AP2A1_HUMAN
ID AP2A1_HUMAN Reviewed; 977 AA.
AC O95782; Q96CI7; Q96PP6; Q96PP7; Q9H070;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 199.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
RX PubMed=12036598; DOI=10.1016/s0378-1119(02)00504-8;
RA Scorilas A., Levesque M.A., Ashworth L.K., Diamandis E.P.;
RT "Cloning, physical mapping and structural characterization of the human
RT alpha(A)-adaptin gene.";
RL Gene 289:191-199(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B), AND VARIANT LEU-270.
RC TISSUE=Muscle;
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 [5]
RP INTERACTION WITH HIP1.
RX PubMed=11532990; DOI=10.1093/hmg/10.17.1807;
RA Waelter S., Scherzinger E., Hasenbank R., Nordhoff E., Lurz R., Goehler H.,
RA Gauss C., Sathasivam K., Bates G.P., Lehrach H., Wanker E.E.;
RT "The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-
RT binding protein involved in receptor-mediated endocytosis.";
RL Hum. Mol. Genet. 10:1807-1817(2001).
RN [6]
RP INTERACTION WITH RAB11FIP2.
RX PubMed=12364336; DOI=10.1074/jbc.m206316200;
RA Cullis D.N., Philip B., Baleja J.D., Feig L.A.;
RT "Rab11-FIP2, an adaptor protein connecting cellular components involved in
RT internalization and recycling of epidermal growth factor receptors.";
RL J. Biol. Chem. 277:49158-49166(2002).
RN [7]
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 [8]
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 [9]
RP INTERACTION WITH PICALM, AND SUBCELLULAR LOCATION.
RX PubMed=16262731; DOI=10.1111/j.1600-0854.2005.00355.x;
RA Meyerholz A., Hinrichsen L., Groos S., Esk P.C., Brandes G.,
RA Ungewickell E.J.;
RT "Effect of clathrin assembly lymphoid myeloid leukemia protein depletion on
RT clathrin coat formation.";
RL Traffic 6:1225-1234(2005).
RN [10]
RP FUNCTION OF THE AP-2 COMPLEX IN NON-CLATHRIN-DEPENDENT ENDOCYTOSIS.
RX PubMed=19033387; DOI=10.1242/jcs.033522;
RA Lau A.W., Chou M.M.;
RT "The adaptor complex AP-2 regulates post-endocytic trafficking through the
RT non-clathrin Arf6-dependent endocytic pathway.";
RL J. Cell Sci. 121:4008-4017(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-626, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-652; THR-653 AND SER-655, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-653, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP INTERACTION WITH ABCB11.
RX PubMed=22262466; DOI=10.1002/hep.25591;
RA Hayashi H., Inamura K., Aida K., Naoi S., Horikawa R., Nagasaka H.,
RA Takatani T., Fukushima T., Hattori A., Yabuki T., Horii I., Sugiyama Y.;
RT "AP2 adaptor complex mediates bile salt export pump internalization and
RT modulates its hepatocanalicular expression and transport function.";
RL Hepatology 55:1889-1900(2012).
RN [17]
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
RP INTERACTION WITH RFTN1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=27022195; DOI=10.4049/jimmunol.1501734;
RA Tatematsu M., Yoshida R., Morioka Y., Ishii N., Funami K., Watanabe A.,
RA Saeki K., Seya T., Matsumoto M.;
RT "Raftlin controls lipopolysaccharide-induced TLR4 internalization and
RT TICAM-1 signaling in a cell type-specific manner.";
RL J. Immunol. 196:3865-3876(2016).
RN [22]
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. During long-term potentiation in hippocampal neurons,
CC AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497).
CC The 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:0000269|PubMed:14745134,
CC ECO:0000269|PubMed:15473838, ECO:0000269|PubMed:19033387,
CC 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 SGIP1 (By
CC similarity). Interacts with HIP1 and RAB11FIP2 (PubMed:11532990,
CC PubMed:12364336). Interacts with SLC12A5 (By similarity). Interacts
CC with clathrin (By similarity). Interacts with RFTN1 (PubMed:27022195).
CC Interacts with KIAA1107 (PubMed:29262337). Interacts with PICALM
CC (PubMed:16262731). Together with AP2B1 and AP2M1, it interacts with
CC ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma
CC membrane during long-term potentiation in hippocampal neurons
CC (PubMed:23676497). Interacts with ABCB11; this interaction regulates
CC cell membrane expression of ABCB11 through its internalization in a
CC clathrin-dependent manner and its subsequent degradation
CC (PubMed:22262466). {ECO:0000250|UniProtKB:P17426,
CC ECO:0000269|PubMed:11532990, ECO:0000269|PubMed:12364336,
CC ECO:0000269|PubMed:16262731, ECO:0000269|PubMed:22262466,
CC ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:27022195,
CC ECO:0000269|PubMed:29262337}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16262731}.
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=O95782-1; Sequence=Displayed;
CC Name=B;
CC IsoId=O95782-2; Sequence=VSP_000161;
CC -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level)
CC (PubMed:23676497). Isoform A: Expressed in forebrain, skeletal muscle,
CC spinal cord, cerebellum, salivary gland, heart and colon. Isoform B:
CC Widely expressed in tissues and also in breast cancer and in prostate
CC carcinoma cells. {ECO:0000269|PubMed:23676497}.
CC -!- SIMILARITY: Belongs to the adaptor complexes large subunit family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD15564.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF289221; AAL11039.1; -; Genomic_DNA.
DR EMBL; AF289221; AAL11040.1; -; Genomic_DNA.
DR EMBL; AL136925; CAB66859.1; -; mRNA.
DR EMBL; AC006942; AAD15564.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC011495; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC098783; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014214; AAH14214.1; -; mRNA.
DR CCDS; CCDS46148.1; -. [O95782-1]
DR CCDS; CCDS46149.1; -. [O95782-2]
DR RefSeq; NP_055018.2; NM_014203.2. [O95782-1]
DR RefSeq; NP_570603.2; NM_130787.2. [O95782-2]
DR AlphaFoldDB; O95782; -.
DR SMR; O95782; -.
DR BioGRID; 106669; 252.
DR ComplexPortal; CPX-5149; AP-2 Adaptor complex, alpha1 variant.
DR CORUM; O95782; -.
DR DIP; DIP-33164N; -.
DR ELM; O95782; -.
DR IntAct; O95782; 115.
DR MINT; O95782; -.
DR STRING; 9606.ENSP00000351926; -.
DR ChEMBL; CHEMBL4295687; -.
DR TCDB; 9.B.278.1.4; the organellar-targeting adaptor protein complex (o-apc) family.
DR GlyGen; O95782; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95782; -.
DR MetOSite; O95782; -.
DR PhosphoSitePlus; O95782; -.
DR SwissPalm; O95782; -.
DR BioMuta; AP2A1; -.
DR EPD; O95782; -.
DR jPOST; O95782; -.
DR MassIVE; O95782; -.
DR MaxQB; O95782; -.
DR PaxDb; O95782; -.
DR PeptideAtlas; O95782; -.
DR PRIDE; O95782; -.
DR ProteomicsDB; 51043; -. [O95782-1]
DR ProteomicsDB; 51044; -. [O95782-2]
DR Antibodypedia; 3805; 307 antibodies from 34 providers.
DR DNASU; 160; -.
DR Ensembl; ENST00000354293.10; ENSP00000346246.4; ENSG00000196961.13. [O95782-2]
DR Ensembl; ENST00000359032.9; ENSP00000351926.4; ENSG00000196961.13. [O95782-1]
DR GeneID; 160; -.
DR KEGG; hsa:160; -.
DR MANE-Select; ENST00000354293.10; ENSP00000346246.4; NM_130787.3; NP_570603.2. [O95782-2]
DR UCSC; uc002ppn.4; human. [O95782-1]
DR CTD; 160; -.
DR DisGeNET; 160; -.
DR GeneCards; AP2A1; -.
DR HGNC; HGNC:561; AP2A1.
DR HPA; ENSG00000196961; Low tissue specificity.
DR MIM; 601026; gene.
DR neXtProt; NX_O95782; -.
DR OpenTargets; ENSG00000196961; -.
DR PharmGKB; PA24852; -.
DR VEuPathDB; HostDB:ENSG00000196961; -.
DR eggNOG; KOG1077; Eukaryota.
DR GeneTree; ENSGT00950000182838; -.
DR HOGENOM; CLU_003824_1_0_1; -.
DR InParanoid; O95782; -.
DR OMA; PINILRY; -.
DR OrthoDB; 751651at2759; -.
DR PhylomeDB; O95782; -.
DR TreeFam; TF300308; -.
DR PathwayCommons; O95782; -.
DR Reactome; R-HSA-167590; Nef Mediated CD4 Down-regulation.
DR Reactome; R-HSA-177504; Retrograde neurotrophin signalling.
DR Reactome; R-HSA-182218; Nef Mediated CD8 Down-regulation.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-HSA-416993; Trafficking of GluR2-containing AMPA receptors.
DR Reactome; R-HSA-437239; Recycling pathway of L1.
DR Reactome; R-HSA-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-HSA-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-8866427; VLDLR internalisation and degradation.
DR Reactome; R-HSA-8964038; LDL clearance.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; O95782; -.
DR BioGRID-ORCS; 160; 48 hits in 1077 CRISPR screens.
DR ChiTaRS; AP2A1; human.
DR GeneWiki; Adaptor-related_protein_complex_2,_alpha_1; -.
DR GenomeRNAi; 160; -.
DR Pharos; O95782; Tbio.
DR PRO; PR:O95782; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O95782; protein.
DR Bgee; ENSG00000196961; Expressed in right adrenal gland and 170 other tissues.
DR ExpressionAtlas; O95782; baseline and differential.
DR Genevisible; O95782; HS.
DR GO; GO:0030122; C:AP-2 adaptor complex; IDA:UniProtKB.
DR GO; GO:0030130; C:clathrin coat of trans-Golgi network vesicle; NAS:UniProtKB.
DR GO; GO:0045334; C:clathrin-coated endocytic vesicle; NAS:ARUK-UCL.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IC:ComplexPortal.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0036020; C:endolysosome membrane; TAS:Reactome.
DR GO; GO:0032433; C:filopodium tip; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
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; IPI:ARUK-UCL.
DR GO; GO:0019901; F:protein kinase binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; NAS:UniProtKB.
DR GO; GO:0006895; P:Golgi to endosome transport; NAS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; NAS:UniProtKB.
DR GO; GO:1900126; P:negative regulation of hyaluronan biosynthetic process; IDA:UniProtKB.
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; IC:ComplexPortal.
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_0000193730"
FT REGION 615..675
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 615..636
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 640..657
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 626
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 652
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 653
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 706..727
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:11230166,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_000161"
FT VARIANT 270
FT /note="P -> L (in dbSNP:rs17851121)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060544"
FT CONFLICT 804
FT /note="Q -> H (in Ref. 1; AAL11039/AAL11040)"
FT /evidence="ECO:0000305"
FT CONFLICT 924..977
FT /note="ENFVGAGIIQTKALQVGCLLRLEPNAQAQMYRLTLRTSKEPVSRHLCELLAQ
FT QF -> GDREDTRVWGMPGTFLRPFVFLFLFICCCLHSGGLGGVPLPPFPPQAQRGEGP
FT GKWMSPPLPPHPVVAPPTPSPSRGCVLL (in Ref. 4; AAH14214)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 977 AA; 107546 MW; D9FB569E7EDDF6ED CRC64;
MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC
KLLFIFLLGH DIDFGHMEAV NLLSSNKYTE KQIGYLFISV LVNSNSELIR LINNAIKNDL
ASRNPTFMCL ALHCIANVGS REMGEAFAAD IPRILVAGDS MDSVKQSAAL CLLRLYKASP
DLVPMGEWTA RVVHLLNDQH MGVVTAAVSL ITCLCKKNPD DFKTCVSLAV 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 GPGAGSALDD GRRDPSSNDI NGGMEPTPST VSTPSPSADL
LGLRAAPPPA APPASAGAGN LLVDVFDGPA AQPSLGPTPE EAFLSELEPP APESPMALLA
DPAPAADPGP EDIGPPIPEA DELLNKFVCK NNGVLFENQL LQIGVKSEFR QNLGRMYLFY
GNKTSVQFQN FSPTVVHPGD LQTQLAVQTK RVAAQVDGGA QVQQVLNIEC LRDFLTPPLL
SVRFRYGGAP QALTLKLPVT INKFFQPTEM AAQDFFQRWK QLSLPQQEAQ KIFKANHPMD
AEVTKAKLLG FGSALLDNVD PNPENFVGAG IIQTKALQVG CLLRLEPNAQ AQMYRLTLRT
SKEPVSRHLC ELLAQQF
