CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-019129
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 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 
Gene Name
 AP2M1 
Gene Synonyms/Alias
 CLAPM1; KIAA0109 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
222NDKIVIEKQGKGTADubiquitination[1]
376ELLPTNDKKKWARPPubiquitination[1]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661
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). 
Sequence Annotation
 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.  
Keyword
 3D-structure; Alternative splicing; Cell membrane; Coated pit; Complete proteome; Lipid-binding; Membrane; Phosphoprotein; Protein transport; Reference proteome; Transport. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 435 AA 
Protein Sequence
MIGGLFIYNH KGEVLISRVY RDDIGRNAVD AFRVNVIHAR QQVRSPVTNI ARTSFFHVKR 60
SNIWLAAVTK QNVNAAMVFE FLYKMCDVMA AYFGKISEEN IKNNFVLIYE LLDEILDFGY 120
PQNSETGALK TFITQQGIKS QTKEEQSQIT SQVTGQIGWR REGIKYRRNE LFLDVLESVN 180
LLMSPQGQVL SAHVSGRVVM KSYLSGMPEC KFGMNDKIVI EKQGKGTADE TSKSGKQSIA 240
IDDCTFHQCV RLSKFDSERS ISFIPPDGEF ELMRYRTTKD IILPFRVIPL VREVGRTKLE 300
VKVVIKSNFK PSLLAQKIEV RIPTPLNTSG VQVICMKGKA KYKASENAIV WKIKRMAGMK 360
ESQISAEIEL LPTNDKKKWA RPPISMNFEV PFAPSGLKVR YLKVFEPKLN YSDHDVIKWV 420
RYIGRSGIYE TRC 433 
Gene Ontology
 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. 
Interpro
 IPR022775; AP_mu_sigma_su.
 IPR015629; Clathrin_AP50.
 IPR001392; Clathrin_mu.
 IPR008968; Clathrin_mu_C.
 IPR018240; Clathrin_mu_CS.
 IPR011012; Longin-like_dom. 
Pfam
 PF00928; Adap_comp_sub
 PF01217; Clat_adaptor_s 
SMART
  
PROSITE
 PS00990; CLAT_ADAPTOR_M_1
 PS00991; CLAT_ADAPTOR_M_2
 PS51072; MHD 
PRINTS
 PR00314; CLATHRINADPT.