UniProtKB - Q9NWQ8 (PHAG1_HUMAN)
Protein
Phosphoprotein associated with glycosphingolipid-enriched microdomains 1
Gene
PAG1
Organism
Homo sapiens (Human)
Status
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-UCL
- signaling adaptor activity Source: HGNC-UCL
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- intracellular signal transduction Source: HGNC-UCL
- negative regulation of T cell activation Source: GO_Central
- regulation of T cell activation Source: ProtInc
- signal transduction Source: ProtInc
- T cell receptor signaling pathway Source: Reactome
Keywordsi
Biological process | Adaptive immunity, Immunity |
Enzyme and pathway databases
PathwayCommonsi | Q9NWQ8 |
Reactomei | R-HSA-180292, GAB1 signalosome R-HSA-202427, Phosphorylation of CD3 and TCR zeta chains |
SignaLinki | Q9NWQ8 |
Names & Taxonomyi
Protein namesi | Recommended name: Phosphoprotein associated with glycosphingolipid-enriched microdomains 1Alternative name(s): Csk-binding protein Transmembrane adapter protein PAG Transmembrane phosphoprotein Cbp |
Gene namesi | Name:PAG1 Synonyms:CBP, PAG |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:30043, PAG1 |
MIMi | 605767, gene |
neXtProti | NX_Q9NWQ8 |
VEuPathDBi | HostDB:ENSG00000076641.4 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Single-pass type III membrane protein 2 Publications
Note: Present in lipid rafts.
Plasma Membrane
- plasma membrane Source: HGNC-UCL
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane raft Source: HGNC-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 16 | ExtracellularSequence analysisAdd BLAST | 16 | |
Transmembranei | 17 – 37 | Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 38 – 432 | CytoplasmicSequence analysisAdd BLAST | 395 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 105 | Y → F: No effect on interaction with FYN or CSK. 1 Publication | 1 | |
Mutagenesisi | 163 | Y → F: No effect on interaction with FYN or CSK. 1 Publication | 1 | |
Mutagenesisi | 181 | Y → F: No effect on interaction with FYN or CSK. 1 Publication | 1 | |
Mutagenesisi | 227 | Y → F: No effect on interaction with FYN or CSK. 1 Publication | 1 | |
Mutagenesisi | 299 | Y → F: No effect on interaction with FYN or CSK. 1 Publication | 1 | |
Mutagenesisi | 317 | Y → F: No effect on interaction with FYN. Abolishes interaction with CSK. 1 Publication | 1 | |
Mutagenesisi | 341 | Y → F: No effect on interaction with FYN or CSK. 1 Publication | 1 | |
Mutagenesisi | 359 | Y → F: No effect on interaction with FYN or CSK. 1 Publication | 1 | |
Mutagenesisi | 387 | Y → F: No effect on interaction with FYN or CSK. 1 Publication | 1 | |
Mutagenesisi | 417 | Y → F: No effect on interaction with FYN or CSK. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 55824 |
OpenTargetsi | ENSG00000076641 |
PharmGKBi | PA142671201 |
Miscellaneous databases
Pharosi | Q9NWQ8, Tbio |
Genetic variation databases
BioMutai | PAG1 |
DMDMi | 84029384 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000083338 | 1 – 432 | Phosphoprotein associated with glycosphingolipid-enriched microdomains 1Add BLAST | 432 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 37 | S-palmitoyl cysteine1 Publication | 1 | |
Lipidationi | 40 | S-palmitoyl cysteine1 Publication | 1 | |
Modified residuei | 50 | PhosphoserineBy similarity | 1 | |
Modified residuei | 61 | PhosphoserineBy similarity | 1 | |
Modified residuei | 105 | Phosphotyrosine; by LYNBy similarity | 1 | |
Modified residuei | 163 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 181 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 227 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 229 | PhosphoserineCombined sources | 1 | |
Modified residuei | 317 | Phosphotyrosine; by FYN and LYNCombined sources2 Publications | 1 | |
Modified residuei | 354 | PhosphoserineBy similarity | 1 | |
Modified residuei | 359 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 380 | PhosphoserineBy similarity | 1 | |
Modified residuei | 387 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 417 | PhosphotyrosineCombined sources | 1 |
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, PhosphoproteinProteomic databases
EPDi | Q9NWQ8 |
jPOSTi | Q9NWQ8 |
MassIVEi | Q9NWQ8 |
MaxQBi | Q9NWQ8 |
PaxDbi | Q9NWQ8 |
PeptideAtlasi | Q9NWQ8 |
PRIDEi | Q9NWQ8 |
ProteomicsDBi | 82961 |
TopDownProteomicsi | Q9NWQ8 |
PTM databases
iPTMneti | Q9NWQ8 |
PhosphoSitePlusi | Q9NWQ8 |
SwissPalmi | Q9NWQ8 |
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
Bgeei | ENSG00000076641, Expressed in secondary oocyte and 216 other tissues |
Genevisiblei | Q9NWQ8, HS |
Organism-specific databases
HPAi | ENSG00000076641, Low tissue specificity |
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 PublicationsBinary interactionsi
Hide detailsQ9NWQ8
With | #Exp. | IntAct |
---|---|---|
CSK [P41240] | 4 | EBI-2828115,EBI-1380630 |
FYN [P06241] | 5 | EBI-2828115,EBI-515315 |
LYN [P07948] | 16 | EBI-2828115,EBI-79452 |
RACK1 [P63244] | 2 | EBI-2828115,EBI-296739 |
GO - Molecular functioni
- SH2 domain binding Source: HGNC-UCL
Protein-protein interaction databases
BioGRIDi | 120931, 47 interactors |
CORUMi | Q9NWQ8 |
IntActi | Q9NWQ8, 47 interactors |
MINTi | Q9NWQ8 |
STRINGi | 9606.ENSP00000220597 |
Miscellaneous databases
RNActi | Q9NWQ8, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 317 – 320 | Interaction with CSK1 Publication | 4 | |
Regioni | 430 – 432 | Interaction with SLC9A3R11 Publication | 3 |
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QUCZ, Eukaryota |
GeneTreei | ENSGT00390000002061 |
HOGENOMi | CLU_051189_1_0_1 |
InParanoidi | Q9NWQ8 |
OMAi | QCRDITR |
OrthoDBi | 1104680at2759 |
PhylomeDBi | Q9NWQ8 |
TreeFami | TF336170 |
Family and domain databases
InterProi | View protein in InterPro IPR032748, PAG |
PANTHERi | PTHR16322, PTHR16322, 1 hit |
Pfami | View protein in Pfam PF15347, PAG, 1 hit |
i Sequence
Sequence statusi: Complete.
Q9NWQ8-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 4 | A → V in AAH90931 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 36 | L → P in BAA91321 (PubMed:14702039).Curated | 1 |
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 |
CCDSi | CCDS6227.1 |
RefSeqi | NP_060910.3, NM_018440.3 XP_016869129.1, XM_017013640.1 XP_016869130.1, XM_017013641.1 XP_016869131.1, XM_017013642.1 XP_016869132.1, XM_017013643.1 |
Genome annotation databases
Ensembli | ENST00000220597; ENSP00000220597; ENSG00000076641 |
GeneIDi | 55824 |
KEGGi | hsa:55824 |
UCSCi | uc003ybz.4, human |
Similar proteinsi
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 |
CCDSi | CCDS6227.1 |
RefSeqi | NP_060910.3, NM_018440.3 XP_016869129.1, XM_017013640.1 XP_016869130.1, XM_017013641.1 XP_016869131.1, XM_017013642.1 XP_016869132.1, XM_017013643.1 |
3D structure databases
SMRi | Q9NWQ8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 120931, 47 interactors |
CORUMi | Q9NWQ8 |
IntActi | Q9NWQ8, 47 interactors |
MINTi | Q9NWQ8 |
STRINGi | 9606.ENSP00000220597 |
PTM databases
iPTMneti | Q9NWQ8 |
PhosphoSitePlusi | Q9NWQ8 |
SwissPalmi | Q9NWQ8 |
Genetic variation databases
BioMutai | PAG1 |
DMDMi | 84029384 |
Proteomic databases
EPDi | Q9NWQ8 |
jPOSTi | Q9NWQ8 |
MassIVEi | Q9NWQ8 |
MaxQBi | Q9NWQ8 |
PaxDbi | Q9NWQ8 |
PeptideAtlasi | Q9NWQ8 |
PRIDEi | Q9NWQ8 |
ProteomicsDBi | 82961 |
TopDownProteomicsi | Q9NWQ8 |
Protocols and materials databases
Antibodypediai | 1175, 355 antibodies |
DNASUi | 55824 |
Genome annotation databases
Ensembli | ENST00000220597; ENSP00000220597; ENSG00000076641 |
GeneIDi | 55824 |
KEGGi | hsa:55824 |
UCSCi | uc003ybz.4, human |
Organism-specific databases
CTDi | 55824 |
DisGeNETi | 55824 |
GeneCardsi | PAG1 |
HGNCi | HGNC:30043, PAG1 |
HPAi | ENSG00000076641, Low tissue specificity |
MIMi | 605767, gene |
neXtProti | NX_Q9NWQ8 |
OpenTargetsi | ENSG00000076641 |
PharmGKBi | PA142671201 |
VEuPathDBi | HostDB:ENSG00000076641.4 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QUCZ, Eukaryota |
GeneTreei | ENSGT00390000002061 |
HOGENOMi | CLU_051189_1_0_1 |
InParanoidi | Q9NWQ8 |
OMAi | QCRDITR |
OrthoDBi | 1104680at2759 |
PhylomeDBi | Q9NWQ8 |
TreeFami | TF336170 |
Enzyme and pathway databases
PathwayCommonsi | Q9NWQ8 |
Reactomei | R-HSA-180292, GAB1 signalosome R-HSA-202427, Phosphorylation of CD3 and TCR zeta chains |
SignaLinki | Q9NWQ8 |
Miscellaneous databases
BioGRID-ORCSi | 55824, 15 hits in 876 CRISPR screens |
ChiTaRSi | PAG1, human |
GeneWikii | PAG1 |
GenomeRNAii | 55824 |
Pharosi | Q9NWQ8, Tbio |
PROi | PR:Q9NWQ8 |
RNActi | Q9NWQ8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000076641, Expressed in secondary oocyte and 216 other tissues |
Genevisiblei | Q9NWQ8, HS |
Family and domain databases
InterProi | View protein in InterPro IPR032748, PAG |
PANTHERi | PTHR16322, PTHR16322, 1 hit |
Pfami | View protein in Pfam PF15347, PAG, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PHAG1_HUMAN | |
Accessioni | Q9NWQ8Primary (citable) accession number: Q9NWQ8 Secondary accession number(s): A8K1A3 Q9NYK0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 20, 2005 |
Last sequence update: | December 20, 2005 | |
Last modified: | February 10, 2021 | |
This is version 152 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Direct protein sequencing, Reference proteomeDocuments
- MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM