InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AP2A1

Summary

InnateDB Protein

IDBP-63461.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

AP2A1

Protein Name

adaptor-related protein complex 2, alpha 1 subunit

Synonyms

ADTAA; AP2-ALPHA; CLAPA1;

Species

Homo sapiens

Ensembl Protein

ENSP00000351926

InnateDB Gene

IDBG-63459 (AP2A1)

Protein Structure

UniProt Annotation

Function

Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin- coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C- terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity). {ECO:0000250}.

Subcellular Localization

Cell membrane {ECO:0000250}. Membrane, coated pit {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Note=AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV. {ECO:0000250}.

Disease Associations

Tissue Specificity

Isoform A expressed in forebrain, skeletal muscle, spinal cord, cerebellum, salivary gland, heart and colon. Isoform B is widely expressed in tissues and also in breast cancer and in prostate carcinoma cells.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 67 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	67 [view]
Protein-Protein	66 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005488	binding
GO:0005515	protein binding
GO:0008022	protein C-terminus binding
GO:0008565	protein transporter activity
GO:0019901	protein kinase binding

Biological Process

GO:0006886	intracellular protein transport
GO:0006895	Golgi to endosome transport
GO:0006897	endocytosis
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007268	synaptic transmission
GO:0007411	axon guidance
GO:0015031	protein transport
GO:0016032	viral process
GO:0016192	vesicle-mediated transport
GO:0019886	antigen processing and presentation of exogenous peptide antigen via MHC class II
GO:0042059	negative regulation of epidermal growth factor receptor signaling pathway
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050690	regulation of defense response to virus by virus
GO:1900126	negative regulation of hyaluronan biosynthetic process

Cellular Component

GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0016323	basolateral plasma membrane
GO:0016324	apical plasma membrane
GO:0030117	membrane coat
GO:0030122	AP-2 adaptor complex
GO:0030130	clathrin coat of trans-Golgi network vesicle
GO:0030131	clathrin adaptor complex
GO:0030666	endocytic vesicle membrane
GO:0030669	clathrin-coated endocytic vesicle membrane
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR002553 Clathrin/coatomer adaptor, adaptin-like, N-terminal
IPR003164 Clathrin adaptor, alpha-adaptin, appendage, C-terminal subdomain
IPR008152 Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain
IPR009028 Coatomer/calthrin adaptor appendage, C-terminal subdomain
IPR013041 Coatomer/clathrin adaptor appendage, Ig-like subdomain
IPR016024 Armadillo-type fold
IPR017104 Adaptor protein complex AP-2, alpha subunit

PFAM

PF01602
PF02296
PF02883

PRINTS

PIRSF

PIRSF037091

SMART

SM00809

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt