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Protein

Phosphoprotein associated with glycosphingolipid-enriched microdomains 1

Gene

Pag1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Promotes CSK activation and recruitment to lipid rafts, which results in LCK inhibition. Inhibits immunological synapse formation by preventing dynamic arrangement of lipid raft proteins. May be involved in cell adhesion signaling.4 Publications

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • intracellular signal transduction Source: HGNC
  • negative regulation of T cell activation Source: HGNC
  • regulation of T cell activation Source: HGNC
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-MMU-180292. GAB1 signalosome.
R-MMU-202427. Phosphorylation of CD3 and TCR zeta chains.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphoprotein associated with glycosphingolipid-enriched microdomains 1
Alternative name(s):
Csk-binding protein
Transmembrane phosphoprotein Cbp
Gene namesi
Name:Pag1
Synonyms:Cbp, Pag
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2443160. Pag1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1717ExtracellularSequence analysisAdd
BLAST
Transmembranei18 – 3821Helical; Signal-anchor for type III membrane proteinSequence analysisAdd
BLAST
Topological domaini39 – 429391CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • intracellular Source: MGI
  • membrane raft Source: HGNC
  • plasma membrane Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are viable and do not show any developmental defect up to 20 months of age. They have normal T-cell development and normal T- and B-cell responses.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi314 – 3141Y → F: Enhances TCR-mediated signaling. 1 Publication
Mutagenesisi429 – 4291L → A: Abolishes interaction with SLC9A3R1 and effect on synapse formation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 429429Phosphoprotein associated with glycosphingolipid-enriched microdomains 1PRO_0000083339Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi39 – 391S-palmitoyl cysteineBy similarity
Lipidationi42 – 421S-palmitoyl cysteineBy similarity
Modified residuei107 – 1071Phosphotyrosine; by LYNBy similarity
Modified residuei165 – 1651PhosphotyrosineCombined sources
Modified residuei183 – 1831PhosphotyrosineCombined sources
Modified residuei224 – 2241PhosphotyrosineCombined sources
Modified residuei226 – 2261PhosphoserineBy similarity
Modified residuei314 – 3141Phosphotyrosine; by FYN3 Publications
Modified residuei351 – 3511PhosphoserineCombined sources
Modified residuei356 – 3561PhosphotyrosineBy similarity
Modified residuei379 – 3791PhosphoserineCombined sources
Modified residuei386 – 3861PhosphotyrosineBy similarity
Modified residuei414 – 4141PhosphotyrosineBy similarity

Post-translational modificationi

Palmitoylated.1 Publication
Phosphorylated by FYN on Tyr-314 in resting T-cells; which promotes interaction with CSK. Dephosphorylated by PTPRC/CD45 upon TCR activation; which leads to CSK dissociation. May also be dephosphorylated by PTPN11. Hyperphosphorylated in mast cells upon FCER1 activation.5 Publications

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiQ3U1F9.
MaxQBiQ3U1F9.
PaxDbiQ3U1F9.
PRIDEiQ3U1F9.

PTM databases

iPTMnetiQ3U1F9.
PhosphoSiteiQ3U1F9.
SwissPalmiQ3U1F9.

Expressioni

Tissue specificityi

Present in T-cells (at protein level).1 Publication

Gene expression databases

BgeeiQ3U1F9.
ExpressionAtlasiQ3U1F9. baseline and differential.
GenevisibleiQ3U1F9. MM.

Interactioni

Subunit structurei

When phosphorylated, interacts with CSK. Interacts with SLC9A3R1/EBP50. In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation.4 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi220469. 3 interactions.
IntActiQ3U1F9. 1 interaction.
STRINGi10090.ENSMUSP00000104021.

Structurei

3D structure databases

ProteinModelPortaliQ3U1F9.
SMRiQ3U1F9. Positions 288-321.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni314 – 3174Interaction with CSK
Regioni427 – 4293Interaction with SLC9A3R1

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFZ3. Eukaryota.
ENOG4111TW0. LUCA.
GeneTreeiENSGT00390000002061.
HOGENOMiHOG000290651.
HOVERGENiHBG055052.
InParanoidiQ3U1F9.
OMAiSPSSCND.
OrthoDBiEOG7VB2G4.
PhylomeDBiQ3U1F9.
TreeFamiTF336170.

Family and domain databases

InterProiIPR032748. PAG.
[Graphical view]
PfamiPF15347. PAG. 1 hit.
[Graphical view]
ProDomiPD340439. PD340439. 1 hit.
[Graphical view] [Entries sharing at least one domain]

Sequencei

Sequence statusi: Complete.

Q3U1F9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGPAGSVLSS GQMQMQMVLW GSLAAVAMFF LITFLVLLCS TCDREKKPRQ
60 70 80 90 100
HSGDHENLMN VPSDKDMFSH SATSLTTDAL ASSEQNGVLT NGDILSEDST
110 120 130 140 150
LTCMQHYEEV QTSASDLLDS QDSTGKAKCH QSRELPRIPP ENAVDEILTA
160 170 180 190 200
RAADTELGPG VEGPYEVLKD SSSQENMVED CLYETVKEIK EVADKGQGGK
210 220 230 240 250
SKSTSALKEL QGAPMEGKAD FAEYASVDRN KKCRHSANAE SILGTCSDLD
260 270 280 290 300
EESPPPVPVK LLDENANLPQ EGGGQAEEQA AEGTGGHSKR FSSLSYKSRE
310 320 330 340 350
EDPTLTEEEI SAMYSSVNKP GQSAHKPGPC MKGPESACHS MKGLPQRSSS
360 370 380 390 400
SCNDLYATVK DFEKTPNSIS TLPPARRPSE EPEPDYEAIQ TLNREDEKVP
410 420
LETNGHHVPK ESDYESIGDL QQCRDVTRL
Length:429
Mass (Da):46,549
Last modified:December 20, 2005 - v2
Checksum:iF5A95257B4C4DADC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti58 – 581L → P in AAG44565 (PubMed:10790433).Curated
Sequence conflicti287 – 2871H → R in AAG44565 (PubMed:10790433).Curated
Sequence conflicti360 – 3601K → R in BAE33539 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF250192 mRNA. Translation: AAG44565.1.
AK156000 mRNA. Translation: BAE33539.1.
AK040230 mRNA. Translation: BAC30545.1.
AK089329 mRNA. Translation: BAC40842.1.
AK172106 mRNA. Translation: BAE42829.1.
CCDSiCCDS17235.1.
RefSeqiNP_001181960.1. NM_001195031.1.
NP_444412.2. NM_053182.5.
XP_006530170.1. XM_006530107.1.
XP_011246453.1. XM_011248151.1.
UniGeneiMm.23897.
Mm.486503.

Genome annotation databases

EnsembliENSMUST00000108384; ENSMUSP00000104021; ENSMUSG00000027508.
ENSMUST00000161949; ENSMUSP00000124529; ENSMUSG00000027508.
GeneIDi94212.
KEGGimmu:94212.
UCSCiuc008opc.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF250192 mRNA. Translation: AAG44565.1.
AK156000 mRNA. Translation: BAE33539.1.
AK040230 mRNA. Translation: BAC30545.1.
AK089329 mRNA. Translation: BAC40842.1.
AK172106 mRNA. Translation: BAE42829.1.
CCDSiCCDS17235.1.
RefSeqiNP_001181960.1. NM_001195031.1.
NP_444412.2. NM_053182.5.
XP_006530170.1. XM_006530107.1.
XP_011246453.1. XM_011248151.1.
UniGeneiMm.23897.
Mm.486503.

3D structure databases

ProteinModelPortaliQ3U1F9.
SMRiQ3U1F9. Positions 288-321.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi220469. 3 interactions.
IntActiQ3U1F9. 1 interaction.
STRINGi10090.ENSMUSP00000104021.

PTM databases

iPTMnetiQ3U1F9.
PhosphoSiteiQ3U1F9.
SwissPalmiQ3U1F9.

Proteomic databases

EPDiQ3U1F9.
MaxQBiQ3U1F9.
PaxDbiQ3U1F9.
PRIDEiQ3U1F9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000108384; ENSMUSP00000104021; ENSMUSG00000027508.
ENSMUST00000161949; ENSMUSP00000124529; ENSMUSG00000027508.
GeneIDi94212.
KEGGimmu:94212.
UCSCiuc008opc.2. mouse.

Organism-specific databases

CTDi55824.
MGIiMGI:2443160. Pag1.

Phylogenomic databases

eggNOGiENOG410IFZ3. Eukaryota.
ENOG4111TW0. LUCA.
GeneTreeiENSGT00390000002061.
HOGENOMiHOG000290651.
HOVERGENiHBG055052.
InParanoidiQ3U1F9.
OMAiSPSSCND.
OrthoDBiEOG7VB2G4.
PhylomeDBiQ3U1F9.
TreeFamiTF336170.

Enzyme and pathway databases

ReactomeiR-MMU-180292. GAB1 signalosome.
R-MMU-202427. Phosphorylation of CD3 and TCR zeta chains.

Miscellaneous databases

ChiTaRSiPag1. mouse.
PROiQ3U1F9.
SOURCEiSearch...

Gene expression databases

BgeeiQ3U1F9.
ExpressionAtlasiQ3U1F9. baseline and differential.
GenevisibleiQ3U1F9. MM.

Family and domain databases

InterProiIPR032748. PAG.
[Graphical view]
PfamiPF15347. PAG. 1 hit.
[Graphical view]
ProDomiPD340439. PD340439. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation."
    Brdicka T., Pavlistova D., Bruyns E., Leo A., Korinek V., Angelisova P., Scherer J., Shevchenko A., Shevchenko A., Hilgert I., Cerny J., Drbal K., Kuramitsu Y., Horejsi V., Schraven B.
    J. Exp. Med. 191:1591-1604(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and NOD.
    Tissue: Spleen and Thymus.
  3. "Negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly."
    Itoh K., Sakakibara M., Yamasaki S., Takeuchi A., Arase H., Miyazaki M., Nakajima N., Okada M., Saito T.
    J. Immunol. 168:541-544(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SLC9A3R1, IDENTIFICATION IN A COMPLEX WITH SLC9A3R1 AND MSN, MUTAGENESIS OF LEU-429, SUBCELLULAR LOCATION, PHOSPHORYLATION.
  4. "Fyn is essential for tyrosine phosphorylation of Csk-binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells."
    Yasuda K., Nagafuku M., Shima T., Okada M., Yagi T., Yamada T., Minaki Y., Kato A., Tani-Ichi S., Hamaoka T., Kosugi A.
    J. Immunol. 169:2813-2817(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-314, INTERACTION WITH CSK, FUNCTION.
  5. "Glucocorticoids alter the lipid and protein composition of membrane rafts of a murine T cell hybridoma."
    Van Laethem F., Liang X., Andris F., Urbain J., Vandenbranden M., Ruysschaert J.-M., Resh M.D., Stulnig T.M., Leo O.
    J. Immunol. 170:2932-2939(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION.
  6. "Phosphorylation-dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor."
    Davidson D., Bakinowski M., Thomas M.L., Horejsi V., Veillette A.
    Mol. Cell. Biol. 23:2017-2028(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-314, MUTAGENESIS OF TYR-314, INTERACTION WITH CSK, SUBCELLULAR LOCATION, FUNCTION.
  7. "Transmembrane phosphoprotein Cbp senses cell adhesion signaling mediated by Src family kinase in lipid rafts."
    Shima T., Nada S., Okada M.
    Proc. Natl. Acad. Sci. U.S.A. 100:14897-14902(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
  8. "Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment."
    Zhang S.Q., Yang W., Kontaridis M.I., Bivona T.G., Wen G., Araki T., Luo J., Thompson J.A., Schraven B.L., Philips M.R., Neel B.G.
    Mol. Cell 13:341-355(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-314, INTERACTION WITH CSK.
  9. "Cbp deficiency alters Csk localization in lipid rafts but does not affect T-cell development."
    Xu S., Huo J., Tan J.E.-L., Lam K.-P.
    Mol. Cell. Biol. 25:8486-8495(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, DISRUPTION PHENOTYPE.
  10. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
    Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
    J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-224, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Mast cell.
  11. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-165; TYR-183; TYR-224 AND SER-379, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-351 AND SER-379, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Kidney, Lung, Spleen and Testis.

Entry informationi

Entry nameiPHAG1_MOUSE
AccessioniPrimary (citable) accession number: Q3U1F9
Secondary accession number(s): Q8BFS1, Q9EQF3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: December 20, 2005
Last modified: June 8, 2016
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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.