AP2A2_BOVIN
ID AP2A2_BOVIN Reviewed; 938 AA.
AC Q0VCK5;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=AP-2 complex subunit alpha-2;
DE AltName: Full=100 kDa coated vesicle protein C;
DE AltName: Full=Adaptor protein complex AP-2 subunit alpha-2;
DE AltName: Full=Adaptor-related protein complex 2 subunit alpha-2;
DE AltName: Full=Alpha-adaptin C;
DE AltName: Full=Alpha2-adaptin;
DE AltName: Full=Clathrin assembly protein complex 2 alpha-C large chain;
DE AltName: Full=Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit;
GN Name=AP2A2;
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=Fetal pons;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 2-17.
RX PubMed=2564002; DOI=10.1083/jcb.108.3.833;
RA Robinson M.S.;
RT "Cloning of cDNAs encoding two related 100-kD coated vesicle proteins
RT (alpha-adaptins).";
RL J. Cell Biol. 108:833-842(1989).
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. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-
CC [LI] endocytosis signal motifs within the cytosolic tails of
CC transmembrane cargo molecules. AP-2 may also play a role in maintaining
CC normal post-endocytic trafficking through the ARF6-regulated, non-
CC clathrin pathway. During long-term potentiation in hippocampal neurons,
CC AP-2 is responsible for the endocytosis of ADAM10 (By similarity). The
CC AP-2 alpha subunit binds polyphosphoinositide-containing lipids,
CC positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its
CC C-terminal appendage domain as a scaffolding platform for endocytic
CC accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought
CC to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P17427}.
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). Binds clathrin (By similarity).
CC Binds EPN1, EPS15, AMPH, SNAP91 and BIN1 (By similarity). Interacts
CC with HIP1 (By similarity). Interacts with DGKD (By similarity).
CC Interacts with DENND1A, DENND1B and DENND1C (By similarity). Interacts
CC with FCHO1 (By similarity). Interacts with ATAT1; this interaction is
CC required for efficient alpha-tubulin acetylation by ATAT1 (By
CC similarity). Interacts with KIAA1107 (By similarity). Together with
CC AP2B1 and AP2M1, 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 CLN3 (via dileucine motif) (By similarity). Interacts with ABCB11; this
CC interaction regulates cell membrane expression of ABCB11 through its
CC internalization in a clathrin-dependent manner and its subsequent
CC degradation (By similarity). {ECO:0000250|UniProtKB:O94973,
CC ECO:0000250|UniProtKB:P17427}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P17427};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P17427}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:P17427}. Membrane, coated pit
CC {ECO:0000250|UniProtKB:P17427}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P17427}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P17427}. 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:P17427}.
CC -!- SIMILARITY: Belongs to the adaptor complexes large subunit family.
CC {ECO:0000305}.
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DR EMBL; BC120121; AAI20122.1; -; mRNA.
DR RefSeq; NP_001069170.1; NM_001075702.1.
DR AlphaFoldDB; Q0VCK5; -.
DR SMR; Q0VCK5; -.
DR BioGRID; 171839; 2.
DR STRING; 9913.ENSBTAP00000048343; -.
DR PaxDb; Q0VCK5; -.
DR PRIDE; Q0VCK5; -.
DR Ensembl; ENSBTAT00000084251; ENSBTAP00000066542; ENSBTAG00000009915.
DR GeneID; 515216; -.
DR KEGG; bta:515216; -.
DR CTD; 161; -.
DR VEuPathDB; HostDB:ENSBTAG00000009915; -.
DR VGNC; VGNC:25984; AP2A2.
DR eggNOG; KOG1077; Eukaryota.
DR GeneTree; ENSGT00950000182838; -.
DR HOGENOM; CLU_003824_1_1_1; -.
DR InParanoid; Q0VCK5; -.
DR OrthoDB; 751651at2759; -.
DR Proteomes; UP000009136; Chromosome 29.
DR Bgee; ENSBTAG00000009915; Expressed in retina and 106 other tissues.
DR ExpressionAtlas; Q0VCK5; baseline and differential.
DR GO; GO:0030122; C:AP-2 adaptor complex; IDA:BHF-UCL.
DR GO; GO:0140312; F:cargo adaptor activity; 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:0048268; P:clathrin coat assembly; IC:BHF-UCL.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; ISS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IBA:GO_Central.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 3.30.310.10; -; 1.
DR InterPro; IPR017104; AP2_complex_asu.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR002553; Clathrin/coatomer_adapt-like_N.
DR InterPro; IPR003164; Clathrin_a-adaptin_app_sub_C.
DR InterPro; IPR008152; Clathrin_a/b/g-adaptin_app_Ig.
DR InterPro; IPR013041; Clathrin_app_Ig-like_sf.
DR InterPro; IPR009028; Coatomer/calthrin_app_sub_C.
DR InterPro; IPR012295; TBP_dom_sf.
DR Pfam; PF01602; Adaptin_N; 1.
DR Pfam; PF02296; Alpha_adaptin_C; 1.
DR Pfam; PF02883; Alpha_adaptinC2; 1.
DR PIRSF; PIRSF037091; AP2_complex_alpha; 1.
DR SMART; SM00809; Alpha_adaptinC2; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49348; SSF49348; 1.
DR SUPFAM; SSF55711; SSF55711; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Coated pit; Direct protein sequencing; Endocytosis;
KW Lipid-binding; Membrane; Protein transport; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P18484"
FT CHAIN 2..938
FT /note="AP-2 complex subunit alpha-2"
FT /id="PRO_0000283799"
FT REGION 616..677
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..639
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 11..12
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:P18484"
FT BINDING 43
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:P18484"
FT BINDING 53
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:P18484"
FT BINDING 57..61
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:P18484"
SQ SEQUENCE 938 AA; 103769 MW; 853700BF86A7A916 CRC64;
MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC
KLLFIFLLGH DIDFGHMEAV NLLSSNRYTE KQIGYLFISV LVNSNSELIR LINNAIKNDL
ASRNPTFMGL ALHCIANVGS REMAEAFAGE IPKILVAGDT MDSVKQSAAL CLLRLHRASP
DLVPVGDWTS RVVHLLNDQH LGVVTAATSL ITTLAQKNPE EFKTSVSLAV SRLSRIVTSA
STDLQDYTYY FVPAPWLSVK LLRLLQCYPP PEDPAVRGRL TECLEAILNK AQEPPKSKKV
QHSNAKNAVL FEAISLVTHH DSEPNLLVRA CNQLGQFLQH RETNLRYLAL ESMCTLASSE
FSHEAVKTHI ETVINALKTE RDVSVRQRAV DLLYAMCDRS NAQQIVAEML SYLETADYSI
REEIVLKVAI LAEKYAVDYT WYVDTILNLI RIAGDYVSEE VWYRVIQIVI NRDDVQGYAA
KTVFEALQAP ACHENLVKVG GYILGEFGNL IAGDPRSSPL TQFHLLHSKF HLCSVPTRAL
LLSTYIKFVN LFPEVKGTIQ DVLRSDSQLK NADVELQQRA VEYLRLSTVA STDILATVLE
EMPPFPERES SILAKLKKKK GPSTVTDLEE AKRERSADVN GGPEPALAST SAVSTPSPSA
DLLGLGAAPP VPAGPPPSSG GLLVDVFSDS PSAAAPLAPG SEDNFARFVC KNNGVLFENQ
LLQIGLKSEF RQNLGRMFIF YGNKTSTQFL NFTPTLICSD DLQANLSLQT KPVDPTVDGG
AQVQQAVNIE CVSDFTEAPV LNIQFRYGGT FQNVSVKLPI TLNKFFQPTE MASQDFFQRW
KQLSNPQQEV QSIFKAKHPM DTEVTKAKII GFGSALLEEV DPNPANFVGA GIIHTRTAQI
GCLLRLEPNL QAQMYRLTLR TSRETVSQRL CELLSEQF
