Q01621 (LCK_RAT) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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.
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 presence of a functional ZAP70 By similarity.
Subcellular location	Cytoplasm By similarity. Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Note: Present in lipid rafts in an inactive form 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 By similarity. Myristoylation is required prior to palmitoylation By similarity. Palmitoylation regulates subcellular location 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.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Disease	Proto-oncogene
Domain	SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell receptor signaling pathway Inferred from electronic annotation. Source: Compara aging Inferred from expression pattern PubMed 15712602. Source: RGD apoptotic process Inferred from expression pattern PubMed 7930951. Source: RGD peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 11034334. Source: RGD positive regulation of gamma-delta T cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from electronic annotation. Source: Compara positive regulation of uterine smooth muscle contraction Inferred from mutant phenotype PubMed 19208792. Source: RGD protein autophosphorylation Inferred from direct assay PubMed 11034334. Source: RGD regulation of T cell receptor signaling pathway Inferred from electronic annotation. Source: Compara release of sequestered calcium ion into cytosol Inferred from electronic annotation. Source: Compara response to hydrogen peroxide Inferred from direct assay PubMed 9325251. Source: RGD response to mechanical stimulus Inferred from mutant phenotype PubMed 19208792. Source: RGD response to zinc ion Inferred from expression pattern PubMed 14652378. Source: RGD
Cellular_component	endocytic vesicle Inferred from direct assay PubMed 9116282. Source: RGD immunological synapse Inferred from electronic annotation. Source: Compara membrane raft Inferred from direct assay PubMed 18178839. Source: RGD plasma membrane Inferred from direct assay PubMed 9116282. Source: RGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW antigen binding Inferred from physical interaction PubMed 18178839. Source: RGD non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein complex binding Inferred from direct assay PubMed 8104794. Source: RGD protein tyrosine kinase activity Inferred from direct assay PubMed 11034334. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 509	509	Proto-oncogene tyrosine-protein kinase LCK		PRO_0000088126
Regions
	Domain	61 – 121	61	SH3
	Domain	127 – 224	98	SH2
	Domain	245 – 498	254	Protein kinase
	Nucleotide binding	251 – 259	9	ATP By similarity
	Region	1 – 72	72	Interactions with CD4 and CD8 By similarity
	Region	154 – 242	89	Interaction with PTPRH By similarity
Sites
	Active site	364	1	Proton acceptor By similarity
	Binding site	273	1	ATP By similarity
Amino acid modifications
	Modified residue	102	1	Phosphoserine By similarity
	Modified residue	159	1	Phosphothreonine By similarity
	Modified residue	162	1	Phosphoserine By similarity
	Modified residue	194	1	Phosphoserine By similarity
	Modified residue	394	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	505	1	Phosphotyrosine; by CSK By similarity
	Lipidation	2	1	N-myristoyl glycine By similarity
	Lipidation	3	1	S-palmitoyl cysteine By similarity
	Lipidation	5	1	S-palmitoyl cysteine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q01621 [UniParc]. Last modified March 24, 2009. Version 3. Checksum: B23F3F4BEF3D6654	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

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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18. Strain: Fischer.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. NM_001100709.1.
UniGene	Rn.22791.
3D structure databases
ProteinModelPortal	Q01621.
SMR	Q01621. Positions 7-35, 64-509.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000012936.
PTM databases
PhosphoSite	Q01621.
Proteomic databases
PaxDb	Q01621.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000012936; ENSRNOP00000012936; ENSRNOG00000009705.
GeneID	313050.
KEGG	rno:313050.
Organism-specific databases
CTD	3932.
RGD	2994. Lck.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00620000087866.
HOGENOM	HOG000233858.
HOVERGEN	HBG008761.
InParanoid	Q01621.
KO	K05856.
OrthoDB	EOG4640BM.
Gene expression databases
ArrayExpress	Q01621.
Genevestigator	Q01621.
GermOnline	ENSRNOG00000009705. Rattus norvegicus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00109. TYRKINASE.
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
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...
Other
NextBio	665540.

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:	April 3, 2013
This is version 111 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program