpenTargetsiENSG00000121351
PharmGKBiPA29579

Chemistry databases

ChEMBLiCHEMBL1914266

Polymorphism and mutation databases

BioMutaiIAPP
DMDMi124006

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
PropeptideiPRO_000000410523 – 319
PeptideiPRO_000000410634 – 70Islet amyloid polypeptideAdd BLAST37
PropeptideiPRO_000000410774 – 89Add BLAST16

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 403 Publications
Modified residuei70Tyrosine amide2 Publications1

Post-translational modificationi

Amyloid fibrils are degraded by IDE.

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

PaxDbiP10997
PeptideAtlasiP10997
PRIDEiP10997
ProteomicsDBi52687

PTM databases

iPTMnetiP10997
PhosphoSitePlusiP10997

Miscellaneous databases

PMAP-CutDBiP10997

Expressioni

Gene expression databases

BgeeiENSG00000121351 Expressed in 34 organ(s), highest expression level in islet of Langerhans
CleanExiHS_IAPP
ExpressionAtlasiP10997 baseline and differential
GenevisibleiP10997 HS

Organism-specific databases

HPAiCAB000352
HPA053194

Interactioni

Subunit structurei

Interacts with IDE and INS. Can form homodimers. Interaction with INS inhibits homodimerization and fibril formation.2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109604, 1 interactor
DIPiDIP-29913N
IntActiP10997, 1 interactor
MINTiP10997
STRINGi9606.ENSP00000240652

Structurei

Secondary structure

189
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP10997
SMRiP10997
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10997

Family & Domainsi

Domaini

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.3 Publications

Sequence similaritiesi

Belongs to the calcitonin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J0NB Eukaryota
ENOG410Z7V7 LUCA
GeneTreeiENSGT00510000048671
HOGENOMiHOG000038203
HOVERGENiHBG096065
InParanoidiP10997
KOiK08039
OMAiSHQMEKR
OrthoDBiEOG091G15QG
PhylomeDBiP10997
TreeFamiTF330783

Family and domain databases

InterProiView protein in InterPro
IPR021117 Calcitonin-like
IPR021116 Calcitonin/adrenomedullin
IPR018360 Calcitonin_CS
IPR001693 Calcitonin_peptide-like
IPR000443 Pro-islet_amyloid_polypep
PANTHERiPTHR10505 PTHR10505, 2 hits
PTHR10505:SF4 PTHR10505:SF4, 2 hits
PfamiView protein in Pfam
PF00214 Calc_CGRP_IAPP, 1 hit
PRINTSiPR00818 ISLETAMYLOID
SMARTiView protein in SMART
SM00113 CALCITONIN, 1 hit
PROSITEiView protein in PROSITE
PS00258 CALCITONIN, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P10997-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGILKLQVFL IVLSVALNHL KATPIESHQV EKRKCNTATC ATQRLANFLV
60 70 80
HSSNNFGAIL SSTNVGSNTY GKRNAVEVLK REPLNYLPL
Length:89
Mass (Da):9,806
Last modified:July 1, 1989 - v1
Checksum:iAA8B1F7FD9FCB4BD
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H0S1F5H0S1_HUMAN
Islet amyloid polypeptide
IAPP
79Annotation score:
F5H1F0F5H1F0_HUMAN
Islet amyloid polypeptide
IAPP
79Annotation score:
H0YF85H0YF85_HUMAN
Islet amyloid polypeptide
IAPP
85Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti53S → C in CAA39504 (PubMed:2365085).Curated1

Mass spectrometryi

Molecular mass is 3936 Da from positions 34 - 70. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01208053S → G2 PublicationsCorresponds to variant dbSNP:rs1800203Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS8688.1
PIRiS04016 TCHUIA
RefSeqiNP_000406.1, NM_000415.2
NP_001316130.1, NM_001329201.1
UniGeneiHs.46835

Genome annotation databases

EnsembliENST00000240652; ENSP00000240652; ENSG00000121351
ENST00000539393; ENSP00000437357; ENSG00000121351
GeneIDi3375
KEGGihsa:3375
UCSCiuc001rev.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Amylin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS8688.1
PIRiS04016 TCHUIA
RefSeqiNP_000406.1, NM_000415.2
NP_001316130.1, NM_001329201.1
UniGeneiHs.46835

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KUWNMR-A53-62[»]
2G48X-ray2.60C/D34-70[»]
2KB8NMR-A34-70[»]
2L86NMR-A34-70[»]
3DG1X-ray1.66A61-66[»]
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[»]
5K5GNMR-A34-70[»]
5KNZelectron microscopy1.90A52-62[»]
5KO0electron microscopy1.40A/B48-58[»]
5MGQNMR-A34-69[»]
ProteinModelPortaliP10997
SMRiP10997
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109604, 1 interactor
DIPiDIP-29913N
IntActiP10997, 1 interactor
MINTiP10997
STRINGi9606.ENSP00000240652

Chemistry databases

ChEMBLiCHEMBL1914266

PTM databases

iPTMnetiP10997
PhosphoSitePlusiP10997

Polymorphism and mutation databases

BioMutaiIAPP
DMDMi124006

Proteomic databases

PaxDbiP10997
PeptideAtlasiP10997
PRIDEiP10997
ProteomicsDBi52687

Protocols and materials databases

DNASUi3375
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000240652; ENSP00000240652; ENSG00000121351
ENST00000539393; ENSP00000437357; ENSG00000121351
GeneIDi3375
KEGGihsa:3375
UCSCiuc001rev.4 human

Organism-specific databases

CTDi3375
DisGeNETi3375
EuPathDBiHostDB:ENSG00000121351.7
GeneCardsiIAPP
HGNCiHGNC:5329 IAPP
HPAiCAB000352
HPA053194
MIMi147940 gene
neXtProtiNX_P10997
OpenTargetsiENSG00000121351
PharmGKBiPA29579
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0NB Eukaryota
ENOG410Z7V7 LUCA
GeneTreeiENSGT00510000048671
HOGENOMiHOG000038203
HOVERGENiHBG096065
InParanoidiP10997
KOiK08039
OMAiSHQMEKR
OrthoDBiEOG091G15QG
PhylomeDBiP10997
TreeFamiTF330783

Enzyme and pathway databases

ReactomeiR-HSA-210745 Regulation of gene expression in beta cells
R-HSA-418555 G alpha (s) signalling events
R-HSA-419812 Calcitonin-like ligand receptors
R-HSA-977225 Amyloid fiber formation

Miscellaneous databases

EvolutionaryTraceiP10997
GeneWikiiAmylin
GenomeRNAii3375
PMAP-CutDBiP10997
PROiPR:P10997
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121351 Expressed in 34 organ(s), highest expression level in islet of Langerhans
CleanExiHS_IAPP
ExpressionAtlasiP10997 baseline and differential
GenevisibleiP10997 HS

Family and domain databases

InterProiView protein in InterPro
IPR021117 Calcitonin-like
IPR021116 Calcitonin/adrenomedullin
IPR018360 Calcitonin_CS
IPR001693 Calcitonin_peptide-like
IPR000443 Pro-islet_amyloid_polypep
PANTHERiPTHR10505 PTHR10505, 2 hits
PTHR10505:SF4 PTHR10505:SF4, 2 hits
PfamiView protein in Pfam
PF00214 Calc_CGRP_IAPP, 1 hit
PRINTSiPR00818 ISLETAMYLOID
SMARTiView protein in SMART
SM00113 CALCITONIN, 1 hit
PROSITEiView protein in PROSITE
PS00258 CALCITONIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIAPP_HUMAN
AccessioniPrimary (citable) accession number: P10997
Secondary accession number(s): Q0ZD87, Q14598
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 7, 2018
This is version 181 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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