AP2M1_BOVIN
ID AP2M1_BOVIN Reviewed; 435 AA.
AC Q3ZC13;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=AP-2 complex subunit mu;
DE AltName: Full=AP-2 mu chain;
DE AltName: Full=Adaptor protein complex AP-2 subunit mu;
DE AltName: Full=Adaptor-related protein complex 2 subunit mu;
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=HA2 50 kDa subunit;
DE AltName: Full=Mu2-adaptin;
DE AltName: Full=Plasma membrane adaptor AP-2 50 kDa protein;
GN Name=AP2M1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-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) (By similarity). Interacts with
CC ATP6V1H and MEGF10 (By similarity). Interacts with EGFR and TTGN1 (By
CC similarity). Interacts with F2R (By similarity). Interacts with
CC PIP5K1C; tyrosine phosphorylation of PIP5K1C weakens the interaction
CC (By similarity). Interacts with KIAA0319; required for clathrin-
CC mediated endocytosis of KIAA0319 (By similarity). Interacts with DVL2
CC (via DEP domain) (By similarity). Interacts with KCNQ1; mediates
CC estrogen-induced internalization via clathrin-coated vesicles (By
CC similarity). Interacts with P2RX4 (via internalization motif) (By
CC similarity). Together with AP2A1 or AP2A2 and AP2B1, it interacts with
CC ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma
CC membrane during long-term potentiation in hippocampal neurons (By
CC similarity). Probably interacts with ACE2 (via endocytic sorting signal
CC motif); the interaction is inhibited by ACE2 phosphorylation (By
CC similarity). Interacts with RALBP1; the interaction is direct (By
CC similarity). {ECO:0000250|UniProtKB:P84091,
CC ECO:0000250|UniProtKB:P84092, 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; BC102983; AAI02984.1; -; mRNA.
DR RefSeq; NP_001029695.1; NM_001034523.2.
DR PDB; 6QH6; X-ray; 5.00 A; M=1-435.
DR PDB; 6QH7; X-ray; 3.40 A; M/N=1-435.
DR PDBsum; 6QH6; -.
DR PDBsum; 6QH7; -.
DR AlphaFoldDB; Q3ZC13; -.
DR SMR; Q3ZC13; -.
DR IntAct; Q3ZC13; 1.
DR STRING; 9913.ENSBTAP00000016526; -.
DR PaxDb; Q3ZC13; -.
DR PRIDE; Q3ZC13; -.
DR Ensembl; ENSBTAT00000071273; ENSBTAP00000068539; ENSBTAG00000020106.
DR GeneID; 517446; -.
DR KEGG; bta:517446; -.
DR CTD; 1173; -.
DR VEuPathDB; HostDB:ENSBTAG00000020106; -.
DR VGNC; VGNC:25985; AP2M1.
DR eggNOG; KOG0938; Eukaryota.
DR GeneTree; ENSGT00940000159223; -.
DR HOGENOM; CLU_026996_5_2_1; -.
DR InParanoid; Q3ZC13; -.
DR OMA; VWKIPRI; -.
DR OrthoDB; 725236at2759; -.
DR TreeFam; TF300722; -.
DR Proteomes; UP000009136; Chromosome 1.
DR Bgee; ENSBTAG00000020106; Expressed in prefrontal cortex and 106 other tissues.
DR ExpressionAtlas; Q3ZC13; baseline.
DR GO; GO:0030122; C:AP-2 adaptor complex; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0035615; F:clathrin adaptor activity; IBA:GO_Central.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
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 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Coated pit; Endocytosis; Lipid-binding;
KW Membrane; Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..435
FT /note="AP-2 complex subunit mu"
FT /id="PRO_0000273970"
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"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 14..18
FT /evidence="ECO:0007829|PDB:6QH7"
FT HELIX 28..35
FT /evidence="ECO:0007829|PDB:6QH7"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 53..60
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 63..71
FT /evidence="ECO:0007829|PDB:6QH7"
FT HELIX 75..93
FT /evidence="ECO:0007829|PDB:6QH7"
FT HELIX 98..103
FT /evidence="ECO:0007829|PDB:6QH7"
FT HELIX 105..115
FT /evidence="ECO:0007829|PDB:6QH7"
FT TURN 126..129
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 172..185
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 191..205
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 245..248
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 269..279
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 286..290
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 293..296
FT /evidence="ECO:0007829|PDB:6QH7"
FT TURN 297..299
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 300..309
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 316..325
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 331..345
FT /evidence="ECO:0007829|PDB:6QH7"
FT TURN 346..349
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 350..359
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 363..371
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 387..394
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 401..407
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 409..412
FT /evidence="ECO:0007829|PDB:6QH7"
FT TURN 415..417
FT /evidence="ECO:0007829|PDB:6QH7"
FT STRAND 418..427
FT /evidence="ECO:0007829|PDB:6QH7"
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
