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P84091

- AP2M1_MOUSE

UniProt

P84091 - AP2M1_MOUSE

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Protein

AP-2 complex subunit mu

Gene
Ap2m1, Clapm1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei341 – 3411Phosphatidylinositol lipid headgroup By similarity
Binding sitei343 – 3431Phosphatidylinositol lipid headgroup By similarity
Binding sitei345 – 3451Phosphatidylinositol lipid headgroup By similarity
Binding sitei354 – 3541Phosphatidylinositol lipid headgroup By similarity
Binding sitei356 – 3561Phosphatidylinositol lipid headgroup By 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
Complete GO annotation...

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
Complete GO annotation...

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 – 451Phosphoserine By similarity
Modified residuei156 – 1561Phosphothreonine By 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.1 Publication

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP84091.
SMRiP84091. Positions 1-435.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini170 – 434265MHDAdd
BLAST

Sequence similaritiesi

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 91 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

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