AP2A1_MOUSE
ID AP2A1_MOUSE Reviewed; 977 AA.
AC P17426;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=AP-2 complex subunit alpha-1;
DE AltName: Full=100 kDa coated vesicle protein A;
DE AltName: Full=Adaptor protein complex AP-2 subunit alpha-1;
DE AltName: Full=Adaptor-related protein complex 2 subunit alpha-1;
DE AltName: Full=Alpha-adaptin A;
DE AltName: Full=Alpha1-adaptin;
DE AltName: Full=Clathrin assembly protein complex 2 alpha-A large chain;
DE AltName: Full=Plasma membrane adaptor HA2/AP2 adaptin alpha A subunit;
GN Name=Ap2a1; Synonyms=Adtaa, Clapa1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
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).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Retina;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH CLATHRIN.
RX PubMed=7559550; DOI=10.1074/jbc.270.40.23768;
RA Goodman O.B. Jr., Keen J.H.;
RT "The alpha chain of the AP-2 adaptor is a clathrin binding subunit.";
RL J. Biol. Chem. 270:23768-23773(1995).
RN [4]
RP CHARACTERIZATION OF ISOFORMS A AND B.
RX PubMed=7593326; DOI=10.1242/jcs.108.8.2865;
RA Ball C.L., Hunt S.P., Robinson M.S.;
RT "Expression and localization of alpha-adaptin isoforms.";
RL J. Cell Sci. 108:2865-2875(1995).
RN [5]
RP FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
RX PubMed=14745134; DOI=10.1247/csf.28.419;
RA Nakatsu F., Ohno H.;
RT "Adaptor protein complexes as the key regulators of protein sorting in the
RT post-Golgi network.";
RL Cell Struct. Funct. 28:419-429(2003).
RN [6]
RP FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
RX PubMed=15473838; DOI=10.1146/annurev.cellbio.20.010403.104543;
RA Owen D.J., Collins B.M., Evans P.R.;
RT "Adaptors for clathrin coats: structure and function.";
RL Annu. Rev. Cell Dev. Biol. 20:153-191(2004).
RN [7]
RP INTERACTION WITH SGIP1.
RX PubMed=17626015; DOI=10.1074/jbc.m703815200;
RA Uezu A., Horiuchi A., Kanda K., Kikuchi N., Umeda K., Tsujita K.,
RA Suetsugu S., Araki N., Yamamoto H., Takenawa T., Nakanishi H.;
RT "SGIP1alpha is an endocytic protein that directly interacts with
RT phospholipids and Eps15.";
RL J. Biol. Chem. 282:26481-26489(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP INTERACTION WITH SLC12A5.
RX PubMed=18625303; DOI=10.1016/j.cellsig.2008.06.011;
RA Zhao B., Wong A.Y.C., Murshid A., Bowie D., Presley J.F., Bedford F.K.;
RT "Identification of a novel di-leucine motif mediating K(+)/Cl(-)
RT cotransporter KCC2 constitutive endocytosis.";
RL Cell. Signal. 20:1769-1779(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-652; THR-653 AND SER-655, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP FUNCTION, INTERACTION WITH ADAM10, AND TISSUE SPECIFICITY.
RX PubMed=23676497; DOI=10.1172/jci65401;
RA Marcello E., Saraceno C., Musardo S., Vara H., de la Fuente A.G.,
RA Pelucchi S., Di Marino D., Borroni B., Tramontano A., Perez-Otano I.,
RA Padovani A., Giustetto M., Gardoni F., Di Luca M.;
RT "Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's
RT disease.";
RL J. Clin. Invest. 123:2523-2538(2013).
RN [12]
RP INTERACTION WITH KIAA1107.
RX PubMed=29262337; DOI=10.1016/j.celrep.2017.11.073;
RA Piccini A., Castroflorio E., Valente P., Guarnieri F.C., Aprile D.,
RA Michetti C., Bramini M., Giansante G., Pinto B., Savardi A., Cesca F.,
RA Bachi A., Cattaneo A., Wren J.D., Fassio A., Valtorta F., Benfenati F.,
RA Giovedi S.;
RT "APache is an AP2-interacting protein involved in synaptic vesicle
RT trafficking and neuronal development.";
RL Cell Rep. 21:3596-3611(2017).
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. The AP-2 alpha subunit binds polyphosphoinositide-
CC containing lipids, positioning AP-2 on the membrane. During long-term
CC potentiation in hippocampal neurons, AP-2 is responsible for the
CC endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit acts
CC via its C-terminal appendage domain as a scaffolding platform for
CC endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits
CC are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI]
CC motif (By similarity). {ECO:0000250, ECO:0000269|PubMed:14745134,
CC ECO:0000269|PubMed:15473838, ECO:0000269|PubMed:23676497}.
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 HIP1 and RAB11FIP2
CC (By similarity). Interacts with SLC12A5 (PubMed:18625303). Interacts
CC with clathrin (PubMed:7559550). Interacts with SGIP1 (PubMed:17626015).
CC Interacts with RFTN1 (By similarity). Interacts with KIAA1107
CC (PubMed:29262337). Interacts with PICALM (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 (PubMed:23676497). Interacts with
CC ABCB11; this interaction regulates cell membrane expression of ABCB11
CC through its internalization in a clathrin-dependent manner and its
CC subsequent degradation (By similarity). Probably interacts with ACE2
CC (via endocytic sorting signal motif); the interaction is inhibited by
CC ACE2 phosphorylation (By similarity). {ECO:0000250|UniProtKB:O95782,
CC ECO:0000250|UniProtKB:Q96CW1, ECO:0000269|PubMed:17626015,
CC ECO:0000269|PubMed:18625303, ECO:0000269|PubMed:23676497,
CC ECO:0000269|PubMed:29262337, ECO:0000269|PubMed:7559550}.
CC -!- INTERACTION:
CC P17426; Q01097: Grin2b; NbExp=2; IntAct=EBI-775189, EBI-400125;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O95782}.
CC Membrane, coated pit {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Note=AP-2 appears to be
CC excluded from internalizing CCVs and to disengage from sites of
CC endocytosis seconds before internalization of the nascent CCV.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=P17426-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P17426-2; Sequence=VSP_000162;
CC -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level)
CC (PubMed:23676497). Isoform A: Expressed only in neuronal tissue and
CC skeletal muscle. Isoform B: Widely expressed.
CC {ECO:0000269|PubMed:23676497}.
CC -!- SIMILARITY: Belongs to the adaptor complexes large subunit family.
CC {ECO:0000305}.
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DR EMBL; X14971; CAA33096.1; -; mRNA.
DR EMBL; BC031433; AAH31433.1; -; mRNA.
DR CCDS; CCDS52238.1; -. [P17426-2]
DR CCDS; CCDS52239.1; -. [P17426-1]
DR PIR; A30111; A30111.
DR RefSeq; NP_001070732.1; NM_001077264.1. [P17426-2]
DR RefSeq; NP_031484.1; NM_007458.2. [P17426-1]
DR AlphaFoldDB; P17426; -.
DR SMR; P17426; -.
DR BioGRID; 198129; 38.
DR ComplexPortal; CPX-5152; AP-2 Adaptor complex, alpha1 variant.
DR CORUM; P17426; -.
DR IntAct; P17426; 21.
DR MINT; P17426; -.
DR STRING; 10090.ENSMUSP00000127842; -.
DR iPTMnet; P17426; -.
DR PhosphoSitePlus; P17426; -.
DR SwissPalm; P17426; -.
DR EPD; P17426; -.
DR jPOST; P17426; -.
DR MaxQB; P17426; -.
DR PaxDb; P17426; -.
DR PeptideAtlas; P17426; -.
DR PRIDE; P17426; -.
DR ProteomicsDB; 281783; -. [P17426-1]
DR ProteomicsDB; 281784; -. [P17426-2]
DR Antibodypedia; 3805; 307 antibodies from 34 providers.
DR DNASU; 11771; -.
DR Ensembl; ENSMUST00000085399; ENSMUSP00000082519; ENSMUSG00000060279. [P17426-1]
DR Ensembl; ENSMUST00000107857; ENSMUSP00000103489; ENSMUSG00000060279. [P17426-2]
DR Ensembl; ENSMUST00000166972; ENSMUSP00000127842; ENSMUSG00000060279. [P17426-1]
DR Ensembl; ENSMUST00000167930; ENSMUSP00000127497; ENSMUSG00000060279. [P17426-2]
DR GeneID; 11771; -.
DR KEGG; mmu:11771; -.
DR UCSC; uc009grv.1; mouse. [P17426-1]
DR UCSC; uc009grw.1; mouse. [P17426-2]
DR CTD; 160; -.
DR MGI; MGI:101921; Ap2a1.
DR VEuPathDB; HostDB:ENSMUSG00000060279; -.
DR eggNOG; KOG1077; Eukaryota.
DR GeneTree; ENSGT00950000182838; -.
DR HOGENOM; CLU_003824_1_0_1; -.
DR InParanoid; P17426; -.
DR OMA; PINILRY; -.
DR OrthoDB; 751651at2759; -.
DR PhylomeDB; P17426; -.
DR TreeFam; TF300308; -.
DR Reactome; R-MMU-177504; Retrograde neurotrophin signalling.
DR Reactome; R-MMU-2132295; MHC class II antigen presentation.
DR Reactome; R-MMU-416993; Trafficking of GluR2-containing AMPA receptors.
DR Reactome; R-MMU-437239; Recycling pathway of L1.
DR Reactome; R-MMU-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-MMU-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-MMU-8866427; VLDLR internalisation and degradation.
DR Reactome; R-MMU-8964038; LDL clearance.
DR BioGRID-ORCS; 11771; 1 hit in 78 CRISPR screens.
DR ChiTaRS; Ap2a1; mouse.
DR PRO; PR:P17426; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P17426; protein.
DR Bgee; ENSMUSG00000060279; Expressed in superior frontal gyrus and 217 other tissues.
DR ExpressionAtlas; P17426; baseline and differential.
DR Genevisible; P17426; MM.
DR GO; GO:0030122; C:AP-2 adaptor complex; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISO:MGI.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IC:ComplexPortal.
DR GO; GO:0032433; C:filopodium tip; IDA:MGI.
DR GO; GO:0030117; C:membrane coat; IDA:MGI.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0030141; C:secretory granule; TAS:MGI.
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:0050750; F:low-density lipoprotein particle receptor binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IDA:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; TAS:MGI.
DR GO; GO:1900126; P:negative regulation of hyaluronan biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISO:MGI.
DR GO; GO:0098884; P:postsynaptic neurotransmitter receptor internalization; IC:ComplexPortal.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IBA:GO_Central.
DR GO; GO:0016192; P:vesicle-mediated transport; TAS:MGI.
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 Alternative splicing; Cell membrane; Coated pit; Endocytosis; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..977
FT /note="AP-2 complex subunit alpha-1"
FT /id="PRO_0000193731"
FT REGION 614..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 614..636
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 637..657
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 626
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95782"
FT MOD_RES 652
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 653
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 706..727
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_000162"
SQ SEQUENCE 977 AA; 107664 MW; F4ED87D3F9EF230A CRC64;
MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC
KLLFIFLLGH DIDFGHMEAV NLLSSNKYTE KQIGYLFISV LVNSNSELIR LINNAIKNDL
ASRNPTFMCL ALHCIANVGS REMGEAFAAD IPRILVAGDS MDSVKQSAAL CLLRLYKASP
DLVPMGEWTA RVVHLLNDQH MGVVTAAVSL ITCLCKKNPD DFKTCISLAV SRLSRIVSSA
STDLQDYTYY FVPAPWLSVK LLRLLQCYPP PEDAAVKGRL VECLETVLNK AQEPPKSKKV
QHSNAKNAIL FETISLIIHY DSEPNLLVRA CNQLGQFLQH RETNLRYLAL ESMCTLASSE
FSHEAVKTHI DTVINALKTE RDVSVRQRAA DLLYAMCDRS NAKQIVSEML RYLETADYAI
REEIVLKVAI LAEKYAVDYS WYVDTILNLI RIAGDYVSEE VWYRVLQIVT NRDDVQGYAA
KTVFEALQAP ACHENMVKVG GYILGEFGNL IAGDPRSSPP VQFSLLHSKF HLCSVATRAL
LLSTYIKFIN LFPETKATIQ GVLRAGSQLR NADVELQQRA VEYLTLSSVA STDVLATVLE
EMPPFPERES SILAKLKRKK GPGAASALDD SRRDTSSNDI NGGVEPTPST VSTPSPSADL
LGLRAAPPPA APPAPVGGNL LVDVFSDGPT AQPSLGPTPE EAFLSELEPP APESPMALLA
DPAPAADPGP EDIGPPIPEA DELLNKFVCK NSGVLFENQL LQIGVKSEFR QNLGRMYLFY
GNKTSVQFQN FLPTVVHPGD LQTQLAVQTK RVAAQVDGGA QVQQVLNIEC LRDFLTPPLL
SVRFRYGGTA QSLTLKLPVT INKFFQPTEM AAQDFFQRWK QLSLPLQEAQ KIFKANHPMD
AEVTKAKLLG FGSALLDNVD PNPENFVGAG IIQTKALQVG CLLRLEPNAQ AQMYRLTLRT
SKEPVSRHLC ELLAQQF
