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P84091 (AP2M1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
AP-2 complex subunit mu
Alternative name(s):
AP-2 mu chain
Adapter-related protein complex 2 subunit mu
Adaptor protein complex AP-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 names
Name:Ap2m1
Synonyms:Clapm1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length435 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6

Subunit structure

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. Ref.8

Subcellular location

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.

Tissue specificity

Detected in spleen.

Post-translational modification

Phosphorylated By similarity.

Disruption phenotype

Embryonic lethal before day 3.5 postcoitus (E3.5). Ref.7

Sequence similarities

Belongs to the adaptor complexes medium subunit family.

Contains 1 MHD (mu homology) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 435435AP-2 complex subunit mu
PRO_0000193775

Regions

Domain170 – 434265MHD

Sites

Binding site3411Phosphatidylinositol lipid headgroup By similarity
Binding site3431Phosphatidylinositol lipid headgroup By similarity
Binding site3451Phosphatidylinositol lipid headgroup By similarity
Binding site3541Phosphatidylinositol lipid headgroup By similarity
Binding site3561Phosphatidylinositol lipid headgroup By similarity

Amino acid modifications

Modified residue451Phosphoserine By similarity
Modified residue1561Phosphothreonine By similarity

Sequences

Sequence LengthMass (Da)Tools
P84091 [UniParc].

Last modified August 16, 2004. Version 1.
Checksum: 82803219BA279954

FASTA43549,655
        10         20         30         40         50         60 
MIGGLFIYNH KGEVLISRVY RDDIGRNAVD AFRVNVIHAR QQVRSPVTNI ARTSFFHVKR 

        70         80         90        100        110        120 
SNIWLAAVTK QNVNAAMVFE FLYKMCDVMA AYFGKISEEN IKNNFVLIYE LLDEILDFGY 

       130        140        150        160        170        180 
PQNSETGALK TFITQQGIKS QHQTKEEQSQ ITSQVTGQIG WRREGIKYRR NELFLDVLES 

       190        200        210        220        230        240 
VNLLMSPQGQ VLSAHVSGRV VMKSYLSGMP ECKFGMNDKI VIEKQGKGTA DETSKSGKQS 

       250        260        270        280        290        300 
IAIDDCTFHQ CVRLSKFDSE RSISFIPPDG EFELMRYRTT KDIILPFRVI PLVREVGRTK 

       310        320        330        340        350        360 
LEVKVVIKSN FKPSLLAQKI EVRIPTPLNT SGVQVICMKG KAKYKASENA IVWKIKRMAG 

       370        380        390        400        410        420 
MKESQISAEI ELLPTNDKKK WARPPISMNF EVPFAPSGLK VRYLKVFEPK LNYSDHDVIK 

       430 
WVRYIGRSGI YETRC 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U27106 mRNA. Translation: AAC53158.1.
AF001923 expand/collapse EMBL AC list , AF001913, AF001914, AF001915, AF001916, AF001917, AF001918, AF001919, AF001920, AF001921, AF001922 Genomic DNA. Translation: AAC53583.1.
BC056352 mRNA. Translation: AAH56352.1.
CCDSCCDS28048.1.
PIRI49327.
JC6563.
RefSeqNP_033809.1. NM_009679.2.
UniGeneMm.18946.

3D structure databases

ProteinModelPortalP84091.
SMRP84091. Positions 1-435.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198131. 7 interactions.
IntActP84091. 8 interactions.
MINTMINT-216926.

PTM databases

PhosphoSiteP84091.

Proteomic databases

MaxQBP84091.
PaxDbP84091.
PRIDEP84091.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000007216; ENSMUSP00000007216; ENSMUSG00000022841.
GeneID11773.
KEGGmmu:11773.
UCSCuc007ypy.1. mouse.

Organism-specific databases

CTD1173.
MGIMGI:1298405. Ap2m1.

Phylogenomic databases

eggNOGNOG315786.
HOGENOMHOG000173246.
HOVERGENHBG050516.
InParanoidP84091.
KOK11826.
OMACTQGKAK.
PhylomeDBP84091.
TreeFamTF300722.

Gene expression databases

BgeeP84091.
CleanExMM_AP2M1.
GenevestigatorP84091.

Family and domain databases

InterProIPR022775. AP_mu_sigma_su.
IPR001392. Clathrin_mu.
IPR008968. Clathrin_mu_C.
IPR018240. Clathrin_mu_CS.
IPR011012. Longin-like_dom.
IPR028565. MHD.
[Graphical view]
PfamPF00928. Adap_comp_sub. 1 hit.
PF01217. Clat_adaptor_s. 1 hit.
[Graphical view]
PIRSFPIRSF005992. Clathrin_mu. 1 hit.
PRINTSPR00314. CLATHRINADPT.
SUPFAMSSF49447. SSF49447. 1 hit.
SSF64356. SSF64356. 1 hit.
PROSITEPS00990. CLAT_ADAPTOR_M_1. 1 hit.
PS00991. CLAT_ADAPTOR_M_2. 1 hit.
PS51072. MHD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAP2M1. mouse.
NextBio279559.
PROP84091.
SOURCESearch...

Entry information

Entry nameAP2M1_MOUSE
AccessionPrimary (citable) accession number: P84091
Secondary accession number(s): P20172, P53679
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: July 9, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot