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Q95KR7 (LCK_SAISC) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Proto-oncogene tyrosine-protein kinase LCK

EC=2.7.10.2
Alternative name(s):
Lymphocyte cell-specific protein-tyrosine kinase
p56-LCK
Gene names
Name:LCK
OrganismSaimiri sciureus (Common squirrel monkey)
Taxonomic identifier9521 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniPlatyrrhiniCebidaeSaimiriinaeSaimiri

Protein attributes

Sequence length509 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP By similarity.

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulation

The relative activities of the inhibitory tyrosine-protein kinase CSK and the activating tyrosine-protein phosphatase PTPRC/CD45 determine the level of LCK activity. These interactions allow rapid and efficient activation of LCK in response to TCR stimulation By similarity. Ref.1

Subunit structure

Binds to the cytoplasmic domain of cell surface receptors, such as AXL, CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB and to other protein kinases including CDK1, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70 through its SH2 domain. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH. Interacts with RUNX3. Forms a signaling complex with EPHA1, PTK2B AND PI3-KINASE; upon activation by EFNA1 which may regulate T-lymphocytes migration. Associates with ZAP70 and RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit phosphorylations in the presence of functional ZAP70 By similarity. Interacts with Saimiriine herpesvirus 2 TIP. Ref.1

Subcellular location

Cytoplasm By similarity. Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Note: Present in lipid rafts in an inactive form By similarity.

Tissue specificity

Expressed specifically in lymphoid cells.

Developmental stage

Levels remain relatively constant throughout T-cell ontogeny.

Domain

The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation By similarity.

Post-translational modification

Autophosphorylated on Tyr-394, increasing enzymatic activity, this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK, decreasing activity. Dephosphorylated by PTPRC/CD45. Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cells differentiation By similarity.

Myristoylation is required prior to palmitoylation By similarity.

Palmitoylation regulates subcellular location By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Caution

LCK seems to be active in all vertebrates, except in squirrel monkey T-cells, in which it is inactivated. The reason seems to be that squirrel monkeys are the natural host for Saimiriine herpesvirus 2, which is able to efficiently transform T-cells through a mechanism involving viral Tip/ host LCK interaction. Its inactivation may a mechanism that specifically counteracts the transformation effects of viral Tip.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
   DiseaseProto-oncogene
   DomainSH2 domain
SH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMLipoprotein
Myristate
Palmitate
Phosphoprotein
Gene Ontology (GO)
   Biological_processT cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

cellular zinc ion homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

dephosphorylation

Inferred from sequence or structural similarity. Source: GOC

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: GOC

positive regulation of T cell activation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

response to drug

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentmembrane raft

Inferred from sequence or structural similarity. Source: UniProtKB

pericentriolar material

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

SH2 domain binding

Inferred from sequence or structural similarity. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein serine/threonine phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 509508Proto-oncogene tyrosine-protein kinase LCK
PRO_0000088127

Regions

Domain61 – 12161SH3
Domain127 – 22498SH2
Domain245 – 498254Protein kinase
Nucleotide binding251 – 2599ATP By similarity
Region2 – 7271Interactions with CD4 and CD8 By similarity
Region154 – 24289Interaction with PTPRH By similarity

Sites

Active site3641Proton acceptor By similarity
Binding site2731ATP By similarity

Amino acid modifications

Modified residue1021Phosphoserine By similarity
Modified residue1591Phosphothreonine By similarity
Modified residue1621Phosphoserine By similarity
Modified residue1941Phosphoserine By similarity
Modified residue3941Phosphotyrosine; by autocatalysis By similarity
Modified residue5051Phosphotyrosine; by CSK By similarity
Lipidation21N-myristoyl glycine By similarity
Lipidation31S-palmitoyl cysteine By similarity
Lipidation51S-palmitoyl cysteine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q95KR7 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 5088C6407D109519

FASTA50958,253
        10         20         30         40         50         60 
MGCGCSSHLE DDWMENIDVC ENCHYPIVPL DGKATLLFRN GSEVRDPLVR YEGSNPPASP 

        70         80         90        100        110        120 
LQDNLVIALH SYEPSHDGDL GFEKGEHLRI LEQNGEWWKA QSLTTGQEGF VPFNFVAKAN 

       130        140        150        160        170        180 
SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS FLIRESESTA GSFSLSVRDF DQNQGEVVKH 

       190        200        210        220        230        240 
YKIRNLDNGG FYISPRITFS GLHELVRHYT NASDGLCTRL SRPCQTQKPQ KPWWEDEWEV 

       250        260        270        280        290        300 
PRETLKLVER LGAGQFGEVW MGYYNEHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHKRL 

       310        320        330        340        350        360 
VRLYAVVTEE PIYIITEYME NGSLVDFLKT PSGIKLTINK LLDMAAQIVE GMAFLEERNY 

       370        380        390        400        410        420 
IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA KFPIKWTAPE AINYGTFTIK 

       430        440        450        460        470        480 
SDVWSFGILM TEIVTHGRIP YPGMTNPEVI QNLERGYRMP RPDNCPEELY KLMMQCWRER 

       490        500 
PDDRPTFDYL RSVLEDFFTA TEGQYQPQP 

« Hide

References

[1]"Downregulation of p56Lck tyrosine kinase activity in T cells of squirrel monkeys (Saimiri sciureus) correlates with the non-transforming and apathogenic properties of herpesvirus saimiri in its natural host."
Greve T., Tamgueney G., Fleischer B., Fickenscher H., Broeker B.M.
J. Virol. 75:9252-9261(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME REGULATION, INTERACTION WITH SAIMIRIINE HERPESVIRUS 2 TIP.
Tissue: T-cell.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ277921 mRNA. Translation: CAC38871.1.

3D structure databases

ProteinModelPortalQ95KR7.
SMRQ95KR7. Positions 7-35, 65-509.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG008761.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameLCK_SAISC
AccessionPrimary (citable) accession number: Q95KR7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 90 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families