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Protein

Tyrosine-protein kinase-interacting protein

Gene
N/A
Organism
Saimiriine herpesvirus 2 (strain 484-77) (SaHV-2) (Herpesvirus saimiri)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Plays a critical role in virus induced T-cell transformation. Binds to T-cell-specific tyrosine kinase LCK SH2 and SH3 domains, thereby activating its kinase activity. Once phosphorylated by host LCK, forms a complex with at least STAT 1 and 3, resulting on the phosphorylation of STAT3 and presumably STAT1, and their migration into the nucleus to induce transcription of target genes. Stimulates host ILF3/NF-AT-90 activity. Association with host NXF1/TAP transduces the signal up-regulating surface expression of adhesion molecules as well as activating NF-kappa-B activity. Acts synergistically with StpC to stimulate NF-kappa-B activity and interleukin-2 gene expression. Activation of NF-kappa-B protects lymphocytes from apoptosis, thereby facilitating viral induced cell transformation. May cause down-regulation of host LCK and cell apoptosis when stably overexpressed ex vivo. Interaction with WDR48 induce degradation of T-cell receptor in a lysosome-dependent fashion, when both proteins are overexpressed. The biological effect of this interaction remains controversial since no T-cell receptor degradation is observed in infected cells.2 Publications

Miscellaneous

In its host, LCK protein is inactivated, preventing T-cell transformation activity.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processHost-virus interaction

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase-interacting protein
Short name:
Tip
OrganismiSaimiriine herpesvirus 2 (strain 484-77) (SaHV-2) (Herpesvirus saimiri)
Taxonomic identifieri10382 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeRhadinovirus
Virus hostiSaimiri sciureus (Common squirrel monkey) [TaxID: 9521]

Subcellular locationi

  • Host cell membrane 1 Publication; Single-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 186CytoplasmicSequence analysisAdd BLAST186
Transmembranei187 – 207HelicalSequence analysisAdd BLAST21
Topological domaini208 – 214ExtracellularSequence analysis7

GO - Cellular componenti

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane

Pathology & Biotechi

Biotechnological usei

Used in cell biology research to transform T-cell lymphocytes. Saimiriine herpesvirus 2 transforms T-cell lymphocytes, including human, to continuous growth in vitro. 2 viral proteins, Tip and StpC, are essential for this function.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi72Y → F: Complete loss of tyrosine phosphorylation; when associated with F-85. Complete loss of STAT activation. 1 Publication1
Mutagenesisi85Y → F: Complete loss of tyrosine phosphorylation; when associated with F-72. 1 Publication1

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001161931 – 214Tyrosine-protein kinase-interacting proteinAdd BLAST214

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei72Phosphotyrosine; by host LCK1 Publication1
Modified residuei85Phosphotyrosine; by host1 Publication1

Post-translational modificationi

Phosphorylation on Tyr-72 acts as a docking site for the recruitment of STATs 1 and 3.

Keywords - PTMi

Phosphoprotein

PTM databases

iPTMnetiP25049.

Interactioni

Subunit structurei

Binds host LCK, human WDR48 and human NXF1/TAP. Forms a complex with activated LCK and STAT1 and STAT3 (By similarity).By similarity

GO - Molecular functioni

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni104 – 113CSKH/LBD210
Regioni132 – 141SH3B/LBD110

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi15 – 72Gly-richAdd BLAST58

Domaini

The SH3B/LBD1 (SH3-binding) region binds LCK SH3 domain and CSKH (C-terminal Src-related kinase homology) region binds the kinase domains of LCK. Both motif are required to activate LCK.

Keywords - Domaini

SH3-binding, Transmembrane, Transmembrane helix

Sequencei

Sequence statusi: Complete.

P25049-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MENQREEIEL TEIPETEKKR TAEEKLLSCS AETAEEKVSL CSEETTDTSS
60 70 80 90 100
SSSSEQTPAP IEVNVNIQTS TYLPQNAATN LNSLYTSFED ARAQGKGLVR
110 120 130 140 150
HNSDDLKSFL EKYPPDYRKP KRDLSESWDP GMPKPTLPPR PANLGASQAS
160 170 180 190 200
TVRRHVREQN FKQLRERKAN EGKIVKDLKR LEYKVNIILC LVVVILAIIL
210
LLTGLSILFI RIKS
Length:214
Mass (Da):24,142
Last modified:May 1, 1992 - v1
Checksum:i9869BDBDA89FA42A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31964 Genomic DNA. Translation: AAA46153.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31964 Genomic DNA. Translation: AAA46153.1.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

PTM databases

iPTMnetiP25049.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

ProtoNetiSearch...

Entry informationi

Entry nameiTIP_SHV24
AccessioniPrimary (citable) accession number: P25049
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: May 10, 2017
This is version 56 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.