user: GUEST
width: 600


MyHits has reached its end of life and no longer provides data or services. Thank you for your support and trust for more than 23 years!
However, the webserver will remain online in its present form at least until end of March 2025.
To ensure the future of MyHits, we would be happy if a person or community would take over the resource or parts of it. Interested? Please contact us (myhits [at] sib.swiss).

Pagni M, Ioannidis V, Cerutti L, Zahn-Zabal M, Jongeneel CV, Hau J, Martin O, Kuznetsov D, Falquet L.
MyHits: improvements to an interactive resource for analyzing protein sequences.
Nucleic Acids Res. 2007 Jul; 35(Web Server issue):W433-7

DescriptionRecName: Full=AP-2 complex subunit alpha-2; AltName: Full=100 kDa coated vesicle protein C; AltName: Full=Adaptor protein complex AP-2 subunit alpha-2; AltName: Full=Adaptor-related protein complex 2 subunit alpha-2; AltName: Full=Alpha-adaptin C; AltName: Full=Alpha2-adaptin; AltName: Full=Clathrin assembly protein complex 2 alpha-C large chain; AltName: Full=Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit;
MyHits logo
MyHits synonymsAP2A2_MOUSE , P17427 , Q8C2J5 , Q921V0 , 183FE8DFE199DBCA
match map segment
ismart:Alpha_adaptinC2 ipfam:Alpha_adaptinC2 ipfam:Adaptin_N ipfam:Alpha_adaptin_C  
Legends: 1, INIT_MET Removed. {ECO:0000250|UniProtKB:P18484}; 2, BINDING Phosphatidylinositol lipid headgroup; 3, MUTAGEN R->E: Reduces interaction with CD4 endocytosis signal motif; when associated with AP2S1 S-15. {ECO:0000269|PubMed:19140243}; 4, MUTAGEN K->Q: Reduces phosphatidylinositol binding. {ECO:0000269|PubMed:10459011}; 5, MUTAGEN R->Q: Reduces phosphatidylinositol binding. {ECO:0000269|PubMed:10459011}; 6, MUTAGEN K->Q: Strongly reduces phosphatidylinositol binding. Abolishes phosphatidylinositol binding; when associated with Q-56 and Q-57. {ECO:0000269|PubMed:10459011}; 7, MUTAGEN K->E: Strongly reduces phosphatidylinositol binding. {ECO:0000269|PubMed:10459011}; 8, MUTAGEN K->Q: Strongly reduces phosphatidylinositol binding. Abolishes phosphatidylinositol binding; when associated with Q-55 and Q-57. {ECO:0000269|PubMed:10459011}; 9, MUTAGEN K->Q: Strongly reduces phosphatidylinositol binding. Abolishes phosphatidylinositol binding; when associated with Q-55 and Q-56. {ECO:0000269|PubMed:10459011}; 10, MUTAGEN K->A: No effect on DENND1A-,DENND1B- nor DENND1C-binding; 11, MUTAGEN Q->A: Reduces DENND1A- and DENND1C- binding. {ECO:0000269|PubMed:20154091}; 12, MUTAGEN F->A: Reduces SNAP91, AMPH and BIN1 binding. Abolishes AMPH and SNAP91 binding; when associated with A-916. Abolishes EPN1 and EPS15 binding; when associated with A-905. {ECO:0000269|PubMed:10380931, ECO:0000269|PubMed:10430869}; 13, MUTAGEN W->A: Abolishes AMPH, BIN1, EPS15, EPN1, auxilin and SNAP91 binding. Abolishes interaction with DGKD. {ECO:0000269|PubMed:10380931, ECO:0000269|PubMed:17880279}; 14, MUTAGEN E->A: No effect. {ECO:0000269|PubMed:10380931}; 15, MUTAGEN R->A: Strongly reduces AMPH, SNAP91, auxilin and BIN1 binding. Abolishes EPN1 and EPS15 binding; when associated with A-837. {ECO:0000269|PubMed:10380931, ECO:0000269|PubMed:10430869}; 16, MUTAGEN E->A: Strongly reduces AMPH, SNAP91 and BIN1 binding. Slightly reduces EPS15 and auxilin binding. {ECO:0000269|PubMed:10380931}; 17, MUTAGEN R->A: Strongly reduces AMPH and SNAP91 binding. Abolishes DENND1B-binding; no effect on DENND1A-, nor DENND1C-binding. Abolishes AMPH and SNAP91 binding; when associated with A-837. {ECO:0000269|PubMed:10430869, ECO:0000269|PubMed:20154091}; 18, MUTAGEN R->A: Abolishes AMPH and BIN1 binding. Reduces EPS15, SNAP91 and auxilin binding. {ECO:0000269|PubMed:10380931}; 19, REGION Lipid-binding; 20, CONFLICT HP -> LE (in Ref. 4; AAH10597). {ECO:0000305}; 21, CONFLICT GA -> VL (in Ref. 1; CAA33097 and 5; AAB62703). {ECO:0000305}; 22, ismart:Alpha_adaptinC2 [T]; 23, ipfam:Alpha_adaptinC2 [T]; 24, ipfam:Alpha_adaptin_C [T]; 25, HELIX {ECO:0000244|PDB:2JKR}; 26, TURN {ECO:0000244|PDB:2JKR}; 27, STRAND {ECO:0000244|PDB:2JKR}; 28, TURN {ECO:0000244|PDB:1QTS}; 29, HELIX {ECO:0000244|PDB:1KYF}; 30, STRAND {ECO:0000244|PDB:1KYF}; 31, TURN {ECO:0000244|PDB:1KYF}.
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   10-MAY-2017, entry version 173.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   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.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   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.,
RA   She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA   Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA   Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA   Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA   Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of
RT   the 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
RT   project: 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
RP   LYS-31; 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
RT   interacts 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
RT   the 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 DKGD, 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,
RC   Pancreas, 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
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [14]
RP   INTERACTION WITH DENND1A; DENND1B AND DENND1C, AND MUTAGENESIS OF
RP   GLN-782 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   INTERACTION WITH ATAT1.
RX   PubMed=24097348; DOI=10.1038/nature12571;
RA   Montagnac G., Meas-Yedid V., Irondelle M., Castro-Castro A.,
RA   Franco M., Shida T., Nachury M.V., Benmerah A., Olivo-Marin J.C.,
RA   Chavrier P.;
RT   "alphaTAT1 catalyses microtubule acetylation at clathrin-coated
RT   pits.";
RL   Nature 502:567-570(2013).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 701-938, MUTAGENESIS OF
RP   PHE-837; TRP-840; GLU-849; ARG-905; GLU-907 AND ARG-920, AND
RP   INTERACTION WITH AMPH; 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.,
RA   Evans P.R., McMahon H.T.;
RT   "A structural explanation for the binding of multiple ligands by the
RT   alpha-adaptin appendage domain.";
RL   Cell 97:805-815(1999).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 9-592 IN COMPLEX WITH AP2B1;
RP   AP2M1; AP2S1 AND AN INOSITOL POLYPHOSPHATE HEADGROUP.
RX   PubMed=12086608; DOI=10.1016/S0092-8674(02)00735-3;
RA   Collins B.M., McCoy A.J., Kent H.M., Evans P.R., Owen D.J.;
RT   "Molecular architecture and functional model of the endocytic AP2
RT   complex.";
RL   Cell 109:523-535(2002).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 701-938 IN COMPLEX WITH
RP   EPS15; 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
RT   endocytosis.";
RL   Structure 10:797-809(2002).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 692-938, MUTAGENESIS OF
RP   PHE-837; ARG-905 AND ARG-916, AND INTERACTION WITH EPN1; EPS15; AMPH;
RP   SNAP91 AND 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
RT   recruitment platform for clathrin-coat assembly.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:8907-8912(1999).
RN   [21]
RP   X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1-620 IN COMPLEX WITH AP2B1;
RP   AP2M1; AP2S1 AND CD4 INTERNALIZATION SIGNAL, AND MUTAGENESIS OF
RP   ARG-21.
RX   PubMed=19140243; DOI=10.1038/nature07422;
RA   Kelly B.T., McCoy A.J., Spaete K., Miller S.E., Evans P.R.,
RA   Hoening S., Owen D.J.;
RT   "A structural explanation for the binding of endocytic dileucine
RT   motifs by the AP2 complex.";
RL   Nature 456:976-979(2008).
CC   -!- FUNCTION: Component of the adaptor protein complex 2 (AP-2).
CC       Adaptor protein complexes function in protein transport via
CC       transport vesicles in different membrane traffic pathways. Adaptor
CC       protein complexes are vesicle coat components and appear to be
CC       involved in cargo selection and vesicle formation. AP-2 is
CC       involved in clathrin-dependent endocytosis in which cargo proteins
CC       are incorporated into vesicles surrounded by clathrin (clathrin-
CC       coated vesicles, CCVs) which are destined for fusion with the
CC       early endosome. The clathrin lattice serves as a mechanical
CC       scaffold but is itself unable to bind directly to membrane
CC       components. Clathrin-associated adaptor protein (AP) complexes
CC       which can bind directly to both the clathrin lattice and to the
CC       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
CC       proteins involved in receptor-mediated endocytosis. AP-2 seems to
CC       play a role in the recycling of synaptic vesicle membranes from
CC       the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi)
CC       and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the
CC       cytosolic tails of transmembrane cargo molecules. AP-2 may also
CC       play a role in maintaining normal post-endocytic trafficking
CC       through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha
CC       subunit binds polyphosphoinositide-containing lipids, positioning
CC       AP-2 on the membrane. The AP-2 alpha subunit acts via its C-
CC       terminal appendage domain as a scaffolding platform for endocytic
CC       accessory proteins. The AP-2 alpha and AP-2 sigma subunits are
CC       thought to contribute to the recognition of the [ED]-X-X-X-L-[LI]
CC       motif. {ECO:0000269|PubMed:10459011, ECO:0000269|PubMed:14745134,
CC       ECO:0000269|PubMed:15473838}.
CC   -!- SUBUNIT: Adaptor protein complex 2 (AP-2) is a heterotetramer
CC       composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2
CC       and beta-type subunit AP2B1), a medium adaptin (mu-type subunit
CC       AP2M1) and a small adaptin (sigma-type subunit AP2S1). Binds EPN1,
CC       EPS15, AMPH, SNAP91 and BIN1. Interacts with HIP1 (By similarity).
CC       Interacts with DGKD isoform 2. Interacts with DENND1A, DENND1B and
CC       DENND1C. Interacts with FCHO1 and DAB2. Interacts with ATAT1; this
CC       interaction is required for efficient alpha-tubulin acetylation by
CC       ATAT1. {ECO:0000250, ECO:0000269|PubMed:10380931,
CC       ECO:0000269|PubMed:10430869, ECO:0000269|PubMed:10459011,
CC       ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:12057195,
CC       ECO:0000269|PubMed:12086608, ECO:0000269|PubMed:17880279,
CC       ECO:0000269|PubMed:19140243, ECO:0000269|PubMed:20154091,
CC       ECO:0000269|PubMed:22484487, ECO:0000269|PubMed:24097348}.
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
CC       pit {ECO:0000269|PubMed:17035303}; Peripheral membrane protein
CC       {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=AP-2 appears
CC       to be excluded from internalizing CCVs and to disengage from sites
CC       of endocytosis seconds before internalization of the nascent CCV.
CC       {ECO:0000269|PubMed:17035303}.
CC   -!- SIMILARITY: Belongs to the adaptor complexes large subunit family.
CC       {ECO:0000305}.
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
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   UniGene; Mm.253090; -.
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   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   ProteinModelPortal; P17427; -.
DR   SMR; P17427; -.
DR   BioGrid; 198130; 12.
DR   DIP; DIP-32160N; -.
DR   IntAct; P17427; 17.
DR   MINT; MINT-101068; -.
DR   STRING; 10090.ENSMUSP00000003038; -.
DR   iPTMnet; P17427; -.
DR   PhosphoSitePlus; P17427; -.
DR   SwissPalm; P17427; -.
DR   EPD; P17427; -.
DR   MaxQB; P17427; -.
DR   PaxDb; P17427; -.
DR   PeptideAtlas; P17427; -.
DR   PRIDE; P17427; -.
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   eggNOG; KOG1077; Eukaryota.
DR   eggNOG; ENOG410XNQE; LUCA.
DR   GeneTree; ENSGT00550000074757; -.
DR   HOVERGEN; HBG050518; -.
DR   InParanoid; P17427; -.
DR   KO; K11824; -.
DR   OMA; PPFSERT; -.
DR   OrthoDB; EOG091G01JZ; -.
DR   TreeFam; TF300308; -.
DR   Reactome; R-MMU-171052; LDL-mediated lipid transport.
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   ChiTaRS; Ap2a2; mouse.
DR   EvolutionaryTrace; P17427; -.
DR   PMAP-CutDB; P17427; -.
DR   PRO; PR:P17427; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   Bgee; ENSMUSG00000002957; -.
DR   CleanEx; MM_AP2A2; -.
DR   ExpressionAtlas; P17427; baseline and differential.
DR   Genevisible; P17427; MM.
DR   GO; GO:0030131; C:clathrin adaptor complex; IEA:InterPro.
DR   GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IDA:BHF-UCL.
DR   GO; GO:0030117; C:membrane coat; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0030141; C:secretory granule; TAS:MGI.
DR   GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR   GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
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:0008565; F:protein transporter activity; IEA:InterPro.
DR   GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0006886; P:intracellular protein transport; TAS:MGI.
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   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; IPR009028; Coatomer/calthrin_app_sub_C.
DR   InterPro; IPR013041; Coatomer/clathrin_app_Ig-like.
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; Complete proteome;
KW   Endocytosis; Lipid-binding; Membrane; Protein transport;
KW   Reference proteome; Transport.
FT   INIT_MET      1      1       Removed. {ECO:0000250|UniProtKB:P18484}.
FT   CHAIN         2    938       AP-2 complex subunit alpha-2.
FT                                /FTId=PRO_0000193733.
FT   REGION        5     80       Lipid-binding.
FT   BINDING      43     43       Phosphatidylinositol lipid headgroup.
FT   BINDING      53     53       Phosphatidylinositol lipid headgroup.
FT   BINDING      57     57       Phosphatidylinositol lipid headgroup.
FT   BINDING      58     58       Phosphatidylinositol lipid headgroup.
FT   BINDING      61     61       Phosphatidylinositol lipid headgroup.
FT   MUTAGEN      21     21       R->E: Reduces interaction with CD4
FT                                endocytosis signal motif; when associated
FT                                with AP2S1 S-15.
FT                                {ECO:0000269|PubMed:19140243}.
FT   MUTAGEN      31     31       K->Q: Reduces phosphatidylinositol
FT                                binding. {ECO:0000269|PubMed:10459011}.
FT   MUTAGEN      32     32       R->Q: Reduces phosphatidylinositol
FT                                binding. {ECO:0000269|PubMed:10459011}.
FT   MUTAGEN      35     35       K->Q: Reduces phosphatidylinositol
FT                                binding. {ECO:0000269|PubMed:10459011}.
FT   MUTAGEN      45     45       K->Q: Reduces phosphatidylinositol
FT                                binding. {ECO:0000269|PubMed:10459011}.
FT   MUTAGEN      55     55       K->Q: Strongly reduces
FT                                phosphatidylinositol binding. Abolishes
FT                                phosphatidylinositol binding; when
FT                                associated with Q-56 and Q-57.
FT                                {ECO:0000269|PubMed:10459011}.
FT   MUTAGEN      56     56       K->E: Strongly reduces
FT                                phosphatidylinositol binding.
FT                                {ECO:0000269|PubMed:10459011}.
FT   MUTAGEN      56     56       K->Q: Strongly reduces
FT                                phosphatidylinositol binding. Abolishes
FT                                phosphatidylinositol binding; when
FT                                associated with Q-55 and Q-57.
FT                                {ECO:0000269|PubMed:10459011}.
FT   MUTAGEN      57     57       K->Q: Strongly reduces
FT                                phosphatidylinositol binding. Abolishes
FT                                phosphatidylinositol binding; when
FT                                associated with Q-55 and Q-56.
FT                                {ECO:0000269|PubMed:10459011}.
FT   MUTAGEN      61     61       K->Q: Reduces phosphatidylinositol
FT                                binding. {ECO:0000269|PubMed:10459011}.
FT   MUTAGEN     727    727       K->A: No effect on DENND1A-,DENND1B- nor
FT                                DENND1C-binding.
FT   MUTAGEN     782    782       Q->A: Reduces DENND1A- and DENND1C-
FT                                binding. {ECO:0000269|PubMed:20154091}.
FT   MUTAGEN     837    837       F->A: Reduces SNAP91, AMPH and BIN1
FT                                binding. Abolishes AMPH and SNAP91
FT                                binding; when associated with A-916.
FT                                Abolishes EPN1 and EPS15 binding; when
FT                                associated with A-905.
FT                                {ECO:0000269|PubMed:10380931,
FT                                ECO:0000269|PubMed:10430869}.
FT   MUTAGEN     840    840       W->A: Abolishes AMPH, BIN1, EPS15, EPN1,
FT                                auxilin and SNAP91 binding. Abolishes
FT                                interaction with DGKD.
FT                                {ECO:0000269|PubMed:10380931,
FT                                ECO:0000269|PubMed:17880279}.
FT   MUTAGEN     849    849       E->A: No effect.
FT                                {ECO:0000269|PubMed:10380931}.
FT   MUTAGEN     905    905       R->A: Strongly reduces AMPH, SNAP91,
FT                                auxilin and BIN1 binding. Abolishes EPN1
FT                                and EPS15 binding; when associated with
FT                                A-837. {ECO:0000269|PubMed:10380931,
FT                                ECO:0000269|PubMed:10430869}.
FT   MUTAGEN     907    907       E->A: Strongly reduces AMPH, SNAP91 and
FT                                BIN1 binding. Slightly reduces EPS15 and
FT                                auxilin binding.
FT                                {ECO:0000269|PubMed:10380931}.
FT   MUTAGEN     916    916       R->A: Strongly reduces AMPH and SNAP91
FT                                binding. Abolishes DENND1B-binding; no
FT                                effect on DENND1A-, nor DENND1C-binding.
FT                                Abolishes AMPH and SNAP91 binding; when
FT                                associated with A-837.
FT                                {ECO:0000269|PubMed:10430869,
FT                                ECO:0000269|PubMed:20154091}.
FT   MUTAGEN     920    920       R->A: Abolishes AMPH and BIN1 binding.
FT                                Reduces EPS15, SNAP91 and auxilin
FT                                binding. {ECO:0000269|PubMed:10380931}.
FT   CONFLICT    858    859       HP -> LE (in Ref. 4; AAH10597).
FT                                {ECO:0000305}.
FT   CONFLICT    889    890       GA -> VL (in Ref. 1; CAA33097 and 5;
FT                                AAB62703). {ECO:0000305}.
FT   HELIX        11     22       {ECO:0000244|PDB:2JKR}.
FT   HELIX        28     40       {ECO:0000244|PDB:2JKR}.
FT   TURN         41     43       {ECO:0000244|PDB:2JKR}.
FT   STRAND       44     48       {ECO:0000244|PDB:2JKR}.
FT   HELIX        52     66       {ECO:0000244|PDB:2JKR}.
FT   TURN         67     69       {ECO:0000244|PDB:2JKR}.
FT   HELIX        76     82       {ECO:0000244|PDB:2JKR}.
FT   HELIX        88    100       {ECO:0000244|PDB:2JKR}.
FT   HELIX       106    121       {ECO:0000244|PDB:2JKR}.
FT   HELIX       125    138       {ECO:0000244|PDB:2JKR}.
FT   HELIX       141    147       {ECO:0000244|PDB:2JKR}.
FT   HELIX       150    156       {ECO:0000244|PDB:2JKR}.
FT   HELIX       162    178       {ECO:0000244|PDB:2JKR}.
FT   HELIX       180    182       {ECO:0000244|PDB:2JKR}.
FT   HELIX       188    193       {ECO:0000244|PDB:2JKR}.
FT   HELIX       194    197       {ECO:0000244|PDB:2JKR}.
FT   HELIX       201    214       {ECO:0000244|PDB:2JKR}.
FT   TURN        215    217       {ECO:0000244|PDB:2JKR}.
FT   HELIX       219    222       {ECO:0000244|PDB:2JKR}.
FT   HELIX       225    238       {ECO:0000244|PDB:2JKR}.
FT   STRAND      241    244       {ECO:0000244|PDB:2JKR}.
FT   TURN        245    247       {ECO:0000244|PDB:2JKR}.
FT   STRAND      252    254       {ECO:0000244|PDB:2JKR}.
FT   HELIX       255    265       {ECO:0000244|PDB:2JKR}.
FT   HELIX       273    291       {ECO:0000244|PDB:2JKR}.
FT   HELIX       299    319       {ECO:0000244|PDB:2JKR}.
FT   HELIX       323    338       {ECO:0000244|PDB:2JKR}.
FT   HELIX       343    355       {ECO:0000244|PDB:2JKR}.
FT   STRAND      359    361       {ECO:0000244|PDB:2JKR}.
FT   HELIX       364    368       {ECO:0000244|PDB:2JKR}.
FT   HELIX       369    378       {ECO:0000244|PDB:2JKR}.
FT   HELIX       382    393       {ECO:0000244|PDB:2JKR}.
FT   TURN        398    400       {ECO:0000244|PDB:2JKR}.
FT   HELIX       401    413       {ECO:0000244|PDB:2JKR}.
FT   HELIX       417    434       {ECO:0000244|PDB:2JKR}.
FT   HELIX       438    450       {ECO:0000244|PDB:2JKR}.
FT   HELIX       453    455       {ECO:0000244|PDB:2JKR}.
FT   HELIX       458    470       {ECO:0000244|PDB:2JKR}.
FT   HELIX       475    485       {ECO:0000244|PDB:2JKR}.
FT   STRAND      488    490       {ECO:0000244|PDB:2JKR}.
FT   HELIX       493    505       {ECO:0000244|PDB:2JKR}.
FT   HELIX       508    510       {ECO:0000244|PDB:2JKR}.
FT   HELIX       514    516       {ECO:0000244|PDB:2JKR}.
FT   HELIX       518    529       {ECO:0000244|PDB:2JKR}.
FT   HELIX       534    550       {ECO:0000244|PDB:2JKR}.
FT   TURN        552    554       {ECO:0000244|PDB:2JKR}.
FT   HELIX       555    562       {ECO:0000244|PDB:2JKR}.
FT   HELIX       565    568       {ECO:0000244|PDB:2JKR}.
FT   HELIX       573    588       {ECO:0000244|PDB:2JKR}.
FT   HELIX       591    597       {ECO:0000244|PDB:2JKR}.
FT   STRAND      610    613       {ECO:0000244|PDB:2JKR}.
FT   STRAND      617    620       {ECO:0000244|PDB:2JKR}.
FT   TURN        701    704       {ECO:0000244|PDB:1QTS}.
FT   HELIX       705    708       {ECO:0000244|PDB:1KYF}.
FT   STRAND      714    718       {ECO:0000244|PDB:1KYF}.
FT   STRAND      720    731       {ECO:0000244|PDB:1KYF}.
FT   STRAND      734    743       {ECO:0000244|PDB:1KYF}.
FT   STRAND      745    747       {ECO:0000244|PDB:1KYF}.
FT   STRAND      749    757       {ECO:0000244|PDB:1KYF}.
FT   HELIX       760    765       {ECO:0000244|PDB:1KYF}.
FT   STRAND      766    770       {ECO:0000244|PDB:1KYF}.
FT   STRAND      782    791       {ECO:0000244|PDB:1KYF}.
FT   STRAND      800    807       {ECO:0000244|PDB:1KYF}.
FT   STRAND      810    817       {ECO:0000244|PDB:1KYF}.
FT   HELIX       822    825       {ECO:0000244|PDB:1KYF}.
FT   STRAND      826    828       {ECO:0000244|PDB:1KYF}.
FT   HELIX       833    840       {ECO:0000244|PDB:1KYF}.
FT   HELIX       846    848       {ECO:0000244|PDB:1KYF}.
FT   STRAND      849    855       {ECO:0000244|PDB:1KYF}.
FT   HELIX       862    872       {ECO:0000244|PDB:1KYF}.
FT   STRAND      874    877       {ECO:0000244|PDB:1KYF}.
FT   STRAND      879    883       {ECO:0000244|PDB:1KYF}.
FT   STRAND      886    894       {ECO:0000244|PDB:1KYF}.
FT   STRAND      899    909       {ECO:0000244|PDB:1KYF}.
FT   TURN        910    913       {ECO:0000244|PDB:1KYF}.
FT   STRAND      914    923       {ECO:0000244|PDB:1KYF}.
FT   HELIX       924    935       {ECO:0000244|PDB:1KYF}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT       706    819       ismart:Alpha_adaptinC2 [T]
FT   MYHIT       712    816       ipfam:Alpha_adaptinC2 [T]
FT   MYHIT        31    587       ipfam:Adaptin_N [T]
FT   MYHIT       825    933       ipfam:Alpha_adaptin_C [T]
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
//