Reviewed, UniProtKB/Swiss-Prot P06239 (LCK_HUMAN)

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
    LSK
    T cell-specific protein-tyrosine kinase

Gene names

Name:

LCK

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at 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 process	Host-virus interaction
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation Proto-oncogene
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Lipoprotein Myristate Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	T 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 component	Golgi 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 function	ATP 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P27958	1	EBI-1348,EBI-706378	From a different organism.
	Q9WMX2	1	EBI-1348,EBI-710918	From a different organism.
CD247	P20963	1	EBI-1348,EBI-1165705
KHDRBS1	Q07666	3	EBI-1348,EBI-1364
LAT	O43561	1	EBI-1348,EBI-1222766
MED28	Q9H204	2	EBI-1348,EBI-514199
PTPN12	Q05209	1	EBI-1348,EBI-2266035
PTPN22	Q9Y2R2	3	EBI-1348,EBI-1211241
PTPN6	P29350	1	EBI-1348,EBI-78260
PTPRB	P23467	1	EBI-1348,EBI-1265766
PTPRC	P08575	1	EBI-1348,EBI-1341
PTPRG	P23470	1	EBI-1348,EBI-2258115
PTPRJ	Q12913	1	EBI-1348,EBI-2264500
PTPRK	Q15262	1	EBI-1348,EBI-474052
PTPRM	P28827	1	EBI-1348,EBI-2257317
PTPRO	Q16827	1	EBI-1348,EBI-723739
PTPRZ1	P23471	1	EBI-1348,EBI-2263175
SH2D2A	Q9NP31	1	EBI-1348,EBI-490630
WASL	O00401	1	EBI-1348,EBI-957615
ZAP70	P43403	1	EBI-1348,EBI-1211276

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Probable

Chain

2 – 509

508

Proto-oncogene tyrosine-protein kinase LCK

PRO_0000088124

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

2 – 72

71

Interactions with CD4 and CD8 By similarity

Region

154 – 242

89

Interaction with PTPRH

Sites

Active site

364

1

Proton acceptor By similarity

Binding site

273

1

ATP By similarity

Amino acid modifications

Modified residue

102

1

Phosphoserine Ref.31

Modified residue

159

1

Phosphothreonine Ref.31

Modified residue

162

1

Phosphoserine Ref.28 Ref.31

Modified residue

179

1

N6-acetyllysine Ref.32

Modified residue

192

1

Phosphotyrosine Ref.27 Ref.28 Ref.31

Modified residue

194

1

Phosphoserine Ref.31

Modified residue

213

1

Phosphoserine Ref.28

Modified residue

394

1

Phosphotyrosine; by autocatalysis Ref.4 Ref.26 Ref.28

Modified residue

501

1

Phosphothreonine Ref.28

Modified residue

505

1

Phosphotyrosine Ref.4 Ref.15 Ref.26 Ref.27 Ref.28 Ref.29 Ref.31

Lipidation

2

1

N-myristoyl glycine By similarity

Lipidation

3

1

S-palmitoyl cysteine By similarity

Lipidation

5

1

S-palmitoyl cysteine By similarity

Natural variations

Alternative sequence

321

1

N → NDTLLDSQLEEKGLGASPWG NLGQQLLLLPT in isoform 3.

VSP_016049

Alternative sequence

348 – 363

16

IAEGM…NYIHR → VRRLGRGAGQGNRPVT in isoform Short.

VSP_005000

Alternative sequence

364 – 509

146

Missing in isoform Short.

VSP_005001

Natural variant

28

1

V → L in leukemia. Ref.4

VAR_013463

Natural variant

201

1

G → S: dbSNP rs11567841.

VAR_051697

Natural variant

232

1

P → PQKP in leukemia.

VAR_013464

Natural variant

353

1

A → V in leukemia. Ref.4

VAR_013465

Natural variant

447

1

P → L in leukemia. Ref.4

VAR_013466

Experimental info

Mutagenesis

59

1

S → E: Allows interaction with SQSTM1. Ref.18

Mutagenesis

154

1

R → K: No effect on interaction with SQSTM1. Ref.18

Sequence conflict

29

1

P → R in AAA59502. Ref.2

Sequence conflict

35

1

T → R in AAA59502. Ref.2

Sequence conflict

87

1

Q → P in CAA31884. Ref.2

Sequence conflict

87

1

Q → P in AAA59502. Ref.2

Sequence conflict

206 – 211

6

VRHYTN → ASAITPI in CAA28691. Ref.1

Sequence conflict

254

1

G → A in AAA59502. Ref.2

Sequence conflict

258 – 267

10

EVWMGYYNGH → RCGWGTTTGT in CAA28691. Ref.1

Sequence conflict

282 – 286

5

PDAFL → AGRLP in CAA28691. Ref.1

Sequence conflict

375

1

T → A Ref.14

Sequence conflict

472

1

L → H Ref.13

Sequence conflict

504 – 509

6

QYQPQP → STA in CAA28691. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

509

Helix Strand Turn

Details...

Helix

12 – 15

4

Beta strand

21 – 23

3

Turn

60 – 63

4

Beta strand

65 – 70

6

Beta strand

87 – 92

6

Beta strand

95 – 102

8

Turn

103 – 105

3

Beta strand

108 – 112

5

Helix

113 – 115

3

Beta strand

116 – 118

3

Helix

134 – 141

8

Beta strand

151 – 155

5

Beta strand

157 – 159

3

Beta strand

163 – 171

9

Turn

172 – 174

3

Beta strand

175 – 185

11

Beta strand

191 – 194

4

Beta strand

199 – 201

3

Helix

202 – 211

10

Beta strand

216 – 218

3

Turn

233 – 235

3

Helix

242 – 244

3

Beta strand

245 – 254

10

Beta strand

257 – 264

8

Turn

265 – 267

3

Beta strand

268 – 275

8

Helix

282 – 294

13

Beta strand

303 – 307

5

Beta strand

309 – 311

3

Beta strand

313 – 317

5

Helix

324 – 327

4

Helix

331 – 334

4

Helix

338 – 357

20

Helix

367 – 369

3

Beta strand

370 – 372

3

Beta strand

378 – 380

3

Beta strand

390 – 392

3

Turn

404 – 406

3

Helix

409 – 414

6

Helix

419 – 434

16

Turn

435 – 437

3

Helix

446 – 454

9

Helix

467 – 476

10

Helix

481 – 483

3

Helix

487 – 500

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified January 23, 2007. Version 6. Checksum: 44BFF0D43FFB420D	FASTA	509	58,001
	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
	Isoform Short. Checksum: AC4AF1AB58D32577	FASTA	363	40,866
	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 LLDMAAQVRR LGRGAGQGNR PVT
	Isoform 3. Checksum: D1024F47D18B289C	FASTA	539	61,190
	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 NDTLLDSQLE EKGLGASPWG NLGQQLLLLP TGSLVDFLKT 370 380 390 400 410 420 PSGIKLTINK LLDMAAQIAE GMAFIEERNY IHRDLRAANI LVSDTLSCKI ADFGLARLIE 430 440 450 460 470 480 DNEYTAREGA KFPIKWTAPE AINYGTFTIK SDVWSFGILL TEIVTHGRIP YPGMTNPEVI 490 500 510 520 530 QNLERGYRMV RPDNCPEELY QLMRLCWKER PEDRPTFDYL RSVLEDFFTA TEGQYQPQP

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

Lck entry

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.

IPI

IPI00411413.
IPI00515097.
IPI00940423.

PIR

OKHULK. JQ0152.

RefSeq

NP_001036236.1.
NP_005347.3.

UniGene

Hs.470627

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BHF	X-ray	1.80	A	119-226	[»]
1BHH	X-ray	1.90	A	119-226	[»]
			B	124-226	[»]
1CWD	X-ray	2.25	L	127-222	[»]
1CWE	X-ray	2.30	A/C	127-222	[»]
1FBZ	X-ray	2.40	A/B	123-226	[»]
1H92	NMR	-	A	59-120	[»]
1IJR	X-ray	2.20	A	124-226	[»]
1KIK	NMR	-	A	64-120	[»]
1LCJ	X-ray	1.80	A	119-226	[»]
1LCK	X-ray	2.50	A	53-226	[»]
			B	502-509	[»]
1LKK	X-ray	1.00	A	122-226	[»]
1LKL	X-ray	1.80	A	123-226	[»]
1Q68	NMR	-	B	7-35	[»]
1Q69	NMR	-	B	7-35	[»]
1QPC	X-ray	1.60	A	231-509	[»]
1QPD	X-ray	2.00	A	231-509	[»]
1QPE	X-ray	2.00	A	231-509	[»]
1QPJ	X-ray	2.20	A	231-509	[»]
1X27	X-ray	2.70	A/B/C/D/E/F	64-226	[»]
2IIM	X-ray	1.00	A	59-119	[»]
2OF2	X-ray	2.00	A	231-501	[»]
2OF4	X-ray	2.70	A	231-501	[»]
2OFU	X-ray	2.00	A	229-501	[»]
2OFV	X-ray	2.00	A/B	226-502	[»]
2OG8	X-ray	2.30	A/B	236-500	[»]
2PL0	X-ray	2.80	A	225-509	[»]
2ZM1	X-ray	2.10	A	225-509	[»]
2ZM4	X-ray	2.70	A	225-509	[»]
2ZYB	X-ray	2.55	A	225-509	[»]
3B2W	X-ray	2.30	A	226-502	[»]
3BRH	X-ray	2.20	C/D	391-397	[»]
3BYM	X-ray	2.00	A	230-501	[»]
3BYO	X-ray	2.00	A	231-501	[»]
3BYS	X-ray	2.20	A	225-501	[»]
3BYU	X-ray	2.30	A	225-501	[»]
3LCK	X-ray	1.70	A	231-501	[»]

SMR

P06239. Positions 65-509.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-553N.

IntAct

P06239. 23 interactions.

STRING

P06239.

PTM databases

PhosphoSite

P06239.

Proteomic databases

PRIDE

P06239.

Genome annotation databases

Ensembl

ENST00000336890; ENSP00000337825; ENSG00000182866; Homo sapiens. [Genome view]
ENST00000398345; ENSP00000381387; ENSG00000182866; Homo sapiens. [Genome view]

GeneID

3932.

KEGG

hsa:3932.

UCSC

uc001bux.1. human.
uc001buz.1. human.

Organism-specific databases

CTD

3932.

GeneCards

GC01P032489.

H-InvDB

HIX0019954.

HGNC

HGNC:6524. LCK.

HPA

CAB003816.
HPA003494.

MIM

153390. gene.

PharmGKB

PA30307.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11382.

HOVERGEN

P06239.

OMA

ATLPMRN.

OrthoDB

EOG9BZQMQ.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.

Pathway_Interaction_DB

alphasynuclein_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.

Reactome

REACT_604. Hemostasis.
REACT_6185. HIV Infection.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P06239.

Bgee

P06239.

CleanEx

HS_LCK.

Genevestigator

P06239.

GermOnline

ENSG00000182866. Homo sapiens.

Family and domain databases

InterPro

IPR011009. 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]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

PANTHER

PTHR23256:SF260. Tyr_kinase_non-rcpt_Lck. 1 hit.
PTHR23256. Tyr_prot_kinase. 1 hit.

Pfam

PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P06239.

DrugBank

DB01254. Dasatinib.

NextBio

15441.

SOURCE

Search...

Entry information

Entry name

LCK_HUMAN

Accession

Primary (citable) accession number: P06239
Secondary accession number(s): P07100 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.