Q9NWQ8 (PAG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphoprotein associated with glycosphingolipid-enriched microdomains 1

Alternative name(s):
Csk-binding protein
Transmembrane adapter protein PAG
Transmembrane phosphoprotein Cbp

Gene names

Name:	PAG1
Synonyms:	CBP, PAG

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	432 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1
Subunit structure	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. Ref.1 Ref.5 Ref.9
Subcellular location	Cell membrane; Single-pass type III membrane protein. Note: Present in lipid rafts. Ref.1 Ref.9
Tissue specificity	Ubiquitously expressed. Present in germinal center B-cells, plasma cells, T-cells, monocytes and platelets (at protein level). Ref.1 Ref.6
Post-translational modification	Palmitoylated. Ref.1 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. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Cell membrane Membrane
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	T cell receptor signaling pathway Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome intracellular signal transduction Inferred from direct assay Ref.1. Source: HGNC
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intracellular Inferred from direct assay Ref.1. Source: GOC membrane raft Inferred from direct assay Ref.1. Source: HGNC plasma membrane Inferred from direct assay Ref.1. Source: HGNC
Molecular function	SH2 domain binding Inferred from direct assay Ref.1. Source: HGNC SH3/SH2 adaptor activity Non-traceable author statement Ref.1. Source: HGNC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 432	432	Phosphoprotein associated with glycosphingolipid-enriched microdomains 1		PRO_0000083338
Regions
	Topological domain	1 – 16	16	Extracellular Potential
	Transmembrane	17 – 37	21	Helical; Signal-anchor for type III membrane protein; Potential
	Topological domain	38 – 432	395	Cytoplasmic Potential
	Region	317 – 320	4	Interaction with CSK
	Region	430 – 432	3	Interaction with SLC9A3R1
Amino acid modifications
	Modified residue	163	1	Phosphotyrosine Ref.11
	Modified residue	181	1	Phosphotyrosine By similarity
	Modified residue	227	1	Phosphotyrosine Ref.10 Ref.11
	Modified residue	317	1	Phosphotyrosine; by FYN and LYN Ref.1 Ref.7 Ref.9 Ref.11
	Modified residue	341	1	Phosphotyrosine Ref.7 Ref.10
	Modified residue	359	1	Phosphotyrosine Ref.7 Ref.11
	Modified residue	380	1	Phosphoserine By similarity
	Modified residue	387	1	Phosphotyrosine Ref.11
	Modified residue	417	1	Phosphotyrosine Ref.7 Ref.8 Ref.11
	Lipidation	37	1	S-palmitoyl cysteine Probable
	Lipidation	40	1	S-palmitoyl cysteine Probable
Experimental info
	Mutagenesis	105	1	Y → F: No effect on interaction with FYN or CSK. Ref.1
	Mutagenesis	163	1	Y → F: No effect on interaction with FYN or CSK. Ref.1
	Mutagenesis	181	1	Y → F: No effect on interaction with FYN or CSK. Ref.1
	Mutagenesis	227	1	Y → F: No effect on interaction with FYN or CSK. Ref.1
	Mutagenesis	299	1	Y → F: No effect on interaction with FYN or CSK. Ref.1
	Mutagenesis	317	1	Y → F: No effect on interaction with FYN. Abolishes interaction with CSK. Ref.1
	Mutagenesis	341	1	Y → F: No effect on interaction with FYN or CSK. Ref.1
	Mutagenesis	359	1	Y → F: No effect on interaction with FYN or CSK. Ref.1
	Mutagenesis	387	1	Y → F: No effect on interaction with FYN or CSK. Ref.1
	Mutagenesis	417	1	Y → F: No effect on interaction with FYN or CSK. Ref.1
	Sequence conflict	4	1	A → V in AAH90931. Ref.4
	Sequence conflict	36	1	L → P in BAA91321. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9NWQ8 [UniParc]. Last modified December 20, 2005. Version 2. Checksum: E86272A0B7E3328C	FASTA	432	46,981
	10 20 30 40 50 60 MGPAGSLLGS GQMQITLWGS LAAVAIFFVI TFLIFLCSSC DREKKPRQHS GDHENLMNVP 70 80 90 100 110 120 SDKEMFSRSV TSLATDAPAS SEQNGALTNG DILSEDSTLT CMQHYEEVQT SASDLLDSQD 130 140 150 160 170 180 STGKPKCHQS RELPRIPPES AVDTMLTARS VDGDQGLGME GPYEVLKDSS SQENMVEDCL 190 200 210 220 230 240 YETVKEIKEV AAAAHLEKGH SGKAKSTSAS KELPGPQTEG KAEFAEYASV DRNKKCRQSV 250 260 270 280 290 300 NVESILGNSC DPEEEAPPPV PVKLLDENEN LQEKEGGEAE ESATDTTSET NKRFSSLSYK 310 320 330 340 350 360 SREEDPTLTE EEISAMYSSV NKPGQLVNKS GQSLTVPEST YTSIQGDPQR SPSSCNDLYA 370 380 390 400 410 420 TVKDFEKTPN STLPPAGRPS EEPEPDYEAI QTLNREEEKA TLGTNGHHGL VPKENDYESI 430 SDLQQGRDIT RL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 10790433] [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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Ileal mucosa.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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: 15489334] [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: 11684085] [Abstract] Cited for: INTERACTION WITH SLC9A3R1.
[6]	"Transmembrane adaptor molecules: a new category of lymphoid-cell markers." Tedoldi S., Paterson J.C., Hansmann M.-L., Natkunam Y., Rudiger T., Angelisova P., Du M.Q., Roberton H., Roncador G., Sanchez L., Pozzobon M., Masir N., Barry R., Pileri S., Mason D.Y., Marafioti T., Horejsi V. Blood 107:213-221(2006) [PubMed: 16160011] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-317; TYR-341; TYR-359 AND TYR-417, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[8]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-417, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[9]	"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: 18070987] [Abstract] Cited for: PHOSPHORYLATION AT TYR-317, INTERACTION WITH LYN AND STAT3, SUBCELLULAR LOCATION.
[10]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-227 AND TYR-341, MASS SPECTROMETRY.
[11]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-163; TYR-227; TYR-317; TYR-359; TYR-387 AND TYR-417, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00020464.
RefSeq	NP_060910.3. NM_018440.3.
UniGene	Hs.266175.
3D structure databases
ProteinModelPortal	Q9NWQ8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NWQ8. 1 interaction.
MINT	MINT-220429.
STRING	Q9NWQ8.
PTM databases
PhosphoSite	Q9NWQ8.
Polymorphism databases
DMDM	84029384.
Proteomic databases
PeptideAtlas	Q9NWQ8.
PRIDE	Q9NWQ8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000220597; ENSP00000220597; ENSG00000076641.
GeneID	55824.
KEGG	hsa:55824.
UCSC	uc003ybz.1. human.
Organism-specific databases
CTD	55824.
GeneCards	GC08M081880.
H-InvDB	HIX0007615.
HGNC	HGNC:30043. PAG1.
HPA	HPA001632.
MIM	605767. gene.
neXtProt	NX_Q9NWQ8.
PharmGKB	PA142671201.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11418.
GeneTree	ENSGT00390000002061.
HOGENOM	HBG279366.
HOVERGEN	HBG055052.
InParanoid	Q9NWQ8.
OMA	VNKPGQS.
OrthoDB	EOG4CRM0T.
PhylomeDB	Q9NWQ8.
Enzyme and pathway databases
Pathway_Interaction_DB	bcr_5pathway. BCR signaling pathway. tcrpathway. TCR signaling in naive CD4+ T cells. cd8tcrpathway. TCR signaling in naive CD8+ T cells.
Reactome	REACT_111102. Signal Transduction. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9NWQ8.
Bgee	Q9NWQ8.
CleanEx	HS_PAG1.
Genevestigator	Q9NWQ8.
GermOnline	ENSG00000076641. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
NextBio	61018.
SOURCE	Search...

Entry information

Entry name

PAG1_HUMAN

Accession

Primary (citable) accession number: Q9NWQ8
Secondary accession number(s): A8K1A3 , Q2M1Z9, Q5BKU4, Q9NYK0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	December 20, 2005
Last modified:	January 25, 2012
This is version 75 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.