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P17426

- AP2A1_MOUSE

UniProt

P17426 - AP2A1_MOUSE

Protein

AP-2 complex subunit alpha-1

Gene

Ap2a1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 1 (01 Aug 1990)
      Previous versions | rss
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    Functioni

    Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif By similarity.By similarity

    GO - Molecular functioni

    1. protein binding Source: UniProtKB
    2. protein kinase binding Source: ParkinsonsUK-UCL
    3. protein transporter activity Source: InterPro

    GO - Biological processi

    1. endocytosis Source: UniProtKB-KW
    2. intracellular protein transport Source: MGI
    3. negative regulation of hyaluronan biosynthetic process Source: UniProtKB
    4. vesicle-mediated transport Source: MGI

    Keywords - Biological processi

    Endocytosis, Protein transport, Transport

    Enzyme and pathway databases

    ReactomeiREACT_196550. MHC class II antigen presentation.
    REACT_202778. Retrograde neurotrophin signalling.
    REACT_203917. EGFR downregulation.
    REACT_222404. WNT5A-dependent internalization of FZD4.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    AP-2 complex subunit alpha-1
    Alternative name(s):
    100 kDa coated vesicle protein A
    Adaptor protein complex AP-2 subunit alpha-1
    Adaptor-related protein complex 2 subunit alpha-1
    Alpha-adaptin A
    Alpha1-adaptin
    Clathrin assembly protein complex 2 alpha-A large chain
    Plasma membrane adaptor HA2/AP2 adaptin alpha A subunit
    Gene namesi
    Name:Ap2a1
    Synonyms:Adtaa, Clapa1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:101921. Ap2a1.

    Subcellular locationi

    Cell membrane By similarity. Membranecoated pit By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
    Note: AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV.By similarity

    GO - Cellular componenti

    1. apical plasma membrane Source: Ensembl
    2. basolateral plasma membrane Source: Ensembl
    3. clathrin adaptor complex Source: InterPro
    4. coated pit Source: UniProtKB-SubCell
    5. membrane coat Source: MGI
    6. secretory granule Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Coated pit, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 977977AP-2 complex subunit alpha-1PRO_0000193731Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei626 – 6261PhosphoserineBy similarity
    Modified residuei652 – 6521PhosphoserineBy similarity
    Modified residuei653 – 6531PhosphothreonineBy similarity
    Modified residuei655 – 6551PhosphoserineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP17426.
    PaxDbiP17426.
    PRIDEiP17426.

    PTM databases

    PhosphoSiteiP17426.

    Miscellaneous databases

    PMAP-CutDBP17426.

    Expressioni

    Tissue specificityi

    Isoform A is expressed only in neuronal tissue and skeletal muscle. Isoform B is widely expressed.

    Gene expression databases

    ArrayExpressiP17426.
    BgeeiP17426.
    CleanExiMM_AP2A1.
    GenevestigatoriP17426.

    Interactioni

    Subunit structurei

    Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Interacts with HIP1 and RAB11FIP2 By similarity. Interacts with SLC12A5. Interacts with clathrin. Interacts with SLC12A5. Interacts with clathrin. Interacts with SGIP1.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Grin2bQ010972EBI-775189,EBI-400125

    Protein-protein interaction databases

    BioGridi198129. 5 interactions.
    IntActiP17426. 12 interactions.
    MINTiMINT-1865011.
    STRINGi10090.ENSMUSP00000082519.

    Structurei

    3D structure databases

    ProteinModelPortaliP17426.
    SMRiP17426. Positions 3-621, 746-977.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG303101.
    GeneTreeiENSGT00550000074757.
    HOGENOMiHOG000170596.
    HOVERGENiHBG050518.
    InParanoidiP17426.
    KOiK11824.
    OMAiNYVGAGI.
    OrthoDBiEOG7GQXV2.
    PhylomeDBiP17426.
    TreeFamiTF300308.

    Family and domain databases

    Gene3Di1.25.10.10. 1 hit.
    2.60.40.1030. 1 hit.
    3.30.310.30. 1 hit.
    InterProiIPR017104. AP2_complex_asu.
    IPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR002553. Clathrin/coatomer_adapt-like_N.
    IPR013038. Clathrin_a-adaptin_app_Ig-like.
    IPR003164. Clathrin_a-adaptin_app_sub_C.
    IPR008152. Clathrin_a/b/g-adaptin_app_Ig.
    IPR015873. Clathrin_a/coatomer_app_sub_C.
    IPR009028. Coatomer/calthrin_app_sub_C.
    IPR013041. Coatomer/clathrin_app_Ig-like.
    [Graphical view]
    PfamiPF01602. Adaptin_N. 1 hit.
    PF02296. Alpha_adaptin_C. 1 hit.
    PF02883. Alpha_adaptinC2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037091. AP2_complex_alpha. 1 hit.
    SMARTiSM00809. Alpha_adaptinC2. 1 hit.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 1 hit.
    SSF49348. SSF49348. 1 hit.
    SSF55711. SSF55711. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform A (identifier: P17426-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL    50
    DGYSKKKYVC KLLFIFLLGH DIDFGHMEAV NLLSSNKYTE KQIGYLFISV 100
    LVNSNSELIR LINNAIKNDL ASRNPTFMCL ALHCIANVGS REMGEAFAAD 150
    IPRILVAGDS MDSVKQSAAL CLLRLYKASP DLVPMGEWTA RVVHLLNDQH 200
    MGVVTAAVSL ITCLCKKNPD DFKTCISLAV SRLSRIVSSA STDLQDYTYY 250
    FVPAPWLSVK LLRLLQCYPP PEDAAVKGRL VECLETVLNK AQEPPKSKKV 300
    QHSNAKNAIL FETISLIIHY DSEPNLLVRA CNQLGQFLQH RETNLRYLAL 350
    ESMCTLASSE FSHEAVKTHI DTVINALKTE RDVSVRQRAA DLLYAMCDRS 400
    NAKQIVSEML RYLETADYAI REEIVLKVAI LAEKYAVDYS WYVDTILNLI 450
    RIAGDYVSEE VWYRVLQIVT NRDDVQGYAA KTVFEALQAP ACHENMVKVG 500
    GYILGEFGNL IAGDPRSSPP VQFSLLHSKF HLCSVATRAL LLSTYIKFIN 550
    LFPETKATIQ GVLRAGSQLR NADVELQQRA VEYLTLSSVA STDVLATVLE 600
    EMPPFPERES SILAKLKRKK GPGAASALDD SRRDTSSNDI NGGVEPTPST 650
    VSTPSPSADL LGLRAAPPPA APPAPVGGNL LVDVFSDGPT AQPSLGPTPE 700
    EAFLSELEPP APESPMALLA DPAPAADPGP EDIGPPIPEA DELLNKFVCK 750
    NSGVLFENQL LQIGVKSEFR QNLGRMYLFY GNKTSVQFQN FLPTVVHPGD 800
    LQTQLAVQTK RVAAQVDGGA QVQQVLNIEC LRDFLTPPLL SVRFRYGGTA 850
    QSLTLKLPVT INKFFQPTEM AAQDFFQRWK QLSLPLQEAQ KIFKANHPMD 900
    AEVTKAKLLG FGSALLDNVD PNPENFVGAG IIQTKALQVG CLLRLEPNAQ 950
    AQMYRLTLRT SKEPVSRHLC ELLAQQF 977
    Length:977
    Mass (Da):107,664
    Last modified:August 1, 1990 - v1
    Checksum:iF4ED87D3F9EF230A
    GO
    Isoform B (identifier: P17426-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         706-727: Missing.

    Show »
    Length:955
    Mass (Da):105,480
    Checksum:iD6EB4672359D66B9
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei706 – 72722Missing in isoform B. CuratedVSP_000162Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14971 mRNA. Translation: CAA33096.1.
    BC031433 mRNA. Translation: AAH31433.1.
    CCDSiCCDS52238.1. [P17426-2]
    CCDS52239.1. [P17426-1]
    PIRiA30111.
    RefSeqiNP_001070732.1. NM_001077264.1. [P17426-2]
    NP_031484.1. NM_007458.2. [P17426-1]
    UniGeneiMm.6877.

    Genome annotation databases

    EnsembliENSMUST00000085399; ENSMUSP00000082519; ENSMUSG00000060279. [P17426-1]
    ENSMUST00000107857; ENSMUSP00000103489; ENSMUSG00000060279. [P17426-2]
    ENSMUST00000166972; ENSMUSP00000127842; ENSMUSG00000060279. [P17426-1]
    ENSMUST00000167930; ENSMUSP00000127497; ENSMUSG00000060279. [P17426-2]
    GeneIDi11771.
    KEGGimmu:11771.
    UCSCiuc009grv.1. mouse. [P17426-1]
    uc009grw.1. mouse. [P17426-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14971 mRNA. Translation: CAA33096.1 .
    BC031433 mRNA. Translation: AAH31433.1 .
    CCDSi CCDS52238.1. [P17426-2 ]
    CCDS52239.1. [P17426-1 ]
    PIRi A30111.
    RefSeqi NP_001070732.1. NM_001077264.1. [P17426-2 ]
    NP_031484.1. NM_007458.2. [P17426-1 ]
    UniGenei Mm.6877.

    3D structure databases

    ProteinModelPortali P17426.
    SMRi P17426. Positions 3-621, 746-977.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198129. 5 interactions.
    IntActi P17426. 12 interactions.
    MINTi MINT-1865011.
    STRINGi 10090.ENSMUSP00000082519.

    PTM databases

    PhosphoSitei P17426.

    Proteomic databases

    MaxQBi P17426.
    PaxDbi P17426.
    PRIDEi P17426.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000085399 ; ENSMUSP00000082519 ; ENSMUSG00000060279 . [P17426-1 ]
    ENSMUST00000107857 ; ENSMUSP00000103489 ; ENSMUSG00000060279 . [P17426-2 ]
    ENSMUST00000166972 ; ENSMUSP00000127842 ; ENSMUSG00000060279 . [P17426-1 ]
    ENSMUST00000167930 ; ENSMUSP00000127497 ; ENSMUSG00000060279 . [P17426-2 ]
    GeneIDi 11771.
    KEGGi mmu:11771.
    UCSCi uc009grv.1. mouse. [P17426-1 ]
    uc009grw.1. mouse. [P17426-2 ]

    Organism-specific databases

    CTDi 160.
    MGIi MGI:101921. Ap2a1.

    Phylogenomic databases

    eggNOGi NOG303101.
    GeneTreei ENSGT00550000074757.
    HOGENOMi HOG000170596.
    HOVERGENi HBG050518.
    InParanoidi P17426.
    KOi K11824.
    OMAi NYVGAGI.
    OrthoDBi EOG7GQXV2.
    PhylomeDBi P17426.
    TreeFami TF300308.

    Enzyme and pathway databases

    Reactomei REACT_196550. MHC class II antigen presentation.
    REACT_202778. Retrograde neurotrophin signalling.
    REACT_203917. EGFR downregulation.
    REACT_222404. WNT5A-dependent internalization of FZD4.

    Miscellaneous databases

    ChiTaRSi AP2A1. mouse.
    NextBioi 279549.
    PMAP-CutDB P17426.
    PROi P17426.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P17426.
    Bgeei P17426.
    CleanExi MM_AP2A1.
    Genevestigatori P17426.

    Family and domain databases

    Gene3Di 1.25.10.10. 1 hit.
    2.60.40.1030. 1 hit.
    3.30.310.30. 1 hit.
    InterProi IPR017104. AP2_complex_asu.
    IPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR002553. Clathrin/coatomer_adapt-like_N.
    IPR013038. Clathrin_a-adaptin_app_Ig-like.
    IPR003164. Clathrin_a-adaptin_app_sub_C.
    IPR008152. Clathrin_a/b/g-adaptin_app_Ig.
    IPR015873. Clathrin_a/coatomer_app_sub_C.
    IPR009028. Coatomer/calthrin_app_sub_C.
    IPR013041. Coatomer/clathrin_app_Ig-like.
    [Graphical view ]
    Pfami PF01602. Adaptin_N. 1 hit.
    PF02296. Alpha_adaptin_C. 1 hit.
    PF02883. Alpha_adaptinC2. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF037091. AP2_complex_alpha. 1 hit.
    SMARTi SM00809. Alpha_adaptinC2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48371. SSF48371. 1 hit.
    SSF49348. SSF49348. 1 hit.
    SSF55711. SSF55711. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of cDNAs encoding two related 100-kD coated vesicle proteins (alpha-adaptins)."
      Robinson M.S.
      J. Cell Biol. 108:833-842(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
      Tissue: Retina.
    3. "The alpha chain of the AP-2 adaptor is a clathrin binding subunit."
      Goodman O.B. Jr., Keen J.H.
      J. Biol. Chem. 270:23768-23773(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CLATHRIN.
    4. "Expression and localization of alpha-adaptin isoforms."
      Ball C.L., Hunt S.P., Robinson M.S.
      J. Cell Sci. 108:2865-2875(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF ISOFORMS A AND B.
    5. "Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network."
      Nakatsu F., Ohno H.
      Cell Struct. Funct. 28:419-429(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
    6. "Adaptors for clathrin coats: structure and function."
      Owen D.J., Collins B.M., Evans P.R.
      Annu. Rev. Cell Dev. Biol. 20:153-191(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
    7. "SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15."
      Uezu A., Horiuchi A., Kanda K., Kikuchi N., Umeda K., Tsujita K., Suetsugu S., Araki N., Yamamoto H., Takenawa T., Nakanishi H.
      J. Biol. Chem. 282:26481-26489(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SGIP1.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    9. "Identification of a novel di-leucine motif mediating K(+)/Cl(-) cotransporter KCC2 constitutive endocytosis."
      Zhao B., Wong A.Y.C., Murshid A., Bowie D., Presley J.F., Bedford F.K.
      Cell. Signal. 20:1769-1779(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SLC12A5.

    Entry informationi

    Entry nameiAP2A1_MOUSE
    AccessioniPrimary (citable) accession number: P17426
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: August 1, 1990
    Last modified: October 1, 2014
    This is version 136 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3