AP2M1_MACFA
ID AP2M1_MACFA Reviewed; 435 AA.
AC Q4R706;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=AP-2 complex subunit mu;
DE AltName: Full=AP-2 mu chain;
DE AltName: Full=Clathrin assembly protein complex 2 mu medium chain;
DE AltName: Full=Clathrin coat assembly protein AP50;
DE AltName: Full=Clathrin coat-associated protein AP50;
DE AltName: Full=Mu2-adaptin;
DE AltName: Full=Plasma membrane adaptor AP-2 50 kDa protein;
GN Name=AP2M1; ORFNames=QtsA-16673;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Component of the adaptor protein complex 2 (AP-2). Adaptor
CC protein complexes function in protein transport via transport vesicles
CC in different membrane traffic pathways. Adaptor protein complexes are
CC vesicle coat components and appear to be involved in cargo selection
CC and vesicle formation. AP-2 is involved in clathrin-dependent
CC endocytosis in which cargo proteins are incorporated into vesicles
CC surrounded by clathrin (clathrin-coated vesicles, CCVs) which are
CC destined for fusion with the early endosome. The clathrin lattice
CC serves as a mechanical scaffold but is itself unable to bind directly
CC to membrane components. Clathrin-associated adaptor protein (AP)
CC complexes which can bind directly to both the clathrin lattice and to
CC the lipid and protein components of membranes are considered to be the
CC major clathrin adaptors contributing the CCV formation. AP-2 also
CC serves as a cargo receptor to selectively sort the membrane proteins
CC involved in receptor-mediated endocytosis. AP-2 seems to play a role in
CC the recycling of synaptic vesicle membranes from the presynaptic
CC surface (By similarity). AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and
CC [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails
CC of transmembrane cargo molecules (By similarity). AP-2 may also play a
CC role in maintaining normal post-endocytic trafficking through the ARF6-
CC regulated, non-clathrin pathway. During long-term potentiation in
CC hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10
CC (By similarity). The AP-2 mu subunit binds to transmembrane cargo
CC proteins; it recognizes the Y-X-X-Phi motifs (By similarity). The
CC surface region interacting with to the Y-X-X-Phi motif is inaccessible
CC in cytosolic AP-2, but becomes accessible through a conformational
CC change following phosphorylation of AP-2 mu subunit at Thr-156 in
CC membrane-associated AP-2. The membrane-specific phosphorylation event
CC appears to involve assembled clathrin which activates the AP-2 mu
CC kinase AAK1 (By similarity). Plays a role in endocytosis of frizzled
CC family members upon Wnt signaling (By similarity).
CC {ECO:0000250|UniProtKB:P84092, ECO:0000250|UniProtKB:Q96CW1}.
CC -!- SUBUNIT: Adaptor protein complex 2 (AP-2) is a heterotetramer composed
CC of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type
CC subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small
CC adaptin (sigma-type subunit AP2S1). Interacts with ATP6V1H and MEGF10.
CC Interacts with EGFR. Interacts with F2R. Interacts with PIP5K1C;
CC tyrosine phosphorylation of PIP5K1C weakens the interaction. Interacts
CC with KIAA0319; required for clathrin-mediated endocytosis of KIAA0319
CC (By similarity). Interacts with DVL2 (via DEP domain) (By similarity).
CC Interacts with KCNQ1; mediates estrogen-induced internalization via
CC clathrin-coated vesicles (By similarity). Together with AP2A1 or AP2A2
CC and AP2B1, it interacts with ADAM10; this interaction facilitates
CC ADAM10 endocytosis from the plasma membrane during long-term
CC potentiation in hippocampal neurons (By similarity). Interacts with
CC RALBP1; the interaction is direct (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P84091, ECO:0000250|UniProtKB:Q96CW1}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q96CW1}.
CC Membrane, coated pit {ECO:0000250|UniProtKB:Q96CW1}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:Q96CW1}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q96CW1}. Note=AP-2 appears to be excluded from
CC internalizing CCVs and to disengage from sites of endocytosis seconds
CC before internalization of the nascent CCV.
CC {ECO:0000250|UniProtKB:P84091}.
CC -!- PTM: Phosphorylation at Thr-156 increases the affinity of the AP-2
CC complex for cargo membrane proteins during the initial stages of
CC endocytosis. {ECO:0000250|UniProtKB:Q96CW1}.
CC -!- SIMILARITY: Belongs to the adaptor complexes medium subunit family.
CC {ECO:0000305}.
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DR EMBL; AB169024; BAE01118.1; -; mRNA.
DR RefSeq; NP_001274653.1; NM_001287724.1.
DR AlphaFoldDB; Q4R706; -.
DR SMR; Q4R706; -.
DR STRING; 9541.XP_005546581.1; -.
DR Ensembl; ENSMFAT00000079126; ENSMFAP00000064062; ENSMFAG00000024802.
DR GeneID; 102131193; -.
DR CTD; 1173; -.
DR eggNOG; KOG0938; Eukaryota.
DR GeneTree; ENSGT00940000159223; -.
DR OrthoDB; 725236at2759; -.
DR Proteomes; UP000233100; Chromosome 2.
DR Bgee; ENSMFAG00000024802; Expressed in frontal cortex and 13 other tissues.
DR GO; GO:0030131; C:clathrin adaptor complex; IEA:InterPro.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR CDD; cd09251; AP-2_Mu2_Cterm; 1.
DR CDD; cd14836; AP2_Mu_N; 1.
DR InterPro; IPR036168; AP2_Mu_C_sf.
DR InterPro; IPR043532; AP2_Mu_N.
DR InterPro; IPR022775; AP_mu_sigma_su.
DR InterPro; IPR001392; Clathrin_mu.
DR InterPro; IPR018240; Clathrin_mu_CS.
DR InterPro; IPR011012; Longin-like_dom_sf.
DR InterPro; IPR028565; MHD.
DR InterPro; IPR043512; Mu2_C.
DR Pfam; PF00928; Adap_comp_sub; 1.
DR Pfam; PF01217; Clat_adaptor_s; 1.
DR PIRSF; PIRSF005992; Clathrin_mu; 1.
DR PRINTS; PR00314; CLATHRINADPT.
DR SUPFAM; SSF49447; SSF49447; 1.
DR SUPFAM; SSF64356; SSF64356; 1.
DR PROSITE; PS00990; CLAT_ADAPTOR_M_1; 1.
DR PROSITE; PS00991; CLAT_ADAPTOR_M_2; 1.
DR PROSITE; PS51072; MHD; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Coated pit; Endocytosis; Lipid-binding; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..435
FT /note="AP-2 complex subunit mu"
FT /id="PRO_0000318892"
FT DOMAIN 170..434
FT /note="MHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00404"
FT BINDING 341
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250|UniProtKB:P84092"
FT BINDING 345
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250|UniProtKB:P84092"
FT BINDING 354
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250|UniProtKB:P84092"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96CW1"
FT MOD_RES 156
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96CW1"
SQ SEQUENCE 435 AA; 49655 MW; 82803219BA279954 CRC64;
MIGGLFIYNH KGEVLISRVY RDDIGRNAVD AFRVNVIHAR QQVRSPVTNI ARTSFFHVKR
SNIWLAAVTK QNVNAAMVFE FLYKMCDVMA AYFGKISEEN IKNNFVLIYE LLDEILDFGY
PQNSETGALK TFITQQGIKS QHQTKEEQSQ ITSQVTGQIG WRREGIKYRR NELFLDVLES
VNLLMSPQGQ VLSAHVSGRV VMKSYLSGMP ECKFGMNDKI VIEKQGKGTA DETSKSGKQS
IAIDDCTFHQ CVRLSKFDSE RSISFIPPDG EFELMRYRTT KDIILPFRVI PLVREVGRTK
LEVKVVIKSN FKPSLLAQKI EVRIPTPLNT SGVQVICMKG KAKYKASENA IVWKIKRMAG
MKESQISAEI ELLPTNDKKK WARPPISMNF EVPFAPSGLK VRYLKVFEPK LNYSDHDVIK
WVRYIGRSGI YETRC
