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Protein

AP-2 complex subunit mu

Gene

Ap2m1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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 similarity4 Publications

Sites

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

GO - Molecular functioni

  • lipid binding Source: UniProtKB-KW
  • low-density lipoprotein particle receptor binding Source: BHF-UCL
  • signal sequence binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Endocytosis, Protein transport, Transport

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

ReactomeiR-RNO-177504. Retrograde neurotrophin signalling.
R-RNO-182971. EGFR downregulation.
R-RNO-190873. Gap junction degradation.
R-RNO-196025. Formation of annular gap junctions.
R-RNO-2132295. MHC class II antigen presentation.
R-RNO-416993. Trafficking of GluR2-containing AMPA receptors.
R-RNO-437239. Recycling pathway of L1.
R-RNO-5099900. 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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 11

Organism-specific databases

RGDi620135. Ap2m1.

Subcellular locationi

GO - Cellular componenti

  • clathrin adaptor complex Source: InterPro
  • clathrin vesicle coat Source: RGD
  • coated pit Source: UniProtKB-SubCell
  • extracellular exosome Source: Ensembl
  • mitochondrion Source: Ensembl
  • plasma membrane Source: Reactome
  • terminal bouton Source: ParkinsonsUK-UCL
  • transport vesicle Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Coated pit, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi156 – 1561T → A: Inhibits endocytosis by AP-2; no effect on membrane association of AP-2. 1 Publication
Mutagenesisi176 – 1761D → A: Abolishes interaction with TTGN1 and EGFR. 1 Publication
Mutagenesisi421 – 4211W → A: Abolishes interaction with TTGN1 and EGFR. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 435435AP-2 complex subunit muPRO_0000193776Add
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

PaxDbiP84092.
PRIDEiP84092.

PTM databases

SwissPalmiP84092.

Expressioni

Tissue specificityi

Detected in brain.

Gene expression databases

GenevisibleiP84092. RN.

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 and TTGN1. Interacts with F2R. Interacts with PIP5K1C isoform 1; tyrosine phosphorylation of PIP5K1C weakens the interaction (By similarity). Interacts with KIAA0319; required for clathrin-mediated endocytosis of KIAA0319 (By similarity). Interacts with DVL2 (via DEP domain). Interacts with KCNQ1; mediates estrogen-induced internalization via clathrin-coated vesicles (By similarity).By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AP2B1P630102EBI-297693,EBI-432924From a different organism.
Ttgn1P198144EBI-297693,EBI-541446

GO - Molecular functioni

  • low-density lipoprotein particle receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi250498. 6 interactions.
DIPiDIP-29761N.
IntActiP84092. 9 interactions.
MINTiMINT-122557.
STRINGi10116.ENSRNOP00000054900.

Structurei

Secondary structure

1
435
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 85Combined sources
Beta strandi14 – 196Combined sources
Beta strandi21 – 233Combined sources
Helixi26 – 3510Combined sources
Turni36 – 383Combined sources
Beta strandi40 – 423Combined sources
Beta strandi46 – 505Combined sources
Beta strandi53 – 608Combined sources
Beta strandi63 – 719Combined sources
Helixi75 – 9319Combined sources
Helixi98 – 1036Combined sources
Helixi105 – 11511Combined sources
Helixi126 – 1294Combined sources
Helixi130 – 1323Combined sources
Helixi145 – 15612Combined sources
Turni160 – 1623Combined sources
Beta strandi172 – 18514Combined sources
Beta strandi191 – 20515Combined sources
Beta strandi207 – 2093Combined sources
Beta strandi211 – 2177Combined sources
Beta strandi218 – 2203Combined sources
Beta strandi238 – 2403Combined sources
Beta strandi244 – 2485Combined sources
Beta strandi252 – 2543Combined sources
Turni255 – 2584Combined sources
Beta strandi263 – 2653Combined sources
Beta strandi269 – 27911Combined sources
Beta strandi287 – 29610Combined sources
Turni297 – 2993Combined sources
Beta strandi300 – 30910Combined sources
Beta strandi316 – 32510Combined sources
Beta strandi330 – 3367Combined sources
Beta strandi338 – 3458Combined sources
Helixi346 – 3483Combined sources
Beta strandi350 – 36112Combined sources
Beta strandi363 – 37210Combined sources
Beta strandi377 – 3793Combined sources
Beta strandi386 – 3949Combined sources
Turni396 – 3983Combined sources
Beta strandi401 – 4077Combined sources
Beta strandi409 – 4124Combined sources
Helixi415 – 4173Combined sources
Beta strandi419 – 43315Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BW8X-ray2.65A122-435[»]
1BXXX-ray2.70A158-435[»]
1HESX-ray3.00A158-435[»]
1I31X-ray2.50A122-435[»]
2BP5X-ray2.80M1-435[»]
2JKRX-ray2.98M/U1-435[»]
2JKTX-ray3.40M/U1-435[»]
2PR9X-ray2.51A158-435[»]
2VGLX-ray2.59M1-435[»]
2XA7X-ray3.10M1-435[»]
3H85X-ray2.60A158-435[»]
3ML6X-ray3.50A/B/C/D/E/F170-435[»]
4UQIX-ray2.79M1-435[»]
5FPIX-ray2.77A1-435[»]
DisProtiDP00455.
ProteinModelPortaliP84092.
SMRiP84092. Positions 1-435.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP84092.

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

eggNOGiKOG0938. Eukaryota.
ENOG410XPFS. LUCA.
GeneTreeiENSGT00530000062779.
HOGENOMiHOG000173246.
HOVERGENiHBG050516.
InParanoidiP84092.
KOiK11826.
OMAiVWKIPRI.
OrthoDBiEOG72RMXV.
PhylomeDBiP84092.
TreeFamiTF300722.

Family and domain databases

InterProiIPR022775. AP_mu_sigma_su.
IPR001392. Clathrin_mu.
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.

P84092-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIGGLFIYNH KGEVLISRVY RDDIGRNAVD AFRVNVIHAR QQVRSPVTNI
60 70 80 90 100
ARTSFFHVKR SNIWLAAVTK QNVNAAMVFE FLYKMCDVMA AYFGKISEEN
110 120 130 140 150
IKNNFVLIYE LLDEILDFGY PQNSETGALK TFITQQGIKS QHQTKEEQSQ
160 170 180 190 200
ITSQVTGQIG WRREGIKYRR NELFLDVLES VNLLMSPQGQ VLSAHVSGRV
210 220 230 240 250
VMKSYLSGMP ECKFGMNDKI VIEKQGKGTA DETSKSGKQS IAIDDCTFHQ
260 270 280 290 300
CVRLSKFDSE RSISFIPPDG EFELMRYRTT KDIILPFRVI PLVREVGRTK
310 320 330 340 350
LEVKVVIKSN FKPSLLAQKI EVRIPTPLNT SGVQVICMKG KAKYKASENA
360 370 380 390 400
IVWKIKRMAG MKESQISAEI ELLPTNDKKK WARPPISMNF EVPFAPSGLK
410 420 430
VRYLKVFEPK LNYSDHDVIK WVRYIGRSGI YETRC
Length:435
Mass (Da):49,655
Last modified:August 16, 2004 - v1
Checksum:i82803219BA279954
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23674 mRNA. Translation: AAA72731.1.
BC087724 mRNA. Translation: AAH87724.1.
PIRiA31596.
RefSeqiNP_446289.1. NM_053837.1.
UniGeneiRn.3172.

Genome annotation databases

EnsembliENSRNOT00000088821; ENSRNOP00000070202; ENSRNOG00000001709.
GeneIDi116563.
KEGGirno:116563.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23674 mRNA. Translation: AAA72731.1.
BC087724 mRNA. Translation: AAH87724.1.
PIRiA31596.
RefSeqiNP_446289.1. NM_053837.1.
UniGeneiRn.3172.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BW8X-ray2.65A122-435[»]
1BXXX-ray2.70A158-435[»]
1HESX-ray3.00A158-435[»]
1I31X-ray2.50A122-435[»]
2BP5X-ray2.80M1-435[»]
2JKRX-ray2.98M/U1-435[»]
2JKTX-ray3.40M/U1-435[»]
2PR9X-ray2.51A158-435[»]
2VGLX-ray2.59M1-435[»]
2XA7X-ray3.10M1-435[»]
3H85X-ray2.60A158-435[»]
3ML6X-ray3.50A/B/C/D/E/F170-435[»]
4UQIX-ray2.79M1-435[»]
5FPIX-ray2.77A1-435[»]
DisProtiDP00455.
ProteinModelPortaliP84092.
SMRiP84092. Positions 1-435.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250498. 6 interactions.
DIPiDIP-29761N.
IntActiP84092. 9 interactions.
MINTiMINT-122557.
STRINGi10116.ENSRNOP00000054900.

PTM databases

SwissPalmiP84092.

Proteomic databases

PaxDbiP84092.
PRIDEiP84092.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000088821; ENSRNOP00000070202; ENSRNOG00000001709.
GeneIDi116563.
KEGGirno:116563.

Organism-specific databases

CTDi1173.
RGDi620135. Ap2m1.

Phylogenomic databases

eggNOGiKOG0938. Eukaryota.
ENOG410XPFS. LUCA.
GeneTreeiENSGT00530000062779.
HOGENOMiHOG000173246.
HOVERGENiHBG050516.
InParanoidiP84092.
KOiK11826.
OMAiVWKIPRI.
OrthoDBiEOG72RMXV.
PhylomeDBiP84092.
TreeFamiTF300722.

Enzyme and pathway databases

ReactomeiR-RNO-177504. Retrograde neurotrophin signalling.
R-RNO-182971. EGFR downregulation.
R-RNO-190873. Gap junction degradation.
R-RNO-196025. Formation of annular gap junctions.
R-RNO-2132295. MHC class II antigen presentation.
R-RNO-416993. Trafficking of GluR2-containing AMPA receptors.
R-RNO-437239. Recycling pathway of L1.
R-RNO-5099900. WNT5A-dependent internalization of FZD4.

Miscellaneous databases

EvolutionaryTraceiP84092.
PROiP84092.

Gene expression databases

GenevisibleiP84092. RN.

Family and domain databases

InterProiIPR022775. AP_mu_sigma_su.
IPR001392. Clathrin_mu.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and complete amino acid sequence of AP50, an assembly protein associated with clathrin-coated vesicles."
    Thurieau C., Brosius J., Burne C., Jolles P., Keen J.H., Mattaliano R.J., Chow E.P., Ramachandran K.L., Kirchhausen T.
    DNA 7:663-669(1988) [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].
    Tissue: Brain.
  3. "Inhibition of the receptor-binding function of clathrin adaptor protein AP-2 by dominant-negative mutant mu2 subunit and its effects on endocytosis."
    Nesterov A., Carter R.E., Sorkina T., Gill G.N., Sorkin A.
    EMBO J. 18:2489-2499(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EGFR AND TTGN1, MUTAGENESIS OF ASP-176 AND TRP-421.
  4. "Phosphorylation of threonine 156 of the mu2 subunit of the AP2 complex is essential for endocytosis in vitro and in vivo."
    Olusanya O., Andrews P.D., Swedlow J.R., Smythe E.
    Curr. Biol. 11:896-900(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF THE AP-2 COMPLEX, MUTAGENESIS OF THR-156.
  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. "A structural explanation for the recognition of tyrosine-based endocytotic signals."
    Owen D.J., Evans P.R.
    Science 282:1327-1332(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 159-435 IN COMPLEX WITH EGFR INTERNALIZATION SIGNAL.
  8. "A third specificity-determining site in mu 2 adaptin for sequences upstream of Yxx phi sorting motifs."
    Owen D.J., Setiadi H., Evans P.R., McEver R.P., Green S.A.
    Traffic 2:105-110(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3 ANGSTROMS) OF 158-435 IN COMPLEX WITH SELP INTERNALIZATION SIGNAL.
  9. "Molecular architecture and functional model of the endocytic AP2 complex."
    Collins B.M., McCoy A.J., Kent H.M., Evans P.R., Owen D.J.
    Cell 109:523-535(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) IN COMPLEX WITH AP2B1; AP2A2; AP2S1 AND AN INOSITOL POLYPHOSPHATE HEADGROUP.
  10. "The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY and YppO sorting signals at distinct sites."
    Boll W., Rapoport I., Brunner C., Modis Y., Prehn S., Kirchhausen T.
    Traffic 3:590-600(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 260-435 IN COMPLEX WITH EGFR INTERNALIZATION SIGNAL.
  11. "A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex."
    Kelly B.T., McCoy A.J., Spaete K., Miller S.E., Evans P.R., Hoening S., Owen D.J.
    Nature 456:976-979(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1-435 IN COMPLEX WITH AP2A2; AP2B1; AP2S1 AND CD4 INTERNALIZATION SIGNAL.
  12. "Structural analysis of the interaction between Dishevelled2 and clathrin AP-2 adaptor, a critical step in noncanonical Wnt signaling."
    Yu A., Xing Y., Harrison S.C., Kirchhausen T.
    Structure 18:1311-1320(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 170-435 IN COMPLEX WITH DVL2, FUNCTION, INTERACTION WITH DVL2.

Entry informationi

Entry nameiAP2M1_RAT
AccessioniPrimary (citable) accession number: P84092
Secondary accession number(s): P20172, P53679
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: June 8, 2016
This is version 114 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.