Skip Header

Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot P06239 (LCK_HUMAN)

Last modified February 9, 2010. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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
    LSK
    T cell-specific protein-tyrosine kinase
Gene names
Name: LCK
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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

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.

Catalytic activity

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

Enzyme regulation

Inhibited by tyrosine phosphorylation.

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. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH. Ref.16 Ref.17 Ref.18 Ref.19 Ref.23 Ref.24 Ref.25

Subcellular location

Cytoplasm. Cell membrane; Lipid-anchor; Cytoplasmic side. Note: Present in lipid rafts in an unactive form. Ref.21

Tissue specificity

Expressed specifically in lymphoid cells.

Domain

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

Post-translational modification

Phosphorylated on Tyr-394, which increases enzymatic activity By similarity. Phosphorylated on Tyr-505, which decreases activity. Ref.4 Ref.15 Ref.26 Ref.27 Ref.28 Ref.29 Ref.31

Involvement in disease

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

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.

Mass spectrometry

Molecular mass is 57869.42 Da from positions 2 - 509. Determined by MALDI. Ref.22

Ontologies

Keywords
   Biological processHost-virus interaction
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
Proto-oncogene
   DomainSH2 domain
SH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMAcetylation
Lipoprotein
Myristate
Palmitate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processT cell differentiation

Inferred from mutant phenotype. Source: UniProtKB

activation of caspase activity

Inferred from direct assay. Source: UniProtKB

cellular zinc ion homeostasis

Inferred from expression pattern. Source: UniProtKB

induction of apoptosis

Inferred from mutant phenotype. Source: UniProtKB

interspecies interaction between organisms

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of T cell activation

Inferred from direct assay. Source: UniProtKB

positive regulation of T cell receptor signaling pathway

Non-traceable author statement. Source: UniProtKB

protein amino acid phosphorylation

Inferred from direct assay. Source: UniProtKB

release of sequestered calcium ion into cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

response to drug

Inferred from direct assay. Source: UniProtKB

   Cellular componentGolgi apparatus

Inferred from direct assay. Source: HPA

anchored to membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from Experiment. Source: Reactome

membrane raft

Inferred from direct assay. Source: UniProtKB

pericentriolar material

Inferred from direct assay. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATPase binding

Inferred from physical interaction. Source: UniProtKB

CD4 receptor binding

Inferred from physical interaction. Source: UniProtKB

CD8 receptor binding

Inferred from physical interaction. Source: UniProtKB

SH2 domain binding Ref.17 Ref.19

Inferred from physical interaction. Source: UniProtKB

glycoprotein binding

Inferred from physical interaction. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: EC

phosphoinositide 3-kinase binding Ref.16

Inferred from physical interaction. Source: UniProtKB

protein C-terminus binding

Inferred from physical interaction. Source: UniProtKB

protein kinase binding Ref.18

Inferred from physical interaction. Source: UniProtKB

protein serine/threonine phosphatase activity

Inferred from direct assay. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P06239-1)

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.
Isoform Short (identifier: P06239-2)

The sequence of this isoform differs from the canonical sequence as follows:
     348-363: IAEGMAFIEERNYIHR → VRRLGRGAGQGNRPVT
     364-509: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P06239-3)

The sequence of this isoform differs from the canonical sequence as follows:
     321-321: N → NDTLLDSQLEEKGLGASPWGNLGQQLLLLPT
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Probable
Chain2 – 509508Proto-oncogene tyrosine-protein kinase LCK
PRO_0000088124

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

Sites

Active site3641Proton acceptor By similarity
Binding site2731ATP By similarity

Amino acid modifications

Modified residue1021Phosphoserine Ref.31
Modified residue1591Phosphothreonine Ref.31
Modified residue1621Phosphoserine Ref.28 Ref.31
Modified residue1791N6-acetyllysine Ref.32
Modified residue1921Phosphotyrosine Ref.27 Ref.28 Ref.31
Modified residue1941Phosphoserine Ref.31
Modified residue2131Phosphoserine Ref.28
Modified residue3941Phosphotyrosine; by autocatalysis Ref.4 Ref.26 Ref.28
Modified residue5011Phosphothreonine Ref.28
Modified residue5051Phosphotyrosine Ref.4 Ref.15 Ref.26 Ref.27 Ref.28 Ref.29 Ref.31
Lipidation21N-myristoyl glycine By similarity
Lipidation31S-palmitoyl cysteine By similarity
Lipidation51S-palmitoyl cysteine By similarity

Natural variations

Alternative sequence3211N → NDTLLDSQLEEKGLGASPWG NLGQQLLLLPT in isoform 3.
VSP_016049
Alternative sequence348 – 36316IAEGM…NYIHR → VRRLGRGAGQGNRPVT in isoform Short.
VSP_005000
Alternative sequence364 – 509146Missing in isoform Short.
VSP_005001
Natural variant281V → L in leukemia. Ref.4
VAR_013463
Natural variant2011G → S: dbSNP rs11567841.
VAR_051697
Natural variant2321P → PQKP in leukemia.
VAR_013464
Natural variant3531A → V in leukemia. Ref.4
VAR_013465
Natural variant4471P → L in leukemia. Ref.4
VAR_013466

Experimental info

Mutagenesis591S → E: Allows interaction with SQSTM1. Ref.18
Mutagenesis1541R → K: No effect on interaction with SQSTM1. Ref.18
Sequence conflict291P → R in AAA59502. Ref.2
Sequence conflict351T → R in AAA59502. Ref.2
Sequence conflict871Q → P in CAA31884. Ref.2
Sequence conflict871Q → P in AAA59502. Ref.2
Sequence conflict206 – 2116VRHYTN → ASAITPI in CAA28691. Ref.1
Sequence conflict2541G → A in AAA59502. Ref.2
Sequence conflict258 – 26710EVWMGYYNGH → RCGWGTTTGT in CAA28691. Ref.1
Sequence conflict282 – 2865PDAFL → AGRLP in CAA28691. Ref.1
Sequence conflict3751T → A Ref.14
Sequence conflict4721L → H Ref.13
Sequence conflict504 – 5096QYQPQP → STA in CAA28691. Ref.1

Secondary structure

................................................................................ 509
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified January 23, 2007. Version 6.
Checksum: 44BFF0D43FFB420D

FASTA50958,001
        10         20         30         40         50         60 
MGCGCSSHPE DDWMENIDVC ENCHYPIVPL DGKGTLLIRN GSEVRDPLVT YEGSNPPASP 

        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 GLHELVRHYT NASDGLCTRL SRPCQTQKPQ KPWWEDEWEV 

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

       310        320        330        340        350        360 
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLTINK LLDMAAQIAE GMAFIEERNY 

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

       430        440        450        460        470        480 
SDVWSFGILL TEIVTHGRIP YPGMTNPEVI QNLERGYRMV RPDNCPEELY QLMRLCWKER 

       490        500 
PEDRPTFDYL RSVLEDFFTA TEGQYQPQP 

« Hide

Isoform Short.

Checksum: AC4AF1AB58D32577
Show »

FASTA36340,866
Isoform 3.

Checksum: D1024F47D18B289C
Show »

FASTA53961,190

References

« Hide 'large scale' references
[1]"A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases."
Koga Y., Caccia N., Toyonaga B., Spolski R., Yanagi Y., Yoshikai Y., Mak T.W.
Eur. J. Immunol. 16:1643-1646(1986) [PubMed: 3493153] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure and expression of lck transcripts in human lymphoid cells."
Perlmutter R.M., Marth J.D., Lewis D.B., Peet R., Ziegler S.F., Wilson C.B.
J. Cell. Biochem. 38:117-126(1988) [PubMed: 3265417] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Structure of the human lck gene: differences in genomic organisation within src-related genes affect only N-terminal exons."
Rouer E., van Huynh T., de Souza S.L., Lang M.C., Fischer S., Benarous R.
Gene 84:105-113(1989) [PubMed: 2558056] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia."
Wright D.D., Sefton B.M., Kamps M.P.
Mol. Cell. Biol. 14:2429-2437(1994) [PubMed: 8139546] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-28; GLN-LYS-PRO-232 INS; VAL-353 AND LEU-447, PHOSPHORYLATION AT TYR-394 AND TYR-505.
Tissue: Leukemia.
[5]"An aberrant lck mRNA in two human T-cell lines."
Vogel L.B., Arthur R., Fujita D.J.
Biochim. Biophys. Acta 1264:168-172(1995) [PubMed: 7495859] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), ALTERNATIVE SPLICING.
Tissue: Leukemic T-cell.
[6]"No association between lck gene polymorphisms and protein level in type 1 diabetes."
Nervi S., Nicodeme S., Gartioux C., Atlan C., Lathrop M., Reviron D., Naquet P., Matsuda F., Imbert J., Vialettes B.
Diabetes 51:3326-3330(2002) [PubMed: 12401726] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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] (ISOFORM 3).
Tissue: Lymph.
[10]"Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line."
Garvin A.M., Pawar S., Marth J.D., Perlmutter R.M.
Mol. Cell. Biol. 8:3058-3064(1988) [PubMed: 2850479] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
[11]"Structure of the two promoters of the human lck gene: differential accumulation of two classes of lck transcripts in T cells."
Takadera T., Leung S., Gernone A., Koga Y., Takihara Y., Miyamoto N.G., Mak T.W.
Mol. Cell. Biol. 9:2173-2180(1989) [PubMed: 2787474] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
[12]"Defective recruitment and activation of ZAP-70 in common variable immunodeficiency patients with T cell defects."
Boncristiano M., Majolini M.B., D'Elios M.M., Pacini S., Valensin S., Ulivieri C., Amedei A., Falini B., Del Prete G., Telford J.L., Baldari C.T.
Eur. J. Immunol. 30:2632-2638(2000) [PubMed: 11009097] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-509.
Tissue: Peripheral blood lymphocyte.
[13]"Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines."
Veillette A., Foss F.M., Sausville E.A., Bolen J.B., Rosen N.
Oncogene Res. 1:357-374(1987) [PubMed: 2835736] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 368-509.
[14]"Human T lymphocytes express a protein-tyrosine kinase homologous to p56LSTRA."
Trevillyan J.M., Lin Y., Chen S.J., Phillips C.A., Canna C., Linna T.J.
Biochim. Biophys. Acta 888:286-295(1986) [PubMed: 3489486] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 375-509.
[15]"The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity."
Bergman M., Mustelin T., Oetken C., Partanen J., Flint N.A., Amrein K.E., Autero M., Burn P., Alitalo K.
EMBO J. 11:2919-2924(1992) [PubMed: 1639064] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-505.
[16]"The SH3 domain of p56lck is involved in binding to phosphatidylinositol 3'-kinase from T lymphocytes."
Vogel L.B., Fujita D.J.
Mol. Cell. Biol. 13:7408-7417(1993) [PubMed: 7504174] [Abstract]
Cited for: INTERACTION WITH PI3K.
[17]"p70 phosphorylation and binding to p56lck is an early event in interleukin-2-induced onset of cell cycle progression in T-lymphocytes."
Vogel L.B., Fujita D.J.
J. Biol. Chem. 270:2506-2511(1995) [PubMed: 7852312] [Abstract]
Cited for: INTERACTION WITH KHDRBS1.
[18]"Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region."
Park I., Chung J., Walsh C.T., Yun Y., Strominger J.L., Shin J.
Proc. Natl. Acad. Sci. U.S.A. 92:12338-12342(1995) [PubMed: 8618896] [Abstract]
Cited for: INTERACTION WITH SQSTM1, MUTAGENESIS OF SER-59 AND ARG-154.
[19]"Human immunodeficiency virus type 1 Nef binds directly to LCK and mitogen-activated protein kinase, inhibiting kinase activity."
Greenway A.L., Azad A., Mills J., McPhee D.A.
J. Virol. 70:6701-6708(1996) [PubMed: 8794306] [Abstract]
Cited for: INTERACTION WITH HIV-1 NEF.
[20]"Lck protein tyrosine kinase is a key regulator of T-cell activation and a target for signal intervention by Herpesvirus saimiri and other viral gene products."
Isakov N., Biesinger B.
Eur. J. Biochem. 267:3413-3421(2000) [PubMed: 10848956] [Abstract]
Cited for: REVIEW.
[21]"Fyn is essential for tyrosine phosphorylation of Csk-binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells."
Yasuda K., Nagafuku M., Shima T., Okada M., Yagi T., Yamada T., Minaki Y., Kato A., Tani-Ichi S., Hamaoka T., Kosugi A.
J. Immunol. 169:2813-2817(2002) [PubMed: 12218089] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[22]"Cluster analysis of an extensive human breast cancer cell line protein expression map database."
Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., Zvelebil M.J.
Proteomics 2:212-223(2002) [PubMed: 11840567] [Abstract]
Cited for: MASS SPECTROMETRY.
Tissue: Mammary cancer.
[23]"LIME: a new membrane raft-associated adaptor protein involved in CD4 and CD8 coreceptor signaling."
Brdickova N., Brdicka T., Angelisova P., Horvath O., Spicka J., Hilgert I., Paces J., Simeoni L., Kliche S., Merten C., Schraven B., Horejsi V.
J. Exp. Med. 198:1453-1462(2003) [PubMed: 14610046] [Abstract]
Cited for: INTERACTION WITH LIME1.
[24]"LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activation."
Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.
J. Exp. Med. 198:1463-1473(2003) [PubMed: 14610044] [Abstract]
Cited for: INTERACTION WITH LIME1.
[25]"Interaction of SAP-1, a transmembrane-type protein-tyrosine phosphatase, with the tyrosine kinase Lck. Roles in regulation of T cell function."
Ito T., Okazawa H., Maruyama K., Tomizawa K., Motegi S., Ohnishi H., Kuwano H., Kosugi A., Matozaki T.
J. Biol. Chem. 278:34854-34863(2003) [PubMed: 12837766] [Abstract]
Cited for: INTERACTION WITH PTPRH.
[26]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-394 AND TYR-505, MASS SPECTROMETRY.
[27]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-192 AND TYR-505, MASS SPECTROMETRY.
[28]"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry."
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H.
Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162; TYR-192; SER-213; TYR-394; THR-501 AND TYR-505, MASS SPECTROMETRY.
[29]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, MASS SPECTROMETRY.
[30]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, MASS SPECTROMETRY.
[31]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; THR-159; SER-162; TYR-192; SER-194 AND TYR-505, MASS SPECTROMETRY.
Tissue: T-cell.
[32]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, MASS SPECTROMETRY.
[33]"Structure of the regulatory domains of the Src-family tyrosine kinase Lck."
Eck M.J., Atweell S.K., Shoelson S.E., Harrison S.C.
Nature 368:764-769(1994) [PubMed: 7512222] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 53-226.
[34]"The crystal structures of the SH2 domain of p56lck complexed with two phosphonopeptides suggest a gated peptide binding site."
Mikol V., Baumann G., Keller T.H., Manning U.M., Zurini M.G.M.
J. Mol. Biol. 246:344-355(1995) [PubMed: 7532720] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 127-221.
[35]"Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0-A and 1.8-A resolution."
Tong L., Warren T.C., King J., Betageri R., Rose J., Jakes S.
J. Mol. Biol. 256:601-610(1996) [PubMed: 8604142] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 122-226.
[36]"Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation."
Yamaguchi H., Hendrickson W.A.
Nature 384:484-489(1996) [PubMed: 8945479] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 231-501.
[37]"Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in SH2 domain binding."
Tong L., Warren T.C., Lukas S., Schembri-King J., Betageri R., Proudfoot J.R., Jakes S.
J. Biol. Chem. 273:20238-20242(1998) [PubMed: 9685372] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 119-226.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
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.
IPIIPI00411413.
IPI00515097.
IPI00940423.
PIROKHULK. JQ0152.
RefSeqNP_001036236.1.
NP_005347.3.
UniGeneHs.470627

3D structure databases

PDBe
RCSB PDB
PDBj
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/B226-502[»]
2OG8X-ray2.30A/B236-500[»]
2PL0X-ray2.80A225-509[»]
2ZM1X-ray2.10A225-509[»]
2ZM4X-ray2.70A225-509[»]
2ZYBX-ray2.55A225-509[»]
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[»]
3LCKX-ray1.70A231-501[»]
SMRP06239. Positions 65-509.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-553N.
IntActP06239. 23 interactions.
STRINGP06239.

PTM databases

PhosphoSiteP06239.

Proteomic databases

PRIDEP06239.

Genome annotation databases

EnsemblENST00000336890; ENSP00000337825; ENSG00000182866; Homo sapiens. [Genome view]
ENST00000398345; ENSP00000381387; ENSG00000182866; Homo sapiens. [Genome view]
GeneID3932.
KEGGhsa:3932.
UCSCuc001bux.1. human.
uc001buz.1. human.

Organism-specific databases

CTD3932.
GeneCardsGC01P032489.
H-InvDBHIX0019954.
HGNCHGNC:6524. LCK.
HPACAB003816.
HPA003494.
MIM153390. gene.
PharmGKBPA30307.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG11382.
HOVERGENP06239.
OMAATLPMRN.
OrthoDBEOG9BZQMQ.

Enzyme and pathway databases

BRENDA2.7.10.2. 247.
Pathway_Interaction_DBalphasynuclein_pathway. Alpha-synuclein signaling.
amb2_neutrophils_pathway. amb2 Integrin signaling.
nfkappabatypicalpathway. Atypical NF-kappaB pathway.
pi3kcipathway. Class I PI3K signaling events.
epha_fwdpathway. EPHA forward signaling.
ephrinbrevpathway. Ephrin B reverse signaling.
glypican_1pathway. Glypican 1 network.
il12_2pathway. IL12-mediated signaling events.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.
pdgfrbpathway. PDGFR-beta signaling pathway.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.
ptp1bpathway. Signaling events mediated by PTP1B.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
txa2pathway. Thromboxane A2 receptor signaling.
ReactomeREACT_604. Hemostasis.
REACT_6185. HIV Infection.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpressP06239.
BgeeP06239.
CleanExHS_LCK.
GenevestigatorP06239.
GermOnlineENSG00000182866. Homo sapiens.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR020473. SH3_region.
IPR020749. Tyr_kinase_non-rcpt_Lck.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
[Graphical view]
Gene3DG3DSA:3.30.505.10. SH2. 1 hit.
PANTHERPTHR23256:SF260. Tyr_kinase_non-rcpt_Lck. 1 hit.
PTHR23256. Tyr_prot_kinase. 1 hit.
PfamPF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
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...

Other Resources

BindingDBP06239.
DrugBankDB01254. Dasatinib.
NextBio15441.
SOURCESearch...

Entry information

Entry nameLCK_HUMAN
AccessionPrimary (citable) accession number: P06239
Secondary accession number(s): P07100 expand/collapse secondary AC list , Q12850, Q13152, Q5TDH8, Q5TDH9, Q7RTZ3, Q96DW4, Q9NYT8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 23, 2007
Last modified: February 9, 2010
This is version 151 of the entry and version 6 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents