InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AP2M1

Summary

InnateDB Protein

IDBP-385914.5

Last Modified

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

Gene Symbol

AP2M1

Protein Name

adaptor-related protein complex 2, mu 1 subunit

Synonyms

AP50; CLAPM1; mu2;

Species

Homo sapiens

Ensembl Protein

ENSP00000409081

InnateDB Gene

IDBG-67524 (AP2M1)

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 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs. The surface region interacting with to the Y-X- X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane- associated AP-2. The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (By similarity). Plays a role in endocytosis of frizzled family members upon Wnt signaling (By similarity). {ECO:0000250}.

Subcellular Localization

Cell membrane. Membrane, coated pit; Peripheral membrane protein; Cytoplasmic side. 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

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 137 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	137 [view]
Protein-Protein	136 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005215	transporter activity
GO:0005515	protein binding
GO:0008289	lipid binding

Biological Process

GO:0006810	transport
GO:0006886	intracellular protein transport
GO:0006897	endocytosis
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007268	synaptic transmission
GO:0007411	axon guidance
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:0061024	membrane organization

Cellular Component

GO:0005765	lysosomal membrane
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005905	coated pit
GO:0030131	clathrin adaptor complex
GO:0030666	endocytic vesicle membrane
GO:0030669	clathrin-coated endocytic vesicle membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR001392 Clathrin adaptor, mu subunit
IPR008968 Clathrin adaptor, mu subunit, C-terminal
IPR011012 Longin-like domain
IPR022775 AP complex, mu/sigma subunit
IPR028565 Mu homology domain

PFAM

PF00928
PF01217

PRINTS

PR00314

PIRSF

PIRSF005992

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt