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Protein

AP-2 complex subunit mu

Gene

AP2M1

Organism
Homo sapiens (Human)
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 similarity).By similarity7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei341Phosphatidylinositol lipid headgroupBy similarity1
Binding sitei343Phosphatidylinositol lipid headgroupBy similarity1
Binding sitei345Phosphatidylinositol lipid headgroupBy similarity1
Binding sitei354Phosphatidylinositol lipid headgroupBy similarity1
Binding sitei356Phosphatidylinositol lipid headgroupBy similarity1

GO - Molecular functioni

  • ion channel binding Source: UniProtKB
  • lipid binding Source: UniProtKB-KW
  • low-density lipoprotein particle receptor binding Source: BHF-UCL
  • signal sequence binding Source: BHF-UCL
  • transporter activity Source: ProtInc

GO - Biological processi

Keywordsi

Biological processEndocytosis, Protein transport, Transport
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-164939 Nef mediated downregulation of CD28 cell surface expression
R-HSA-167590 Nef Mediated CD4 Down-regulation
R-HSA-177504 Retrograde neurotrophin signalling
R-HSA-182218 Nef Mediated CD8 Down-regulation
R-HSA-190873 Gap junction degradation
R-HSA-196025 Formation of annular gap junctions
R-HSA-2132295 MHC class II antigen presentation
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors
R-HSA-437239 Recycling pathway of L1
R-HSA-5099900 WNT5A-dependent internalization of FZD4
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8866427 VLDLR internalisation and degradation
R-HSA-8964038 LDL clearance
SignaLinkiQ96CW1
SIGNORiQ96CW1

Names & Taxonomyi

Protein namesi
Recommended name:
AP-2 complex subunit mu
Alternative name(s):
AP-2 mu chain
Adaptin-mu2
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
HA2 50 kDa subunit
Plasma membrane adaptor AP-2 50 kDa protein
Gene namesi
Name:AP2M1
Synonyms:CLAPM1, KIAA0109
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000161203.13
HGNCiHGNC:564 AP2M1
MIMi601024 gene
neXtProtiNX_Q96CW1

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

Organism-specific databases

DisGeNETi1173
OpenTargetsiENSG00000161203
PharmGKBiPA24855

Polymorphism and mutation databases

BioMutaiAP2M1
DMDMi51316978

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001937741 – 435AP-2 complex subunit muAdd BLAST435

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei45PhosphoserineCombined sources1
Modified residuei156PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96CW1
MaxQBiQ96CW1
PaxDbiQ96CW1
PeptideAtlasiQ96CW1
PRIDEiQ96CW1
ProteomicsDBi76229
76230 [Q96CW1-2]

PTM databases

iPTMnetiQ96CW1
PhosphoSitePlusiQ96CW1
SwissPalmiQ96CW1

Expressioni

Gene expression databases

BgeeiENSG00000161203 Expressed in 236 organ(s), highest expression level in anterior cingulate cortex
CleanExiHS_AP2M1
ExpressionAtlasiQ96CW1 baseline and differential
GenevisibleiQ96CW1 HS

Organism-specific databases

HPAiHPA036849
HPA069870

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) (By similarity). Interacts with ATP6V1H and MEGF10 (PubMed:12032142, PubMed:17643423). Interacts with EGFR and TTGN1 (By similarity). Interacts with F2R (PubMed:16581796). Interacts with PIP5K1C; tyrosine phosphorylation of PIP5K1C weakens the interaction (By similarity). Interacts with KIAA0319; required for clathrin-mediated endocytosis of KIAA0319 (PubMed:19419997). Interacts with DVL2 (via DEP domain) (By similarity). Interacts with KCNQ1; mediates estrogen-induced internalization via clathrin-coated vesicles (PubMed:23529131). Interacts with P2RX4 (via internalization motif) (By similarity).By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107587, 241 interactors
CORUMiQ96CW1
IntActiQ96CW1, 121 interactors
MINTiQ96CW1
STRINGi9606.ENSP00000292807

Structurei

3D structure databases

ProteinModelPortaliQ96CW1
SMRiQ96CW1
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96CW1

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0937 Eukaryota
ENOG410XPFS LUCA
GeneTreeiENSGT00530000062779
HOGENOMiHOG000173246
HOVERGENiHBG050516
InParanoidiQ96CW1
KOiK11826
PhylomeDBiQ96CW1
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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q96CW1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 - v2
Checksum:i82803219BA279954
GO
Isoform 2 (identifier: Q96CW1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     141-142: Missing.

Show »
Length:433
Mass (Da):49,389
Checksum:i76399E78B0AC7E8A
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PFW3E9PFW3_HUMAN
AP-2 complex subunit mu
AP2M1
460Annotation score:
A0A087WY71A0A087WY71_HUMAN
AP-2 complex subunit mu
AP2M1
434Annotation score:
C9JJ47C9JJ47_HUMAN
AP-2 complex subunit mu
AP2M1
252Annotation score:
C9JTK4C9JTK4_HUMAN
AP-2 complex subunit mu
AP2M1
160Annotation score:
C9JGT8C9JGT8_HUMAN
AP-2 complex subunit mu
AP2M1
195Annotation score:
H7C4C3H7C4C3_HUMAN
AP-2 complex subunit mu
AP2M1
122Annotation score:
C9JJD3C9JJD3_HUMAN
AP-2 complex subunit mu
AP2M1
113Annotation score:
C9JPV8C9JPV8_HUMAN
AP-2 complex subunit mu
AP2M1
136Annotation score:

Sequence cautioni

The sequence BAA09762 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106V → L in AAA93254 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_034599141 – 142Missing in isoform 2. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U36188 mRNA Translation: AAA93254.1
D63475 mRNA Translation: BAA09762.2 Different initiation.
BT007308 mRNA Translation: AAP35972.1
AC131235 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW78290.1
CH471052 Genomic DNA Translation: EAW78291.1
BC004996 mRNA Translation: AAH04996.1
BC013796 mRNA Translation: AAH13796.1
BC014030 mRNA Translation: AAH14030.1
CCDSiCCDS43177.1 [Q96CW1-1]
CCDS43178.1 [Q96CW1-2]
PIRiG02088
RefSeqiNP_001020376.1, NM_001025205.1 [Q96CW1-2]
NP_001298127.1, NM_001311198.1
NP_004059.2, NM_004068.3 [Q96CW1-1]
UniGeneiHs.518460

Genome annotation databases

EnsembliENST00000292807; ENSP00000292807; ENSG00000161203 [Q96CW1-1]
ENST00000382456; ENSP00000371894; ENSG00000161203 [Q96CW1-2]
ENST00000439647; ENSP00000409081; ENSG00000161203 [Q96CW1-2]
GeneIDi1173
KEGGihsa:1173
UCSCiuc003fmw.4 human [Q96CW1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U36188 mRNA Translation: AAA93254.1
D63475 mRNA Translation: BAA09762.2 Different initiation.
BT007308 mRNA Translation: AAP35972.1
AC131235 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW78290.1
CH471052 Genomic DNA Translation: EAW78291.1
BC004996 mRNA Translation: AAH04996.1
BC013796 mRNA Translation: AAH13796.1
BC014030 mRNA Translation: AAH14030.1
CCDSiCCDS43177.1 [Q96CW1-1]
CCDS43178.1 [Q96CW1-2]
PIRiG02088
RefSeqiNP_001020376.1, NM_001025205.1 [Q96CW1-2]
NP_001298127.1, NM_001311198.1
NP_004059.2, NM_004068.3 [Q96CW1-1]
UniGeneiHs.518460

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H6EX-ray3.60A164-435[»]
ProteinModelPortaliQ96CW1
SMRiQ96CW1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107587, 241 interactors
CORUMiQ96CW1
IntActiQ96CW1, 121 interactors
MINTiQ96CW1
STRINGi9606.ENSP00000292807

PTM databases

iPTMnetiQ96CW1
PhosphoSitePlusiQ96CW1
SwissPalmiQ96CW1

Polymorphism and mutation databases

BioMutaiAP2M1
DMDMi51316978

Proteomic databases

EPDiQ96CW1
MaxQBiQ96CW1
PaxDbiQ96CW1
PeptideAtlasiQ96CW1
PRIDEiQ96CW1
ProteomicsDBi76229
76230 [Q96CW1-2]

Protocols and materials databases

DNASUi1173
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000292807; ENSP00000292807; ENSG00000161203 [Q96CW1-1]
ENST00000382456; ENSP00000371894; ENSG00000161203 [Q96CW1-2]
ENST00000439647; ENSP00000409081; ENSG00000161203 [Q96CW1-2]
GeneIDi1173
KEGGihsa:1173
UCSCiuc003fmw.4 human [Q96CW1-1]

Organism-specific databases

CTDi1173
DisGeNETi1173
EuPathDBiHostDB:ENSG00000161203.13
GeneCardsiAP2M1
HGNCiHGNC:564 AP2M1
HPAiHPA036849
HPA069870
MIMi601024 gene
neXtProtiNX_Q96CW1
OpenTargetsiENSG00000161203
PharmGKBiPA24855
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0937 Eukaryota
ENOG410XPFS LUCA
GeneTreeiENSGT00530000062779
HOGENOMiHOG000173246
HOVERGENiHBG050516
InParanoidiQ96CW1
KOiK11826
PhylomeDBiQ96CW1
TreeFamiTF300722

Enzyme and pathway databases

ReactomeiR-HSA-164939 Nef mediated downregulation of CD28 cell surface expression
R-HSA-167590 Nef Mediated CD4 Down-regulation
R-HSA-177504 Retrograde neurotrophin signalling
R-HSA-182218 Nef Mediated CD8 Down-regulation
R-HSA-190873 Gap junction degradation
R-HSA-196025 Formation of annular gap junctions
R-HSA-2132295 MHC class II antigen presentation
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors
R-HSA-437239 Recycling pathway of L1
R-HSA-5099900 WNT5A-dependent internalization of FZD4
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8866427 VLDLR internalisation and degradation
R-HSA-8964038 LDL clearance
SignaLinkiQ96CW1
SIGNORiQ96CW1

Miscellaneous databases

ChiTaRSiAP2M1 human
EvolutionaryTraceiQ96CW1
GeneWikiiAP2M1
GenomeRNAii1173
PROiPR:Q96CW1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000161203 Expressed in 236 organ(s), highest expression level in anterior cingulate cortex
CleanExiHS_AP2M1
ExpressionAtlasiQ96CW1 baseline and differential
GenevisibleiQ96CW1 HS

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_HUMAN
AccessioniPrimary (citable) accession number: Q96CW1
Secondary accession number(s): A6NE12
, D3DNT1, P20172, P53679
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: September 12, 2018
This is version 165 of the entry and version 2 of the sequence. See 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 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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