PHAG1_RAT
ID PHAG1_RAT Reviewed; 424 AA.
AC Q9JM80;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Phosphoprotein associated with glycosphingolipid-enriched microdomains 1;
DE AltName: Full=Csk-binding protein;
DE AltName: Full=Transmembrane phosphoprotein Cbp;
GN Name=Pag1; Synonyms=Cbp, Pag;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY,
RP INTERACTION WITH CSK, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS
RP OF TYR-107; TYR-165; TYR-183; TYR-224; TYR-296; TYR-314; TYR-351; TYR-381
RP AND TYR-409, PHOSPHORYLATION AT TYR-314, AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=10801129; DOI=10.1038/35010121;
RA Kawabuchi M., Satomi Y., Takao T., Shimonishi Y., Nada S., Nagai K.,
RA Tarakhovsky A., Okada M.;
RT "Transmembrane phosphoprotein Cbp regulates the activities of Src-family
RT tyrosine kinases.";
RL Nature 404:999-1003(2000).
RN [2]
RP PHOSPHORYLATION AT TYR-165; TYR-183; TYR-224; TYR-314; TYR-381 AND TYR-409,
RP AND FUNCTION.
RX PubMed=10918051; DOI=10.1074/jbc.c000326200;
RA Takeuchi S., Takayama Y., Ogawa A., Tamura K., Okada M.;
RT "Transmembrane phosphoprotein Cbp positively regulates the activity of the
RT carboxyl-terminal Src kinase, Csk.";
RL J. Biol. Chem. 275:29183-29186(2000).
RN [3]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH CSK,
RP PHOSPHORYLATION, AND FUNCTION.
RX PubMed=11859092; DOI=10.4049/jimmunol.168.5.2087;
RA Ohtake H., Ichikawa N., Okada M., Yamashita T.;
RT "Transmembrane phosphoprotein Csk-binding protein/phosphoprotein associated
RT with glycosphingolipid-enriched microdomains as a negative feedback
RT regulator of mast cell signaling through the FcepsilonRI.";
RL J. Immunol. 168:2087-2090(2002).
RN [4]
RP INTERACTION WITH CSK, PHOSPHORYLATION, AND MUTAGENESIS OF TYR-314.
RX PubMed=14613929; DOI=10.1074/jbc.m311278200;
RA Matsuoka H., Nada S., Okada M.;
RT "Mechanism of Csk-mediated down-regulation of Src family tyrosine kinases
RT in epidermal growth factor signaling.";
RL J. Biol. Chem. 279:5975-5983(2004).
RN [5]
RP INTERACTION WITH LYN AND CSK, AND PHOSPHORYLATION AT TYR-107 AND TYR-314.
RX PubMed=16920712; DOI=10.1074/jbc.m602637200;
RA Ingley E., Schneider J.R., Payne C.J., McCarthy D.J., Harder K.W.,
RA Hibbs M.L., Klinken S.P.;
RT "Csk-binding protein mediates sequential enzymatic down-regulation and
RT degradation of Lyn in erythropoietin-stimulated cells.";
RL J. Biol. Chem. 281:31920-31929(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52; SER-63 AND SER-157, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Negatively regulates TCR (T-cell antigen receptor)-mediated
CC signaling in T-cells and FCER1 (high affinity immunoglobulin epsilon
CC receptor)-mediated signaling in mast cells. Promotes CSK activation and
CC recruitment to lipid rafts, which results in LCK inhibition. Inhibits
CC immunological synapse formation by preventing dynamic arrangement of
CC lipid raft proteins. May be involved in cell adhesion signaling.
CC {ECO:0000269|PubMed:10801129, ECO:0000269|PubMed:10918051,
CC ECO:0000269|PubMed:11859092}.
CC -!- SUBUNIT: Interacts with SLC9A3R1/EBP50. In resting T-cells, part of a
CC PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation (By
CC similarity). When phosphorylated, interacts with CSK. Identified in a
CC complex with LYN and STAT3 (By similarity). Interacts with LYN.
CC {ECO:0000250, ECO:0000269|PubMed:10801129, ECO:0000269|PubMed:11859092,
CC ECO:0000269|PubMed:14613929, ECO:0000269|PubMed:16920712}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10801129,
CC ECO:0000269|PubMed:11859092}; Single-pass type III membrane protein
CC {ECO:0000269|PubMed:10801129, ECO:0000269|PubMed:11859092}.
CC Note=Present in lipid rafts.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC developing brain, lung, thymus, spleen and testis. Present in mast
CC cells. {ECO:0000269|PubMed:10801129, ECO:0000269|PubMed:11859092}.
CC -!- PTM: Palmitoylated. {ECO:0000250}.
CC -!- PTM: Phosphorylated by FYN on Tyr-314 in resting T-cells; which
CC promotes interaction with CSK. Dephosphorylated by PTPRC/CD45 upon TCR
CC activation; which leads to CSK dissociation. May also be
CC dephosphorylated by PTPN11. Hyperphosphorylated in mast cells upon
CC FCER1 activation. Phosphorylated by LYN in response to EPO.
CC {ECO:0000269|PubMed:10801129, ECO:0000269|PubMed:10918051,
CC ECO:0000269|PubMed:11859092, ECO:0000269|PubMed:14613929,
CC ECO:0000269|PubMed:16920712}.
CC -!- CAUTION: In contrast to the human ortholog, does not seem to interact
CC with FYN. {ECO:0000305|PubMed:10801129}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB038038; BAA95413.1; -; mRNA.
DR RefSeq; NP_071589.1; NM_022253.1.
DR PDB; 2RSY; NMR; -; B=288-321.
DR PDBsum; 2RSY; -.
DR AlphaFoldDB; Q9JM80; -.
DR BMRB; Q9JM80; -.
DR SMR; Q9JM80; -.
DR BioGRID; 248938; 2.
DR STRING; 10116.ENSRNOP00000065200; -.
DR iPTMnet; Q9JM80; -.
DR PhosphoSitePlus; Q9JM80; -.
DR PaxDb; Q9JM80; -.
DR PRIDE; Q9JM80; -.
DR Ensembl; ENSRNOT00000119112; ENSRNOP00000079316; ENSRNOG00000061328.
DR GeneID; 64019; -.
DR KEGG; rno:64019; -.
DR CTD; 55824; -.
DR RGD; 620394; Pag1.
DR eggNOG; ENOG502QUCZ; Eukaryota.
DR GeneTree; ENSGT00390000002061; -.
DR InParanoid; Q9JM80; -.
DR OrthoDB; 1104680at2759; -.
DR PhylomeDB; Q9JM80; -.
DR Reactome; R-RNO-180292; GAB1 signalosome.
DR Reactome; R-RNO-202427; Phosphorylation of CD3 and TCR zeta chains.
DR PRO; PR:Q9JM80; -.
DR Proteomes; UP000002494; Chromosome 2.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:RGD.
DR GO; GO:0045121; C:membrane raft; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; TAS:RGD.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0050868; P:negative regulation of T cell activation; ISO:RGD.
DR GO; GO:0050863; P:regulation of T cell activation; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; TAS:RGD.
DR InterPro; IPR032748; PAG.
DR PANTHER; PTHR16322; PTHR16322; 1.
DR Pfam; PF15347; PAG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Immunity; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..424
FT /note="Phosphoprotein associated with glycosphingolipid-
FT enriched microdomains 1"
FT /id="PRO_0000083340"
FT TOPO_DOM 1..17
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 18..38
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..424
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 194..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 314..317
FT /note="Interaction with CSK"
FT REGION 361..424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 422..424
FT /note="Interaction with SLC9A3R1"
FT /evidence="ECO:0000250"
FT COMPBIAS 213..236
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 266..284
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 309..347
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 373..389
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 107
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000269|PubMed:16920712"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 165
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10918051"
FT MOD_RES 183
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10918051"
FT MOD_RES 224
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10918051"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NWQ8"
FT MOD_RES 314
FT /note="Phosphotyrosine; by FYN and LYN"
FT /evidence="ECO:0000269|PubMed:10801129,
FT ECO:0000269|PubMed:10918051, ECO:0000269|PubMed:16920712"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3U1F9"
FT MOD_RES 351
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9NWQ8"
FT MOD_RES 381
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10918051"
FT MOD_RES 409
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10918051"
FT LIPID 39
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 42
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 107
FT /note="Y->F: No effect on interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10801129"
FT MUTAGEN 165
FT /note="Y->F: No effect on interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10801129"
FT MUTAGEN 183
FT /note="Y->F: No effect on interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10801129"
FT MUTAGEN 224
FT /note="Y->F: No effect on interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10801129"
FT MUTAGEN 296
FT /note="Y->F: No effect on interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10801129"
FT MUTAGEN 314
FT /note="Y->F: Abolishes interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10801129,
FT ECO:0000269|PubMed:14613929"
FT MUTAGEN 351
FT /note="Y->F: No effect on interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10801129"
FT MUTAGEN 381
FT /note="Y->F: No effect on interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10801129"
FT MUTAGEN 409
FT /note="Y->F: No effect on interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10801129"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:2RSY"
FT HELIX 307..312
FT /evidence="ECO:0007829|PDB:2RSY"
SQ SEQUENCE 424 AA; 45915 MW; 49ED52D44B3FB154 CRC64;
MGPAGSALSS GQMQMQMVLW GSLAAVAMFF LITFLILLCS SCDRDKKPRQ HSGDHESLMN
VPSDKEMFSH SATSLTTDAL ASSEQNGVLT NGDILSEDST MTCMQHYEEV QTSASDLLDS
QDSTGKAKCH QSRELPRIPP ENAVDAMLTA RAADGDSGPG VEGPYEVLKD SSSQENMVED
CLYETVKEIK EVADKSQGGK SKSTSALKEL QGAHAEGKAD FAEYASVDRN KKCRHSTNAE
SILGTSSDLD EETPPPVPVK LLDENANLPE KGEHGAEEQA PEAPSGHSKR FSSLSYKSRE
EDPTLTEEEI SAMYSSVNKP GQSAHKPGPE STCQCPQGPP QRSSSSCNDL YATVKDFEKT
PNSISMLPPA RRPGEEPEPD YEAIQTLNRE DDKVPLGTNG HLVPKENDYE SIGDLQQGRD
VTRL
