AP2A2_MOUSE
ID AP2A2_MOUSE Reviewed; 938 AA.
AC P17427; Q8C2J5; Q921V0;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 210.
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; Synonyms=Adtab;
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].
RC STRAIN=NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 104-859.
RC TISSUE=Mammary tumor;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 379-938.
RC TISSUE=Fetal liver;
RX PubMed=9618202; DOI=10.1006/abio.1998.2653;
RA Jurecic R., Nachtman R.G., Colicos S.M., Belmont J.W.;
RT "Identification and cloning of differentially expressed genes by long-
RT distance differential display.";
RL Anal. Biochem. 259:235-244(1998).
RN [6]
RP FUNCTION, SUBUNIT, INTERACTION WITH CLATHRIN, AND MUTAGENESIS OF LYS-31;
RP ARG-32; LYS-35; LYS-45; LYS-55; LYS-56; LYS-57 AND LYS-61.
RX PubMed=10459011; DOI=10.1083/jcb.146.4.755;
RA Gaidarov I., Keen J.H.;
RT "Phosphoinositide-AP-2 interactions required for targeting to plasma
RT membrane clathrin-coated pits.";
RL J. Cell Biol. 146:755-764(1999).
RN [7]
RP INTERACTION WITH DAB2.
RX PubMed=11247302; DOI=10.1034/j.1600-0854.2001.020206.x;
RA Morris S.M., Cooper J.A.;
RT "Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts
RT with AP-2.";
RL Traffic 2:111-123(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 SUBCELLULAR LOCATION.
RX PubMed=14530274; DOI=10.1074/jbc.c300390200;
RA Rappoport J.Z., Taha B.W., Lemeer S., Benmerah A., Simon S.M.;
RT "The AP-2 complex is excluded from the dynamic population of plasma
RT membrane-associated clathrin.";
RL J. Biol. Chem. 278:47357-47360(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 SUBCELLULAR LOCATION.
RX PubMed=17035303; DOI=10.1152/ajpcell.00160.2006;
RA Rappoport J.Z., Kemal S., Benmerah A., Simon S.M.;
RT "Dynamics of clathrin and adaptor proteins during endocytosis.";
RL Am. J. Physiol. 291:C1072-C1081(2006).
RN [12]
RP INTERACTION WITH DGKD, AND MUTAGENESIS OF TRP-840.
RX PubMed=17880279; DOI=10.1042/bj20070755;
RA Kawasaki T., Kobayashi T., Ueyama T., Shirai Y., Saito N.;
RT "Regulation of clathrin-dependent endocytosis by diacylglycerol kinase
RT delta: importance of kinase activity and binding to AP2alpha.";
RL Biochem. J. 409:471-479(2008).
RN [13]
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 [14]
RP INTERACTION WITH DENND1A; DENND1B AND DENND1C, AND MUTAGENESIS OF GLN-782
RP AND ARG-916.
RX PubMed=20154091; DOI=10.1074/jbc.m109.050930;
RA Marat A.L., McPherson P.S.;
RT "The connecdenn family, Rab35 guanine nucleotide exchange factors
RT interfacing with the clathrin machinery.";
RL J. Biol. Chem. 285:10627-10637(2010).
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 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).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 701-938, MUTAGENESIS OF PHE-837;
RP TRP-840; GLU-849; ARG-905; GLU-907 AND ARG-920, AND INTERACTION WITH AMPH;
RP EPS15; EPN1; SNAP91; BIN1 AND AUXILIN.
RX PubMed=10380931; DOI=10.1016/s0092-8674(00)80791-6;
RA Owen D.J., Vallis Y., Noble M.E.M., Hunter J.B., Dafforn T.R., Evans P.R.,
RA McMahon H.T.;
RT "A structural explanation for the binding of multiple ligands by the alpha-
RT adaptin appendage domain.";
RL Cell 97:805-815(1999).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 701-938 IN COMPLEX WITH EPS15;
RP EPN1 OR AMPH.
RX PubMed=12057195; DOI=10.1016/s0969-2126(02)00784-0;
RA Brett T.J., Traub L.M., Fremont D.H.;
RT "Accessory protein recruitment motifs in clathrin-mediated endocytosis.";
RL Structure 10:797-809(2002).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 692-938, MUTAGENESIS OF PHE-837;
RP ARG-905 AND ARG-916, AND INTERACTION WITH EPN1; EPS15; AMPH; SNAP91 AND
RP BIN1.
RX PubMed=10430869; DOI=10.1073/pnas.96.16.8907;
RA Traub L.M., Downs M.A., Westrich J.L., Fremont D.H.;
RT "Crystal structure of the alpha appendage of AP-2 reveals a recruitment
RT platform for clathrin-coat assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:8907-8912(1999).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1-620 IN COMPLEX WITH AP2B1;
RP AP2M1; AP2S1 AND CD4 INTERNALIZATION SIGNAL, AND MUTAGENESIS OF ARG-21.
RX PubMed=19140243; DOI=10.1038/nature07422;
RA Kelly B.T., McCoy A.J., Spaete K., Miller S.E., Evans P.R., Hoening S.,
RA Owen D.J.;
RT "A structural explanation for the binding of endocytic dileucine motifs by
RT the AP2 complex.";
RL Nature 456:976-979(2008).
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.
CC {ECO:0000269|PubMed:10459011, 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) (PubMed:19140243). Binds EPN1,
CC EPS15, AMPH, SNAP91 and BIN1 (PubMed:10380931, PubMed:10430869,
CC PubMed:12057195). Interacts with clathrin (PubMed:10459011). Interacts
CC with HIP1 (By similarity). Interacts with DGKD (PubMed:17880279).
CC Interacts with DENND1A, DENND1B and DENND1C (PubMed:20154091).
CC Interacts with FCHO1 and DAB2 (PubMed:11247302, 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) (By
CC similarity). Interacts with ABCB11; this interaction regulates cell
CC membrane expression of ABCB11 through its internalization in a
CC clathrin-dependent manner and its subsequent degradation (By
CC similarity). {ECO:0000250|UniProtKB:O94973,
CC ECO:0000269|PubMed:10380931, ECO:0000269|PubMed:10430869,
CC ECO:0000269|PubMed:10459011, ECO:0000269|PubMed:11247302,
CC ECO:0000269|PubMed:12057195, ECO:0000269|PubMed:17880279,
CC ECO:0000269|PubMed:19140243, ECO:0000269|PubMed:20154091,
CC ECO:0000269|PubMed:22484487, ECO:0000269|PubMed:23676497,
CC ECO:0000269|PubMed:24097348, ECO:0000269|PubMed:29262337}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14530274,
CC ECO:0000269|PubMed:17035303}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Membrane, coated pit
CC {ECO:0000269|PubMed:17035303}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. 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:0000269|PubMed:17035303}.
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; X14972; CAA33097.1; -; mRNA.
DR EMBL; AK088500; BAC40392.1; -; mRNA.
DR EMBL; AC158224; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC102524; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010597; AAH10597.1; -; mRNA.
DR EMBL; AF006990; AAB62703.1; -; mRNA.
DR CCDS; CCDS40188.1; -.
DR PIR; B30111; B30111.
DR PIR; S12471; S12471.
DR RefSeq; NP_031485.3; NM_007459.3.
DR PDB; 1B9K; X-ray; 1.90 A; A=701-938.
DR PDB; 1KY6; X-ray; 2.00 A; A=701-938.
DR PDB; 1KY7; X-ray; 2.15 A; A=701-938.
DR PDB; 1KYD; X-ray; 2.00 A; A=701-938.
DR PDB; 1KYF; X-ray; 1.22 A; A=701-938.
DR PDB; 1KYU; X-ray; 1.80 A; A=701-938.
DR PDB; 1QTP; X-ray; 1.60 A; A=701-938.
DR PDB; 1QTS; X-ray; 1.40 A; A=701-938.
DR PDB; 1W80; X-ray; 1.90 A; A=695-938.
DR PDB; 2JKR; X-ray; 2.98 A; A/L=1-620.
DR PDB; 2JKT; X-ray; 3.40 A; A/L=1-620.
DR PDB; 2VJ0; X-ray; 1.60 A; A=695-938.
DR PDB; 3HS8; X-ray; 1.90 A; A=702-938.
DR PDB; 6OWO; EM; 3.20 A; A=1-620.
DR PDB; 6OXL; EM; 3.50 A; A=1-620.
DR PDB; 7RW8; EM; 3.50 A; A=1-620.
DR PDB; 7RW9; EM; 3.90 A; A=1-620.
DR PDB; 7RWA; EM; 4.70 A; A/a=1-620.
DR PDB; 7RWB; EM; 3.90 A; A/a=1-620.
DR PDB; 7RWC; EM; 3.80 A; A=1-620.
DR PDBsum; 1B9K; -.
DR PDBsum; 1KY6; -.
DR PDBsum; 1KY7; -.
DR PDBsum; 1KYD; -.
DR PDBsum; 1KYF; -.
DR PDBsum; 1KYU; -.
DR PDBsum; 1QTP; -.
DR PDBsum; 1QTS; -.
DR PDBsum; 1W80; -.
DR PDBsum; 2JKR; -.
DR PDBsum; 2JKT; -.
DR PDBsum; 2VJ0; -.
DR PDBsum; 3HS8; -.
DR PDBsum; 6OWO; -.
DR PDBsum; 6OXL; -.
DR PDBsum; 7RW8; -.
DR PDBsum; 7RW9; -.
DR PDBsum; 7RWA; -.
DR PDBsum; 7RWB; -.
DR PDBsum; 7RWC; -.
DR AlphaFoldDB; P17427; -.
DR BMRB; P17427; -.
DR SMR; P17427; -.
DR BioGRID; 198130; 42.
DR ComplexPortal; CPX-5153; AP-2 Adaptor complex, alpha2 variant.
DR CORUM; P17427; -.
DR DIP; DIP-32160N; -.
DR IntAct; P17427; 21.
DR MINT; P17427; -.
DR STRING; 10090.ENSMUSP00000003038; -.
DR iPTMnet; P17427; -.
DR PhosphoSitePlus; P17427; -.
DR SwissPalm; P17427; -.
DR EPD; P17427; -.
DR jPOST; P17427; -.
DR MaxQB; P17427; -.
DR PaxDb; P17427; -.
DR PeptideAtlas; P17427; -.
DR PRIDE; P17427; -.
DR ProteomicsDB; 296326; -.
DR Antibodypedia; 4304; 220 antibodies from 31 providers.
DR Ensembl; ENSMUST00000003038; ENSMUSP00000003038; ENSMUSG00000002957.
DR GeneID; 11772; -.
DR KEGG; mmu:11772; -.
DR UCSC; uc009kls.2; mouse.
DR CTD; 161; -.
DR MGI; MGI:101920; Ap2a2.
DR VEuPathDB; HostDB:ENSMUSG00000002957; -.
DR eggNOG; KOG1077; Eukaryota.
DR GeneTree; ENSGT00950000182838; -.
DR HOGENOM; CLU_003824_1_0_1; -.
DR InParanoid; P17427; -.
DR OMA; SPIEQFM; -.
DR OrthoDB; 751651at2759; -.
DR PhylomeDB; P17427; -.
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-6798695; Neutrophil degranulation.
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; 11772; 6 hits in 74 CRISPR screens.
DR ChiTaRS; Ap2a2; mouse.
DR EvolutionaryTrace; P17427; -.
DR PRO; PR:P17427; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P17427; protein.
DR Bgee; ENSMUSG00000002957; Expressed in perirhinal cortex and 263 other tissues.
DR ExpressionAtlas; P17427; baseline and differential.
DR Genevisible; P17427; MM.
DR GO; GO:0030122; C:AP-2 adaptor complex; IDA:UniProtKB.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IC:ComplexPortal.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:BHF-UCL.
DR GO; GO:0030117; C:membrane coat; IDA:MGI.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0030141; C:secretory granule; TAS:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISO: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:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; IPI:CAFA.
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:0098884; P:postsynaptic neurotransmitter receptor internalization; IC:ComplexPortal.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IBA:GO_Central.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; NAS:BHF-UCL.
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 3D-structure; Cell membrane; Coated pit; Endocytosis; Lipid-binding;
KW Membrane; Protein transport; Reference proteome; Transport.
FT CHAIN 1..938
FT /note="AP-2 complex subunit alpha-2"
FT /id="PRO_0000193733"
FT REGION 615..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 615..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 MUTAGEN 21
FT /note="R->E: Reduces interaction with CD4 endocytosis
FT signal motif; when associated with AP2S1 S-15."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 31
FT /note="K->Q: Reduces phosphatidylinositol binding."
FT /evidence="ECO:0000269|PubMed:10459011"
FT MUTAGEN 32
FT /note="R->Q: Reduces phosphatidylinositol binding."
FT /evidence="ECO:0000269|PubMed:10459011"
FT MUTAGEN 35
FT /note="K->Q: Reduces phosphatidylinositol binding."
FT /evidence="ECO:0000269|PubMed:10459011"
FT MUTAGEN 45
FT /note="K->Q: Reduces phosphatidylinositol binding."
FT /evidence="ECO:0000269|PubMed:10459011"
FT MUTAGEN 55
FT /note="K->Q: Strongly reduces phosphatidylinositol binding.
FT Abolishes phosphatidylinositol binding; when associated
FT with Q-56 and Q-57."
FT /evidence="ECO:0000269|PubMed:10459011"
FT MUTAGEN 56
FT /note="K->E: Strongly reduces phosphatidylinositol
FT binding."
FT /evidence="ECO:0000269|PubMed:10459011"
FT MUTAGEN 56
FT /note="K->Q: Strongly reduces phosphatidylinositol binding.
FT Abolishes phosphatidylinositol binding; when associated
FT with Q-55 and Q-57."
FT /evidence="ECO:0000269|PubMed:10459011"
FT MUTAGEN 57
FT /note="K->Q: Strongly reduces phosphatidylinositol binding.
FT Abolishes phosphatidylinositol binding; when associated
FT with Q-55 and Q-56."
FT /evidence="ECO:0000269|PubMed:10459011"
FT MUTAGEN 61
FT /note="K->Q: Reduces phosphatidylinositol binding."
FT /evidence="ECO:0000269|PubMed:10459011"
FT MUTAGEN 727
FT /note="K->A: No effect on DENND1A-,DENND1B- nor DENND1C-
FT binding."
FT MUTAGEN 782
FT /note="Q->A: Reduces DENND1A- and DENND1C-binding."
FT /evidence="ECO:0000269|PubMed:20154091"
FT MUTAGEN 837
FT /note="F->A: Reduces SNAP91, AMPH and BIN1 binding.
FT Abolishes AMPH and SNAP91 binding; when associated with A-
FT 916. Abolishes EPN1 and EPS15 binding; when associated with
FT A-905."
FT /evidence="ECO:0000269|PubMed:10380931,
FT ECO:0000269|PubMed:10430869"
FT MUTAGEN 840
FT /note="W->A: Abolishes AMPH, BIN1, DGKD, EPS15, EPN1,
FT auxilin and SNAP91 binding."
FT /evidence="ECO:0000269|PubMed:10380931,
FT ECO:0000269|PubMed:17880279"
FT MUTAGEN 849
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:10380931"
FT MUTAGEN 905
FT /note="R->A: Strongly reduces AMPH, SNAP91, auxilin and
FT BIN1 binding. Abolishes EPN1 and EPS15 binding; when
FT associated with A-837."
FT /evidence="ECO:0000269|PubMed:10380931,
FT ECO:0000269|PubMed:10430869"
FT MUTAGEN 907
FT /note="E->A: Strongly reduces AMPH, SNAP91 and BIN1
FT binding. Slightly reduces EPS15 and auxilin binding."
FT /evidence="ECO:0000269|PubMed:10380931"
FT MUTAGEN 916
FT /note="R->A: Strongly reduces AMPH and SNAP91 binding.
FT Abolishes DENND1B-binding; no effect on DENND1A-, nor
FT DENND1C-binding. Abolishes AMPH and SNAP91 binding; when
FT associated with A-837."
FT /evidence="ECO:0000269|PubMed:10430869,
FT ECO:0000269|PubMed:20154091"
FT MUTAGEN 920
FT /note="R->A: Abolishes AMPH and BIN1 binding. Reduces
FT EPS15, SNAP91 and auxilin binding."
FT /evidence="ECO:0000269|PubMed:10380931"
FT CONFLICT 858..859
FT /note="HP -> LE (in Ref. 4; AAH10597)"
FT /evidence="ECO:0000305"
FT CONFLICT 889..890
FT /note="GA -> VL (in Ref. 1; CAA33097 and 5; AAB62703)"
FT /evidence="ECO:0000305"
FT HELIX 11..22
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:6OXL"
FT HELIX 28..40
FT /evidence="ECO:0007829|PDB:2JKR"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 44..48
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 52..66
FT /evidence="ECO:0007829|PDB:2JKR"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 76..82
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 88..100
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 106..121
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 125..138
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 141..147
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 150..156
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 162..178
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 188..193
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 201..214
FT /evidence="ECO:0007829|PDB:2JKR"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 225..238
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:2JKR"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:6OWO"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 255..265
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 273..291
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 299..319
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 323..338
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 343..355
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:6OXL"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 364..368
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 369..378
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 382..393
FT /evidence="ECO:0007829|PDB:2JKR"
FT TURN 398..400
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 401..413
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 417..434
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 438..450
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 453..455
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 458..470
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 475..485
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 488..490
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 493..505
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 508..510
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 514..516
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 518..529
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 530..532
FT /evidence="ECO:0007829|PDB:6OWO"
FT HELIX 534..550
FT /evidence="ECO:0007829|PDB:2JKR"
FT TURN 552..554
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 555..562
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 565..568
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 573..588
FT /evidence="ECO:0007829|PDB:2JKR"
FT HELIX 591..597
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 610..613
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 617..620
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 698..700
FT /evidence="ECO:0007829|PDB:1QTS"
FT TURN 701..704
FT /evidence="ECO:0007829|PDB:1QTS"
FT HELIX 705..708
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 714..718
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 720..731
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 734..743
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 745..747
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 749..757
FT /evidence="ECO:0007829|PDB:1KYF"
FT HELIX 760..765
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 766..770
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 782..791
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 800..807
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 810..817
FT /evidence="ECO:0007829|PDB:1KYF"
FT HELIX 822..825
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 826..828
FT /evidence="ECO:0007829|PDB:1KYF"
FT HELIX 833..840
FT /evidence="ECO:0007829|PDB:1KYF"
FT HELIX 846..848
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 849..855
FT /evidence="ECO:0007829|PDB:1KYF"
FT HELIX 862..872
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 874..877
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 879..883
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 886..894
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 899..909
FT /evidence="ECO:0007829|PDB:1KYF"
FT TURN 910..913
FT /evidence="ECO:0007829|PDB:1KYF"
FT STRAND 914..923
FT /evidence="ECO:0007829|PDB:1KYF"
FT HELIX 924..935
FT /evidence="ECO:0007829|PDB:1KYF"
SQ SEQUENCE 938 AA; 104017 MW; 183FE8DFE199DBCA CRC64;
MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC
KLLFIFLLGH DIDFGHMEAV NLLSSNRYTE KQIGYLFISV LVNSNSELIR LINNAIKNDL
ASRNPTFMGL ALHCIANVGS REMAEAFAGE IPKILVAGDT MDSVKQSAAL CLLRLYRTSP
DLVPMGDWTS RVVHLLNDQH LGVVTAATSL ITTLAQKNPE EFKTSVSLAV SRLSRIVTSA
STDLQDYTYY FVPAPWLSVK LLRLLQCYPP PDPAVRGRLT ECLETILNKA QEPPKSKKVQ
HSNAKNAVLF EAISLIIHHD SEPNLLVRAC NQLGQFLQHR ETNLRYLALE SMCTLASSEF
SHEAVKTHIE TVINALKTER DVSVRQRAVD LLYAMCDRSN AQQIVAEMLS YLETADYSIR
EEIVLKVAIL AEKYAVDYTW YVDTILNLIR IAGDYVSEEV WYRVIQIVIN RDDVQGYAAK
TVFEALQAPA CHENLVKVGG YILGEFGNLI AGDPRSSPLI QFNLLHSKFH LCSVPTRALL
LSTYIKFVNL FPEVKATIQD VLRSDSQLKN ADVELQQRAV EYLRLSTVAS TDILATVLEE
MPPFPERESS ILAKLKKKKG PSTVTDLEET KRERSIDVNG GPEPVPASTS AASTPSPSAD
LLGLGAVPPA PTGPPPSSGG GLLVDVFSDS ASAVAPLAPG SEDNFARFVC KNNGVLFENQ
LLQIGLKSEF RQNLGRMFIF YGNKTSTQFL NFTPTLICAD DLQTNLNLQT KPVDPTVDGG
AQVQQVVNIE CISDFTEAPV LNIQFRYGGT FQNVSVKLPI TLNKFFQPTE MASQDFFQRW
KQLSNPQQEV QNIFKAKHPM DTEITKAKII GFGSALLEEV DPNPANFVGA GIIHTKTTQI
GCLLRLEPNL QAQMYRLTLR TSKDTVSQRL CELLSEQF
