Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Phosphoprotein associated with glycosphingolipid-enriched microdomains 1

Gene

PAG1

Organism
Homo sapiens (Human)
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.1 Publication

GO - Molecular functioni

  • SH2 domain binding Source: HGNC
  • SH3/SH2 adaptor activity Source: HGNC

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • epidermal growth factor receptor signaling pathway Source: Reactome
  • intracellular signal transduction Source: HGNC
  • negative regulation of T cell activation Source: Ensembl
  • positive regulation of signal transduction Source: GOC
  • regulation of T cell activation Source: ProtInc
  • signal transduction Source: ProtInc
  • T cell receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-180292. GAB1 signalosome.
R-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
SignaLinkiQ9NWQ8.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphoprotein associated with glycosphingolipid-enriched microdomains 1
Alternative name(s):
Csk-binding protein
Transmembrane adapter protein PAG
Transmembrane phosphoprotein Cbp
Gene namesi
Name:PAG1
Synonyms:CBP, PAG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:30043. PAG1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1616ExtracellularSequence analysisAdd
BLAST
Transmembranei17 – 3721Helical; Signal-anchor for type III membrane proteinSequence analysisAdd
BLAST
Topological domaini38 – 432395CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi105 – 1051Y → F: No effect on interaction with FYN or CSK. 1 Publication
Mutagenesisi163 – 1631Y → F: No effect on interaction with FYN or CSK. 1 Publication
Mutagenesisi181 – 1811Y → F: No effect on interaction with FYN or CSK. 1 Publication
Mutagenesisi227 – 2271Y → F: No effect on interaction with FYN or CSK. 1 Publication
Mutagenesisi299 – 2991Y → F: No effect on interaction with FYN or CSK. 1 Publication
Mutagenesisi317 – 3171Y → F: No effect on interaction with FYN. Abolishes interaction with CSK. 1 Publication
Mutagenesisi341 – 3411Y → F: No effect on interaction with FYN or CSK. 1 Publication
Mutagenesisi359 – 3591Y → F: No effect on interaction with FYN or CSK. 1 Publication
Mutagenesisi387 – 3871Y → F: No effect on interaction with FYN or CSK. 1 Publication
Mutagenesisi417 – 4171Y → F: No effect on interaction with FYN or CSK. 1 Publication

Organism-specific databases

PharmGKBiPA142671201.

Polymorphism and mutation databases

BioMutaiPAG1.
DMDMi84029384.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 432432Phosphoprotein associated with glycosphingolipid-enriched microdomains 1PRO_0000083338Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi37 – 371S-palmitoyl cysteine1 Publication
Lipidationi40 – 401S-palmitoyl cysteine1 Publication
Modified residuei105 – 1051Phosphotyrosine; by LYNBy similarity
Modified residuei163 – 1631PhosphotyrosineBy similarity
Modified residuei181 – 1811PhosphotyrosineBy similarity
Modified residuei227 – 2271PhosphotyrosineCombined sources
Modified residuei229 – 2291PhosphoserineCombined sources
Modified residuei317 – 3171Phosphotyrosine; by FYN and LYNCombined sources2 Publications
Modified residuei354 – 3541PhosphoserineBy similarity
Modified residuei359 – 3591PhosphotyrosineCombined sources
Modified residuei380 – 3801PhosphoserineBy similarity
Modified residuei387 – 3871PhosphotyrosineCombined sources
Modified residuei417 – 4171PhosphotyrosineCombined sources

Post-translational modificationi

Palmitoylated.1 Publication
Phosphorylated by FYN on Tyr-317 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. Phosphorylated by LYN.2 Publications

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiQ9NWQ8.
MaxQBiQ9NWQ8.
PaxDbiQ9NWQ8.
PeptideAtlasiQ9NWQ8.
PRIDEiQ9NWQ8.
TopDownProteomicsiQ9NWQ8.

PTM databases

iPTMnetiQ9NWQ8.
PhosphoSiteiQ9NWQ8.
SwissPalmiQ9NWQ8.

Expressioni

Tissue specificityi

Ubiquitously expressed. Present in germinal center B-cells, plasma cells, T-cells, monocytes and platelets (at protein level).2 Publications

Gene expression databases

BgeeiQ9NWQ8.
CleanExiHS_PAG1.
GenevisibleiQ9NWQ8. HS.

Organism-specific databases

HPAiHPA001632.

Interactioni

Subunit structurei

Interacts with FYN. 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. Interacts with LYN on plasma membrane lipid rafts. Identified in a complex with LYN and STAT3.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CSKP412403EBI-2828115,EBI-1380630
FYNP062415EBI-2828115,EBI-515315
GNB2L1P632442EBI-2828115,EBI-296739
LYNP0794816EBI-2828115,EBI-79452

GO - Molecular functioni

  • SH2 domain binding Source: HGNC
  • SH3/SH2 adaptor activity Source: HGNC

Protein-protein interaction databases

BioGridi120931. 39 interactions.
IntActiQ9NWQ8. 11 interactions.
MINTiMINT-220429.
STRINGi9606.ENSP00000220597.

Structurei

3D structure databases

ProteinModelPortaliQ9NWQ8.
SMRiQ9NWQ8. Positions 291-324.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni317 – 3204Interaction with CSK
Regioni430 – 4323Interaction with SLC9A3R1

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFZ3. Eukaryota.
ENOG4111TW0. LUCA.
GeneTreeiENSGT00390000002061.
HOGENOMiHOG000290651.
HOVERGENiHBG055052.
InParanoidiQ9NWQ8.
OMAiSPSSCND.
OrthoDBiEOG7VB2G4.
PhylomeDBiQ9NWQ8.
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.

Q9NWQ8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGPAGSLLGS GQMQITLWGS LAAVAIFFVI TFLIFLCSSC DREKKPRQHS
60 70 80 90 100
GDHENLMNVP SDKEMFSRSV TSLATDAPAS SEQNGALTNG DILSEDSTLT
110 120 130 140 150
CMQHYEEVQT SASDLLDSQD STGKPKCHQS RELPRIPPES AVDTMLTARS
160 170 180 190 200
VDGDQGLGME GPYEVLKDSS SQENMVEDCL YETVKEIKEV AAAAHLEKGH
210 220 230 240 250
SGKAKSTSAS KELPGPQTEG KAEFAEYASV DRNKKCRQSV NVESILGNSC
260 270 280 290 300
DPEEEAPPPV PVKLLDENEN LQEKEGGEAE ESATDTTSET NKRFSSLSYK
310 320 330 340 350
SREEDPTLTE EEISAMYSSV NKPGQLVNKS GQSLTVPEST YTSIQGDPQR
360 370 380 390 400
SPSSCNDLYA TVKDFEKTPN STLPPAGRPS EEPEPDYEAI QTLNREEEKA
410 420 430
TLGTNGHHGL VPKENDYESI SDLQQGRDIT RL
Length:432
Mass (Da):46,981
Last modified:December 20, 2005 - v2
Checksum:iE86272A0B7E3328C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti4 – 41A → V in AAH90931 (PubMed:15489334).Curated
Sequence conflicti36 – 361L → P in BAA91321 (PubMed:14702039).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF240634 mRNA. Translation: AAF67343.1.
AK000680 mRNA. Translation: BAA91321.1.
AK289818 mRNA. Translation: BAF82507.1.
CH471068 Genomic DNA. Translation: EAW87086.1.
BC090931 mRNA. Translation: AAH90931.1.
BC112159 mRNA. Translation: AAI12160.1.
CCDSiCCDS6227.1.
RefSeqiNP_060910.3. NM_018440.3.
XP_011515863.1. XM_011517561.1.
XP_011515864.1. XM_011517562.1.
XP_011515865.1. XM_011517563.1.
XP_011515866.1. XM_011517564.1.
XP_011515867.1. XM_011517565.1.
UniGeneiHs.266175.

Genome annotation databases

EnsembliENST00000220597; ENSP00000220597; ENSG00000076641.
GeneIDi55824.
KEGGihsa:55824.
UCSCiuc003ybz.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF240634 mRNA. Translation: AAF67343.1.
AK000680 mRNA. Translation: BAA91321.1.
AK289818 mRNA. Translation: BAF82507.1.
CH471068 Genomic DNA. Translation: EAW87086.1.
BC090931 mRNA. Translation: AAH90931.1.
BC112159 mRNA. Translation: AAI12160.1.
CCDSiCCDS6227.1.
RefSeqiNP_060910.3. NM_018440.3.
XP_011515863.1. XM_011517561.1.
XP_011515864.1. XM_011517562.1.
XP_011515865.1. XM_011517563.1.
XP_011515866.1. XM_011517564.1.
XP_011515867.1. XM_011517565.1.
UniGeneiHs.266175.

3D structure databases

ProteinModelPortaliQ9NWQ8.
SMRiQ9NWQ8. Positions 291-324.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120931. 39 interactions.
IntActiQ9NWQ8. 11 interactions.
MINTiMINT-220429.
STRINGi9606.ENSP00000220597.

PTM databases

iPTMnetiQ9NWQ8.
PhosphoSiteiQ9NWQ8.
SwissPalmiQ9NWQ8.

Polymorphism and mutation databases

BioMutaiPAG1.
DMDMi84029384.

Proteomic databases

EPDiQ9NWQ8.
MaxQBiQ9NWQ8.
PaxDbiQ9NWQ8.
PeptideAtlasiQ9NWQ8.
PRIDEiQ9NWQ8.
TopDownProteomicsiQ9NWQ8.

Protocols and materials databases

DNASUi55824.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220597; ENSP00000220597; ENSG00000076641.
GeneIDi55824.
KEGGihsa:55824.
UCSCiuc003ybz.4. human.

Organism-specific databases

CTDi55824.
GeneCardsiPAG1.
HGNCiHGNC:30043. PAG1.
HPAiHPA001632.
MIMi605767. gene.
neXtProtiNX_Q9NWQ8.
PharmGKBiPA142671201.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFZ3. Eukaryota.
ENOG4111TW0. LUCA.
GeneTreeiENSGT00390000002061.
HOGENOMiHOG000290651.
HOVERGENiHBG055052.
InParanoidiQ9NWQ8.
OMAiSPSSCND.
OrthoDBiEOG7VB2G4.
PhylomeDBiQ9NWQ8.
TreeFamiTF336170.

Enzyme and pathway databases

ReactomeiR-HSA-180292. GAB1 signalosome.
R-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
SignaLinkiQ9NWQ8.

Miscellaneous databases

ChiTaRSiPAG1. human.
GeneWikiiPAG1.
GenomeRNAii55824.
NextBioi61018.
PROiQ9NWQ8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NWQ8.
CleanExiHS_PAG1.
GenevisibleiQ9NWQ8. HS.

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], PROTEIN SEQUENCE OF 264-274, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-317, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-37 AND CYS-40, MUTAGENESIS OF TYR-105; TYR-163; TYR-181; TYR-227; TYR-299; TYR-317; TYR-341; TYR-359; TYR-387 AND TYR-417, INTERACTION WITH FYN AND CSK, FUNCTION.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain and Ileal mucosa.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain and Lymph.
  5. "Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton."
    Brdickova N., Brdicka T., Andera L., Spicka J., Angelisova P., Milgram S.L., Horejsi V.
    FEBS Lett. 507:133-136(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SLC9A3R1.
  6. "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
    Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
    Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  7. Cited for: TISSUE SPECIFICITY.
  8. "Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine kinase in human B-NHL rafts."
    Tauzin S., Ding H., Khatib K., Ahmad I., Burdevet D., van Echten-Deckert G., Lindquist J.A., Schraven B., Din N.U., Borisch B., Hoessli D.C.
    Blood 111:2310-2320(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-317, INTERACTION WITH LYN AND STAT3, SUBCELLULAR LOCATION.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-227; SER-229; TYR-317; TYR-359; TYR-387 AND TYR-417, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.

Entry informationi

Entry nameiPHAG1_HUMAN
AccessioniPrimary (citable) accession number: Q9NWQ8
Secondary accession number(s): A8K1A3
, Q2M1Z9, Q5BKU4, Q9NYK0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: December 20, 2005
Last modified: May 11, 2016
This is version 115 of the entry and version 2 of the sequence. [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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) 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.