Dbfetch

Tyrosine-protein kinase, active site

AccessionIPR008266; (Tyr_kinase_AS) matches 34901 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.

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. Roskoski R Jr. (2005)
    Src kinase regulation by phosphorylation and dephosphorylation.
    Biochem. Biophys. Res. Commun. 331: 1-14
    [PUBMED:15845350] [PUB00052412]
  7. 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]
  8. 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]
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: 2xyu; PDB: 2y6m; PDB: 2y6o; PDB: 2yfx; PDB: 2yhv; PDB: 2yjr; PDB: 2yjs; 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: 3oez; PDB: 3of0; 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: 3pxk; PDB: 3pyy; PDB: 3q32; PDB: 3q6u; PDB: 3q6w; PDB: 3qgw; PDB: 3qgy; PDB: 3qlf; PDB: 3qlg; PDB: 3qqu; PDB: 3qri; PDB: 3qrj; PDB: 3qrk; PDB: 3qti; PDB: 3qup; PDB: 3r7o; PDB: 3rcd; PDB: 3rhk; PDB: 3rhx; PDB: 3ri1; PDB: 3rvg; PDB: 3srv; PDB: 3svv; PDB: 3sxr; PDB: 3sxs; PDB: 3t9t; PDB: 3tcp; PDB: 3tjc; PDB: 3tjd; PDB: 3tt0; PDB: 3tub; PDB: 3tuc; PDB: 3tud; PDB: 3tz7; PDB: 3tz8; PDB: 3tz9; PDB: 3u4w; PDB: 3u51; PDB: 3u6h; PDB: 3u6i; PDB: 3u6j; PDB: 3ue4; PDB: 3ug1; PDB: 3ug2; PDB: 3ugc; PDB: 3uqf; PDB: 3uqg; PDB: 3v5j; PDB: 3v5l; PDB: 3v5q; PDB: 3v8t; PDB: 3v8w; PDB: 3vf8; PDB: 3vf9; PDB: 3vhe; PDB: 3vhk; PDB: 3vid; PDB: 3vjn; PDB: 3vjo; PDB: 3vnt; PDB: 3vo3; PDB: 3w2o; PDB: 3w2p; PDB: 3w2q; PDB: 3w2r; PDB: 3zxz; PDB: 3zze; PDB: 3zzw; PDB: 4ag8; PDB: 4agc; PDB: 4agd; PDB: 4agw; PDB: 4aoi; PDB: 4aoj; PDB: 4ap7; PDB: 4aqc; PDB: 4asd; PDB: 4ase; PDB: 4asz; PDB: 4at3; PDB: 4at4; PDB: 4at5; PDB: 4aw5; PDB: 4bb4; PDB: 4bbe; PDB: 4bbf; PDB: 4dce; PDB: 4deg; PDB: 4deh; PDB: 4dei; PDB: 4dfl; PDB: 4dfn; PDB: 4dgg; PDB: 4e1z; PDB: 4e20; PDB: 4e4l; PDB: 4e4m; PDB: 4e4n; PDB: 4e5w; PDB: 4e6d; PDB: 4e6q; PDB: 4e93; PDB: 4ehz; PDB: 4ei4; PDB: 4f08; PDB: 4f09; PDB: 4f0i; PDB: 4f4p; PDB: 4f63; PDB: 4f64; PDB: 4f65; PDB: 4fk6; PDB: 4fl1; PDB: 4fnw; PDB: 4fnx; PDB: 4fny; PDB: 4fnz; PDB: 4fob; PDB: 4foc; PDB: 4fod; PDB: 4fyn; PDB: 4fyo; PDB: 4fz6; PDB: 4g2f; PDB: 4g5j; PDB: 4g5p; PDB: 4gk2; PDB: 4gk3; PDB: 4gk4; PDB: 4gl9; PDB: 4gt4; PDB: 4gt5; PDB: 4hct; PDB: 4hcu; PDB: 4hcv; PDB: 4hge; PDB: 4hvd; PDB: 4hvg; PDB: 4hvh; PDB: 4hvi; PDB: 4i21; PDB: 4i22; CATH: 1.10.510.10; SCOP: d.144.1.7; SCOP: d.144.1.9;
Taxonomy DistributionCaenorhabditis elegans: 105
Archaea: 2
Cyanobacteria: 8
Eukaryota: 106
Eukaryota: 37
PlastidGroup: 321
Bacteria: 31
Eukaryota: 526
Eukaryota: 321
Bacteria: 252
Eukaryota: 118
Bacteria: 6
Eukaryota: 15
Eukaryota: 20
Bacteria: 3
PlastidGroup: 526
Cyanobacteria: 33
Nematoda: 909
OtherEukaryotes: 20
PlastidGroup: 37
PlastidGroup: 118
Unclassified: 2
Bacteria: 159
Cyanobacteria: 87
Eukaryota: 68
OtherEukaryotes: 68
PlastidGroup: 106
Fungi: 143
Metazoa: 242
OtherEukaryotes: 15
Saccharomyces cerevisiae: 111
Fungi: 36
OtherEukaryotes: 140
Eukaryota: 140
PlastidGroup: 9
Eukaryota: 9
Bacteria: 200
Cyanobacteria: 200
Fungi: 5
OtherEukaryotes: 44
Eukaryota: 44
Virus: 44
Cyanobacteria: 20
Eukaryota: 2942
PlastidGroup: 2942
GreenPlants: 2942
Eukaryota: 26099
Bacteria: 1
Fungi: 10
Bacteria: 1
Bacteria: 1
Bacteria: 28
Bacteria: 2157
Bacteria: 6
Eukaryota: 17
OtherEukaryotes: 17
Bacteria: 11
Bacteria: 5
Bacteria: 6
Arabidopsis thaliana: 31
Archaea: 529
Arthropoda: 4800
Bacteria: 3431
Chordata: 12713
Eukaryota: 30462
FruitFly: 341
Fungi: 4109
Human: 456
Metazoa: 21621
Mouse: 335
Nematoda: 2844
Rice: 106
Viruses: 416
Virus: 416
Archaea: 74
Arthropoda: 160
Bacteria: 531
Chordata: 179
Fungi: 2077
GreenPlants: 144
Metazoa: 21356
Unclassified: 61
Archaea: 401
Chordata: 12255
Fungi: 1802
GreenPlants: 2798
Nematoda: 1935
Archaea: 20
Arthropoda: 4640
Chordata: 279
Fungi: 9
Metazoa: 114
Virus: 372
Archaea: 7
Fungi: 22
Metazoa: 23
Bacteria: 13
Cyanobacteria: 52