InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AP2S1

Summary

InnateDB Protein

IDBP-59078.5

Last Modified

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

Gene Symbol

AP2S1

Protein Name

adaptor-related protein complex 2, sigma 1 subunit

Synonyms

AP17; CLAPS2; FBH3; FBHOk; HHC3;

Species

Homo sapiens

Ensembl Protein

ENSP00000263270

InnateDB Gene

IDBG-59076 (AP2S1)

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 and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity). May also play a role in extracellular calcium homeostasis. {ECO:0000250, ECO:0000269PubMed:14745134, ECO:0000269PubMed:15473838, ECO:0000269PubMed:19033387, ECO:0000269PubMed:23222959}.

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

Hypocalciuric hypercalcemia, familial 3 (HHC3) [MIM:600740]: A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults. {ECO:0000269PubMed:23222959}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 18 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	18 [view]
Protein-Protein	17 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005215	transporter activity
GO:0008565	protein transporter activity

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: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:0030100	regulation of endocytosis
GO:0042059	negative regulation of epidermal growth factor receptor signaling pathway
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048268	clathrin coat assembly
GO:0050690	regulation of defense response to virus by virus

Cellular Component

GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0030122	AP-2 adaptor complex
GO:0030666	endocytic vesicle membrane
GO:0030669	clathrin-coated endocytic vesicle membrane