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UniProtKB - Q96CW1 (AP2M1_HUMAN)

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Protein

AP-2 complex subunit mu

Gene

AP2M1

Organism
Homo sapiens (Human)
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 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
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:564. AP2M1.

Subcellular locationi

GO - Cellular componenti

  • AP-2 adaptor complex Source: BHF-UCL
  • clathrin-coated endocytic vesicle membrane Source: Reactome
  • cytosol Source: Reactome
  • endocytic vesicle membrane Source: Reactome
  • endolysosome membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • lysosomal membrane Source: Reactome
  • plasma membrane Source: HPA
Complete GO annotation...

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.

PTM databases

iPTMnetiQ96CW1.
PhosphoSitePlusiQ96CW1.
SwissPalmiQ96CW1.

Expressioni

Gene expression databases

BgeeiENSG00000161203.
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). Interacts with ATP6V1H and MEGF10. Interacts with EGFR. Interacts with F2R. Interacts with PIP5K1C; tyrosine phosphorylation of PIP5K1C weakens the interaction (By similarity). Interacts with KIAA0319; required for clathrin-mediated endocytosis of KIAA0319. Interacts with DVL2 (via DEP domain) (By similarity). Interacts with KCNQ1; mediates estrogen-induced internalization via clathrin-coated vesicles (PubMed:23529131).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • ion channel binding Source: UniProtKB
  • low-density lipoprotein particle receptor binding Source: BHF-UCL
Complete GO annotation...

Protein-protein interaction databases

BioGridi107587. 229 interactors.
IntActiQ96CW1. 113 interactors.
MINTiMINT-140451.
STRINGi9606.ENSP00000292807.

Structurei

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...

Miscellaneous databases

EvolutionaryTraceiQ96CW1.

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Belongs to the adaptor complexes medium subunit family.Curated

Phylogenomic databases

eggNOGiKOG0937. Eukaryota.
ENOG410XPFS. LUCA.
GeneTreeiENSGT00530000062779.
HOGENOMiHOG000173246.
HOVERGENiHBG050516.
InParanoidiQ96CW1.
KOiK11826.
PhylomeDBiQ96CW1.
TreeFamiTF300722.

Family and domain databases

InterProiView protein in InterPro
IPR022775. AP_mu_sigma_su.
IPR001392. Clathrin_mu.
IPR018240. Clathrin_mu_CS.
IPR011012. Longin-like_dom.
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

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

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

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.

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: July 5, 2017
This is version 154 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families