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O00189

- AP4M1_HUMAN

UniProt

O00189 - AP4M1_HUMAN

Protein

AP-4 complex subunit mu-1

Gene

AP4M1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 2 (17 Apr 2007)
      Previous versions | rss
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    Functioni

    Component of the AP-4 complex, a novel type of clathrin- or non-clathrin-associated protein coat involved in targeting proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. Plays a role in the intracellular trafficking of APP from the trans-Golgi network (TGN) to endosomes, and thereby inhibits amyloidogenic processing of APP.2 Publications

    GO - Molecular functioni

    1. transporter activity Source: ProtInc

    GO - Biological processi

    1. Golgi to endosome transport Source: UniProtKB
    2. intracellular protein transport Source: UniProtKB
    3. vesicle-mediated transport Source: ProtInc

    Keywords - Biological processi

    Protein transport, Transport

    Enzyme and pathway databases

    SignaLinkiO00189.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    AP-4 complex subunit mu-1
    Alternative name(s):
    AP-4 adaptor complex mu subunit
    Adaptor-related protein complex 4 subunit mu-1
    Mu subunit of AP-4
    Mu-adaptin-related protein 2
    Short name:
    mu-ARP2
    Mu4-adaptin
    Short name:
    mu4
    Gene namesi
    Name:AP4M1
    Synonyms:MUARP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:574. AP4M1.

    Subcellular locationi

    Golgi apparatustrans-Golgi network. Membranecoated pit
    Note: Associated with the trans-Golgi network. Found in soma and dendritic shafts of neuronal cells.

    GO - Cellular componenti

    1. AP-type membrane coat adaptor complex Source: ProtInc
    2. clathrin adaptor complex Source: InterPro
    3. coated pit Source: UniProtKB-SubCell
    4. extracellular vesicular exosome Source: UniProt
    5. Golgi trans cisterna Source: ProtInc
    6. trans-Golgi network Source: UniProtKB

    Keywords - Cellular componenti

    Coated pit, Golgi apparatus, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Cerebral palsy, spastic quadriplegic 3 (CPSQ3) [MIM:612936]: A non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals present postnatally with early infantile hypotonia, delayed psychomotor development, strabismus, lack of independent walking and severe mental retardation. They develop progressive spasticity of all limbs with generalized hypertonia, hyperreflexia, and extensor plantar responses by the end of the first year of life. Speech is absent or limited. Pseudobulbar signs, such as drooling, stereotypic laughter, and exaggerated jaw jerk, are part of the clinical picture.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi255 – 2551F → A: Abolishes interaction with APP. 1 Publication
    Mutagenesisi283 – 2831R → D: Strongly reduced interaction with APP. 1 Publication

    Organism-specific databases

    MIMi612936. phenotype.
    Orphaneti280763. Severe intellectual disability and progressive spastic paraplegia.
    PharmGKBiPA24866.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 453453AP-4 complex subunit mu-1PRO_0000193787Add
    BLAST

    Proteomic databases

    MaxQBiO00189.
    PaxDbiO00189.
    PRIDEiO00189.

    PTM databases

    PhosphoSiteiO00189.

    Expressioni

    Tissue specificityi

    Ubiquitous. Highly expressed in testis and lowly expressed in brain and lung.2 Publications

    Gene expression databases

    ArrayExpressiO00189.
    BgeeiO00189.
    CleanExiHS_AP4M1.
    GenevestigatoriO00189.

    Interactioni

    Subunit structurei

    Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1). Interacts with the C-terminal domain of GRID2 By similarity. Interacts with tyrosine-based sorting signals on the cytoplasmic tail of cargo proteins, such as LAMP2 and APP.By similarity3 Publications

    Protein-protein interaction databases

    BioGridi114616. 7 interactions.
    IntActiO00189. 3 interactions.
    STRINGi9606.ENSP00000352603.

    Structurei

    Secondary structure

    1
    453
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi186 – 19914
    Beta strandi205 – 21814
    Beta strandi225 – 2306
    Beta strandi235 – 2373
    Turni240 – 2423
    Beta strandi246 – 25611
    Helixi264 – 2674
    Beta strandi269 – 2724
    Beta strandi276 – 28611
    Beta strandi295 – 30410
    Turni306 – 3083
    Beta strandi309 – 31911
    Beta strandi326 – 33510
    Beta strandi341 – 3499
    Beta strandi353 – 3575
    Beta strandi360 – 3656
    Beta strandi373 – 3819
    Beta strandi405 – 4128
    Beta strandi421 – 4277
    Beta strandi437 – 45115

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3L81X-ray1.60A160-453[»]
    4MDRX-ray1.85A160-453[»]
    ProteinModelPortaliO00189.
    SMRiO00189. Positions 1-453.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO00189.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini184 – 452269MHDPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiNOG281769.
    HOGENOMiHOG000173245.
    HOVERGENiHBG102734.
    InParanoidiO00189.
    KOiK12402.
    PhylomeDBiO00189.
    TreeFamiTF329745.

    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.
    PROSITEiPS00991. CLAT_ADAPTOR_M_2. 1 hit.
    PS51072. MHD. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O00189-1 [UniParc]FASTAAdd to Basket

    « Hide

    MISQFFILSS KGDPLIYKDF RGDSGGRDVA ELFYRKLTGL PGDESPVVMH    50
    HHGRHFIHIR HSGLYLVVTT SENVSPFSLL ELLSRLATLL GDYCGSLGEG 100
    TISRNVALVY ELLDEVLDYG YVQTTSTEML RNFIQTEAVV SKPFSLFDLS 150
    SVGLFGAETQ QSKVAPSSAA SRPVLSSRSD QSQKNEVFLD VVERLSVLIA 200
    SNGSLLKVDV QGEIRLKSFL PSGSEMRIGL TEEFCVGKSE LRGYGPGIRV 250
    DEVSFHSSVN LDEFESHRIL RLQPPQGELT VMRYQLSDDL PSPLPFRLFP 300
    SVQWDRGSGR LQVYLKLRCD LLSKSQALNV RLHLPLPRGV VSLSQELSSP 350
    EQKAELAEGA LRWDLPRVQG GSQLSGLFQM DVPGPPGPPS HGLSTSASPL 400
    GLGPASLSFE LPRHTCSGLQ VRFLRLAFRP CGNANPHKWV RHLSHSDAYV 450
    IRI 453
    Length:453
    Mass (Da):49,977
    Last modified:April 17, 2007 - v2
    Checksum:iAE3DCA8C5AED08B7
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti338 – 3381R → G in AAD43328. (PubMed:10436028)Curated
    Sequence conflicti345 – 3451Q → R in CAA69667. (PubMed:9013859)Curated
    Sequence conflicti345 – 3451Q → R in AAD25869. (PubMed:11139587)Curated
    Sequence conflicti400 – 4001L → M in AAD43328. (PubMed:10436028)Curated
    Sequence conflicti417 – 4171S → C in AAD43328. (PubMed:10436028)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y08387 mRNA. Translation: CAA69667.1.
    AF155158 mRNA. Translation: AAD43328.1.
    AF020796 mRNA. Translation: AAD25869.1.
    CH471091 Genomic DNA. Translation: EAW76594.1.
    CH471091 Genomic DNA. Translation: EAW76597.1.
    BC018705 mRNA. Translation: AAH18705.1.
    CCDSiCCDS5685.1.
    RefSeqiNP_004713.2. NM_004722.3.
    UniGeneiHs.632317.

    Genome annotation databases

    EnsembliENST00000359593; ENSP00000352603; ENSG00000221838.
    ENST00000421755; ENSP00000412185; ENSG00000221838.
    GeneIDi9179.
    KEGGihsa:9179.
    UCSCiuc003utb.4. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y08387 mRNA. Translation: CAA69667.1 .
    AF155158 mRNA. Translation: AAD43328.1 .
    AF020796 mRNA. Translation: AAD25869.1 .
    CH471091 Genomic DNA. Translation: EAW76594.1 .
    CH471091 Genomic DNA. Translation: EAW76597.1 .
    BC018705 mRNA. Translation: AAH18705.1 .
    CCDSi CCDS5685.1.
    RefSeqi NP_004713.2. NM_004722.3.
    UniGenei Hs.632317.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3L81 X-ray 1.60 A 160-453 [» ]
    4MDR X-ray 1.85 A 160-453 [» ]
    ProteinModelPortali O00189.
    SMRi O00189. Positions 1-453.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114616. 7 interactions.
    IntActi O00189. 3 interactions.
    STRINGi 9606.ENSP00000352603.

    PTM databases

    PhosphoSitei O00189.

    Proteomic databases

    MaxQBi O00189.
    PaxDbi O00189.
    PRIDEi O00189.

    Protocols and materials databases

    DNASUi 9179.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000359593 ; ENSP00000352603 ; ENSG00000221838 .
    ENST00000421755 ; ENSP00000412185 ; ENSG00000221838 .
    GeneIDi 9179.
    KEGGi hsa:9179.
    UCSCi uc003utb.4. human.

    Organism-specific databases

    CTDi 9179.
    GeneCardsi GC07P099699.
    HGNCi HGNC:574. AP4M1.
    MIMi 602296. gene.
    612936. phenotype.
    neXtProti NX_O00189.
    Orphaneti 280763. Severe intellectual disability and progressive spastic paraplegia.
    PharmGKBi PA24866.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG281769.
    HOGENOMi HOG000173245.
    HOVERGENi HBG102734.
    InParanoidi O00189.
    KOi K12402.
    PhylomeDBi O00189.
    TreeFami TF329745.

    Enzyme and pathway databases

    SignaLinki O00189.

    Miscellaneous databases

    ChiTaRSi AP4M1. human.
    EvolutionaryTracei O00189.
    GeneWikii AP4M1.
    GenomeRNAii 9179.
    NextBioi 34413.
    PROi O00189.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O00189.
    Bgeei O00189.
    CleanExi HS_AP4M1.
    Genevestigatori O00189.

    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 PS00991. CLAT_ADAPTOR_M_2. 1 hit.
    PS51072. MHD. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification of two new mu-adaptin-related proteins, mu-ARP1 and mu-ARP2."
      Wang X., Kilimann M.W.
      FEBS Lett. 402:57-61(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Tissue: Brain.
    2. "Characterization of a fourth adaptor-related protein complex."
      Hirst J., Bright N.A., Rous B., Robinson M.S.
      Mol. Biol. Cell 10:2787-2802(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, TISSUE SPECIFICITY.
      Tissue: Brain.
    3. "Signal-binding specificity of the mu4 subunit of the adaptor protein complex, AP-4."
      Aguilar R.C., Boehm M., Gorshkova I., Crouch R.J., Tomita K., Saito T., Ohno H., Bonifacino J.S.
      J. Biol. Chem. 276:13145-13152(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, INTERACTION WITH LAMP2, SUBCELLULAR LOCATION.
      Tissue: Spleen.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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].
      Tissue: Brain.
    6. Cited for: INVOLVEMENT IN CPSQ3.
    7. "Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex."
      Burgos P.V., Mardones G.A., Rojas A.L., daSilva L.L., Prabhu Y., Hurley J.H., Bonifacino J.S.
      Dev. Cell 18:425-436(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 160-453 IN COMPLEX WITH APP PEPTIDE, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-255 AND ARG-283, SUBUNIT.

    Entry informationi

    Entry nameiAP4M1_HUMAN
    AccessioniPrimary (citable) accession number: O00189
    Secondary accession number(s): D6W5U1, Q8WV65, Q9UHK9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: April 17, 2007
    Last modified: October 1, 2014
    This is version 125 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3