TIP_SHV2C
ID TIP_SHV2C Reviewed; 256 AA.
AC P22575; Q778B4;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 29-SEP-2021, entry version 88.
DE RecName: Full=Tyrosine-protein kinase-interacting protein;
DE Short=Tip;
OS Saimiriine herpesvirus 2 (strain 488) (SaHV-2) (Herpesvirus saimiri).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=10384;
OH NCBI_TaxID=9521; Saimiri sciureus (Common squirrel monkey).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14554077; DOI=10.1016/s0042-6822(03)00449-5;
RA Ensser A., Thurau M., Wittmann S., Fickenscher H.;
RT "The genome of herpesvirus saimiri C488 which is capable of transforming
RT human T cells.";
RL Virology 314:471-487(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2161148; DOI=10.1016/0042-6822(90)90020-r;
RA Biesinger B., Trimble J.J., Desrosiers R.C., Fleckenstein B.;
RT "The divergence between two oncogenic Herpesvirus saimiri strains in a
RT genomic region related to the transforming phenotype.";
RL Virology 176:505-514(1990).
RN [3]
RP INTERACTION WITH HOST LCK.
RX PubMed=7876245; DOI=10.1074/jbc.270.9.4729;
RA Biesinger B., Tsygankov A.Y., Fickenscher H., Emmrich F., Fleckenstein B.,
RA Bolen J.B., Broker B.M.;
RT "The product of the Herpesvirus saimiri open reading frame 1 (tip)
RT interacts with T cell-specific kinase p56lck in transformed cells.";
RL J. Biol. Chem. 270:4729-4734(1995).
RN [4]
RP INTERACTION WITH HOST LCK, AND MUTAGENESIS OF SER-150; PHE-151 AND LEU-152.
RX PubMed=7544793; DOI=10.1074/jbc.270.35.20660;
RA Jung J.U., Lang S.M., Friedrich U., Jun T., Roberts T.M., Desrosiers R.C.,
RA Biesinger B.;
RT "Identification of Lck-binding elements in tip of herpesvirus saimiri.";
RL J. Biol. Chem. 270:20660-20667(1995).
RN [5]
RP INTERACTION WITH HOST NXF1/TAP.
RX PubMed=9175835; DOI=10.1016/s1074-7613(00)80345-3;
RA Yoon D.-W., Lee H., Seol W., DeMaria M., Rosenzweig M., Jung J.U.;
RT "Tap: a novel cellular protein that interacts with tip of herpesvirus
RT saimiri and induces lymphocyte aggregation.";
RL Immunity 6:571-582(1997).
RN [6]
RP MUTAGENESIS OF TYR-114.
RX PubMed=12083826; DOI=10.1006/viro.2002.1419;
RA Kjellen P., Amdjadi K., Lund T.C., Medveczky P.G., Sefton B.M.;
RT "The herpesvirus saimiri tip484 and tip488 proteins both stimulate lck
RT tyrosine protein kinase activity in vivo and in vitro.";
RL Virology 297:281-288(2002).
RN [7]
RP INTERACTION WITH HOST WDR48.
RX PubMed=12196293; DOI=10.1016/s1074-7613(02)00368-0;
RA Park J., Lee B.-S., Choi J.-K., Means R.E., Choe J., Jung J.U.;
RT "Herpesviral protein targets a cellular WD repeat endosomal protein to
RT downregulate T lymphocyte receptor expression.";
RL Immunity 17:221-233(2002).
RN [8]
RP REVIEW.
RX PubMed=15389624; DOI=10.1002/jcp.20225;
RA Tsygankov A.Y.;
RT "Cell transformation by Herpesvirus saimiri.";
RL J. Cell. Physiol. 203:305-318(2005).
CC -!- FUNCTION: Plays a critical role in virus induced T-cell transformation.
CC Binds to T-cell-specific tyrosine kinase LCK SH2 and SH3 domains,
CC thereby activating its kinase activity. Once phosphorylated by host
CC LCK, forms a complex with at least STAT 1 and 3, resulting on the
CC phosphorylation of STAT3 and presumably STAT1, and their migration into
CC the nucleus to induce transcription of target genes. Stimulates host
CC ILF3/NF-AT-90 activity. Association with host NXF1/TAP transduces the
CC signal up-regulating surface expression of adhesion molecules as well
CC as activating NF-kappa-B activity. Acts synergistically with StpC to
CC stimulate NF-kappa-B activity and interleukin-2 gene expression.
CC Activation of NF-kappa-B protects lymphocytes from apoptosis, thereby
CC facilitating viral induced cell transformation. May cause down-
CC regulation of host LCK and cell apoptosis when stably overexpressed ex
CC vivo. Interaction with WDR48 induce degradation of T-cell receptor in a
CC lysosome-dependent fashion, when both proteins are overexpressed. The
CC biological effect of this interaction remains controversial since no T-
CC cell receptor degradation is observed in infected cells.
CC -!- SUBUNIT: Binds host LCK, human WDR48 and human NXF1/TAP. Forms a
CC complex with activated LCK and STAT1 and STAT3.
CC -!- INTERACTION:
CC P22575; P06239: LCK; Xeno; NbExp=7; IntAct=EBI-866709, EBI-1348;
CC P22575; P07948: LYN; Xeno; NbExp=3; IntAct=EBI-866709, EBI-79452;
CC P22575; Q9UBU9: NXF1; Xeno; NbExp=6; IntAct=EBI-866709, EBI-398874;
CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000250}; Single-pass
CC membrane protein {ECO:0000250}.
CC -!- DOMAIN: The SH3B/LBD1 (SH3-binding) region binds LCK SH3 domain and
CC CSKH (C-terminal Src-related kinase homology) region binds the kinase
CC domains of LCK. Both motif are required to activate LCK.
CC -!- PTM: Phosphorylation on Tyr-114 acts as a docking site for the
CC recruitment of STATs 1 and 3. {ECO:0000250}.
CC -!- BIOTECHNOLOGY: Used in cell biology research to transform T-cell
CC lymphocytes. Saimiriine herpesvirus 2 transforms T-cell lymphocytes,
CC including human, to continuous growth in vitro. 2 viral proteins, Tip
CC and StpC, are essential for this function.
CC -!- MISCELLANEOUS: In its host, LCK protein is inactivated, preventing T-
CC cell transformation activity.
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DR EMBL; AJ410493; CAC84294.1; -; Genomic_DNA.
DR EMBL; M55264; AAA72928.1; -; Genomic_DNA.
DR PDB; 1WA7; NMR; -; B=170-191.
DR PDBsum; 1WA7; -.
DR BMRB; P22575; -.
DR SMR; P22575; -.
DR IntAct; P22575; 4.
DR MINT; P22575; -.
DR EvolutionaryTrace; P22575; -.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Host cell membrane; Host membrane; Host-virus interaction;
KW Membrane; Oncogene; Phosphoprotein; SH3-binding; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..256
FT /note="Tyrosine-protein kinase-interacting protein"
FT /id="PRO_0000116192"
FT TOPO_DOM 1..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..256
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 146..155
FT /note="CSKH/LBD2"
FT REGION 162..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 174..183
FT /note="SH3B/LBD1"
FT COMPBIAS 13..29
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 114
FT /note="Phosphotyrosine; by host LCK"
FT /evidence="ECO:0000250"
FT MOD_RES 127
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000250"
FT MUTAGEN 114
FT /note="Y->F: Complete loss of STAT activation."
FT /evidence="ECO:0000269|PubMed:12083826"
FT MUTAGEN 150
FT /note="S->R: Partial decrease of LCK binding."
FT /evidence="ECO:0000269|PubMed:7544793"
FT MUTAGEN 151
FT /note="F->C: Partial decrease of LCK binding."
FT /evidence="ECO:0000269|PubMed:7544793"
FT MUTAGEN 151
FT /note="F->H: Partial decrease of LCK binding."
FT /evidence="ECO:0000269|PubMed:7544793"
FT MUTAGEN 152
FT /note="L->M: Partial decrease of LCK binding."
FT /evidence="ECO:0000269|PubMed:7544793"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:1WA7"
SQ SEQUENCE 256 AA; 28662 MW; E04BA49D27A59D3A CRC64;
MANEGEEIEL TEFPETEKER KDEEKLSSCS EETTNTSSSS GSDHVPVPIE VNVIIQNSSR
TEDELQNSKE IELTGFQGKL SSCSEETTAP SSSYSSKQAS VFIEENGDNE TSTYRPQNVL
TNLNSLYTTF EDARAQGKGM VRHKSEDLQS FLEKYPPDFR KPKRDLSATW DPGMPTPPLP
PRPANLGERQ ASTVRLHVKE SNCKQPRERK ANERNIVKDL KRLENKINVI ICLVVVILAV
LLLVTVLSIL HIGMKS
