TIP_SHV24
ID TIP_SHV24 Reviewed; 214 AA.
AC P25049;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 23-FEB-2022, entry version 66.
DE RecName: Full=Tyrosine-protein kinase-interacting protein;
DE Short=Tip;
OS Saimiriine herpesvirus 2 (strain 484-77) (SaHV-2) (Herpesvirus saimiri).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=10382;
OH NCBI_TaxID=9521; Saimiri sciureus (Common squirrel monkey).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2161952; DOI=10.1128/jvi.64.7.3509-3515.1990;
RA Geck P., Whitaker S.A., Medveczky M.M., Medveczky P.G.;
RT "Expression of collagenlike sequences by a tumor virus, herpesvirus
RT saimiri.";
RL J. Virol. 64:3509-3515(1990).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=7769710; DOI=10.1128/jvi.69.7.4495-4499.1995;
RA Lund T., Medveczky M.M., Geck P., Medveczky P.G.;
RT "A herpesvirus saimiri protein required for interleukin-2 independence is
RT associated with membranes of transformed T cells.";
RL J. Virol. 69:4495-4499(1995).
RN [3]
RP INTERACTION WITH HOST LCK.
RX PubMed=11040125; DOI=10.1006/viro.2000.0570;
RA Hartley D.A., Amdjadi K., Hurley T.R., Lund T.C., Medveczky P.G.,
RA Sefton B.M.;
RT "Activation of the Lck tyrosine protein kinase by the Herpesvirus saimiri
RT tip protein involves two binding interactions.";
RL Virology 276:339-348(2000).
RN [4]
RP MUTAGENESIS OF TYR-72 AND TYR-85, AND PHOSPHORYLATION AT TYR-72 AND TYR-85.
RX PubMed=10747948; DOI=10.1074/jbc.m000709200;
RA Hartley D.A., Cooper G.M.;
RT "Direct binding and activation of STAT transcription factors by the
RT herpesvirus saimiri protein tip.";
RL J. Biol. Chem. 275:16925-16932(2000).
RN [5]
RP INTERACTION WITH HOST LCK.
RX PubMed=11533187; DOI=10.1128/jvi.75.19.9252-9261.2001;
RA Greve T., Tamgueney G., Fleischer B., Fickenscher H., Broeker B.M.;
RT "Downregulation of p56Lck tyrosine kinase activity in T cells of squirrel
RT monkeys (Saimiri sciureus) correlates with the non-transforming and
RT apathogenic properties of herpesvirus saimiri in its natural host.";
RL J. Virol. 75:9252-9261(2001).
RN [6]
RP FUNCTION.
RX PubMed=11145913; DOI=10.1006/viro.2000.0714;
RA Merlo J.J., Tsygankov A.Y.;
RT "Herpesvirus saimiri oncoproteins Tip and StpC synergistically stimulate
RT NF-kappaB activity and interleukin-2 gene expression.";
RL Virology 279:325-338(2001).
RN [7]
RP FUNCTION IN APOPTOSIS.
RX PubMed=15016553; DOI=10.1016/j.virol.2003.11.032;
RA Hasham M.G., Tsygankov A.Y.;
RT "Tip, an Lck-interacting protein of Herpesvirus saimiri, causes Fas- and
RT Lck-dependent apoptosis of T lymphocytes.";
RL Virology 320:313-329(2004).
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 {ECO:0000269|PubMed:11145913, ECO:0000269|PubMed:15016553}.
CC -!- SUBUNIT: Binds host LCK, human WDR48 and human NXF1/TAP. Forms a
CC complex with activated LCK and STAT1 and STAT3 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000269|PubMed:7769710};
CC Single-pass membrane protein {ECO:0000269|PubMed:7769710}.
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-72 acts as a docking site for the
CC recruitment of STATs 1 and 3.
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; M31964; AAA46153.1; -; Genomic_DNA.
DR SMR; P25049; -.
DR iPTMnet; P25049; -.
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 Host cell membrane; Host membrane; Host-virus interaction; Membrane;
KW Oncogene; Phosphoprotein; SH3-binding; Transmembrane; Transmembrane helix.
FT CHAIN 1..214
FT /note="Tyrosine-protein kinase-interacting protein"
FT /id="PRO_0000116193"
FT TOPO_DOM 1..186
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 208..214
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 104..113
FT /note="CSKH/LBD2"
FT REGION 117..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 132..141
FT /note="SH3B/LBD1"
FT COMPBIAS 1..42
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..59
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 72
FT /note="Phosphotyrosine; by host LCK"
FT /evidence="ECO:0000269|PubMed:10747948"
FT MOD_RES 85
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000269|PubMed:10747948"
FT MUTAGEN 72
FT /note="Y->F: Complete loss of tyrosine phosphorylation;
FT when associated with F-85. Complete loss of STAT
FT activation."
FT /evidence="ECO:0000269|PubMed:10747948"
FT MUTAGEN 85
FT /note="Y->F: Complete loss of tyrosine phosphorylation;
FT when associated with F-72."
FT /evidence="ECO:0000269|PubMed:10747948"
SQ SEQUENCE 214 AA; 24142 MW; 9869BDBDA89FA42A CRC64;
MENQREEIEL TEIPETEKKR TAEEKLLSCS AETAEEKVSL CSEETTDTSS SSSSEQTPAP
IEVNVNIQTS TYLPQNAATN LNSLYTSFED ARAQGKGLVR HNSDDLKSFL EKYPPDYRKP
KRDLSESWDP GMPKPTLPPR PANLGASQAS TVRRHVREQN FKQLRERKAN EGKIVKDLKR
LEYKVNIILC LVVVILAIIL LLTGLSILFI RIKS
