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EBI Dbfetch

Tyrosine-protein kinase, active site

AccessionIPR008266; (Tyr_kinase_AS) matches 21230 proteins
FullNameTyrosine-protein kinase, active site
TypeActive_site
SignaturesPROSITE: PS00109 PROTEIN_KINASE_TYR
Found inIPR000719; IPR001245; IPR009136; IPR009220; IPR011009; IPR012234; IPR015782; IPR016243; IPR016244; IPR016245; IPR016246; IPR016247; IPR016248; IPR016249; IPR016250; IPR016251; IPR016257; IPR020446; IPR020455; IPR020461; IPR020635; IPR020693; IPR020775; IPR020776; IPR020777; IPR022495;
Abstract

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:

  • Serine/threonine-protein kinases
  • Tyrosine-protein kinases
  • Dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human []. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].

Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups []:

  • Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis []. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction [].

  • Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [].

This entry represents the tyrosine protein kinase active site. It also matches a number of proteins belonging to the atypical serine/threonine protein kinase BUD32 family, which lack the conventional structural elements necessary for the substrate recognition and also lack the lysine residue that in all other serine/threonine kinases participates in the catalytic event.

ExamplesSWISSPROT: O00444;
SWISSPROT: O97143;
SWISSPROT: P00520;
SWISSPROT: P03949;
SWISSPROT: P53323;
References
  1. Hanks SK, Quinn AM, Hunter T. (1988)
    The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.
    Science 241: 42-52
    [PUBMED:3291115] [PUB00005115]
  2. Manning G, Plowman GD, Hunter T, Sudarsanam S. (2002)
    Evolution of protein kinase signaling from yeast to man.
    Trends Biochem. Sci. 27: 514-20
    [PUBMED:12368087] [PUB00015362]
  3. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. (2002)
    The protein kinase complement of the human genome.
    Science 298: 1912-34
    [PUBMED:12471243] [PUB00020114]
  4. Stout TJ, Foster PG, Matthews DJ. (2004)
    High-throughput structural biology in drug discovery: protein kinases.
    Curr. Pharm. Des. 10: 1069-82
    [PUBMED:15078142] [PUB00034898]
  5. Li B, Liu Y, Uno T, Gray N. (2004)
    Creating chemical diversity to target protein kinases.
    Comb. Chem. High Throughput Screen. 7: 453-72
    [PUBMED:15320712] [PUB00034899]
  6. Sharma PS, Sharma R, Tyagi T. (2009)
    Receptor tyrosine kinase inhibitors as potent weapons in war against cancers.
    Curr. Pharm. Des. 15: 758-76
    [PUBMED:19275641] [PUB00052410]
  7. Li E, Hristova K. (2006)
    Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies.
    Biochemistry 45: 6241-51
    [PUBMED:16700535] [PUB00052411]
  8. Roskoski R Jr. (2005)
    Src kinase regulation by phosphorylation and dephosphorylation.
    Biochem. Biophys. Res. Commun. 331: 1-14
    [PUBMED:15845350] [PUB00052412]
Database linksMSDsite: PS00109;
BLOCKS: IPB008266;
EC: 2.7;
PROSITEDOC: PDOC00100;
PDB: 1ad5; PDB: 1agw; PDB: 1byg; PDB: 1fgi; PDB: 1fgk; PDB: 1fmk; PDB: 1fpu; PDB: 1fvr; PDB: 1gag; PDB: 1gjo; PDB: 1i44; PDB: 1iep; PDB: 1ir3; PDB: 1irk; PDB: 1jpa; PDB: 1jqh; PDB: 1k2p; PDB: 1k3a; PDB: 1k9a; PDB: 1ksw; PDB: 1luf; PDB: 1m14; PDB: 1m17; PDB: 1m52; PDB: 1m7n; PDB: 1mp8; PDB: 1mqb; PDB: 1oec; PDB: 1opj; PDB: 1opk; PDB: 1opl; PDB: 1p14; PDB: 1p4o; PDB: 1pkg; PDB: 1qcf; PDB: 1qpc; PDB: 1qpd; PDB: 1qpe; PDB: 1qpj; PDB: 1r0p; PDB: 1r1w; PDB: 1rjb; PDB: 1rqq; PDB: 1sm2; PDB: 1snu; PDB: 1snx; PDB: 1t45; PDB: 1t46; PDB: 1tki; PDB: 1tqi; PDB: 1tqm; PDB: 1tqp; PDB: 1u46; PDB: 1u4d; PDB: 1u54; PDB: 1u59; PDB: 1vr2; PDB: 1xba; PDB: 1xbb; PDB: 1xbc; PDB: 1xkk; PDB: 1y57; PDB: 1y6a; PDB: 1y6b; PDB: 1yi6; PDB: 1yoj; PDB: 1yol; PDB: 1yom; PDB: 1yvj; PDB: 1ywn; PDB: 1zao; PDB: 1zar; PDB: 2auh; PDB: 2b4s; PDB: 2b7a; PDB: 2bdf; PDB: 2bdj; PDB: 2c0i; PDB: 2c0o; PDB: 2c0t; PDB: 2dq7; PDB: 2e2b; PDB: 2eb2; PDB: 2eb3; PDB: 2etm; PDB: 2f4j; PDB: 2fgi; PDB: 2fo0; PDB: 2g15; PDB: 2g1t; PDB: 2g2f; PDB: 2g2h; PDB: 2g2i; PDB: 2gqg; PDB: 2gs2; PDB: 2gs6; PDB: 2gs7; PDB: 2gsf; PDB: 2h8h; PDB: 2hck; PDB: 2hel; PDB: 2hen; PDB: 2hiw; PDB: 2hk5; PDB: 2hwo; PDB: 2hwp; PDB: 2hyy; PDB: 2hz0; PDB: 2hz4; PDB: 2hzi; PDB: 2hzn; PDB: 2i0v; PDB: 2i0y; PDB: 2i1m; PDB: 2ijm; PDB: 2itn; PDB: 2ito; PDB: 2itp; PDB: 2itq; PDB: 2itt; PDB: 2itu; PDB: 2itv; PDB: 2itw; PDB: 2itx; PDB: 2ity; PDB: 2itz; PDB: 2ivs; PDB: 2ivt; PDB: 2ivu; PDB: 2ivv; PDB: 2j0l; PDB: 2j0m; PDB: 2j5e; PDB: 2j5f; PDB: 2j6m; PDB: 2jit; PDB: 2jiu; PDB: 2jiv; PDB: 2jkk; PDB: 2jkm; PDB: 2jko; PDB: 2jkq; PDB: 2of2; PDB: 2of4; PDB: 2ofu; PDB: 2ofv; PDB: 2og8; PDB: 2ogv; PDB: 2oh4; PDB: 2oiq; PDB: 2oj9; PDB: 2oo8; PDB: 2osc; PDB: 2ozo; PDB: 2p0c; PDB: 2p2h; PDB: 2p2i; PDB: 2p4i; PDB: 2pl0; PDB: 2psq; PDB: 2ptk; PDB: 2pvf; PDB: 2pvy; PDB: 2pwl; PDB: 2py3; PDB: 2pz5; PDB: 2pzp; PDB: 2pzr; PDB: 2q0b; PDB: 2qi8; PDB: 2qlq; PDB: 2qo2; PDB: 2qo7; PDB: 2qo9; PDB: 2qob; PDB: 2qoc; PDB: 2qod; PDB: 2qof; PDB: 2qoh; PDB: 2qoi; PDB: 2qok; PDB: 2qol; PDB: 2qon; PDB: 2qoo; PDB: 2qoq; PDB: 2qq7; PDB: 2qu5; PDB: 2qu6; PDB: 2r2p; PDB: 2r4b; PDB: 2rei; PDB: 2rf9; PDB: 2rfd; PDB: 2rfe; PDB: 2rfn; PDB: 2rfs; PDB: 2rgp; PDB: 2rl5; PDB: 2src; PDB: 2v7a; PDB: 2vwu; PDB: 2vwv; PDB: 2vww; PDB: 2vwx; PDB: 2vwy; PDB: 2vwz; PDB: 2vx0; PDB: 2vx1; PDB: 2w1i; PDB: 2wd1; PDB: 2wgj; PDB: 2wkm; PDB: 2wqb; PDB: 2x2k; PDB: 2x2l; PDB: 2x2m; PDB: 2x9f; PDB: 2xa4; PDB: 2xb7; PDB: 2xba; PDB: 2xir; PDB: 2xp2; PDB: 2xvd; PDB: 2xyn; PDB: 2yfx; PDB: 2yhv; PDB: 2z60; PDB: 2z8c; PDB: 2zm1; PDB: 2zm3; PDB: 2zm4; PDB: 2zv7; PDB: 2zv8; PDB: 2zv9; PDB: 2zva; PDB: 2zyb; PDB: 3a4o; PDB: 3a4p; PDB: 3ac1; PDB: 3ac2; PDB: 3ac3; PDB: 3ac4; PDB: 3ac5; PDB: 3ac8; PDB: 3acj; PDB: 3ack; PDB: 3ad4; PDB: 3ad5; PDB: 3ad6; PDB: 3aox; PDB: 3b2t; PDB: 3b2w; PDB: 3b8q; PDB: 3b8r; PDB: 3bbt; PDB: 3bbw; PDB: 3bce; PDB: 3be2; PDB: 3bea; PDB: 3bel; PDB: 3bkb; PDB: 3bpr; PDB: 3brb; PDB: 3bu3; PDB: 3bu5; PDB: 3bu6; PDB: 3bym; PDB: 3byo; PDB: 3bys; PDB: 3byu; PDB: 3bz3; PDB: 3c1x; PDB: 3c4f; PDB: 3c7q; PDB: 3cbl; PDB: 3cc6; PDB: 3ccn; PDB: 3cd3; PDB: 3cd8; PDB: 3ce3; PDB: 3cjf; PDB: 3cjg; PDB: 3cly; PDB: 3cok; PDB: 3cp9; PDB: 3cpb; PDB: 3cpc; PDB: 3cs9; PDB: 3cth; PDB: 3ctj; PDB: 3d7t; PDB: 3d7u; PDB: 3d94; PDB: 3dk3; PDB: 3dk6; PDB: 3dk7; PDB: 3dkc; PDB: 3dkf; PDB: 3dkg; PDB: 3dko; PDB: 3dpk; PDB: 3dqw; PDB: 3dqx; PDB: 3dtw; PDB: 3dzq; PDB: 3e62; PDB: 3e63; PDB: 3e64; PDB: 3efj; PDB: 3efk; PDB: 3efl; PDB: 3ekk; PDB: 3ekn; PDB: 3el7; PDB: 3el8; PDB: 3emg; PDB: 3en4; PDB: 3en5; PDB: 3en6; PDB: 3en7; PDB: 3eqp; PDB: 3eqr; PDB: 3et7; PDB: 3eta; PDB: 3ewh; PDB: 3eyg; PDB: 3eyh; PDB: 3f3t; PDB: 3f3u; PDB: 3f3v; PDB: 3f3w; PDB: 3f5p; PDB: 3f66; PDB: 3f6x; PDB: 3f82; PDB: 3fqe; PDB: 3fqh; PDB: 3fqs; PDB: 3fup; PDB: 3fxx; PDB: 3fy2; PDB: 3fzo; PDB: 3fzp; PDB: 3fzr; PDB: 3fzs; PDB: 3fzt; PDB: 3g0e; PDB: 3g0f; PDB: 3g5d; PDB: 3g6g; PDB: 3g6h; PDB: 3gen; PDB: 3geq; PDB: 3gop; PDB: 3gqi; PDB: 3gql; PDB: 3gt8; PDB: 3gvu; PDB: 3h3c; PDB: 3hmi; PDB: 3hng; PDB: 3i5n; PDB: 3i81; PDB: 3ik3; PDB: 3ika; PDB: 3io7; PDB: 3iok; PDB: 3js2; PDB: 3jy9; PDB: 3k54; PDB: 3k5v; PDB: 3kck; PDB: 3kf4; PDB: 3kfa; PDB: 3kmm; PDB: 3krj; PDB: 3krl; PDB: 3krr; PDB: 3kul; PDB: 3kxx; PDB: 3kxz; PDB: 3ky2; PDB: 3l8p; PDB: 3l8v; PDB: 3l9p; PDB: 3lcd; PDB: 3lck; PDB: 3lco; PDB: 3lcs; PDB: 3lct; PDB: 3lok; PDB: 3lpb; PDB: 3lq8; PDB: 3lvp; PDB: 3lw0; PDB: 3lxk; PDB: 3lxl; PDB: 3lxn; PDB: 3lxp; PDB: 3lzb; PDB: 3miy; PDB: 3mj1; PDB: 3mj2; PDB: 3mpm; PDB: 3ms9; PDB: 3mss; PDB: 3nw5; PDB: 3nw6; PDB: 3nw7; PDB: 3nyx; PDB: 3nz0; PDB: 3o23; PDB: 3ocs; PDB: 3oct; PDB: 3oxz; PDB: 3oy3; PDB: 3p08; PDB: 3pix; PDB: 3piy; PDB: 3piz; PDB: 3pj1; PDB: 3pj2; PDB: 3pj3; PDB: 3pjc; PDB: 3pls; PDB: 3poz; PDB: 3pp0; PDB: 3pyy; PDB: 3q32; PDB: 3q6u; PDB: 3q6w; PDB: 3qgw; PDB: 3qgy; PDB: 3qqu; PDB: 3qri; PDB: 3qrj; PDB: 3qrk; PDB: 3qti; PDB: 3rhk; PDB: 3rhx; PDB: 3ri1; CATH: 1.10.510.10; SCOP: d.144.1.7; SCOP: d.144.1.9;
Taxonomy DistributionCaenorhabditis elegans: 100
Archaea: 1
Cyanobacteria: 8
Eukaryota: 104
Fungi: 29
OtherEukaryotes: 138
PlastidGroup: 9
Bacteria: 118
Eukaryota: 37
OtherEukaryotes: 26
PlastidGroup: 256
Virus: 44
Cyanobacteria: 3
Eukaryota: 1738
PlastidGroup: 1738
Bacteria: 21
Eukaryota: 15296
Bacteria: 1
Eukaryota: 345
Bacteria: 4
Eukaryota: 256
Bacteria: 428
Eukaryota: 91
Bacteria: 6
Bacteria: 1
Bacteria: 17
Eukaryota: 26
Bacteria: 1237
Bacteria: 16
Eukaryota: 138
Eukaryota: 17
Eukaryota: 20
Bacteria: 15
Bacteria: 5
Archaea: 323
Arthropoda: 1913
Bacteria: 2385
Chordata: 9059
Cyanobacteria: 118
Eukaryota: 18145
FruitFly: 334
Fungi: 1964
GreenPlants: 1738
Human: 431
Mouse: 329
Nematoda: 1070
OtherEukaryotes: 17
PlastidGroup: 345
Viruses: 343
Arthropoda: 112
Cyanobacteria: 29
Fungi: 1186
Metazoa: 12739
Nematoda: 27
OtherEukaryotes: 20
PlastidGroup: 37
Fungi: 594
Nematoda: 1043
PlastidGroup: 91
Unclassified: 2
Archaea: 1
Arthropoda: 1801
Bacteria: 192
Chordata: 279
Virus: 299
Archaea: 5
Bacteria: 7
Cyanobacteria: 46
Eukaryota: 68
Fungi: 5
Metazoa: 23
OtherEukaryotes: 68
PlastidGroup: 104
Bacteria: 9
Eukaryota: 9
Fungi: 143
Saccharomyces cerevisiae: 19
Virus: 343
Metazoa: 242
Bacteria: 1
Bacteria: 2
Arabidopsis thaliana: 32
Metazoa: 13004
Rice: 102
Archaea: 58
Bacteria: 304
Chordata: 179
GreenPlants: 84
Unclassified: 32
Archaea: 245
Chordata: 8601
GreenPlants: 1654
Fungi: 7
Metazoa: 112
Cyanobacteria: 32

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