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Protein

AP-2 complex subunit mu

Gene

Ap2m1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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 similarity5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei341Phosphatidylinositol lipid headgroup1
Binding sitei343Phosphatidylinositol lipid headgroup1
Binding sitei345Phosphatidylinositol lipid headgroup1
Binding sitei354Phosphatidylinositol lipid headgroup1
Binding sitei356Phosphatidylinositol lipid headgroup1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processEndocytosis, Protein transport, Transport
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-RNO-177504 Retrograde neurotrophin signalling
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
R-RNO-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-RNO-8856825 Cargo recognition for clathrin-mediated endocytosis
R-RNO-8856828 Clathrin-mediated endocytosis
R-RNO-8866427 VLDLR internalisation and degradation
R-RNO-8964038 LDL clearance

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 11

Organism-specific databases

RGDi620135 Ap2m1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Coated pit, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi156T → A: Inhibits endocytosis by AP-2; no effect on membrane association of AP-2. 1 Publication1
Mutagenesisi176D → A: Abolishes interaction with TTGN1 and EGFR. 1 Publication1
Mutagenesisi421W → A: Abolishes interaction with TTGN1 and EGFR. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001937761 – 435AP-2 complex subunit muAdd BLAST435

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei45PhosphoserineBy similarity1
Modified residuei156PhosphothreonineBy similarity1

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

BgeeiENSRNOG00000001709 Expressed in 10 organ(s), highest expression level in brain
ExpressionAtlasiP84092 baseline and differential
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) (PubMed:19140243). Interacts with ATP6V1H and MEGF10 (By similarity). Interacts with EGFR and TTGN1 (PubMed:10228163, PubMed:9812899, PubMed:12121421). Interacts with F2R (By similarity). Interacts with PIP5K1C; 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) (PubMed:20947020). Interacts with KCNQ1; mediates estrogen-induced internalization via clathrin-coated vesicles (By similarity). Interacts with P2RX4 (via internalization motif) (PubMed:15985462).By similarity6 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi250498, 6 interactors
CORUMiP84092
DIPiDIP-29761N
IntActiP84092, 19 interactors
MINTiP84092
STRINGi10116.ENSRNOP00000054900

Structurei

Secondary structure

1435
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00455
ProteinModelPortaliP84092
SMRiP84092
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP84092

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini170 – 434MHDPROSITE-ProRule annotationAdd BLAST265

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0938 Eukaryota
ENOG410XPFS LUCA
GeneTreeiENSGT00530000062779
HOGENOMiHOG000173246
HOVERGENiHBG050516
InParanoidiP84092
KOiK11826
OMAiSIKWVRY
PhylomeDBiP84092
TreeFamiTF300722

Family and domain databases

InterProiView protein in InterPro
IPR036168 AP2_Mu_C_sf
IPR022775 AP_mu_sigma_su
IPR001392 Clathrin_mu
IPR018240 Clathrin_mu_CS
IPR011012 Longin-like_dom_sf
IPR028565 MHD
PfamiView protein in Pfam
PF00928 Adap_comp_sub, 1 hit
PF01217 Clat_adaptor_s, 1 hit
PIRSFiPIRSF005992 Clathrin_mu, 1 hit
PRINTSiPR00314 CLATHRINADPT
SUPFAMiSSF49447 SSF49447, 1 hit
SSF64356 SSF64356, 1 hit
PROSITEiView protein in PROSITE
PS00990 CLAT_ADAPTOR_M_1, 1 hit
PS00991 CLAT_ADAPTOR_M_2, 1 hit
PS51072 MHD, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A140TAH5A0A140TAH5_RAT
AP-2 complex subunit mu
Ap2m1
434Annotation score:

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

Similar proteinsi

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
PDB 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[»]
5C7ZX-ray2.77A159-435[»]
5FPIX-ray2.77A1-435[»]
5WRKX-ray2.62A158-435[»]
5WRLX-ray3.10A158-435[»]
5WRMX-ray2.60A158-435[»]
DisProtiDP00455
ProteinModelPortaliP84092
SMRiP84092
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250498, 6 interactors
CORUMiP84092
DIPiDIP-29761N
IntActiP84092, 19 interactors
MINTiP84092
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
OMAiSIKWVRY
PhylomeDBiP84092
TreeFamiTF300722

Enzyme and pathway databases

ReactomeiR-RNO-177504 Retrograde neurotrophin signalling
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
R-RNO-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-RNO-8856825 Cargo recognition for clathrin-mediated endocytosis
R-RNO-8856828 Clathrin-mediated endocytosis
R-RNO-8866427 VLDLR internalisation and degradation
R-RNO-8964038 LDL clearance

Miscellaneous databases

EvolutionaryTraceiP84092
PROiPR:P84092

Gene expression databases

BgeeiENSRNOG00000001709 Expressed in 10 organ(s), highest expression level in brain
ExpressionAtlasiP84092 baseline and differential
GenevisibleiP84092 RN

Family and domain databases

InterProiView protein in InterPro
IPR036168 AP2_Mu_C_sf
IPR022775 AP_mu_sigma_su
IPR001392 Clathrin_mu
IPR018240 Clathrin_mu_CS
IPR011012 Longin-like_dom_sf
IPR028565 MHD
PfamiView protein in Pfam
PF00928 Adap_comp_sub, 1 hit
PF01217 Clat_adaptor_s, 1 hit
PIRSFiPIRSF005992 Clathrin_mu, 1 hit
PRINTSiPR00314 CLATHRINADPT
SUPFAMiSSF49447 SSF49447, 1 hit
SSF64356 SSF64356, 1 hit
PROSITEiView protein in PROSITE
PS00990 CLAT_ADAPTOR_M_1, 1 hit
PS00991 CLAT_ADAPTOR_M_2, 1 hit
PS51072 MHD, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAP2M1_RAT
AccessioniPrimary (citable) accession number: P84092
Secondary accession number(s): P20172, P53679
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: November 7, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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