Proto-oncogene tyrosine-protein kinase LCK

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Reviewed, UniProtKB/Swiss-Prot Q01621 (LCK_RAT)

Last modified October 13, 2009. Version 77. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended 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

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

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General annotation (Comments)

Function	Tyrosine kinase that plays an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function. Is constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors and plays a key role in T-cell antigen receptor(TCR)-linked signal transduction pathways. 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, and thereby recruits the associated LCK to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosines-based activation motifs (ITAMs) in the cytoplasmic tails of the TCRgamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. In addition, contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, and upon engagement of the CD2 molecule, LCK undergoes hyperphosphorylation and activation. Also plays a role in the IL2 receptor-linked signaling pathway that controls 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 By similarity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Binds to the cytoplasmic domain of cell surface receptors, such as 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 CDC2, 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 By similarity.
Subcellular location	Cytoplasm By similarity. Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Note: Present in lipid rafts in an unactive form By similarity.
Involvement in disease	Proviral insertion upstream of the Lck gene causes overexpression, leading to the development of thymic lymphoma.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

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Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Disease	Proto-oncogene
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Lipoprotein Myristate Palmitate Phosphoprotein
Gene Ontology (GO)
Biological process	aging Inferred from expression pattern. Source: RGD apoptosis Inferred from expression pattern. Source: RGD peptidyl-tyrosine phosphorylation Inferred from direct assay. Source: RGD protein amino acid autophosphorylation Inferred from direct assay. Source: RGD response to hydrogen peroxide Inferred from direct assay. Source: RGD response to zinc ion Inferred from expression pattern. Source: RGD
Cellular component	endocytic vesicle Inferred from direct assay. Source: RGD internal side of plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein complex binding Inferred from direct assay. Source: RGD
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Probable

Chain

2 – 509

508

Proto-oncogene tyrosine-protein kinase LCK

PRO_0000088126

Regions

Domain

61 – 121

SH3

Domain

127 – 224

SH2

Domain

245 – 498

254

Protein kinase

Nucleotide binding

251 – 259

ATP By similarity

Region

2 – 72

Interactions with CD4 and CD8 By similarity

Region

154 – 242

Interaction with PTPRH By similarity

Sites

Active site

364

Proton acceptor By similarity

Binding site

273

ATP By similarity

Amino acid modifications

Modified residue

162

Phosphoserine By similarity

Modified residue

179

N6-acetyllysine By similarity

Modified residue

192

Phosphotyrosine By similarity

Modified residue

213

Phosphoserine By similarity

Modified residue

394

Phosphotyrosine; by autocatalysis By similarity

Modified residue

501

Phosphothreonine By similarity

Modified residue

505

Phosphotyrosine By similarity

Lipidation

N-myristoyl glycine By similarity

Lipidation

S-palmitoyl cysteine By similarity

Lipidation

S-palmitoyl cysteine By similarity

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Sequences

Sequence

Length

Mass (Da)

Tools

Q01621-1 [UniParc].

Last modified March 24, 2009. Version 3.
Checksum: B23F3F4BEF3D6654
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FASTA

509

57,890

        10         20         30         40         50         60 
MGCVCSSNPE DDWMENIDVC ENCHYPIVPL DSKSTLPIRT GSEVRDPLVT YEGSLPPASP 

        70         80         90        100        110        120 
LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA QSLTTGQEGF IPFNFVAKAN 

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

       190        200        210        220        230        240 
YKIRNLDNGG FYISPRITFP GLHDLVRHYT NASDGLCTKL SRPCQTQKPQ KPWWEDEWEV 

       250        260        270        280        290        300 
PRETLKLVER LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHPRL 

       310        320        330        340        350        360 
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLNVNK LLDMAAQIAE GMAFIEEQNY 

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

       430        440        450        460        470        480 
SDVWSFGILL TEIVTHGRIP YPGMTNPEVI QNLEKGYRMV RPDNCPEELY HLMMLCWKER 

       490        500 
PEDRPTFDYL RSVLDDFFTA TEGQYQPQP

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[3]	"Frequent activation of the lck gene by promoter insertion and aberrant splicing in murine leukemia virus-induced rat lymphomas." Shin S., Steffen D.L. Oncogene 8:141-149(1993) [PubMed: 8423992] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18. Strain: Fischer.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	CH473968 Genomic DNA. Translation: EDL80546.1. BC160881 mRNA. Translation: AAI60881.1. Z15029 Genomic DNA. Translation: CAA78748.1.
IPI	IPI00205116.
PIR	S24780. I58370.
RefSeq	NP_001094179.1.
UniGene	Rn.220426
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q01621.
PTM databases
PhosphoSite	Q01621.
Genome annotation databases
Ensembl	ENSRNOT00000012936; ENSRNOP00000012936; ENSRNOG00000009705; Rattus norvegicus. [Genome view]
GeneID	313050.
KEGG	rno:313050.
Organism-specific databases
CTD	313050.
RGD	2994. Lck.
Phylogenomic databases
HOVERGEN	Q01621.
Enzyme and pathway databases
BRENDA	2.7.10.2. 248.
Gene expression databases
ArrayExpress	Q01621.
Genevestigator	Q01621.
GermOnline	ENSRNOG00000009705. Rattus norvegicus.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR000980. SH2. IPR001452. SH3_domain. IPR020473. SH3_region. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 1 hit.
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00109. TYRKINASE.
ProDom	PD000001. Prot_kinase. 1 hit. PD000093. SH2. 1 hit. PD000066. SH3. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
PROSITE	PS00107. 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]
ProtoNet	Search...

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Entry information

Entry name

LCK_RAT

Accession

Primary (citable) accession number: Q01621
Secondary accession number(s): B1H265

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	March 24, 2009
Last modified:	October 13, 2009
This is version 77 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Entry information

Relevant documents