Entry euk:AP2A1_MOUSE

ID   AP2A1_MOUSE             Reviewed;         977 AA.
AC   P17426;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   10-MAY-2017, entry version 161.
DE   RecName: Full=AP-2 complex subunit alpha-1;
DE   AltName: Full=100 kDa coated vesicle protein A;
DE   AltName: Full=Adaptor protein complex AP-2 subunit alpha-1;
DE   AltName: Full=Adaptor-related protein complex 2 subunit alpha-1;
DE   AltName: Full=Alpha-adaptin A;
DE   AltName: Full=Alpha1-adaptin;
DE   AltName: Full=Clathrin assembly protein complex 2 alpha-A large chain;
DE   AltName: Full=Plasma membrane adaptor HA2/AP2 adaptin alpha A subunit;
GN   Name=Ap2a1; Synonyms=Adtaa, Clapa1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
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] (ISOFORM A).
RC   TISSUE=Retina;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   INTERACTION WITH CLATHRIN.
RX   PubMed=7559550; DOI=10.1074/jbc.270.40.23768;
RA   Goodman O.B. Jr., Keen J.H.;
RT   "The alpha chain of the AP-2 adaptor is a clathrin binding subunit.";
RL   J. Biol. Chem. 270:23768-23773(1995).
RN   [4]
RP   CHARACTERIZATION OF ISOFORMS A AND B.
RX   PubMed=7593326;
RA   Ball C.L., Hunt S.P., Robinson M.S.;
RT   "Expression and localization of alpha-adaptin isoforms.";
RL   J. Cell Sci. 108:2865-2875(1995).
RN   [5]
RP   FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
RX   PubMed=14745134; DOI=10.1247/csf.28.419;
RA   Nakatsu F., Ohno H.;
RT   "Adaptor protein complexes as the key regulators of protein sorting in
RT   the post-Golgi network.";
RL   Cell Struct. Funct. 28:419-429(2003).
RN   [6]
RP   FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
RX   PubMed=15473838; DOI=10.1146/annurev.cellbio.20.010403.104543;
RA   Owen D.J., Collins B.M., Evans P.R.;
RT   "Adaptors for clathrin coats: structure and function.";
RL   Annu. Rev. Cell Dev. Biol. 20:153-191(2004).
RN   [7]
RP   INTERACTION WITH SGIP1.
RX   PubMed=17626015; DOI=10.1074/jbc.M703815200;
RA   Uezu A., Horiuchi A., Kanda K., Kikuchi N., Umeda K., Tsujita K.,
RA   Suetsugu S., Araki N., Yamamoto H., Takenawa T., Nakanishi H.;
RT   "SGIP1alpha is an endocytic protein that directly interacts with
RT   phospholipids and Eps15.";
RL   J. Biol. Chem. 282:26481-26489(2007).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [9]
RP   INTERACTION WITH SLC12A5.
RX   PubMed=18625303; DOI=10.1016/j.cellsig.2008.06.011;
RA   Zhao B., Wong A.Y.C., Murshid A., Bowie D., Presley J.F.,
RA   Bedford F.K.;
RT   "Identification of a novel di-leucine motif mediating K(+)/Cl(-)
RT   cotransporter KCC2 constitutive endocytosis.";
RL   Cell. Signal. 20:1769-1779(2008).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-652; THR-653 AND
RP   SER-655, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   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).
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 (By similarity). {ECO:0000250, 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). Interacts
CC       with HIP1 and RAB11FIP2 (By similarity). Interacts with SLC12A5.
CC       Interacts with clathrin. Interacts with SLC12A5. Interacts with
CC       clathrin. Interacts with SGIP1. {ECO:0000250,
CC       ECO:0000269|PubMed:17626015, ECO:0000269|PubMed:18625303,
CC       ECO:0000269|PubMed:7559550}.
CC   -!- INTERACTION:
CC       Q01097:Grin2b; NbExp=2; IntAct=EBI-775189, EBI-400125;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}. Membrane,
CC       coated pit {ECO:0000250}; Peripheral membrane protein
CC       {ECO:0000250}; Cytoplasmic side {ECO:0000250}. 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:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=A;
CC         IsoId=P17426-1; Sequence=Displayed;
CC       Name=B;
CC         IsoId=P17426-2; Sequence=VSP_000162;
CC   -!- TISSUE SPECIFICITY: Isoform A is expressed only in neuronal tissue
CC       and skeletal muscle. Isoform B is widely expressed.
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; X14971; CAA33096.1; -; mRNA.
DR   EMBL; BC031433; AAH31433.1; -; mRNA.
DR   CCDS; CCDS52238.1; -. [P17426-2]
DR   CCDS; CCDS52239.1; -. [P17426-1]
DR   PIR; A30111; A30111.
DR   RefSeq; NP_001070732.1; NM_001077264.1. [P17426-2]
DR   RefSeq; NP_031484.1; NM_007458.2. [P17426-1]
DR   UniGene; Mm.6877; -.
DR   ProteinModelPortal; P17426; -.
DR   SMR; P17426; -.
DR   BioGrid; 198129; 6.
DR   IntAct; P17426; 13.
DR   MINT; MINT-1865011; -.
DR   STRING; 10090.ENSMUSP00000127842; -.
DR   iPTMnet; P17426; -.
DR   PhosphoSitePlus; P17426; -.
DR   SwissPalm; P17426; -.
DR   MaxQB; P17426; -.
DR   PaxDb; P17426; -.
DR   PeptideAtlas; P17426; -.
DR   PRIDE; P17426; -.
DR   Ensembl; ENSMUST00000085399; ENSMUSP00000082519; ENSMUSG00000060279. [P17426-1]
DR   Ensembl; ENSMUST00000107857; ENSMUSP00000103489; ENSMUSG00000060279. [P17426-2]
DR   Ensembl; ENSMUST00000166972; ENSMUSP00000127842; ENSMUSG00000060279. [P17426-1]
DR   Ensembl; ENSMUST00000167930; ENSMUSP00000127497; ENSMUSG00000060279. [P17426-2]
DR   GeneID; 11771; -.
DR   KEGG; mmu:11771; -.
DR   UCSC; uc009grv.1; mouse. [P17426-1]
DR   UCSC; uc009grw.1; mouse. [P17426-2]
DR   CTD; 160; -.
DR   MGI; MGI:101921; Ap2a1.
DR   eggNOG; KOG1077; Eukaryota.
DR   eggNOG; ENOG410XNQE; LUCA.
DR   GeneTree; ENSGT00550000074757; -.
DR   HOGENOM; HOG000170596; -.
DR   HOVERGEN; HBG050518; -.
DR   InParanoid; P17426; -.
DR   KO; K11824; -.
DR   OMA; INIKFRY; -.
DR   OrthoDB; EOG091G01JZ; -.
DR   PhylomeDB; P17426; -.
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-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; Ap2a1; mouse.
DR   PMAP-CutDB; P17426; -.
DR   PRO; PR:P17426; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   Bgee; ENSMUSG00000060279; -.
DR   CleanEx; MM_AP2A1; -.
DR   ExpressionAtlas; P17426; baseline and differential.
DR   Genevisible; P17426; MM.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR   GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR   GO; GO:0030131; C:clathrin adaptor complex; IEA:InterPro.
DR   GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR   GO; GO:0032433; C:filopodium tip; IDA:MGI.
DR   GO; GO:0016020; C:membrane; ISO:MGI.
DR   GO; GO:0030117; C:membrane coat; IDA:MGI.
DR   GO; GO:0030141; C:secretory granule; TAS:MGI.
DR   GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR   GO; GO:0032403; F:protein complex binding; IEA:Ensembl.
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:1900126; P:negative regulation of hyaluronan biosynthetic process; ISS:UniProtKB.
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   Alternative splicing; Cell membrane; Coated pit; Complete proteome;
KW   Endocytosis; Membrane; Phosphoprotein; Protein transport;
KW   Reference proteome; Transport.
FT   CHAIN         1    977       AP-2 complex subunit alpha-1.
FT                                /FTId=PRO_0000193731.
FT   MOD_RES     626    626       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:O95782}.
FT   MOD_RES     652    652       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     653    653       Phosphothreonine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     655    655       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   VAR_SEQ     706    727       Missing (in isoform B). {ECO:0000305}.
FT                                /FTId=VSP_000162.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT       752    857       ipfam:Alpha_adaptinC2 [T]
FT   MYHIT       745    858       ismart:Alpha_adaptinC2 [T]
FT   MYHIT       864    972       ipfam:Alpha_adaptin_C [T]
FT   MYHIT        31    588       ipfam:Adaptin_N [T]
SQ   SEQUENCE   977 AA;  107664 MW;  F4ED87D3F9EF230A CRC64;
     MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC
     KLLFIFLLGH DIDFGHMEAV NLLSSNKYTE KQIGYLFISV LVNSNSELIR LINNAIKNDL
     ASRNPTFMCL ALHCIANVGS REMGEAFAAD IPRILVAGDS MDSVKQSAAL CLLRLYKASP
     DLVPMGEWTA RVVHLLNDQH MGVVTAAVSL ITCLCKKNPD DFKTCISLAV SRLSRIVSSA
     STDLQDYTYY FVPAPWLSVK LLRLLQCYPP PEDAAVKGRL VECLETVLNK AQEPPKSKKV
     QHSNAKNAIL FETISLIIHY DSEPNLLVRA CNQLGQFLQH RETNLRYLAL ESMCTLASSE
     FSHEAVKTHI DTVINALKTE RDVSVRQRAA DLLYAMCDRS NAKQIVSEML RYLETADYAI
     REEIVLKVAI LAEKYAVDYS WYVDTILNLI RIAGDYVSEE VWYRVLQIVT NRDDVQGYAA
     KTVFEALQAP ACHENMVKVG GYILGEFGNL IAGDPRSSPP VQFSLLHSKF HLCSVATRAL
     LLSTYIKFIN LFPETKATIQ GVLRAGSQLR NADVELQQRA VEYLTLSSVA STDVLATVLE
     EMPPFPERES SILAKLKRKK GPGAASALDD SRRDTSSNDI NGGVEPTPST VSTPSPSADL
     LGLRAAPPPA APPAPVGGNL LVDVFSDGPT AQPSLGPTPE EAFLSELEPP APESPMALLA
     DPAPAADPGP EDIGPPIPEA DELLNKFVCK NSGVLFENQL LQIGVKSEFR QNLGRMYLFY
     GNKTSVQFQN FLPTVVHPGD LQTQLAVQTK RVAAQVDGGA QVQQVLNIEC LRDFLTPPLL
     SVRFRYGGTA QSLTLKLPVT INKFFQPTEM AAQDFFQRWK QLSLPLQEAQ KIFKANHPMD
     AEVTKAKLLG FGSALLDNVD PNPENFVGAG IIQTKALQVG CLLRLEPNAQ AQMYRLTLRT
     SKEPVSRHLC ELLAQQF
//