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EBIDatabasesDatabase BrowsingDbfetchInterPro: IPR008266

EBI Dbfetch

Tyrosine-protein kinase, active site

AccessionIPR008266; (Tyr_kinase_AS) matches 16691 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.
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: 96
Archaea: 1
Cyanobacteria: 8
Eukaryota: 104
Fungi: 13
OtherEukaryotes: 138
PlastidGroup: 9
Bacteria: 111
Eukaryota: 37
PlastidGroup: 89
Virus: 44
Cyanobacteria: 3
Eukaryota: 1209
PlastidGroup: 1209
Bacteria: 19
Eukaryota: 12504
Bacteria: 1
Eukaryota: 128
Virus: 5
Bacteria: 6
Eukaryota: 89
Bacteria: 243
Eukaryota: 68
Bacteria: 2
Bacteria: 17
Bacteria: 919
Bacteria: 16
Eukaryota: 138
Eukaryota: 17
Bacteria: 1
Eukaryota: 20
Bacteria: 15
Bacteria: 2
Arabidopsis thaliana: 32
Archaea: 288
Arthropoda: 1499
Bacteria: 1707
Chordata: 8060
Cyanobacteria: 111
Eukaryota: 14360
Fungi: 1221
GreenPlants: 1209
Metazoa: 10959
Nematoda: 721
OtherEukaryotes: 17
PlastidGroup: 128
Rice: 102
Viruses: 326
Archaea: 50
Bacteria: 219
Cyanobacteria: 26
Fungi: 826
GreenPlants: 81
Metazoa: 10694
Nematoda: 27
OtherEukaryotes: 20
PlastidGroup: 37
Unclassified: 8
Archaea: 229
GreenPlants: 1128
Nematoda: 694
PlastidGroup: 68
Unclassified: 2
Arthropoda: 1451
Bacteria: 114
Chordata: 279
Virus: 277
Bacteria: 7
Cyanobacteria: 43
Eukaryota: 37
Fungi: 5
Metazoa: 23
OtherEukaryotes: 37
PlastidGroup: 104
Bacteria: 9
Cyanobacteria: 31
Eukaryota: 9
Saccharomyces cerevisiae: 14
Virus: 326
Metazoa: 242
Bacteria: 5
FruitFly: 333
Human: 399
Mouse: 329
Arthropoda: 48
Chordata: 179
Chordata: 7602
Fungi: 370
Archaea: 1
Fungi: 7
Metazoa: 91
Archaea: 1

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