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Q01621

- LCK_RAT

UniProt

Q01621 - LCK_RAT

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Protein

Proto-oncogene tyrosine-protein kinase LCK

Gene

Lck

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

Functioni

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). Interacts with UNC119; this interaction plays a crucial role in activation of LCK (By similarity).By similarity

Catalytic activityi

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

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei273 – 2731ATPPROSITE-ProRule annotation
Active sitei364 – 3641Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi251 – 2599ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. antigen binding Source: RGD
  2. ATP binding Source: UniProtKB-KW
  3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
  4. protein complex binding Source: RGD
  5. protein tyrosine kinase activity Source: RGD

GO - Biological processi

  1. aging Source: RGD
  2. apoptotic process Source: RGD
  3. B cell receptor signaling pathway Source: Ensembl
  4. peptidyl-tyrosine phosphorylation Source: RGD
  5. positive regulation of gamma-delta T cell differentiation Source: Ensembl
  6. positive regulation of gene expression Source: Ensembl
  7. positive regulation of tyrosine phosphorylation of Stat5 protein Source: Ensembl
  8. positive regulation of uterine smooth muscle contraction Source: RGD
  9. protein autophosphorylation Source: RGD
  10. regulation of T cell receptor signaling pathway Source: Ensembl
  11. release of sequestered calcium ion into cytosol Source: Ensembl
  12. response to hydrogen peroxide Source: RGD
  13. response to mechanical stimulus Source: RGD
  14. response to metal ion Source: RGD
  15. response to zinc ion Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_195025. Signaling by SCF-KIT.
REACT_197451. Regulation of KIT signaling.
REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_212418. DAP12 signaling.
REACT_230090. GPVI-mediated activation cascade.
REACT_233097. Generation of second messenger molecules.
REACT_235261. CD28 dependent PI3K/Akt signaling.
REACT_235622. CD28 dependent Vav1 pathway.
REACT_235800. Interleukin-2 signaling.
REACT_244383. CTLA4 inhibitory signaling.
REACT_253779. Phosphorylation of CD3 and TCR zeta chains.
REACT_254949. Downstream TCR signaling.
REACT_257653. PIP3 activates AKT signaling.
REACT_258816. CD28 co-stimulation.
REACT_260327. PD-1 signaling.
REACT_263109. Translocation of ZAP-70 to Immunological synapse.

Names & Taxonomyi

Protein namesi
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 namesi
Name:Lck
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 5

Organism-specific databases

RGDi2994. Lck.

Subcellular locationi

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

GO - Cellular componenti

  1. cell-cell junction Source: Ensembl
  2. endocytic vesicle Source: RGD
  3. extracellular vesicular exosome Source: Ensembl
  4. immunological synapse Source: Ensembl
  5. membrane raft Source: RGD
  6. plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Proviral insertion upstream of the Lck gene causes overexpression, leading to the development of thymic lymphoma.

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 509508Proto-oncogene tyrosine-protein kinase LCKPRO_0000088126Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Lipidationi3 – 31S-palmitoyl cysteineBy similarity
Lipidationi5 – 51S-palmitoyl cysteineBy similarity
Modified residuei102 – 1021PhosphoserineBy similarity
Modified residuei159 – 1591PhosphothreonineBy similarity
Modified residuei162 – 1621PhosphoserineBy similarity
Modified residuei194 – 1941PhosphoserineBy similarity
Modified residuei394 – 3941Phosphotyrosine; by autocatalysisBy similarity
Modified residuei505 – 5051Phosphotyrosine; by CSKBy similarity

Post-translational modificationi

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).By similarity
Myristoylation is required prior to palmitoylation.By similarity
Palmitoylation regulates subcellular location.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ01621.

PTM databases

PhosphoSiteiQ01621.

Expressioni

Gene expression databases

ExpressionAtlasiQ01621. baseline.
GenevestigatoriQ01621.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000012936.

Structurei

3D structure databases

ProteinModelPortaliQ01621.
SMRiQ01621. Positions 7-35, 64-509.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini61 – 12161SH3PROSITE-ProRule annotationAdd
BLAST
Domaini127 – 22498SH2PROSITE-ProRule annotationAdd
BLAST
Domaini245 – 498254Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 7271Interactions with CD4 and CD8By similarityAdd
BLAST
Regioni154 – 24289Interaction with PTPRHBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiQ01621.
KOiK05856.
OMAiDIHESCS.
OrthoDBiEOG7GTT2V.
PhylomeDBiQ01621.
TreeFamiTF351634.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. 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]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q01621-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGCVCSSNPE DDWMENIDVC ENCHYPIVPL DSKSTLPIRT GSEVRDPLVT
60 70 80 90 100
YEGSLPPASP LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA
110 120 130 140 150
QSLTTGQEGF IPFNFVAKAN SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS
160 170 180 190 200
FLIRESESTA GSFSLSVRDF DQNQGEVVKH YKIRNLDNGG FYISPRITFP
210 220 230 240 250
GLHDLVRHYT NASDGLCTKL SRPCQTQKPQ KPWWEDEWEV PRETLKLVER
260 270 280 290 300
LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHPRL
310 320 330 340 350
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLNVNK LLDMAAQIAE
360 370 380 390 400
GMAFIEEQNY IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA
410 420 430 440 450
KFPIKWTAPE AINYGTFTIK SDVWSFGILL TEIVTHGRIP YPGMTNPEVI
460 470 480 490 500
QNLEKGYRMV RPDNCPEELY HLMMLCWKER PEDRPTFDYL RSVLDDFFTA

TEGQYQPQP
Length:509
Mass (Da):57,890
Last modified:March 24, 2009 - v3
Checksum:iB23F3F4BEF3D6654
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH473968 Genomic DNA. Translation: EDL80546.1.
BC160881 mRNA. Translation: AAI60881.1.
Z15029 Genomic DNA. Translation: CAA78748.1.
PIRiI58370. S24780.
RefSeqiNP_001094179.1. NM_001100709.1.
XP_006238995.1. XM_006238933.2.
XP_008762362.1. XM_008764140.1.
UniGeneiRn.22791.

Genome annotation databases

EnsembliENSRNOT00000012936; ENSRNOP00000012936; ENSRNOG00000009705.
GeneIDi313050.
KEGGirno:313050.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH473968 Genomic DNA. Translation: EDL80546.1 .
BC160881 mRNA. Translation: AAI60881.1 .
Z15029 Genomic DNA. Translation: CAA78748.1 .
PIRi I58370. S24780.
RefSeqi NP_001094179.1. NM_001100709.1.
XP_006238995.1. XM_006238933.2.
XP_008762362.1. XM_008764140.1.
UniGenei Rn.22791.

3D structure databases

ProteinModelPortali Q01621.
SMRi Q01621. Positions 7-35, 64-509.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000012936.

PTM databases

PhosphoSitei Q01621.

Proteomic databases

PaxDbi Q01621.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000012936 ; ENSRNOP00000012936 ; ENSRNOG00000009705 .
GeneIDi 313050.
KEGGi rno:313050.

Organism-specific databases

CTDi 3932.
RGDi 2994. Lck.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118938.
HOGENOMi HOG000233858.
HOVERGENi HBG008761.
InParanoidi Q01621.
KOi K05856.
OMAi DIHESCS.
OrthoDBi EOG7GTT2V.
PhylomeDBi Q01621.
TreeFami TF351634.

Enzyme and pathway databases

Reactomei REACT_195025. Signaling by SCF-KIT.
REACT_197451. Regulation of KIT signaling.
REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_212418. DAP12 signaling.
REACT_230090. GPVI-mediated activation cascade.
REACT_233097. Generation of second messenger molecules.
REACT_235261. CD28 dependent PI3K/Akt signaling.
REACT_235622. CD28 dependent Vav1 pathway.
REACT_235800. Interleukin-2 signaling.
REACT_244383. CTLA4 inhibitory signaling.
REACT_253779. Phosphorylation of CD3 and TCR zeta chains.
REACT_254949. Downstream TCR signaling.
REACT_257653. PIP3 activates AKT signaling.
REACT_258816. CD28 co-stimulation.
REACT_260327. PD-1 signaling.
REACT_263109. Translocation of ZAP-70 to Immunological synapse.

Miscellaneous databases

NextBioi 665540.

Gene expression databases

ExpressionAtlasi Q01621. baseline.
Genevestigatori Q01621.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR011009. 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 ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTi SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiLCK_RAT
AccessioniPrimary (citable) accession number: Q01621
Secondary accession number(s): B1H265
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: March 24, 2009
Last modified: November 26, 2014
This is version 125 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3