AP2S1_MOUSE
ID AP2S1_MOUSE Reviewed; 142 AA.
AC P62743; P70626; P97626; Q00380;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=AP-2 complex subunit sigma;
DE AltName: Full=Adaptor protein complex AP-2 subunit sigma;
DE AltName: Full=Adaptor-related protein complex 2 subunit sigma;
DE AltName: Full=Clathrin assembly protein 2 sigma small chain;
DE AltName: Full=Clathrin coat assembly protein AP17;
DE AltName: Full=Clathrin coat-associated protein AP17;
DE AltName: Full=Plasma membrane adaptor AP-2 17 kDa protein;
DE AltName: Full=Sigma-adaptin 3b;
DE AltName: Full=Sigma2-adaptin;
GN Name=Ap2s1; Synonyms=Ap17, Claps2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Marra M., Hillier L., Allen M., Bowles M., Dietrich N., Dubuque T.,
RA Geisel S., Kucaba T., Lacy M., Le M., Martin J., Morris M.,
RA Schellenberg K., Steptoe M., Tan F., Underwood K., Moore B., Theising B.,
RA Wylie T., Lennon G., Soares B., Wilson R., Waterston R.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
RX PubMed=14745134; DOI=10.1247/csf.28.419;
RA Nakatsu F., Ohno H.;
RT "Adaptor protein complexes as the key regulators of protein sorting in the
RT post-Golgi network.";
RL Cell Struct. Funct. 28:419-429(2003).
RN [3]
RP FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
RX PubMed=15473838; DOI=10.1146/annurev.cellbio.20.010403.104543;
RA Owen D.J., Collins B.M., Evans P.R.;
RT "Adaptors for clathrin coats: structure and function.";
RL Annu. Rev. Cell Dev. Biol. 20:153-191(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) IN COMPLEX WITH AP2B1; AP2M1; AP2A2
RP AND AN INOSITOL POLYPHOSPHATE HEADGROUP.
RX PubMed=12086608; DOI=10.1016/s0092-8674(02)00735-3;
RA Collins B.M., McCoy A.J., Kent H.M., Evans P.R., Owen D.J.;
RT "Molecular architecture and functional model of the endocytic AP2
RT complex.";
RL Cell 109:523-535(2002).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.98 ANGSTROMS) IN COMPLEX WITH AP2A2; AP2B1; AP2M1
RP AND CD4 INTERNALIZATION SIGNAL, AND MUTAGENESIS OF ARG-15; TYR-62; ALA-63;
RP LEU-65; VAL-88; ASN-92; VAL-98; GLU-100 AND LEU-103.
RX PubMed=19140243; DOI=10.1038/nature07422;
RA Kelly B.T., McCoy A.J., Spaete K., Miller S.E., Evans P.R., Hoening S.,
RA Owen D.J.;
RT "A structural explanation for the binding of endocytic dileucine motifs by
RT the AP2 complex.";
RL Nature 456:976-979(2008).
CC -!- FUNCTION: Component of the adaptor protein complex 2 (AP-2). Adaptor
CC protein complexes function in protein transport via Transport vesicles
CC in different membrane traffic pathways. Adaptor protein complexes are
CC vesicle coat components and appear to be involved in cargo selection
CC and vesicle formation. AP-2 is involved in clathrin-dependent
CC endocytosis in which cargo proteins are incorporated into vesicles
CC surrounded by clathrin (clathrin-coated vesicles, CCVs) which are
CC destined for fusion with the early endosome. The clathrin lattice
CC serves as a mechanical scaffold but is itself unable to bind directly
CC to membrane components. Clathrin-associated adaptor protein (AP)
CC complexes which can bind directly to both the clathrin lattice and to
CC the lipid and protein components of membranes are considered to be the
CC major clathrin adaptors contributing the CCV formation. AP-2 also
CC serves as a cargo receptor to selectively sort the membrane proteins
CC involved in receptor-mediated endocytosis. AP-2 seems to play a role in
CC the recycling of synaptic vesicle membranes from the presynaptic
CC surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-
CC [LI] endocytosis signal motifs within the cytosolic tails of
CC transmembrane cargo molecules. AP-2 may also play a role in maintaining
CC normal post-endocytic trafficking through the ARF6-regulated, non-
CC clathrin pathway. The AP-2 alpha and AP-2 sigma subunits are thought to
CC contribute to the recognition of the [ED]-X-X-X-L-[LI] motif. May also
CC play a role in extracellular calcium homeostasis (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:14745134,
CC ECO:0000269|PubMed:15473838}.
CC -!- SUBUNIT: Adaptor protein complex 2 (AP-2) is a heterotetramer composed
CC of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type
CC subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small
CC adaptin (sigma-type subunit AP2S1). {ECO:0000269|PubMed:12086608,
CC ECO:0000269|PubMed:19140243}.
CC -!- SUBCELLULAR LOCATION: Cell membrane. Membrane, coated pit; Peripheral
CC membrane protein; Cytoplasmic side. Note=AP-2 appears to be excluded
CC from internalizing CCVs and to disengage from sites of endocytosis
CC seconds before internalization of the nascent CCV. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the adaptor complexes small subunit family.
CC {ECO:0000305}.
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DR EMBL; AA277150; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS52042.1; -.
DR RefSeq; NP_941015.2; NM_198613.2.
DR PDB; 2JKR; X-ray; 2.98 A; I/S=1-142.
DR PDB; 2JKT; X-ray; 3.40 A; I/S=1-142.
DR PDB; 2VGL; X-ray; 2.59 A; S=1-142.
DR PDB; 2XA7; X-ray; 3.10 A; S=1-142.
DR PDB; 4UQI; X-ray; 2.79 A; S=1-142.
DR PDB; 6QH5; X-ray; 2.56 A; S=1-142.
DR PDB; 6QH6; X-ray; 5.00 A; S=1-142.
DR PDB; 6QH7; X-ray; 3.40 A; S=1-142.
DR PDB; 6YAE; EM; 3.90 A; S=1-142.
DR PDB; 6YAF; EM; 9.10 A; S=1-142.
DR PDB; 6YAH; EM; 10.20 A; S=1-142.
DR PDB; 7RW8; EM; 3.50 A; S=1-142.
DR PDB; 7RW9; EM; 3.90 A; S=1-142.
DR PDB; 7RWA; EM; 4.70 A; S/s=1-142.
DR PDB; 7RWB; EM; 3.90 A; S/s=1-142.
DR PDB; 7RWC; EM; 3.80 A; S=1-142.
DR PDBsum; 2JKR; -.
DR PDBsum; 2JKT; -.
DR PDBsum; 2VGL; -.
DR PDBsum; 2XA7; -.
DR PDBsum; 4UQI; -.
DR PDBsum; 6QH5; -.
DR PDBsum; 6QH6; -.
DR PDBsum; 6QH7; -.
DR PDBsum; 6YAE; -.
DR PDBsum; 6YAF; -.
DR PDBsum; 6YAH; -.
DR PDBsum; 7RW8; -.
DR PDBsum; 7RW9; -.
DR PDBsum; 7RWA; -.
DR PDBsum; 7RWB; -.
DR PDBsum; 7RWC; -.
DR AlphaFoldDB; P62743; -.
DR SMR; P62743; -.
DR BioGRID; 231318; 11.
DR ComplexPortal; CPX-5152; AP-2 Adaptor complex, alpha1 variant.
DR ComplexPortal; CPX-5153; AP-2 Adaptor complex, alpha2 variant.
DR CORUM; P62743; -.
DR DIP; DIP-37505N; -.
DR IntAct; P62743; 5.
DR MINT; P62743; -.
DR STRING; 10090.ENSMUSP00000083281; -.
DR iPTMnet; P62743; -.
DR PhosphoSitePlus; P62743; -.
DR SwissPalm; P62743; -.
DR EPD; P62743; -.
DR jPOST; P62743; -.
DR PaxDb; P62743; -.
DR PeptideAtlas; P62743; -.
DR PRIDE; P62743; -.
DR ProteomicsDB; 296358; -.
DR Antibodypedia; 31506; 166 antibodies from 26 providers.
DR DNASU; 232910; -.
DR Ensembl; ENSMUST00000086112; ENSMUSP00000083281; ENSMUSG00000008036.
DR GeneID; 232910; -.
DR KEGG; mmu:232910; -.
DR UCSC; uc012faj.1; mouse.
DR CTD; 1175; -.
DR MGI; MGI:2141861; Ap2s1.
DR VEuPathDB; HostDB:ENSMUSG00000008036; -.
DR eggNOG; KOG0935; Eukaryota.
DR GeneTree; ENSGT00970000193421; -.
DR HOGENOM; CLU_061221_3_1_1; -.
DR InParanoid; P62743; -.
DR OMA; IYLSHIH; -.
DR OrthoDB; 1307450at2759; -.
DR PhylomeDB; P62743; -.
DR TreeFam; TF300139; -.
DR Reactome; R-MMU-177504; Retrograde neurotrophin signalling.
DR Reactome; R-MMU-2132295; MHC class II antigen presentation.
DR Reactome; R-MMU-416993; Trafficking of GluR2-containing AMPA receptors.
DR Reactome; R-MMU-437239; Recycling pathway of L1.
DR Reactome; R-MMU-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-MMU-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-MMU-8866427; VLDLR internalisation and degradation.
DR Reactome; R-MMU-8964038; LDL clearance.
DR BioGRID-ORCS; 232910; 29 hits in 77 CRISPR screens.
DR ChiTaRS; Ap2s1; mouse.
DR EvolutionaryTrace; P62743; -.
DR PRO; PR:P62743; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P62743; protein.
DR Bgee; ENSMUSG00000008036; Expressed in cortical plate and 242 other tissues.
DR ExpressionAtlas; P62743; baseline and differential.
DR Genevisible; P62743; MM.
DR GO; GO:0030122; C:AP-2 adaptor complex; IDA:CAFA.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IC:ComplexPortal.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0035615; F:clathrin adaptor activity; IEA:InterPro.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IC:ComplexPortal.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0098884; P:postsynaptic neurotransmitter receptor internalization; IC:ComplexPortal.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd14833; AP2_sigma; 1.
DR IDEAL; IID50124; -.
DR InterPro; IPR016635; AP_complex_ssu.
DR InterPro; IPR022775; AP_mu_sigma_su.
DR InterPro; IPR027156; APS2.
DR InterPro; IPR000804; Clathrin_sm-chain_CS.
DR InterPro; IPR011012; Longin-like_dom_sf.
DR PANTHER; PTHR11753; PTHR11753; 1.
DR PANTHER; PTHR11753:SF6; PTHR11753:SF6; 1.
DR Pfam; PF01217; Clat_adaptor_s; 1.
DR PIRSF; PIRSF015588; AP_complex_sigma; 1.
DR SUPFAM; SSF64356; SSF64356; 1.
DR PROSITE; PS00989; CLAT_ADAPTOR_S; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Coated pit; Endocytosis; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..142
FT /note="AP-2 complex subunit sigma"
FT /id="PRO_0000193805"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53680"
FT MUTAGEN 15
FT /note="R->S: Reduces interaction with CD4 endocytosis
FT signal motif; when associated with AP2A2 E-21."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 62
FT /note="Y->S: Abolishes interaction with CD4 endocytosis
FT signal motif."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 63
FT /note="A->W: Abolishes interaction with CD4 endocytosis
FT signal motif."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 65
FT /note="L->S: Slightly reduces interaction with CD4
FT endocytosis signal motif."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 88
FT /note="V->D: Abolishes interaction with CD4 endocytosis
FT signal motif."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 92
FT /note="N->W: Abolishes interaction with CD4 endocytosis
FT signal motif."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 98
FT /note="V->F: Reduces interaction with CD4 endocytosis
FT signal motif."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 98
FT /note="V->S: Abolishes interaction with CD4 endocytosis
FT signal motif."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 100
FT /note="E->Y: Abolishes interaction with CD4 endocytosis
FT signal motif."
FT /evidence="ECO:0000269|PubMed:19140243"
FT MUTAGEN 103
FT /note="L->S: Abolishes interaction with CD4 endocytosis
FT signal motif."
FT /evidence="ECO:0000269|PubMed:19140243"
FT STRAND 2..9
FT /evidence="ECO:0007829|PDB:6QH5"
FT STRAND 14..21
FT /evidence="ECO:0007829|PDB:6QH5"
FT HELIX 25..39
FT /evidence="ECO:0007829|PDB:6QH5"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:2JKR"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:6QH5"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:6QH5"
FT STRAND 65..71
FT /evidence="ECO:0007829|PDB:6QH5"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:2XA7"
FT HELIX 77..94
FT /evidence="ECO:0007829|PDB:6QH5"
FT HELIX 100..105
FT /evidence="ECO:0007829|PDB:6QH5"
FT HELIX 107..117
FT /evidence="ECO:0007829|PDB:6QH5"
FT HELIX 128..140
FT /evidence="ECO:0007829|PDB:6QH5"
SQ SEQUENCE 142 AA; 17018 MW; CA3FD868C65AEDF6 CRC64;
MIRFILIQNR AGKTRLAKWY MQFDDDEKQK LIEEVHAVVT VRDAKHTNFV EFRNFKIIYR
RYAGLYFCIC VDVNDNNLAY LEAIHNFVEV LNEYFHNVCE LDLVFNFYKV YTVVDEMFLA
GEIRETSQTK VLKQLLMLQS LE
