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P84091

- AP2M1_MOUSE

UniProt

P84091 - AP2M1_MOUSE

Protein

AP-2 complex subunit mu

Gene

Ap2m1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 92 (01 Oct 2014)
      Sequence version 1 (16 Aug 2004)
      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 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs. The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane-associated AP-2. The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 By similarity. Plays a role in endocytosis of frizzled family members upon Wnt signaling By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei341 – 3411Phosphatidylinositol lipid headgroupBy similarity
    Binding sitei343 – 3431Phosphatidylinositol lipid headgroupBy similarity
    Binding sitei345 – 3451Phosphatidylinositol lipid headgroupBy similarity
    Binding sitei354 – 3541Phosphatidylinositol lipid headgroupBy similarity
    Binding sitei356 – 3561Phosphatidylinositol lipid headgroupBy similarity

    GO - Molecular functioni

    1. lipid binding Source: UniProtKB-KW

    GO - Biological processi

    1. endocytosis Source: UniProtKB-KW
    2. intracellular protein transport Source: MGI
    3. vesicle-mediated transport Source: MGI

    Keywords - Biological processi

    Endocytosis, Protein transport, Transport

    Keywords - Ligandi

    Lipid-binding

    Enzyme and pathway databases

    ReactomeiREACT_196550. MHC class II antigen presentation.
    REACT_202778. Retrograde neurotrophin signalling.
    REACT_203917. EGFR downregulation.
    REACT_209040. Gap junction degradation.
    REACT_220352. Formation of annular gap junctions.
    REACT_222404. WNT5A-dependent internalization of FZD4.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    AP-2 complex subunit mu
    Alternative name(s):
    AP-2 mu chain
    Adaptor protein complex AP-2 subunit mu
    Adaptor-related protein complex 2 subunit mu
    Clathrin assembly protein complex 2 mu medium chain
    Clathrin coat assembly protein AP50
    Clathrin coat-associated protein AP50
    Mu2-adaptin
    Plasma membrane adaptor AP-2 50 kDa protein
    Gene namesi
    Name:Ap2m1
    Synonyms:Clapm1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 16

    Organism-specific databases

    MGIiMGI:1298405. Ap2m1.

    Subcellular locationi

    Cell membrane. Membranecoated pit; Peripheral membrane protein; Cytoplasmic side
    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. clathrin adaptor complex Source: InterPro
    2. coated pit Source: UniProtKB-SubCell
    3. mitochondrion Source: MGI
    4. plasma membrane Source: UniProtKB-SubCell
    5. secretory granule Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Coated pit, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Embryonic lethal before day 3.5 postcoitus (E3.5).1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 435435AP-2 complex subunit muPRO_0000193775Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei45 – 451PhosphoserineBy similarity
    Modified residuei156 – 1561PhosphothreonineBy similarity

    Post-translational modificationi

    Phosphorylated.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP84091.
    PaxDbiP84091.
    PRIDEiP84091.

    PTM databases

    PhosphoSiteiP84091.

    Expressioni

    Tissue specificityi

    Detected in spleen.

    Gene expression databases

    BgeeiP84091.
    CleanExiMM_AP2M1.
    GenevestigatoriP84091.

    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 ATP6V1H and MEGF10. Interacts with EGFR. Interacts with F2R. Interacts with KIAA0319; required for clathrin-mediated endocytosis of KIAA0319 By similarity. Interacts with PIP5K1C isoform 1; tyrosine phosphorylation of PIP5K1C weakens the interaction. Does not interact with PIP5K1C isoform 3. Interacts with DVL2 (via DEP domain) By similarity.By similarity

    Protein-protein interaction databases

    BioGridi198131. 7 interactions.
    IntActiP84091. 8 interactions.
    MINTiMINT-216926.

    Structurei

    3D structure databases

    ProteinModelPortaliP84091.
    SMRiP84091. Positions 1-435.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini170 – 434265MHDPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 MHD (mu homology) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG315786.
    HOGENOMiHOG000173246.
    HOVERGENiHBG050516.
    InParanoidiP84091.
    KOiK11826.
    OMAiCTQGKAK.
    PhylomeDBiP84091.
    TreeFamiTF300722.

    Family and domain databases

    InterProiIPR022775. AP_mu_sigma_su.
    IPR001392. Clathrin_mu.
    IPR008968. Clathrin_mu_C.
    IPR018240. Clathrin_mu_CS.
    IPR011012. Longin-like_dom.
    IPR028565. MHD.
    [Graphical view]
    PfamiPF00928. Adap_comp_sub. 1 hit.
    PF01217. Clat_adaptor_s. 1 hit.
    [Graphical view]
    PIRSFiPIRSF005992. Clathrin_mu. 1 hit.
    PRINTSiPR00314. CLATHRINADPT.
    SUPFAMiSSF49447. SSF49447. 1 hit.
    SSF64356. SSF64356. 1 hit.
    PROSITEiPS00990. CLAT_ADAPTOR_M_1. 1 hit.
    PS00991. CLAT_ADAPTOR_M_2. 1 hit.
    PS51072. MHD. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P84091-1 [UniParc]FASTAAdd to Basket

    « Hide

    MIGGLFIYNH KGEVLISRVY RDDIGRNAVD AFRVNVIHAR QQVRSPVTNI    50
    ARTSFFHVKR SNIWLAAVTK QNVNAAMVFE FLYKMCDVMA AYFGKISEEN 100
    IKNNFVLIYE LLDEILDFGY PQNSETGALK TFITQQGIKS QHQTKEEQSQ 150
    ITSQVTGQIG WRREGIKYRR NELFLDVLES VNLLMSPQGQ VLSAHVSGRV 200
    VMKSYLSGMP ECKFGMNDKI VIEKQGKGTA DETSKSGKQS IAIDDCTFHQ 250
    CVRLSKFDSE RSISFIPPDG EFELMRYRTT KDIILPFRVI PLVREVGRTK 300
    LEVKVVIKSN FKPSLLAQKI EVRIPTPLNT SGVQVICMKG KAKYKASENA 350
    IVWKIKRMAG MKESQISAEI ELLPTNDKKK WARPPISMNF EVPFAPSGLK 400
    VRYLKVFEPK LNYSDHDVIK WVRYIGRSGI YETRC 435
    Length:435
    Mass (Da):49,655
    Last modified:August 16, 2004 - v1
    Checksum:i82803219BA279954
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U27106 mRNA. Translation: AAC53158.1.
    AF001923
    , AF001913, AF001914, AF001915, AF001916, AF001917, AF001918, AF001919, AF001920, AF001921, AF001922 Genomic DNA. Translation: AAC53583.1.
    BC056352 mRNA. Translation: AAH56352.1.
    CCDSiCCDS28048.1.
    PIRiI49327.
    JC6563.
    RefSeqiNP_033809.1. NM_009679.2.
    UniGeneiMm.18946.

    Genome annotation databases

    EnsembliENSMUST00000007216; ENSMUSP00000007216; ENSMUSG00000022841.
    GeneIDi11773.
    KEGGimmu:11773.
    UCSCiuc007ypy.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U27106 mRNA. Translation: AAC53158.1 .
    AF001923
    , AF001913 , AF001914 , AF001915 , AF001916 , AF001917 , AF001918 , AF001919 , AF001920 , AF001921 , AF001922 Genomic DNA. Translation: AAC53583.1 .
    BC056352 mRNA. Translation: AAH56352.1 .
    CCDSi CCDS28048.1.
    PIRi I49327.
    JC6563.
    RefSeqi NP_033809.1. NM_009679.2.
    UniGenei Mm.18946.

    3D structure databases

    ProteinModelPortali P84091.
    SMRi P84091. Positions 1-435.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198131. 7 interactions.
    IntActi P84091. 8 interactions.
    MINTi MINT-216926.

    PTM databases

    PhosphoSitei P84091.

    Proteomic databases

    MaxQBi P84091.
    PaxDbi P84091.
    PRIDEi P84091.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000007216 ; ENSMUSP00000007216 ; ENSMUSG00000022841 .
    GeneIDi 11773.
    KEGGi mmu:11773.
    UCSCi uc007ypy.1. mouse.

    Organism-specific databases

    CTDi 1173.
    MGIi MGI:1298405. Ap2m1.

    Phylogenomic databases

    eggNOGi NOG315786.
    HOGENOMi HOG000173246.
    HOVERGENi HBG050516.
    InParanoidi P84091.
    KOi K11826.
    OMAi CTQGKAK.
    PhylomeDBi P84091.
    TreeFami TF300722.

    Enzyme and pathway databases

    Reactomei REACT_196550. MHC class II antigen presentation.
    REACT_202778. Retrograde neurotrophin signalling.
    REACT_203917. EGFR downregulation.
    REACT_209040. Gap junction degradation.
    REACT_220352. Formation of annular gap junctions.
    REACT_222404. WNT5A-dependent internalization of FZD4.

    Miscellaneous databases

    ChiTaRSi AP2M1. mouse.
    NextBioi 279559.
    PROi P84091.
    SOURCEi Search...

    Gene expression databases

    Bgeei P84091.
    CleanExi MM_AP2M1.
    Genevestigatori P84091.

    Family and domain databases

    InterProi IPR022775. AP_mu_sigma_su.
    IPR001392. Clathrin_mu.
    IPR008968. Clathrin_mu_C.
    IPR018240. Clathrin_mu_CS.
    IPR011012. Longin-like_dom.
    IPR028565. MHD.
    [Graphical view ]
    Pfami PF00928. Adap_comp_sub. 1 hit.
    PF01217. Clat_adaptor_s. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF005992. Clathrin_mu. 1 hit.
    PRINTSi PR00314. CLATHRINADPT.
    SUPFAMi SSF49447. SSF49447. 1 hit.
    SSF64356. SSF64356. 1 hit.
    PROSITEi PS00990. CLAT_ADAPTOR_M_1. 1 hit.
    PS00991. CLAT_ADAPTOR_M_2. 1 hit.
    PS51072. MHD. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Interaction of tyrosine-based sorting signals with clathrin-associated proteins."
      Ohno H., Stewart J., Fournier M.C., Bosshart H., Rhee I.R., Miyatake S., Saito T., Gallusser A., Kirchhausen T., Bonifacino J.S.
      Science 269:1872-1875(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
      Tissue: Spleen.
    2. "Cloning of the gene encoding the murine clathrin-associated adaptor medium chain mu 2: gene organization, alternative splicing and chromosomal assignment."
      Ohno H., Poy G., Bonifacino J.S.
      Gene 210:187-193(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129.
    3. "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].
      Strain: C57BL/6.
      Tissue: Brain.
    4. Lubec G., Kang S.U.
      Submitted (APR-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 61-70; 131-139 AND 282-288, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: C57BL/6.
      Tissue: Brain.
    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. "Clathrin adaptor AP-2 is essential for early embryonal development."
      Mitsunari T., Nakatsu F., Shioda N., Love P.E., Grinberg A., Bonifacino J.S., Ohno H.
      Mol. Cell. Biol. 25:9318-9323(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    8. "Type Igamma661 phosphatidylinositol phosphate kinase directly interacts with AP2 and regulates endocytosis."
      Bairstow S.F., Ling K., Su X., Firestone A.J., Carbonara C., Anderson R.A.
      J. Biol. Chem. 281:20632-20642(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PIP5K1C.

    Entry informationi

    Entry nameiAP2M1_MOUSE
    AccessioniPrimary (citable) accession number: P84091
    Secondary accession number(s): P20172, P53679
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 16, 2004
    Last sequence update: August 16, 2004
    Last modified: October 1, 2014
    This is version 92 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, Direct protein sequencing, 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