CPLM-019128

Genbank Nucleotide ID

AP-2 complex subunit mu

Protein Synonyms/Alias

AP-2 mu chain; Adapter-related protein complex 2 mu subunit; Adaptin-mu2; Adaptor protein complex AP-2 subunit mu; Clathrin assembly protein complex 2 medium chain; Clathrin coat assembly protein AP50; Clathrin coat-associated protein AP50; HA2 50 kDa subunit; Plasma membrane adaptor AP-2 50 kDa protein

Homo sapiens (Human)

Position	Peptide	Type	References
139	FITQQGIKSQHQTKE	ubiquitination	[1]
224	NDKIVIEKQGKGTAD	ubiquitination	[1, 2]
227	IVIEKQGKGTADETS	ubiquitination	[1]
235	GTADETSKSGKQSIA	ubiquitination	[1]
256	HQCVRLSKFDSERSI	ubiquitination	[1]
281	LMRYRTTKDIILPFR	ubiquitination	[3]
312	VVIKSNFKPSLLAQK	ubiquitination	[1, 3]
378	ELLPTNDKKKWARPP	ubiquitination	[1, 4]
405	GLKVRYLKVFEPKLN	ubiquitination	[3]
410	YLKVFEPKLNYSDHD	ubiquitination	[1, 3]
420	YSDHDVIKWVRYIGR	ubiquitination	[3]

[1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[2] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[4] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]

Functional Description

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).

DOMAIN 170 434 MHD.
BINDING 341 341 Phosphatidylinositol lipid headgroup (By
BINDING 343 343 Phosphatidylinositol lipid headgroup (By
BINDING 345 345 Phosphatidylinositol lipid headgroup (By
BINDING 354 354 Phosphatidylinositol lipid headgroup (By
BINDING 356 356 Phosphatidylinositol lipid headgroup (By
MOD_RES 45 45 Phosphoserine.
MOD_RES 156 156 Phosphothreonine.

3D-structure; Alternative splicing; Cell membrane; Coated pit; Complete proteome; Lipid-binding; Membrane; Phosphoprotein; Protein transport; Reference proteome; Transport.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0030131; C:clathrin adaptor complex; IEA:InterPro.
GO:0030132; C:clathrin coat of coated pit; IEA:InterPro.
GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0005765; C:lysosomal membrane; TAS:Reactome.
GO:0005739; C:mitochondrion; IEA:Compara.
GO:0005886; C:plasma membrane; TAS:Reactome.
GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
GO:0005215; F:transporter activity; TAS:ProtInc.
GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
GO:0007411; P:axon guidance; TAS:Reactome.
GO:0016044; P:cellular membrane organization; TAS:Reactome.
GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
GO:0006886; P:intracellular protein transport; IEA:InterPro.
GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
GO:0007268; P:synaptic transmission; TAS:Reactome.
GO:0016192; P:vesicle-mediated transport; IEA:InterPro.
GO:0016032; P:viral reproduction; TAS:Reactome.

IPR022775; AP_mu_sigma_su.
IPR015629; Clathrin_AP50.
IPR001392; Clathrin_mu.
IPR008968; Clathrin_mu_C.
IPR018240; Clathrin_mu_CS.
IPR011012; Longin-like_dom.

PF00928; Adap_comp_sub
PF01217; Clat_adaptor_s

PS00990; CLAT_ADAPTOR_M_1
PS00991; CLAT_ADAPTOR_M_2
PS51072; MHD

PR00314; CLATHRINADPT.