TIP_SHV48
ID TIP_SHV48 Reviewed; 265 AA.
AC P88825;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 29-SEP-2021, entry version 55.
DE RecName: Full=Tyrosine protein kinase-interacting protein;
DE Short=Tip;
DE AltName: Full=TipC484;
OS Saimiriine herpesvirus 2 (strain 484) (SaHV-2) (Herpesvirus saimiri).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=353282;
OH NCBI_TaxID=9521; Saimiri sciureus (Common squirrel monkey).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C484;
RX PubMed=9032360; DOI=10.1128/jvi.71.3.2252-2263.1997;
RA Fickenscher H., Bokel C., Knappe A., Biesinger B., Meinl E., Fleischer B.,
RA Fleckenstein B., Broker B.M.;
RT "Functional phenotype of transformed human alpha/beta and gamma/delta T
RT cells determined by different subgroup C strains of herpesvirus saimiri.";
RL J. Virol. 71:2252-2263(1997).
RN [2]
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 (By
CC similarity). {ECO:0000250}.
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: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 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation on Tyr-123 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; X99519; CAA67872.1; -; Genomic_DNA.
DR SMR; P88825; -.
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..265
FT /note="Tyrosine protein kinase-interacting protein"
FT /id="PRO_0000116194"
FT TOPO_DOM 1..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..265
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 155..164
FT /note="CSKH/LBD2"
FT /evidence="ECO:0000250"
FT REGION 172..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 183..192
FT /note="SH3B/LBD1"
FT /evidence="ECO:0000250"
FT REGION 225..234
FT /note="SH3 binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 13..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..49
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 123
FT /note="Phosphotyrosine; by host LCK"
FT /evidence="ECO:0000250"
FT MOD_RES 136
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000250"
SQ SEQUENCE 265 AA; 29517 MW; 55605A91601AD6FA CRC64;
MANEGEEIEL TEFPETEKER KDEEKLSSCS EETTDTSSSS SSDHVPAPIE VNVIIQNSSR
TEDELQNSTK FAVANEGKEI ELTGFQGKLS SCSEETTATS SSYSSKQASV CIEENGDNET
STYRPQNVLT NLNSLYTTFE DARAQGKGMV RYKSEDLQSF LEKYPPDYRK PKRDLSATWD
PGMPTPALPP RPANLGERQA STVRLHVKES NCKQPRERKA NERNIVKDLK RLENKVNAII
CLVVVILAVL LLVTVLSILH IGMKS
