Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tyrosine-protein kinase-interacting protein

Gene
N/A
Organism
Saimiriine herpesvirus 2 (strain 488) (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.

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Host-virus interaction

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase-interacting protein
Short name:
Tip
OrganismiSaimiriine herpesvirus 2 (strain 488) (SaHV-2) (Herpesvirus saimiri)
Taxonomic identifieri10384 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeRhadinovirus
Virus hostiSaimiri sciureus (Common squirrel monkey) [TaxID: 9521]

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 228CytoplasmicSequence analysisAdd BLAST228
Transmembranei229 – 249HelicalSequence analysisAdd BLAST21
Topological domaini250 – 256ExtracellularSequence analysis7

GO - Cellular componenti

Complete GO annotation...

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
Mutagenesisi114Y → F: Complete loss of STAT activation. 1 Publication1
Mutagenesisi150S → R: Partial decrease of LCK binding. 1 Publication1
Mutagenesisi151F → C: Partial decrease of LCK binding. 1 Publication1
Mutagenesisi151F → H: Partial decrease of LCK binding. 1 Publication1
Mutagenesisi152L → M: Partial decrease of LCK binding. 1 Publication1

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001161921 – 256Tyrosine-protein kinase-interacting proteinAdd BLAST256

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei114Phosphotyrosine; by host LCKBy similarity1
Modified residuei127Phosphotyrosine; by hostBy similarity1

Post-translational modificationi

Phosphorylation on Tyr-114 acts as a docking site for the recruitment of STATs 1 and 3.By similarity

Keywords - PTMi

Phosphoprotein

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
LCKP062397EBI-866709,EBI-1348From a different organism.
LYNP079483EBI-866709,EBI-79452From a different organism.
NXF1Q9UBU96EBI-866709,EBI-398874From a different organism.

Protein-protein interaction databases

IntActiP22575. 4 interactors.
MINTiMINT-1210438.

Structurei

Secondary structure

1256
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni186 – 188Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WA7NMR-B170-191[»]
SMRiP22575.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22575.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni146 – 155CSKH/LBD210
Regioni174 – 183SH3B/LBD110

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.

P22575-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANEGEEIEL TEFPETEKER KDEEKLSSCS EETTNTSSSS GSDHVPVPIE
60 70 80 90 100
VNVIIQNSSR TEDELQNSKE IELTGFQGKL SSCSEETTAP SSSYSSKQAS
110 120 130 140 150
VFIEENGDNE TSTYRPQNVL TNLNSLYTTF EDARAQGKGM VRHKSEDLQS
160 170 180 190 200
FLEKYPPDFR KPKRDLSATW DPGMPTPPLP PRPANLGERQ ASTVRLHVKE
210 220 230 240 250
SNCKQPRERK ANERNIVKDL KRLENKINVI ICLVVVILAV LLLVTVLSIL

HIGMKS
Length:256
Mass (Da):28,662
Last modified:August 1, 1991 - v1
Checksum:iE04BA49D27A59D3A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ410493 Genomic DNA. Translation: CAC84294.1.
M55264 Genomic DNA. Translation: AAA72928.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ410493 Genomic DNA. Translation: CAC84294.1.
M55264 Genomic DNA. Translation: AAA72928.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WA7NMR-B170-191[»]
SMRiP22575.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP22575. 4 interactors.
MINTiMINT-1210438.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP22575.

Family and domain databases

ProtoNetiSearch...

Entry informationi

Entry nameiTIP_SHV2C
AccessioniPrimary (citable) accession number: P22575
Secondary accession number(s): Q778B4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: November 2, 2016
This is version 70 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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.