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Protein

Tyrosine-protein kinase Lck

Gene

LCK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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.7 Publications

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei273ATPPROSITE-ProRule annotation1
Active sitei364Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi251 – 259ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATPase binding Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • CD4 receptor binding Source: UniProtKB
  • CD8 receptor binding Source: UniProtKB
  • glycoprotein binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • kinase activity Source: Reactome
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • protein C-terminus binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • protein serine/threonine phosphatase activity Source: UniProtKB
  • protein tyrosine kinase activity Source: UniProtKB
  • SH2 domain binding Source: UniProtKB

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • B cell receptor signaling pathway Source: GO_Central
  • cellular zinc ion homeostasis Source: UniProtKB
  • hemopoiesis Source: UniProtKB
  • innate immune response Source: GO_Central
  • leukocyte migration Source: Reactome
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • phosphatidylinositol-mediated signaling Source: Reactome
  • platelet activation Source: Reactome
  • positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  • positive regulation of T cell activation Source: UniProtKB
  • positive regulation of T cell receptor signaling pathway Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of cell proliferation Source: GO_Central
  • regulation of defense response to virus by virus Source: Reactome
  • regulation of lymphocyte activation Source: UniProtKB
  • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
  • release of sequestered calcium ion into cytosol Source: UniProtKB
  • response to drug Source: UniProtKB
  • T cell costimulation Source: Reactome
  • T cell differentiation Source: UniProtKB
  • T cell receptor signaling pathway Source: Reactome
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Host-virus interaction

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00023-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-114604. GPVI-mediated activation cascade.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1433559. Regulation of KIT signaling.
R-HSA-164944. Nef and signal transduction.
R-HSA-167590. Nef Mediated CD4 Down-regulation.
R-HSA-202424. Downstream TCR signaling.
R-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
R-HSA-202430. Translocation of ZAP-70 to Immunological synapse.
R-HSA-202433. Generation of second messenger molecules.
R-HSA-210990. PECAM1 interactions.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-2424491. DAP12 signaling.
R-HSA-389356. CD28 co-stimulation.
R-HSA-389357. CD28 dependent PI3K/Akt signaling.
R-HSA-389359. CD28 dependent Vav1 pathway.
R-HSA-389513. CTLA4 inhibitory signaling.
R-HSA-389948. PD-1 signaling.
R-HSA-451927. Interleukin-2 signaling.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SignaLinkiP06239.
SIGNORiP06239.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase Lck (EC:2.7.10.2)
Alternative name(s):
Leukocyte C-terminal Src kinase
Short name:
LSK
Lymphocyte cell-specific protein-tyrosine kinase
Protein YT16
Proto-oncogene Lck
T cell-specific protein-tyrosine kinase
p56-LCK
Gene namesi
Name:LCK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6524. LCK.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • immunological synapse Source: MGI
  • membrane raft Source: UniProtKB
  • pericentriolar material Source: UniProtKB
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.

Immunodeficiency 22 (IMD22)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary immunodeficiency characterized by T-cell dysfunction. Affected individuals present with lymphopenia, recurrent infections, severe diarrhea, and failure to thrive.
See also OMIM:615758
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071291341L → P in IMD22. 1 PublicationCorresponds to variant rs587777335dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi59S → E: Allows interaction with SQSTM1. 1 Publication1
Mutagenesisi154R → K: No effect on interaction with SQSTM1. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi3932.
MalaCardsiLCK.
MIMi615758. phenotype.
OpenTargetsiENSG00000182866.
Orphaneti280142. Severe combined immunodeficiency due to LCK deficiency.
PharmGKBiPA30307.

Chemistry databases

ChEMBLiCHEMBL258.
DrugBankiDB01254. Dasatinib.
DB09079. Nintedanib.
DB08901. Ponatinib.
GuidetoPHARMACOLOGYi2053.

Polymorphism and mutation databases

BioMutaiLCK.
DMDMi125474.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000881242 – 509Tyrosine-protein kinase LckAdd BLAST508

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi3S-palmitoyl cysteineBy similarity1
Lipidationi5S-palmitoyl cysteineBy similarity1
Modified residuei102PhosphoserineCombined sources1
Modified residuei159PhosphothreonineCombined sources1
Modified residuei162PhosphoserineCombined sources1
Modified residuei192PhosphotyrosineBy similarity1
Modified residuei194PhosphoserineCombined sources1
Modified residuei394Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei505Phosphotyrosine; by CSKCombined sources3 Publications1

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-cell receptor signaling.4 Publications
Myristoylation is required prior to palmitoylation.By similarity
Palmitoylation regulates subcellular location.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein

Proteomic databases

EPDiP06239.
MaxQBiP06239.
PaxDbiP06239.
PeptideAtlasiP06239.
PRIDEiP06239.

PTM databases

iPTMnetiP06239.
PhosphoSitePlusiP06239.
SwissPalmiP06239.

Expressioni

Tissue specificityi

Expressed specifically in lymphoid cells.

Gene expression databases

BgeeiENSG00000182866.
CleanExiHS_LCK.
ExpressionAtlasiP06239. baseline and differential.
GenevisibleiP06239. HS.

Organism-specific databases

HPAiCAB003816.
HPA003494.

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. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with herpes simplex virus 1 UL46; this interaction activates LCK. 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-lymphocyte migration. Associates with ZAP70 and RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit phosphorylation in the presence of functional ZAP70. Interacts with UNC119; this interaction plays a crucial role in activation of LCK. Interacts with CEACAM1 (via cytoplasmic domain); mediates CEACAM1 phosphorylation resulting in PTPN6 recruitment that dephosphorylates TCR stimulation-induced CD247 and ZAP70 (PubMed:18424730).12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-1348,EBI-1348
P225757EBI-1348,EBI-866709From a different organism.
Q9YJQ82EBI-1348,EBI-7709835From a different organism.
ADAM15Q134443EBI-1348,EBI-77818
ARP102757EBI-1348,EBI-608057
BCL3P207493EBI-1348,EBI-958997
CD4P017302EBI-1348,EBI-353826
CDKAL1Q5VV423EBI-1348,EBI-10194801
GAB1Q1348010EBI-1348,EBI-517684
HSP90AB1P082382EBI-1348,EBI-352572
KHDRBS1Q076665EBI-1348,EBI-1364
KITP107218EBI-1348,EBI-1379503
LATO435612EBI-1348,EBI-1222766
LZTS2Q9BRK43EBI-1348,EBI-741037
MED28Q9H2044EBI-1348,EBI-514199
METP085813EBI-1348,EBI-1039152
NR3C1P041503EBI-1348,EBI-493507
PRKCQQ047592EBI-1348,EBI-374762
PTPN22Q9Y2R26EBI-1348,EBI-1211241
PTPN6P293505EBI-1348,EBI-78260
PTPRCP085757EBI-1348,EBI-1341
SH2D2AQ9NP3112EBI-1348,EBI-490630
SYKP434057EBI-1348,EBI-78302
UBCP0CG482EBI-1348,EBI-3390054
ZAP70P434032EBI-1348,EBI-1211276

GO - Molecular functioni

  • ATPase binding Source: UniProtKB
  • CD4 receptor binding Source: UniProtKB
  • CD8 receptor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110124. 88 interactors.
DIPiDIP-553N.
IntActiP06239. 72 interactors.
MINTiMINT-110378.
STRINGi9606.ENSP00000337825.

Chemistry databases

BindingDBiP06239.

Structurei

Secondary structure

1509
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi12 – 15Combined sources4
Beta strandi21 – 23Combined sources3
Beta strandi24 – 27Combined sources4
Turni60 – 63Combined sources4
Beta strandi65 – 70Combined sources6
Beta strandi76 – 79Combined sources4
Beta strandi87 – 92Combined sources6
Beta strandi95 – 102Combined sources8
Turni103 – 105Combined sources3
Beta strandi108 – 112Combined sources5
Helixi113 – 115Combined sources3
Beta strandi116 – 118Combined sources3
Beta strandi128 – 131Combined sources4
Helixi134 – 141Combined sources8
Beta strandi151 – 155Combined sources5
Beta strandi157 – 159Combined sources3
Beta strandi163 – 171Combined sources9
Turni172 – 174Combined sources3
Beta strandi175 – 185Combined sources11
Turni187 – 189Combined sources3
Beta strandi191 – 194Combined sources4
Beta strandi199 – 201Combined sources3
Helixi202 – 211Combined sources10
Beta strandi216 – 218Combined sources3
Turni233 – 235Combined sources3
Beta strandi237 – 239Combined sources3
Helixi242 – 244Combined sources3
Beta strandi245 – 254Combined sources10
Beta strandi257 – 264Combined sources8
Turni265 – 267Combined sources3
Beta strandi268 – 275Combined sources8
Turni277 – 279Combined sources3
Helixi282 – 294Combined sources13
Beta strandi303 – 307Combined sources5
Beta strandi309 – 311Combined sources3
Beta strandi313 – 317Combined sources5
Helixi324 – 327Combined sources4
Helixi331 – 334Combined sources4
Helixi338 – 357Combined sources20
Helixi367 – 369Combined sources3
Beta strandi370 – 372Combined sources3
Beta strandi378 – 380Combined sources3
Helixi383 – 385Combined sources3
Helixi386 – 389Combined sources4
Beta strandi390 – 392Combined sources3
Beta strandi393 – 395Combined sources3
Turni404 – 406Combined sources3
Helixi409 – 414Combined sources6
Helixi419 – 434Combined sources16
Turni435 – 437Combined sources3
Helixi446 – 454Combined sources9
Helixi467 – 476Combined sources10
Helixi481 – 483Combined sources3
Helixi487 – 500Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BHFX-ray1.80A119-226[»]
1BHHX-ray1.90A119-226[»]
B124-226[»]
1CWDX-ray2.25L127-222[»]
1CWEX-ray2.30A/C127-222[»]
1FBZX-ray2.40A/B123-226[»]
1H92NMR-A59-120[»]
1IJRX-ray2.20A124-226[»]
1KIKNMR-A64-120[»]
1LCJX-ray1.80A119-226[»]
1LCKX-ray2.50A53-226[»]
B502-509[»]
1LKKX-ray1.00A122-226[»]
1LKLX-ray1.80A123-226[»]
1Q68NMR-B7-35[»]
1Q69NMR-B7-35[»]
1QPCX-ray1.60A231-509[»]
1QPDX-ray2.00A231-509[»]
1QPEX-ray2.00A231-509[»]
1QPJX-ray2.20A231-509[»]
1X27X-ray2.70A/B/C/D/E/F64-226[»]
2IIMX-ray1.00A59-119[»]
2OF2X-ray2.00A231-501[»]
2OF4X-ray2.70A231-501[»]
2OFUX-ray2.00A229-501[»]
2OFVX-ray2.00A/B232-498[»]
2OG8X-ray2.30A/B237-499[»]
2PL0X-ray2.80A225-509[»]
2ZM1X-ray2.10A225-509[»]
2ZM4X-ray2.70A225-509[»]
2ZYBX-ray2.55A225-509[»]
3AC1X-ray1.99A225-509[»]
3AC2X-ray2.10A225-509[»]
3AC3X-ray2.55A225-509[»]
3AC4X-ray2.70A225-509[»]
3AC5X-ray2.50A225-509[»]
3AC8X-ray2.30A225-509[»]
3ACJX-ray2.20A225-509[»]
3ACKX-ray2.60A225-509[»]
3AD4X-ray2.20A225-509[»]
3AD5X-ray2.00A225-509[»]
3AD6X-ray2.15A225-509[»]
3B2WX-ray2.30A226-502[»]
3BRHX-ray2.20C/D391-397[»]
3BYMX-ray2.00A230-501[»]
3BYOX-ray2.00A231-501[»]
3BYSX-ray2.20A225-501[»]
3BYUX-ray2.30A225-501[»]
3KMMX-ray2.80A229-509[»]
3KXZX-ray2.37A225-509[»]
3LCKX-ray1.70A231-501[»]
3MPMX-ray1.95A237-501[»]
4C3FX-ray1.72A237-501[»]
4D8KX-ray2.36A53-226[»]
ProteinModelPortaliP06239.
SMRiP06239.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06239.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini61 – 121SH3PROSITE-ProRule annotationAdd BLAST61
Domaini127 – 224SH2PROSITE-ProRule annotationAdd BLAST98
Domaini245 – 498Protein kinasePROSITE-ProRule annotationAdd BLAST254

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 72Interactions with CD4 and CD8By similarityAdd BLAST71
Regioni154 – 242Interaction with PTPRH1 PublicationAdd BLAST89

Domaini

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

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

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOVERGENiHBG008761.
InParanoidiP06239.
KOiK05856.
OMAiHTKVAIK.
OrthoDBiEOG091G0D46.
PhylomeDBiP06239.
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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P06239-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGCGCSSHPE DDWMENIDVC ENCHYPIVPL DGKGTLLIRN GSEVRDPLVT
60 70 80 90 100
YEGSNPPASP 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
GLHELVRHYT NASDGLCTRL SRPCQTQKPQ KPWWEDEWEV PRETLKLVER
260 270 280 290 300
LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHQRL
310 320 330 340 350
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLTINK LLDMAAQIAE
360 370 380 390 400
GMAFIEERNY IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA
410 420 430 440 450
KFPIKWTAPE AINYGTFTIK SDVWSFGILL TEIVTHGRIP YPGMTNPEVI
460 470 480 490 500
QNLERGYRMV RPDNCPEELY QLMRLCWKER PEDRPTFDYL RSVLEDFFTA

TEGQYQPQP
Length:509
Mass (Da):58,001
Last modified:January 23, 2007 - v6
Checksum:i44BFF0D43FFB420D
GO
Isoform Short (identifier: P06239-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     348-363: IAEGMAFIEERNYIHR → VRRLGRGAGQGNRPVT
     364-509: Missing.

Note: No experimental confirmation available.
Show »
Length:363
Mass (Da):40,866
Checksum:iAC4AF1AB58D32577
GO
Isoform 3 (identifier: P06239-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     321-321: N → NDTLLDSQLEEKGLGASPWGNLGQQLLLLPT

Note: No experimental confirmation available.
Show »
Length:539
Mass (Da):61,190
Checksum:iD1024F47D18B289C
GO

Sequence cautioni

The sequence CAI22320 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAI22321 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti29P → R in AAA59502 (PubMed:3265417).Curated1
Sequence conflicti35T → R in AAA59502 (PubMed:3265417).Curated1
Sequence conflicti87Q → P in CAA31884 (PubMed:3265417).Curated1
Sequence conflicti87Q → P in AAA59502 (PubMed:3265417).Curated1
Sequence conflicti206 – 211VRHYTN → ASAITPI in CAA28691 (PubMed:3493153).Curated6
Sequence conflicti254G → A in AAA59502 (PubMed:3265417).Curated1
Sequence conflicti258 – 267EVWMGYYNGH → RCGWGTTTGT in CAA28691 (PubMed:3493153).Curated10
Sequence conflicti282 – 286PDAFL → AGRLP in CAA28691 (PubMed:3493153).Curated5
Sequence conflicti375T → A in CAA28165 (PubMed:3489486).Curated1
Sequence conflicti472L → H in CAA29667 (PubMed:2835736).Curated1
Sequence conflicti504 – 509QYQPQP → STA in CAA28691 (PubMed:3493153).Curated6

Mass spectrometryi

Molecular mass is 57869.42 Da from positions 2 - 509. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01346328V → L Found in leukemia. 1 Publication1
Natural variantiVAR_051697201G → S.Corresponds to variant rs11567841dbSNPEnsembl.1
Natural variantiVAR_013464232P → PQKP in leukemia. 1
Natural variantiVAR_071291341L → P in IMD22. 1 PublicationCorresponds to variant rs587777335dbSNPEnsembl.1
Natural variantiVAR_013465353A → V Found in leukemia. 1 Publication1
Natural variantiVAR_013466447P → L Found in leukemia. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016049321N → NDTLLDSQLEEKGLGASPWG NLGQQLLLLPT in isoform 3. 1 Publication1
Alternative sequenceiVSP_005000348 – 363IAEGM…NYIHR → VRRLGRGAGQGNRPVT in isoform Short. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_005001364 – 509Missing in isoform Short. 1 PublicationAdd BLAST146

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05027 mRNA. Translation: CAA28691.1.
X13529 mRNA. Translation: CAA31884.1.
M36881 mRNA. Translation: AAA59502.1.
X14055, X14053, X14054 Genomic DNA. Translation: CAA32211.1.
U07236 mRNA. Translation: AAA18225.1.
U23852 mRNA. Translation: AAC50287.1.
BN000073 Genomic DNA. Translation: CAD55807.1.
AL121991 Genomic DNA. Translation: CAI22320.1. Different initiation.
AL121991 Genomic DNA. Translation: CAI22321.1. Different initiation.
CH471059 Genomic DNA. Translation: EAX07543.1.
CH471059 Genomic DNA. Translation: EAX07546.1.
BC013200 mRNA. Translation: AAH13200.1.
M21510 Genomic DNA. Translation: AAA59501.1. Different termination.
M26692 Genomic DNA. Translation: AAA59503.1.
AF228313 mRNA. Translation: AAF34794.1.
X06369 mRNA. Translation: CAA29667.1.
X04476 mRNA. Translation: CAA28165.1.
CCDSiCCDS359.1. [P06239-1]
PIRiJQ0152. OKHULK.
RefSeqiNP_001036236.1. NM_001042771.2. [P06239-1]
NP_005347.3. NM_005356.4. [P06239-1]
UniGeneiHs.470627.

Genome annotation databases

EnsembliENST00000333070; ENSP00000328213; ENSG00000182866. [P06239-3]
ENST00000336890; ENSP00000337825; ENSG00000182866. [P06239-1]
ENST00000619559; ENSP00000477713; ENSG00000182866. [P06239-1]
GeneIDi3932.
KEGGihsa:3932.
UCSCiuc001bux.3. human. [P06239-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Wikipedia

Lck entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05027 mRNA. Translation: CAA28691.1.
X13529 mRNA. Translation: CAA31884.1.
M36881 mRNA. Translation: AAA59502.1.
X14055, X14053, X14054 Genomic DNA. Translation: CAA32211.1.
U07236 mRNA. Translation: AAA18225.1.
U23852 mRNA. Translation: AAC50287.1.
BN000073 Genomic DNA. Translation: CAD55807.1.
AL121991 Genomic DNA. Translation: CAI22320.1. Different initiation.
AL121991 Genomic DNA. Translation: CAI22321.1. Different initiation.
CH471059 Genomic DNA. Translation: EAX07543.1.
CH471059 Genomic DNA. Translation: EAX07546.1.
BC013200 mRNA. Translation: AAH13200.1.
M21510 Genomic DNA. Translation: AAA59501.1. Different termination.
M26692 Genomic DNA. Translation: AAA59503.1.
AF228313 mRNA. Translation: AAF34794.1.
X06369 mRNA. Translation: CAA29667.1.
X04476 mRNA. Translation: CAA28165.1.
CCDSiCCDS359.1. [P06239-1]
PIRiJQ0152. OKHULK.
RefSeqiNP_001036236.1. NM_001042771.2. [P06239-1]
NP_005347.3. NM_005356.4. [P06239-1]
UniGeneiHs.470627.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BHFX-ray1.80A119-226[»]
1BHHX-ray1.90A119-226[»]
B124-226[»]
1CWDX-ray2.25L127-222[»]
1CWEX-ray2.30A/C127-222[»]
1FBZX-ray2.40A/B123-226[»]
1H92NMR-A59-120[»]
1IJRX-ray2.20A124-226[»]
1KIKNMR-A64-120[»]
1LCJX-ray1.80A119-226[»]
1LCKX-ray2.50A53-226[»]
B502-509[»]
1LKKX-ray1.00A122-226[»]
1LKLX-ray1.80A123-226[»]
1Q68NMR-B7-35[»]
1Q69NMR-B7-35[»]
1QPCX-ray1.60A231-509[»]
1QPDX-ray2.00A231-509[»]
1QPEX-ray2.00A231-509[»]
1QPJX-ray2.20A231-509[»]
1X27X-ray2.70A/B/C/D/E/F64-226[»]
2IIMX-ray1.00A59-119[»]
2OF2X-ray2.00A231-501[»]
2OF4X-ray2.70A231-501[»]
2OFUX-ray2.00A229-501[»]
2OFVX-ray2.00A/B232-498[»]
2OG8X-ray2.30A/B237-499[»]
2PL0X-ray2.80A225-509[»]
2ZM1X-ray2.10A225-509[»]
2ZM4X-ray2.70A225-509[»]
2ZYBX-ray2.55A225-509[»]
3AC1X-ray1.99A225-509[»]
3AC2X-ray2.10A225-509[»]
3AC3X-ray2.55A225-509[»]
3AC4X-ray2.70A225-509[»]
3AC5X-ray2.50A225-509[»]
3AC8X-ray2.30A225-509[»]
3ACJX-ray2.20A225-509[»]
3ACKX-ray2.60A225-509[»]
3AD4X-ray2.20A225-509[»]
3AD5X-ray2.00A225-509[»]
3AD6X-ray2.15A225-509[»]
3B2WX-ray2.30A226-502[»]
3BRHX-ray2.20C/D391-397[»]
3BYMX-ray2.00A230-501[»]
3BYOX-ray2.00A231-501[»]
3BYSX-ray2.20A225-501[»]
3BYUX-ray2.30A225-501[»]
3KMMX-ray2.80A229-509[»]
3KXZX-ray2.37A225-509[»]
3LCKX-ray1.70A231-501[»]
3MPMX-ray1.95A237-501[»]
4C3FX-ray1.72A237-501[»]
4D8KX-ray2.36A53-226[»]
ProteinModelPortaliP06239.
SMRiP06239.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110124. 88 interactors.
DIPiDIP-553N.
IntActiP06239. 72 interactors.
MINTiMINT-110378.
STRINGi9606.ENSP00000337825.

Chemistry databases

BindingDBiP06239.
ChEMBLiCHEMBL258.
DrugBankiDB01254. Dasatinib.
DB09079. Nintedanib.
DB08901. Ponatinib.
GuidetoPHARMACOLOGYi2053.

PTM databases

iPTMnetiP06239.
PhosphoSitePlusiP06239.
SwissPalmiP06239.

Polymorphism and mutation databases

BioMutaiLCK.
DMDMi125474.

Proteomic databases

EPDiP06239.
MaxQBiP06239.
PaxDbiP06239.
PeptideAtlasiP06239.
PRIDEiP06239.

Protocols and materials databases

DNASUi3932.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000333070; ENSP00000328213; ENSG00000182866. [P06239-3]
ENST00000336890; ENSP00000337825; ENSG00000182866. [P06239-1]
ENST00000619559; ENSP00000477713; ENSG00000182866. [P06239-1]
GeneIDi3932.
KEGGihsa:3932.
UCSCiuc001bux.3. human. [P06239-1]

Organism-specific databases

CTDi3932.
DisGeNETi3932.
GeneCardsiLCK.
H-InvDBHIX0019954.
HGNCiHGNC:6524. LCK.
HPAiCAB003816.
HPA003494.
MalaCardsiLCK.
MIMi153390. gene.
615758. phenotype.
neXtProtiNX_P06239.
OpenTargetsiENSG00000182866.
Orphaneti280142. Severe combined immunodeficiency due to LCK deficiency.
PharmGKBiPA30307.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOVERGENiHBG008761.
InParanoidiP06239.
KOiK05856.
OMAiHTKVAIK.
OrthoDBiEOG091G0D46.
PhylomeDBiP06239.
TreeFamiTF351634.

Enzyme and pathway databases

BioCyciZFISH:HS00023-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-114604. GPVI-mediated activation cascade.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1433559. Regulation of KIT signaling.
R-HSA-164944. Nef and signal transduction.
R-HSA-167590. Nef Mediated CD4 Down-regulation.
R-HSA-202424. Downstream TCR signaling.
R-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
R-HSA-202430. Translocation of ZAP-70 to Immunological synapse.
R-HSA-202433. Generation of second messenger molecules.
R-HSA-210990. PECAM1 interactions.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-2424491. DAP12 signaling.
R-HSA-389356. CD28 co-stimulation.
R-HSA-389357. CD28 dependent PI3K/Akt signaling.
R-HSA-389359. CD28 dependent Vav1 pathway.
R-HSA-389513. CTLA4 inhibitory signaling.
R-HSA-389948. PD-1 signaling.
R-HSA-451927. Interleukin-2 signaling.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SignaLinkiP06239.
SIGNORiP06239.

Miscellaneous databases

ChiTaRSiLCK. human.
EvolutionaryTraceiP06239.
GeneWikiiLck.
GenomeRNAii3932.
PROiP06239.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182866.
CleanExiHS_LCK.
ExpressionAtlasiP06239. baseline and differential.
GenevisibleiP06239. HS.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiLCK_HUMAN
AccessioniPrimary (citable) accession number: P06239
Secondary accession number(s): D3DPP8
, P07100, Q12850, Q13152, Q5TDH8, Q5TDH9, Q7RTZ3, Q96DW4, Q9NYT8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 225 of the entry and version 6 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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.