AP2A2_HUMAN
ID AP2A2_HUMAN Reviewed; 939 AA.
AC O94973; O75403; Q53ET1; Q96SI8;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 205.
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=Huntingtin yeast partner J;
DE AltName: Full=Huntingtin-interacting protein 9;
DE Short=HIP-9;
DE AltName: Full=Huntingtin-interacting protein J;
DE AltName: Full=Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit;
GN Name=AP2A2; Synonyms=ADTAB, CLAPA2, HIP9, HYPJ, KIAA0899;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 318-476.
RC TISSUE=Testis;
RX PubMed=9700202; DOI=10.1093/hmg/7.9.1463;
RA Faber P.W., Barnes G.T., Srinidhi J., Chen J., Gusella J.F.,
RA MacDonald M.E.;
RT "Huntingtin interacts with a family of WW domain proteins.";
RL Hum. Mol. Genet. 7:1463-1474(1998).
RN [7]
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 [8]
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 [9]
RP FUNCTION IN CLATHRIN-MEDIATED ENDOCYTOSIS.
RX PubMed=12960147; DOI=10.1074/jbc.m307290200;
RA Hinrichsen L., Harborth J., Andrees L., Weber K., Ungewickell E.J.;
RT "Effect of clathrin heavy chain- and alpha-adaptin-specific small
RT inhibitory RNAs on endocytic accessory proteins and receptor trafficking in
RT HeLa cells.";
RL J. Biol. Chem. 278:45160-45170(2003).
RN [10]
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 [11]
RP INTERACTION WITH CLN3.
RX PubMed=15598649; DOI=10.1074/jbc.m411862200;
RA Kyttaelae A., Yliannala K., Schu P., Jalanko A., Luzio J.P.;
RT "AP-1 and AP-3 facilitate lysosomal targeting of Batten disease protein
RT CLN3 via its dileucine motif.";
RL J. Biol. Chem. 280:10277-10283(2005).
RN [12]
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 [13]
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 [14]
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 [15]
RP INTERACTION WITH FCHO1.
RX PubMed=22484487; DOI=10.1038/ncb2473;
RA Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B.,
RA Tsang M., Traub L.M.;
RT "Distinct and separable activities of the endocytic clathrin-coat
RT components Fcho1/2 and AP-2 in developmental patterning.";
RL Nat. Cell Biol. 14:488-501(2012).
RN [16]
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 [17]
RP INTERACTION WITH ATAT1.
RX PubMed=24097348; DOI=10.1038/nature12571;
RA Montagnac G., Meas-Yedid V., Irondelle M., Castro-Castro A., Franco M.,
RA Shida T., Nachury M.V., Benmerah A., Olivo-Marin J.C., Chavrier P.;
RT "alphaTAT1 catalyses microtubule acetylation at clathrin-coated pits.";
RL Nature 502:567-570(2013).
RN [18]
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 [19]
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:12960147,
CC ECO:0000269|PubMed:14745134, ECO:0000269|PubMed:15473838,
CC ECO:0000269|PubMed:19033387, 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). Binds EPN1, EPS15, AMPH, SNAP91 and
CC BIN1 (By similarity). Interacts with HIP1 (PubMed:11532990). Interacts
CC with DGKD (By similarity). Interacts with DENND1A, DENND1B and DENND1C
CC (By similarity). Interacts with FCHO1 and DAB2 (PubMed:22484487).
CC Interacts with ATAT1; this interaction is required for efficient alpha-
CC tubulin acetylation by ATAT1 (PubMed:24097348). Interacts with KIAA1107
CC (PubMed:29262337). 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 CLN3 (via dileucine motif)
CC (PubMed:15598649). 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:P17427,
CC ECO:0000269|PubMed:11532990, ECO:0000269|PubMed:15598649,
CC ECO:0000269|PubMed:22262466, ECO:0000269|PubMed:22484487,
CC ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:24097348,
CC ECO:0000269|PubMed:29262337}.
CC -!- INTERACTION:
CC O94973; Q6PD74: AAGAB; NbExp=3; IntAct=EBI-1642835, EBI-719906;
CC O94973; P98078: Dab2; Xeno; NbExp=2; IntAct=EBI-1642835, EBI-1391846;
CC O94973; Q61743: Kcnj11; Xeno; NbExp=2; IntAct=EBI-1642835, EBI-8603527;
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O94973-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O94973-2; Sequence=VSP_035762;
CC Name=3;
CC IsoId=O94973-3; Sequence=VSP_035762, VSP_035763, VSP_035764;
CC -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level).
CC {ECO:0000269|PubMed:23676497}.
CC -!- SIMILARITY: Belongs to the adaptor complexes large subunit family.
CC {ECO:0000305}.
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DR EMBL; AB020706; BAA74922.2; -; mRNA.
DR EMBL; AK223558; BAD97278.1; -; mRNA.
DR EMBL; AK027891; BAB55435.1; -; mRNA.
DR EMBL; BC006155; AAH06155.1; -; mRNA.
DR EMBL; AF049527; AAC27505.1; -; mRNA.
DR CCDS; CCDS44512.1; -. [O94973-1]
DR CCDS; CCDS73234.1; -. [O94973-2]
DR RefSeq; NP_001229766.1; NM_001242837.1. [O94973-2]
DR RefSeq; NP_036437.1; NM_012305.3. [O94973-1]
DR AlphaFoldDB; O94973; -.
DR SMR; O94973; -.
DR BioGRID; 106670; 156.
DR ComplexPortal; CPX-5150; AP-2 Adaptor complex, alpha2 variant.
DR ELM; O94973; -.
DR IntAct; O94973; 66.
DR MINT; O94973; -.
DR STRING; 9606.ENSP00000327694; -.
DR TCDB; 9.B.278.1.4; the organellar-targeting adaptor protein complex (o-apc) family.
DR GlyGen; O94973; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O94973; -.
DR MetOSite; O94973; -.
DR PhosphoSitePlus; O94973; -.
DR SwissPalm; O94973; -.
DR BioMuta; AP2A2; -.
DR EPD; O94973; -.
DR jPOST; O94973; -.
DR MassIVE; O94973; -.
DR MaxQB; O94973; -.
DR PaxDb; O94973; -.
DR PeptideAtlas; O94973; -.
DR PRIDE; O94973; -.
DR ProteomicsDB; 50592; -. [O94973-1]
DR ProteomicsDB; 50593; -. [O94973-2]
DR ProteomicsDB; 50594; -. [O94973-3]
DR Antibodypedia; 4304; 220 antibodies from 31 providers.
DR DNASU; 161; -.
DR Ensembl; ENST00000332231.9; ENSP00000327694.5; ENSG00000183020.15. [O94973-2]
DR Ensembl; ENST00000448903.7; ENSP00000413234.3; ENSG00000183020.15. [O94973-1]
DR Ensembl; ENST00000528815.5; ENSP00000431630.1; ENSG00000183020.15. [O94973-3]
DR GeneID; 161; -.
DR KEGG; hsa:161; -.
DR MANE-Select; ENST00000448903.7; ENSP00000413234.3; NM_012305.4; NP_036437.1.
DR UCSC; uc001lss.4; human. [O94973-1]
DR CTD; 161; -.
DR DisGeNET; 161; -.
DR GeneCards; AP2A2; -.
DR HGNC; HGNC:562; AP2A2.
DR HPA; ENSG00000183020; Low tissue specificity.
DR MIM; 607242; gene.
DR neXtProt; NX_O94973; -.
DR OpenTargets; ENSG00000183020; -.
DR PharmGKB; PA24853; -.
DR VEuPathDB; HostDB:ENSG00000183020; -.
DR eggNOG; KOG1077; Eukaryota.
DR GeneTree; ENSGT00950000182838; -.
DR HOGENOM; CLU_003824_1_0_1; -.
DR InParanoid; O94973; -.
DR OMA; CCRVEAN; -.
DR OrthoDB; 751651at2759; -.
DR PhylomeDB; O94973; -.
DR TreeFam; TF300308; -.
DR PathwayCommons; O94973; -.
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. [O94973-3]
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-6798695; Neutrophil degranulation.
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; O94973; -.
DR SIGNOR; O94973; -.
DR BioGRID-ORCS; 161; 13 hits in 1085 CRISPR screens.
DR ChiTaRS; AP2A2; human.
DR GeneWiki; AP2A2; -.
DR GenomeRNAi; 161; -.
DR Pharos; O94973; Tbio.
DR PRO; PR:O94973; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O94973; protein.
DR Bgee; ENSG00000183020; Expressed in right hemisphere of cerebellum and 93 other tissues.
DR ExpressionAtlas; O94973; baseline and differential.
DR Genevisible; O94973; HS.
DR GO; GO:0030122; C:AP-2 adaptor complex; IDA: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:0031410; C:cytoplasmic vesicle; ISS:BHF-UCL.
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:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
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:0097718; F:disordered domain specific binding; IEA:Ensembl.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IDA:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
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;
KW Lipid-binding; Membrane; Protein transport; Reference proteome; Transport.
FT CHAIN 1..939
FT /note="AP-2 complex subunit alpha-2"
FT /id="PRO_0000193732"
FT REGION 612..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 612..638
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"
FT VAR_SEQ 271
FT /note="P -> PE (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_035762"
FT VAR_SEQ 653..655
FT /note="STP -> VCL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_035763"
FT VAR_SEQ 656..939
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_035764"
FT CONFLICT 20
FT /note="I -> T (in Ref. 4; BAB55435)"
FT /evidence="ECO:0000305"
FT CONFLICT 450
FT /note="R -> Q (in Ref. 6; AAC27505)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 939 AA; 103960 MW; A8D3CC1B15B8C6BF CRC64;
MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC
KLLFIFLLGH DIDFGHMEAV NLLSSNRYTE KQIGYLFISV LVNSNSELIR LINNAIKNDL
ASRNPTFMGL ALHCIASVGS REMAEAFAGE IPKVLVAGDT MDSVKQSAAL CLLRLYRTSP
DLVPMGDWTS RVVHLLNDQH LGVVTAATSL ITTLAQKNPE EFKTSVSLAV SRLSRIVTSA
STDLQDYTYY FVPAPWLSVK LLRLLQCYPP PDPAVRGRLT ECLETILNKA QEPPKSKKVQ
HSNAKNAVLF EAISLIIHHD SEPNLLVRAC NQLGQFLQHR ETNLRYLALE SMCTLASSEF
SHEAVKTHIE TVINALKTER DVSVRQRAVD LLYAMCDRSN APQIVAEMLS YLETADYSIR
EEIVLKVAIL AEKYAVDYTW YVDTILNLIR IAGDYVSEEV WYRVIQIVIN RDDVQGYAAK
TVFEALQAPA CHENLVKVGG YILGEFGNLI AGDPRSSPLI QFHLLHSKFH LCSVPTRALL
LSTYIKFVNL FPEVKPTIQD VLRSDSQLRN ADVELQQRAV EYLRLSTVAS TDILATVLEE
MPPFPERESS ILAKLKKKKG PSTVTDLEDT KRDRSVDVNG GPEPAPASTS AVSTPSPSAD
LLGLGAAPPA PAGPPPSSGG SGLLVDVFSD SASVVAPLAP GSEDNFARFV CKNNGVLFEN
QLLQIGLKSE FRQNLGRMFI FYGNKTSTQF LNFTPTLICS DDLQPNLNLQ TKPVDPTVEG
GAQVQQVVNI ECVSDFTEAP VLNIQFRYGG TFQNVSVQLP ITLNKFFQPT EMASQDFFQR
WKQLSNPQQE VQNIFKAKHP MDTEVTKAKI IGFGSALLEE VDPNPANFVG AGIIHTKTTQ
IGCLLRLEPN LQAQMYRLTL RTSKEAVSQR LCELLSAQF
