ID   AP2M_CAEEL              Reviewed;         441 AA.
AC   P35603; Q8MXF2; Q9TZC9;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   15-AUG-2003, sequence version 2.
DT   03-AUG-2022, entry version 153.
DE   RecName: Full=AP-2 complex subunit mu;
DE   AltName: Full=Clathrin assembly protein complex 2 mu medium chain;
DE   AltName: Full=Clathrin coat assembly protein AP50;
DE   AltName: Full=Clathrin coat-associated protein AP50;
DE   AltName: Full=Mu2-adaptin;
DE   AltName: Full=Plasma membrane adaptor AP-2 50 kDa protein;
DE   AltName: Full=Protein dumpy-23;
GN   Name=dpy-23; Synonyms=ap50; ORFNames=R160.1;
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC   STRAIN=Bristol N2;
RX   PubMed=8288128; DOI=10.1101/gad.8.1.60;
RA   Lee J., Jongeward G.D., Sternberg P.W.;
RT   "unc-101, a gene required for many aspects of Caenorhabditis elegans
RT   development and behavior, encodes a clathrin-associated protein.";
RL   Genes Dev. 8:60-73(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC   STRAIN=Bristol N2;
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18160346; DOI=10.1016/j.devcel.2007.12.001;
RA   Pan C.L., Baum P.D., Gu M., Jorgensen E.M., Clark S.G., Garriga G.;
RT   "C. elegans AP-2 and retromer control Wnt signaling by regulating mig-
RT   14/Wntless.";
RL   Dev. Cell 14:132-139(2008).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18160347; DOI=10.1016/j.devcel.2007.12.004;
RA   Yang P.T., Lorenowicz M.J., Silhankova M., Coudreuse D.Y., Betist M.C.,
RA   Korswagen H.C.;
RT   "Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in
RT   Wnt-producing cells.";
RL   Dev. Cell 14:140-147(2008).
CC   -!- FUNCTION: Component of the adaptor complexes which link clathrin to
CC       receptors in coated vesicles (By similarity). Clathrin-associated
CC       protein complexes are believed to interact with the cytoplasmic tails
CC       of membrane proteins, leading to their selection and concentration (By
CC       similarity). AP50 is a subunit of the plasma membrane adaptor (By
CC       similarity). Essential wnt/egl-20 signaling protein that functions in
CC       wnt/egl-20-producing cells (PubMed:18160346, PubMed:18160347). Required
CC       for the AP-2 complex-mediated endocytosis of membrane proteins
CC       including wntless homolog mig-14 in egl-20-producing cells
CC       (PubMed:18160346, PubMed:18160347). During development, regulates the
CC       migration of HSN neurons and the left and right Q neuroblasts (QL and
CC       QR, respectively) and their descendants, possibly through hox gene and
CC       wnt/egl-20 gene target mab-5, and plays a role in establishing ALM and
CC       PLM neuronal cell polarity (PubMed:18160346). Required for the
CC       asymmetric divisions of V5 cells (PubMed:18160346).
CC       {ECO:0000250|UniProtKB:Q09718, ECO:0000250|UniProtKB:Q99186,
CC       ECO:0000269|PubMed:18160346, ECO:0000269|PubMed:18160347}.
CC   -!- SUBUNIT: Adaptor protein complex 2 (AP-2) is a heterotetramer composed
CC       of two large adaptins (alpha-type subunit and beta-type subunits), a
CC       medium adaptin (mu-type subunit AP50) and a small adaptin (sigma-type
CC       subunit AP17).
CC   -!- SUBCELLULAR LOCATION: Cell membrane. Membrane, coated pit; Peripheral
CC       membrane protein; Cytoplasmic side. Note=Component of the coat
CC       surrounding the cytoplasmic face of coated vesicles in the plasma
CC       membrane.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=a;
CC         IsoId=P35603-1; Sequence=Displayed;
CC       Name=b;
CC         IsoId=P35603-2; Sequence=VSP_008037;
CC   -!- TISSUE SPECIFICITY: Brain, heart, lung, liver, testis and spleen.
CC   -!- DISRUPTION PHENOTYPE: Mutants display a squat body statue referred to
CC       as a dumpy phenotype and have defective HSN neuronal cell migration
CC       (PubMed:18160346). RNAi-mediated knockdown results in impaired function
CC       of the AP-2 complex and accumulation of the wntless homolog mig-14 at
CC       the cell membrane (PubMed:18160347). {ECO:0000269|PubMed:18160346,
CC       ECO:0000269|PubMed:18160347}.
CC   -!- SIMILARITY: Belongs to the adaptor complexes medium subunit family.
CC       {ECO:0000305}.
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DR   EMBL; L26290; AAA27981.1; -; mRNA.
DR   EMBL; FO081006; CCD68418.1; -; Genomic_DNA.
DR   EMBL; FO081006; CCD68419.1; -; Genomic_DNA.
DR   PIR; B49837; B49837.
DR   RefSeq; NP_001024865.1; NM_001029694.3. [P35603-2]
DR   RefSeq; NP_741770.1; NM_171670.4. [P35603-1]
DR   AlphaFoldDB; P35603; -.
DR   SMR; P35603; -.
DR   BioGRID; 45648; 16.
DR   STRING; 6239.R160.1a; -.
DR   EPD; P35603; -.
DR   PaxDb; P35603; -.
DR   PeptideAtlas; P35603; -.
DR   PRIDE; P35603; -.
DR   EnsemblMetazoa; R160.1a.1; R160.1a.1; WBGene00001082. [P35603-1]
DR   EnsemblMetazoa; R160.1b.1; R160.1b.1; WBGene00001082. [P35603-2]
DR   GeneID; 180713; -.
DR   KEGG; cel:CELE_R160.1; -.
DR   UCSC; R160.1b; c. elegans. [P35603-1]
DR   CTD; 180713; -.
DR   WormBase; R160.1a; CE33813; WBGene00001082; dpy-23. [P35603-1]
DR   WormBase; R160.1b; CE33814; WBGene00001082; dpy-23. [P35603-2]
DR   eggNOG; KOG0938; Eukaryota.
DR   GeneTree; ENSGT00940000165747; -.
DR   InParanoid; P35603; -.
DR   OMA; VWKIPRI; -.
DR   OrthoDB; 725236at2759; -.
DR   PhylomeDB; P35603; -.
DR   Reactome; R-CEL-190873; Gap junction degradation.
DR   Reactome; R-CEL-196025; Formation of annular gap junctions.
DR   Reactome; R-CEL-437239; Recycling pathway of L1.
DR   Reactome; R-CEL-5099900; WNT5A-dependent internalization of FZD4.
DR   Reactome; R-CEL-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR   Reactome; R-CEL-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-CEL-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-CEL-8866427; VLDLR internalisation and degradation.
DR   Reactome; R-CEL-8964038; LDL clearance.
DR   SignaLink; P35603; -.
DR   PRO; PR:P35603; -.
DR   Proteomes; UP000001940; Chromosome X.
DR   Bgee; WBGene00001082; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR   GO; GO:0030122; C:AP-2 adaptor complex; IBA:GO_Central.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR   GO; GO:1990075; C:periciliary membrane compartment; IDA:WormBase.
DR   GO; GO:0045202; C:synapse; IDA:WormBase.
DR   GO; GO:0008021; C:synaptic vesicle; IDA:WormBase.
DR   GO; GO:0035615; F:clathrin adaptor activity; IBA:GO_Central.
DR   GO; GO:0010171; P:body morphogenesis; IMP:WormBase.
DR   GO; GO:0072583; P:clathrin-dependent endocytosis; IMP:WormBase.
DR   GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR   GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR   GO; GO:0010940; P:positive regulation of necrotic cell death; IGI:WormBase.
DR   GO; GO:0061357; P:positive regulation of Wnt protein secretion; IMP:WormBase.
DR   GO; GO:0097499; P:protein localization to non-motile cilium; IMP:WormBase.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; IMP:WormBase.
DR   GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR   CDD; cd09251; AP-2_Mu2_Cterm; 1.
DR   CDD; cd14836; AP2_Mu_N; 1.
DR   InterPro; IPR036168; AP2_Mu_C_sf.
DR   InterPro; IPR043532; AP2_Mu_N.
DR   InterPro; IPR022775; AP_mu_sigma_su.
DR   InterPro; IPR001392; Clathrin_mu.
DR   InterPro; IPR018240; Clathrin_mu_CS.
DR   InterPro; IPR011012; Longin-like_dom_sf.
DR   InterPro; IPR028565; MHD.
DR   InterPro; IPR043512; Mu2_C.
DR   Pfam; PF00928; Adap_comp_sub; 1.
DR   Pfam; PF01217; Clat_adaptor_s; 1.
DR   PIRSF; PIRSF005992; Clathrin_mu; 1.
DR   PRINTS; PR00314; CLATHRINADPT.
DR   SUPFAM; SSF49447; SSF49447; 1.
DR   SUPFAM; SSF64356; SSF64356; 1.
DR   PROSITE; PS00990; CLAT_ADAPTOR_M_1; 1.
DR   PROSITE; PS00991; CLAT_ADAPTOR_M_2; 1.
DR   PROSITE; PS51072; MHD; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cell membrane; Coated pit; Endocytosis; Membrane;
KW   Protein transport; Reference proteome; Transport.
FT   CHAIN           1..441
FT                   /note="AP-2 complex subunit mu"
FT                   /id="PRO_0000193791"
FT   DOMAIN          174..440
FT                   /note="MHD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00404"
FT   VAR_SEQ         142..147
FT                   /note="Missing (in isoform b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_008037"
FT   CONFLICT        80
FT                   /note="E -> A (in Ref. 1; AAA27981)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   441 AA;  50300 MW;  D8F8B7760CAB164F CRC64;
     MIGGLFVYNH KGEVLISRIY RDDVTRNAVD AFRVNVIHAR QQVRSPVTNM ARTSFFHVKR
     GNVWICAVTR QNVNAAMVFE FLKRFADTMQ SYFGKLNEEN VKNNFVLIYE LLDEILDFGY
     PQNTDPGVLK TFITQQGVRT ADAPVPVTKE EQSQITSQVT GQIGWRREGI KYRRNELFLD
     VIEYVNLLMN QQGQVLSAHV AGKVAMKSYL SGMPECKFGI NDKITIEGKS KPGSDDPNKA
     SRAAVAIDDC QFHQCVKLTK FETEHAISFI PPDGEYELMR YRTTKDIQLP FRVIPLVREV
     SRNKMEVKVV VKSNFKPSLL AQKLEVRIPT PPNTSGVQLI CMKGKAKYKA GENAIVWKIK
     RMAGMKESQI SAEIDLLSTG NVEKKKWNRP PVSMNFEVPF APSGLKVRYL KVFEPKLNYS
     DHDVIKWVRY IGRSGLYETR C