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UniProtKB - P10997 (IAPP_HUMAN)
Protein
Islet amyloid polypeptide
Gene
IAPP
Organism
Homo sapiens (Human)
Status
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
- adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: ARUK-UCL
- amylin receptor signaling pathway Source: ARUK-UCL
- amyloid fibril formation Source: UniProtKB
- apoptotic process Source: ProtInc
- cell-cell signaling Source: ProtInc
- eating behavior Source: Ensembl
- negative regulation of amyloid fibril formation Source: ARUK-UCL
- negative regulation of bone resorption Source: Ensembl
- negative regulation of cell differentiation Source: Ensembl
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of mitochondrion organization Source: ARUK-UCL
- negative regulation of protein-containing complex assembly Source: ARUK-UCL
- positive regulation of apoptotic process Source: ARUK-UCL
- positive regulation of calcium ion import across plasma membrane Source: ARUK-UCL
- positive regulation of cell death Source: ARUK-UCL
- positive regulation of cytosolic calcium ion concentration Source: ARUK-UCL
- positive regulation of ERK1 and ERK2 cascade Source: ARUK-UCL
- positive regulation of gene expression Source: ARUK-UCL
- positive regulation of MAPK cascade Source: ARUK-UCL
- positive regulation of peptidyl-serine phosphorylation Source: ARUK-UCL
- positive regulation of protein kinase A signaling Source: ARUK-UCL
- positive regulation of protein kinase B signaling Source: ARUK-UCL
- protein destabilization Source: UniProtKB
- protein homooligomerization Source: UniProtKB
- sensory perception of pain Source: Ensembl
- signal transduction Source: ProtInc
Keywordsi
Molecular function | Hormone |
Enzyme and pathway databases
PathwayCommonsi | P10997 |
Reactomei | R-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-9660821, ADORA2B mediated anti-inflammatory cytokines production R-HSA-977225, Amyloid fiber formation |
SignaLinki | P10997 |
SIGNORi | P10997 |
Names & Taxonomyi
Protein namesi | Recommended name: Islet amyloid polypeptideAlternative name(s): Amylin Diabetes-associated peptide Short name: DAP Insulinoma amyloid peptide |
Gene namesi | Name:IAPP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5329, IAPP |
MIMi | 147940, gene |
neXtProti | NX_P10997 |
VEuPathDBi | HostDB:ENSG00000121351 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: GO_Central
Other locations
- inclusion body Source: UniProtKB
Keywords - Cellular componenti
Amyloid, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 48 | F → A, D or S: Promotes formation of fibrillar aggregates. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 3375 |
OpenTargetsi | ENSG00000121351 |
PharmGKBi | PA29579 |
Miscellaneous databases
Pharosi | P10997, Tbio |
Chemistry databases
ChEMBLi | CHEMBL1914266 |
DrugBanki | DB09130, Copper |
Genetic variation databases
BioMutai | IAPP |
DMDMi | 124006 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | Sequence analysisAdd BLAST | 22 | |
PropeptideiPRO_0000004105 | 23 – 31 | 9 | ||
PeptideiPRO_0000004106 | 34 – 70 | Islet amyloid polypeptideAdd BLAST | 37 | |
PropeptideiPRO_0000004107 | 74 – 89 | Add BLAST | 16 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 35 ↔ 40 | 3 Publications | ||
Modified residuei | 70 | Tyrosine amide2 Publications | 1 |
Post-translational modificationi
Amyloid fibrils are degraded by IDE.
Keywords - PTMi
Amidation, Cleavage on pair of basic residues, Disulfide bondProteomic databases
MassIVEi | P10997 |
PaxDbi | P10997 |
PeptideAtlasi | P10997 |
PRIDEi | P10997 |
ProteomicsDBi | 52687 |
PTM databases
iPTMneti | P10997 |
PhosphoSitePlusi | P10997 |
Expressioni
Gene expression databases
Bgeei | ENSG00000121351, Expressed in islet of Langerhans and 58 other tissues |
ExpressionAtlasi | P10997, baseline and differential |
Genevisiblei | P10997, HS |
Organism-specific databases
HPAi | ENSG00000121351, Tissue enriched (pancreas) |
Interactioni
Subunit structurei
Interacts with IDE and INS. Can form homodimers. Interaction with INS inhibits homodimerization and fibril formation.
2 PublicationsBinary interactionsi
P10997
With | #Exp. | IntAct |
---|---|---|
BACE1 [P56817] | 2 | EBI-8526679,EBI-2433139 |
BACE2 [Q9Y5Z0] | 3 | EBI-8526679,EBI-11282723 |
itself | 14 | EBI-8526679,EBI-8526679 |
IDE - isoform 1 [P14735-1] | 3 | EBI-8526679,EBI-15607031 |
GO - Molecular functioni
- hormone activity Source: UniProtKB-KW
- identical protein binding Source: UniProtKB
- signaling receptor binding Source: ProtInc
Protein-protein interaction databases
BioGRIDi | 109604, 14 interactors |
DIPi | DIP-29913N |
IntActi | P10997, 3 interactors |
MINTi | P10997 |
STRINGi | 9606.ENSP00000240652 |
Miscellaneous databases
RNActi | P10997, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
AlphaFoldDBi | P10997 |
BMRBi | P10997 |
SMRi | P10997 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P10997 |
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
SignalPhylogenomic databases
eggNOGi | ENOG502S4AQ, Eukaryota |
GeneTreei | ENSGT00510000048671 |
InParanoidi | P10997 |
OMAi | CATQRLT |
OrthoDBi | 1454612at2759 |
PhylomeDBi | P10997 |
TreeFami | TF330783 |
Family and domain databases
InterProi | View protein in InterPro IPR021117, Calcitonin-like IPR021116, Calcitonin/adrenomedullin IPR018360, Calcitonin_CS IPR001693, Calcitonin_peptide-like IPR000443, IAPP |
PANTHERi | PTHR10505, PTHR10505, 2 hits PTHR10505:SF4, PTHR10505:SF4, 2 hits |
Pfami | View protein in Pfam PF00214, Calc_CGRP_IAPP, 1 hit |
PRINTSi | PR00818, ISLETAMYLOID |
SMARTi | View protein in SMART SM00113, CALCITONIN, 1 hit |
PROSITEi | View protein in PROSITE PS00258, CALCITONIN, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
P10997-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGILKLQVFL IVLSVALNHL KATPIESHQV EKRKCNTATC ATQRLANFLV
60 70 80
HSSNNFGAIL SSTNVGSNTY GKRNAVEVLK REPLNYLPL
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF5H0S1 | F5H0S1_HUMAN | Islet amyloid polypeptide | IAPP | 79 | Annotation score: | ||
H0YF85 | H0YF85_HUMAN | Islet amyloid polypeptide | IAPP | 85 | Annotation score: | ||
F5H1F0 | F5H1F0_HUMAN | Islet amyloid polypeptide | IAPP | 79 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 53 | S → C in CAA39504 (PubMed:2365085).Curated | 1 |
Mass spectrometryi
Molecular mass is 3936 Da. Determined by MALDI. 1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_012080 | 53 | S → 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 |
CCDSi | CCDS8688.1 |
PIRi | S04016, TCHUIA |
RefSeqi | NP_000406.1, NM_000415.2 NP_001316130.1, NM_001329201.1 |
Genome annotation databases
Ensembli | ENST00000240652.8; ENSP00000240652.3; ENSG00000121351.8 ENST00000539393.5; ENSP00000437357.1; ENSG00000121351.8 |
GeneIDi | 3375 |
KEGGi | hsa:3375 |
MANE-Selecti | ENST00000240652.8; ENSP00000240652.3; NM_000415.3; NP_000406.1 |
UCSCi | uc001rev.4, human |
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 |
CCDSi | CCDS8688.1 |
PIRi | S04016, TCHUIA |
RefSeqi | NP_000406.1, NM_000415.2 NP_001316130.1, NM_001329201.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
3DG1 | X-ray | 1.66 | A | 61-66 | [»] | |
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 | [»] | |
5K5G | NMR | - | A | 34-70 | [»] | |
5KNZ | electron microscopy | 1.90 | A | 52-62 | [»] | |
5KO0 | electron microscopy | 1.40 | A/B | 48-58 | [»] | |
5MGQ | NMR | - | A | 34-69 | [»] | |
6UCJ | NMR | - | A | 23-89 | [»] | |
6UCK | NMR | - | A | 23-89 | [»] | |
6VW2 | electron microscopy | 3.40 | A/B/C/D/E/F/G/H/I/J | 34-70 | [»] | |
6Y1A | electron microscopy | 4.20 | A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P | 34-70 | [»] | |
6ZRF | electron microscopy | 3.60 | A/B/C/D/E/F/G/H/I/J/K/L | 34-70 | [»] | |
6ZRQ | electron microscopy | 3.90 | A/B/C/D/E/F/G/H/I/J/K/L | 34-70 | [»] | |
6ZRR | electron microscopy | 4.00 | A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R | 34-70 | [»] | |
7BG0 | X-ray | 2.89 | A/B/D/E | 34-70 | [»] | |
7M61 | electron microscopy | 3.80 | A/B/C/D/E/F/G/H/I/J | 34-70 | [»] | |
7M62 | electron microscopy | 3.90 | A/B/C/D/E/F/G/H/I/J | 34-70 | [»] | |
7M64 | electron microscopy | 4.00 | A/B/C/D/E/F/G/H/I/J | 34-70 | [»] | |
7M65 | electron microscopy | 4.10 | A/B/C/D/E/F/G/H/I/J | 34-70 | [»] | |
AlphaFoldDBi | P10997 | |||||
BMRBi | P10997 | |||||
SMRi | P10997 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109604, 14 interactors |
DIPi | DIP-29913N |
IntActi | P10997, 3 interactors |
MINTi | P10997 |
STRINGi | 9606.ENSP00000240652 |
Chemistry databases
ChEMBLi | CHEMBL1914266 |
DrugBanki | DB09130, Copper |
PTM databases
iPTMneti | P10997 |
PhosphoSitePlusi | P10997 |
Genetic variation databases
BioMutai | IAPP |
DMDMi | 124006 |
Proteomic databases
MassIVEi | P10997 |
PaxDbi | P10997 |
PeptideAtlasi | P10997 |
PRIDEi | P10997 |
ProteomicsDBi | 52687 |
Protocols and materials databases
ABCDi | P10997, 20 sequenced antibodies |
Antibodypediai | 4370, 440 antibodies from 35 providers |
DNASUi | 3375 |
Genome annotation databases
Ensembli | ENST00000240652.8; ENSP00000240652.3; ENSG00000121351.8 ENST00000539393.5; ENSP00000437357.1; ENSG00000121351.8 |
GeneIDi | 3375 |
KEGGi | hsa:3375 |
MANE-Selecti | ENST00000240652.8; ENSP00000240652.3; NM_000415.3; NP_000406.1 |
UCSCi | uc001rev.4, human |
Organism-specific databases
CTDi | 3375 |
DisGeNETi | 3375 |
GeneCardsi | IAPP |
HGNCi | HGNC:5329, IAPP |
HPAi | ENSG00000121351, Tissue enriched (pancreas) |
MIMi | 147940, gene |
neXtProti | NX_P10997 |
OpenTargetsi | ENSG00000121351 |
PharmGKBi | PA29579 |
VEuPathDBi | HostDB:ENSG00000121351 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S4AQ, Eukaryota |
GeneTreei | ENSGT00510000048671 |
InParanoidi | P10997 |
OMAi | CATQRLT |
OrthoDBi | 1454612at2759 |
PhylomeDBi | P10997 |
TreeFami | TF330783 |
Enzyme and pathway databases
PathwayCommonsi | P10997 |
Reactomei | R-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-9660821, ADORA2B mediated anti-inflammatory cytokines production R-HSA-977225, Amyloid fiber formation |
SignaLinki | P10997 |
SIGNORi | P10997 |
Miscellaneous databases
BioGRID-ORCSi | 3375, 6 hits in 1065 CRISPR screens |
ChiTaRSi | IAPP, human |
EvolutionaryTracei | P10997 |
GeneWikii | Amylin |
GenomeRNAii | 3375 |
Pharosi | P10997, Tbio |
PROi | PR:P10997 |
RNActi | P10997, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000121351, Expressed in islet of Langerhans and 58 other tissues |
ExpressionAtlasi | P10997, baseline and differential |
Genevisiblei | P10997, HS |
Family and domain databases
InterProi | View protein in InterPro IPR021117, Calcitonin-like IPR021116, Calcitonin/adrenomedullin IPR018360, Calcitonin_CS IPR001693, Calcitonin_peptide-like IPR000443, IAPP |
PANTHERi | PTHR10505, PTHR10505, 2 hits PTHR10505:SF4, PTHR10505:SF4, 2 hits |
Pfami | View protein in Pfam PF00214, Calc_CGRP_IAPP, 1 hit |
PRINTSi | PR00818, ISLETAMYLOID |
SMARTi | View protein in SMART SM00113, CALCITONIN, 1 hit |
PROSITEi | View protein in PROSITE PS00258, CALCITONIN, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IAPP_HUMAN | |
Accessioni | P10997Primary (citable) accession number: P10997 Secondary accession number(s): Q0ZD87, Q14598 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1989 |
Last sequence update: | July 1, 1989 | |
Last modified: | May 25, 2022 | |
This is version 201 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families