Human Gene IAPP (ENST00000539393.5)
  Description: Homo sapiens islet amyloid polypeptide (IAPP), transcript variant 2, mRNA. (from RefSeq NM_001329201)
RefSeq Summary (NM_001329201): This gene encodes a member of the calcitonin family of peptide hormones. This hormone is released from pancreatic beta cells following food intake to regulate blood glucose levels and act as a satiation signal. Human patients with type 1 and advanced type 2 diabetes exhibit reduced levels of the encoded hormone in blood and pancreas. This protein also exhibits a bactericidal, antimicrobial activity. [provided by RefSeq, Jul 2016].
Gencode Transcript: ENST00000539393.5
Gencode Gene: ENSG00000121351.8
Transcript (Including UTRs)
   Position: hg38 chr12:21,354,959-21,378,495 Size: 23,537 Total Exon Count: 3 Strand: +
Coding Region
   Position: hg38 chr12:21,373,352-21,378,426 Size: 5,075 Coding Exon Count: 2 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:21,354,959-21,378,495)mRNA (may differ from genome)Protein (89 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: IAPP_HUMAN
DESCRIPTION: RecName: Full=Islet amyloid polypeptide; AltName: Full=Amylin; AltName: Full=Diabetes-associated peptide; Short=DAP; AltName: Full=Insulinoma amyloid peptide; Flags: Precursor;
FUNCTION: Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism.
SUBUNIT: Interacts with IDE and INS. Can form homodimers. Interaction with INS inhibits homodimerization and fibril formation.
SUBCELLULAR LOCATION: Secreted.
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.
PTM: Amyloid fibrils are degraded by IDE.
MASS SPECTROMETRY: Mass=3936; Method=MALDI; Range=34-70; Source=PubMed:17374526;
MISCELLANEOUS: IAPP is the peptide subunit of amyloid found in pancreatic islets of type 2 diabetic patients and in insulinomas.
SIMILARITY: Belongs to the calcitonin family.
WEB RESOURCE: Name=Wikipedia; Note=Amylin entry; URL="http://en.wikipedia.org/wiki/Amylin";

-  MalaCards Disease Associations
  MalaCards Gene Search: IAPP
Diseases sorted by gene-association score: insulinoma (21), diabetes mellitus, insulin-dependent (13), hyperglycemia (10), nasu-hakola disease (9), amyloidosis (7), diabetes mellitus, noninsulin-dependent (7), endocrine gland cancer (6), monogenic diabetes (6), glucose metabolism disease (5), cloacal exstrophy (4), amyloidosis, familial visceral (4), monocarboxylate transporter 1 deficiency (4), maturity-onset diabetes of the young (2), acquired metabolic disease (2), obesity (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.40 RPKM in Pancreas
Total median expression: 10.14 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -5.5070-0.079 Picture PostScript Text
3' UTR -7.9069-0.114 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR018360 - Calcitonin_CS
IPR001693 - Calcitonin_peptide-like
IPR000443 - Pro-islet_amyloid_polypep
IPR021117 - Procalcitonin-like
IPR021116 - Procalcitonin/adrenomedullin

Pfam Domains:
PF00214 - Calcitonin / CGRP / IAPP family

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1KUW
- NMR

2G48
- X-ray MuPIT

2KB8
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2L86 - NMR 3FPO - X-ray 3FR1 - X-ray
3FTH - X-ray 3FTK - X-ray 3FTL - X-ray
3FTR - X-ray 3G7V - X-ray MuPIT 3G7W - X-ray MuPIT
3HGZ - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P10997
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001540 beta-amyloid binding
GO:0005102 receptor binding
GO:0005179 hormone activity
GO:0005515 protein binding
GO:0042802 identical protein binding

Biological Process:
GO:0006915 apoptotic process
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007267 cell-cell signaling
GO:0008285 negative regulation of cell proliferation
GO:0010469 regulation of receptor activity
GO:0010628 positive regulation of gene expression
GO:0010739 positive regulation of protein kinase A signaling
GO:0010823 negative regulation of mitochondrion organization
GO:0010942 positive regulation of cell death
GO:0019233 sensory perception of pain
GO:0030816 positive regulation of cAMP metabolic process
GO:0031648 protein destabilization
GO:0032463 negative regulation of protein homooligomerization
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0042755 eating behavior
GO:0043065 positive regulation of apoptotic process
GO:0043410 positive regulation of MAPK cascade
GO:0044267 cellular protein metabolic process
GO:0045596 negative regulation of cell differentiation
GO:0045779 negative regulation of bone resorption
GO:0051260 protein homooligomerization
GO:0051897 positive regulation of protein kinase B signaling
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0097647 amylin receptor signaling pathway
GO:1905665 positive regulation of calcium ion import across plasma membrane
GO:1990000 amyloid fibril formation
GO:1900019 regulation of protein kinase C activity

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0016234 inclusion body
GO:0043025 neuronal cell body


-  Descriptions from all associated GenBank mRNAs
  J04422 - Human islet amyloid protein mRNA, complete cds.
X14904 - Human IAPP mRNA for islet amyloid polypeptide precursor (IAP-cI).
JD309449 - Sequence 290473 from Patent EP1572962.
JD450577 - Sequence 431601 from Patent EP1572962.
AB463806 - Synthetic construct DNA, clone: pF1KE0224, Homo sapiens IAPP gene for islet amyloid polypeptide, without stop codon, in Flexi system.
BC111849 - Synthetic construct Homo sapiens clone IMAGE:40080837, MGC:133391 IAPP protein (IAPP) mRNA, encodes complete protein.
DQ516082 - Homo sapiens islet amyloid polypeptide precursor (IAPP) mRNA, complete cds.
X14905 - Human IAPP mRNA 5' region for islet amyloid polypeptide precursor (IAP-c2).
JD093259 - Sequence 74283 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04950 - Maturity onset diabetes of the young

Reactome (by CSHL, EBI, and GO)

Protein P10997 (Reactome details) participates in the following event(s):

R-HSA-420265 Amylin receptors can bind Amylin
R-HSA-744886 The Ligand:GPCR:Gs complex dissociates
R-HSA-744887 Liganded Gs-activating GPCRs bind inactive heterotrimeric Gs
R-HSA-379044 Liganded Gs-activating GPCR acts as a GEF for Gs
R-HSA-210745 Regulation of gene expression in beta cells
R-HSA-419812 Calcitonin-like ligand receptors
R-HSA-186712 Regulation of beta-cell development
R-HSA-418555 G alpha (s) signalling events
R-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-1266738 Developmental Biology
R-HSA-388396 GPCR downstream signalling
R-HSA-977225 Amyloid fiber formation
R-HSA-500792 GPCR ligand binding
R-HSA-372790 Signaling by GPCR
R-HSA-392499 Metabolism of proteins
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000539393.1, ENST00000539393.2, ENST00000539393.3, ENST00000539393.4, IAPP_HUMAN, NM_001329201, P10997, Q0ZD87, Q14598, uc058lui.1
UCSC ID: ENST00000539393.5
RefSeq Accession: NM_001329201
Protein: P10997 (aka IAPP_HUMAN)
CCDS: CCDS8688.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.