ID   LCK_CHICK               Reviewed;         508 AA.
AC   P42683; Q53WS8;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   08-NOV-2023, entry version 151.
DE   RecName: Full=Proto-oncogene tyrosine-protein kinase LCK;
DE            EC=2.7.10.2;
DE   AltName: Full=Protein-tyrosine kinase C-TKL;
DE   AltName: Full=p56tk1;
GN   Name=LCK;
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Spleen;
RA   Gaertner T., Khnel H., Strebhardt K., Ruebsamen-Waigmann H.;
RL   Submitted (AUG-1991) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-89.
RX   PubMed=1545804; DOI=10.1128/mcb.12.3.1226-1233.1992;
RA   Chow L., Ratcliffe M., Veillette A.;
RT   "tkl is the avian homolog of the mammalian lck tyrosine protein kinase
RT   gene.";
RL   Mol. Cell. Biol. 12:1226-1233(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 47-508.
RX   PubMed=3321053; DOI=10.1073/pnas.84.24.8778;
RA   Strebhardt K., Mullins J.I., Bruck C., Ruebsamen-Waigmann H.;
RT   "Additional member of the protein-tyrosine kinase family: the src- and lck-
RT   related protooncogene c-tkl.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:8778-8782(1987).
CC   -!- FUNCTION: Tyrosine kinase that plays an essential role for the
CC       selection and maturation of developing T-cell in the thymus and in
CC       mature T-cell function. Is constitutively associated with the
CC       cytoplasmic portions of the CD4 and CD8 surface receptors and plays a
CC       key role in T-cell antigen receptor(TCR)-linked signal transduction
CC       pathways (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC         [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC   -!- ACTIVITY REGULATION: Inhibited by tyrosine phosphorylation.
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Binds to the cytoplasmic domain of cell surface receptors,
CC       such as CD4, CD8. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P06239};
CC       Lipid-anchor {ECO:0000250|UniProtKB:P06239}; Cytoplasmic side
CC       {ECO:0000250|UniProtKB:P06239}. Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P06239}.
CC   -!- PTM: Phosphorylated on Tyr-393, which increases enzymatic activity,
CC       this site is dephosphorylated by PTN22. Phosphorylated on Tyr-504,
CC       presumably by CSK, which decreases activity. Dephosphorylated by
CC       PTPRC/CD45. Dephosphorylation at Tyr-393 by PTPN2 negatively regulates
CC       T-cells differentiation (By similarity). {ECO:0000250}.
CC   -!- PTM: Palmitoylation regulates association with the plasma membrane.
CC       {ECO:0000250|UniProtKB:P06239}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA49081.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; X60380; CAA42930.1; -; mRNA.
DR   EMBL; M85043; AAA49003.1; -; mRNA.
DR   EMBL; J03579; AAA49081.1; ALT_INIT; mRNA.
DR   PIR; A42126; A39939.
DR   AlphaFoldDB; P42683; -.
DR   SMR; P42683; -.
DR   STRING; 9031.ENSGALP00000000634; -.
DR   iPTMnet; P42683; -.
DR   PaxDb; 9031-ENSGALP00000000634; -.
DR   VEuPathDB; HostDB:geneid_396460; -.
DR   eggNOG; KOG0197; Eukaryota.
DR   InParanoid; P42683; -.
DR   PhylomeDB; P42683; -.
DR   BRENDA; 2.7.10.2; 1306.
DR   Proteomes; UP000000539; Unassembled WGS sequence.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR   GO; GO:0000242; C:pericentriolar material; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR   GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR   GO; GO:0042169; F:SH2 domain binding; ISS:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR   GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR   GO; GO:0050853; P:B cell receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR   GO; GO:0006882; P:intracellular zinc ion homeostasis; ISS:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR   GO; GO:0050870; P:positive regulation of T cell activation; ISS:UniProtKB.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; ISS:UniProtKB.
DR   GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR   GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR   CDD; cd05067; PTKc_Lck_Blk; 1.
DR   CDD; cd10362; SH2_Src_Lck; 1.
DR   CDD; cd12005; SH3_Lck; 1.
DR   Gene3D; 3.30.505.10; SH2 domain; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR035850; Lck_SH2.
DR   InterPro; IPR035749; Lck_SH3.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR000980; SH2.
DR   InterPro; IPR036860; SH2_dom_sf.
DR   InterPro; IPR036028; SH3-like_dom_sf.
DR   InterPro; IPR001452; SH3_domain.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1.
DR   PANTHER; PTHR24418:SF39; TYROSINE-PROTEIN KINASE LCK; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   Pfam; PF00017; SH2; 1.
DR   Pfam; PF00018; SH3_1; 1.
DR   PRINTS; PR00401; SH2DOMAIN.
DR   PRINTS; PR00452; SH3DOMAIN.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00252; SH2; 1.
DR   SMART; SM00326; SH3; 1.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF55550; SH2 domain; 1.
DR   SUPFAM; SSF50044; SH3-domain; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR   PROSITE; PS50001; SH2; 1.
DR   PROSITE; PS50002; SH3; 1.
PE   2: Evidence at transcript level;
KW   ATP-binding; Cell membrane; Cytoplasm; Kinase; Lipoprotein; Membrane;
KW   Myristate; Nucleotide-binding; Palmitate; Phosphoprotein; Proto-oncogene;
KW   Reference proteome; SH2 domain; SH3 domain; Transferase;
KW   Tyrosine-protein kinase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000305"
FT   CHAIN           2..508
FT                   /note="Proto-oncogene tyrosine-protein kinase LCK"
FT                   /id="PRO_0000088128"
FT   DOMAIN          60..120
FT                   /note="SH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   DOMAIN          126..223
FT                   /note="SH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT   DOMAIN          244..497
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   ACT_SITE        363
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         250..258
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         272
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         393
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         504
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250"
FT   LIPID           2
FT                   /note="N-myristoyl glycine"
FT                   /evidence="ECO:0000250"
FT   LIPID           3
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           5
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   508 AA;  58140 MW;  BC83C4E61CB66170 CRC64;
     MGCCCSSDYD EDWIENIDIC EHCNYPIDPD SKRQQLIRNV SEVRDPLVSY EAMSPPCSPL
     QDKLVVALYD YEPTHDGDLG LKQGEKLRVL EESGEWWRAQ SLTTGQEGLI PHNFVAMVNS
     LEPEPWFFKN LSRKNAEARL LASGNTHGSF LIRESETSKG SYSLSVRDFD QNQGETVKHY
     KIRNMDNGGY YISPRVTFSS LHELVEYYSS SSDGLCTRLG KPCRTQKPQK PWWQDEWEVP
     RESLKLVEKL GAGQFGEVWM GFYNGHTKVA IKNLKQGSMS PSAFLAEANL MKNLQHPRLV
     RLYAVVTKEP IYIITEYMEK GSLVDFLKTS EGIKLSINKL LDMAAQIAEG MAFIEAKNYI
     HRDLRAANIL VSEALCCKIA DFGLARLIED NEYTAREGAK FPIKWTAPEA INYGTFTIKS
     DVWSFGILLT EIVTYGRIPY PGMTNPEVIQ NLERGYRMPQ PDNCPQELYE LMMQCWKEQP
     EERPTFEYMK SVLEDFFTAT EGQYQQQP
//