Summary: Protein kinase domain
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Protein kinase domain Edit Wikipedia article
|Protein kinase domain|
Structure of the catalytic subunit of cAMP-dependent protein kinase.
The protein kinase domain is a structurally conserved protein domain containing the catalytic function of protein kinases. Protein kinases are a group of enzymes that move a phosphate group onto proteins, in a process called phosphorylation. This functions as an on/off switch for many cellular processes, including metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. They also function in embryonic development, physiological responses, and in the nervous and immune system. Abnormal phosphorylation causes many human diseases, including cancer, and drugs that affect phosphorylation can treat those diseases.
Protein kinases possess a catalytic subunit which transfers the gamma phosphate from nucleoside triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. These enzymes fall into two broad classes, characterised with respect to substrate specificity: serine/threonine specific and tyrosine specific.
Protein kinase function has been evolutionarily conserved from Escherichia coli to Homo sapiens. 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.
Eukaryotic protein kinases are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common with both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the catalytic domain of protein kinases. In the N-terminal extremity of the catalytic domain there is a glycine-rich stretch of residues in the vicinity of a lysine residue, which has been shown to be involved in ATP binding. In the central part of the catalytic domain there is a conserved aspartic acid residue which is important for the catalytic activity of the enzyme.
The following is a list of human proteins containing the protein kinase domain:
AAK1; ABL1; ABL2; ACVR1; ACVR1B; ACVR1C; ACVR2A; ACVR2B; ACVRL1; ADCK1; ADCK2; ADCK3; ADCK4; ADCK5; ADRBK1; ADRBK2; AKT1; AKT2; AKT3; ALPK1; ALPK2; ALPK3; STRADB; CDK15; AMHR2; ANKK1; ARAF; ATM; ATR; AURKA; AURKB; AURKC; AXL; BCKDK; BLK; BMP2K; BMPR1A; BMPR1B; BMPR2; BMX; BRAF; BRSK1; BRSK2; BTK; BUB1; C21orf7; CALM1; CALM2; CALM3; CAMK1; CAMK1D; CAMK1G; CAMK2A; CAMK2B; CAMK2D; CAMK2G; CAMK4; CAMKK1; CAMKK2; CAMKV; CASK; CDK20; CDK1; CDK11B; CDK11A; CDK13; CDK19; CDC42BPA; CDC42BPB; CDC42BPG; CDC7; CDK10; CDK2; CDK3; CDK4; CDK5; CDK6; CDK7; CDK8; CDK9; CDK12; CDK14; CDK16; CDK17; CDK18; CDKL1; CDKL2; CDKL3; CDKL4; CDKL5; CHEK1; CHEK2; CHUK; CIT; CKB; CKM; CLK1; CLK2; CLK3; CLK4; CSF1R; CSK; CSNK1A1; CSNK1A1L; CSNK1D; CSNK1E; CSNK1G1; CSNK1G2; CSNK1G3; CSNK2A1; CSNK2A2; DAPK1; DAPK2; DAPK3; DCLK1; DCLK2; DCLK3; DDR1; DDR2; DMPK; DYRK1A; DYRK1B; DYRK2; DYRK3; DYRK4; EGFR; EIF2AK1; EIF2AK2; EIF2AK3; EIF2AK4; ELK1; EPHA1; EPHA2; EPHA3; EPHA4; EPHA5; EPHA6; EPHA7; EPHA8; EPHB1; EPHB2; EPHB3; EPHB4; ERBB2; ERBB3; ERBB4; ERN1; ERN2; FER; FES; FGFR1; FGFR2; FGFR3; FGFR4; FGR; FLT1; FLT3; FLT4; FYN; GAK; GRK1; GRK4; GRK5; GRK6; GRK7; GSK3A; GSK3B; GUCY2C; GUCY2D; GUCY2E; GUCY2F; HCK; HIPK1; HIPK2; HIPK3; HIPK4; HUNK; ICK; IGF1R; IGF2R; IKBKB; IKBKE; ILK; INSR; IRAK1; IRAK2; IRAK3; IRAK4; ITK; JAK1; JAK2; JAK3; KALRN; KDR; SIK3; KSR2; LATS1; LATS2; LIMK1; LCK; LIMK2; LRRK1; LRRK2; LYN; MAK; MAP2K1; MAP2K2; MAP2K3; MAP2K4; MAP2K5; MAP2K6; MAP2K7; MAP3K1; MAP3K10; MAP3K11; MAP3K12; MAP3K13; MAP3K14; MAP3K15; MAP3K2; MAP3K3; MAP3K4; MAP3K5; MAP3K6; MAP3K7; MAP3K8; MAP3K9; MAP4K1; MAP4K2; MAP4K3; MAP4K4; MAP4K5; MAPK1; MAPK10; MAPK12; MAPK13; MAPK14; MAPK15; MAPK3; MAPK4; MAPK6; MAPK7; MAPK8; MAPK9; MAPKAPK2; MAPKAPK3; MAPKAPK5; MARK1; MARK2; MARK3; MARK4; MAST1; MAST2; MAST3; MAST4; MASTL; MELK; MERTK; MET; MINK1; MKNK1; MKNK2; MLKL; MOS; MST1R; MST4; MTOR; MYLK; MYLK2; MYLK3; MYLK4; NEK1; NEK10; NEK11; NEK2; NEK3; NEK4; NEK5; LOC100506859; NEK6; NEK7; NEK8; NEK9; MGC42105; NLK; NRK; NTRK1; NTRK2; NTRK3; NUAK1; NUAK2; OBSCN; OXSR1; PAK1; PAK2; PAK3; PAK4; PAK6; PAK7; PASK; PBK; PDGFRA; PDGFRB; PDIK1L; PDPK1; PHKA1; PHKB; PHKG1; PHKG2; PIK3R4; PIM1; PIM2; PIM3; PINK1; PKMYT1; PKN1; PKN2; PKN3; PLK1; PLK2; PLK3; PLK4; PNCK; PRKAA1; PRKAA2; PRKACA; PRKACB; PRKACG; PRKCA; PRKCB; PRKCD; PRKCE; PRKCG; PRKCH; PRKCI; PRKCQ; PRKCZ; PRKD1; PRKD2; PRKD3; PRKG1; PRKG2; PRKX; LOC389906; PRKY; PRPF4B; PSKH1; PSKH2; PTK2; PTK2B; RAF1; RAGE; RET; RIP3; RIPK1; RIPK2; RIPK3; RIPK4; ROCK1; ROCK2; ROR1; ROR2; ROS1; RPS6KA1; RPS6KA2; RPS6KA3; RPS6KA4; RPS6KA5; RPS6KA6; RPS6KB1; RPS6KB2; RPS6KC1; RPS6KL1; RYK; SCYL1; SCYL2; SCYL3; SGK1; LOC100130827; SGK196; SGK2; SGK3; SGK494; SIK1; SIK2; SLK; SNRK; SPEG; SRC; SRPK1; SRPK2; SRPK3; STK10; STK11; STK16; STK17A; STK17B; STK19; STK24; STK25; STK3; STK31; STK32A; STK32B; STK32C; STK33; STK35; STK36; STK38; STK38L; STK39; STK4; STK40; SYK; TAOK1; TAOK2; TAOK3; TBCK; TBK1[disambiguation needed]; TEC; TESK1; TESK2; TGFBR1; TGFBR2; TIE1; TIE2; TLK1; TLK2; TNIK; TNK1; TNK2; TSSK1B; TSSK2; TSSK3; TSSK4; TTBK1; TTBK2; TTK; TWF2; TXK; TYK2; TYRO3; UHMK1; ULK1; ULK2; ULK3; ULK4; VRK1; VRK2; VRK3; WEE1; WEE2; WNK1; WNK2; WNK3; WNK4; YES1; ZAK; ZAP70;
- Knighton DR, Bell SM, Zheng J, et al. (May 1993). "2.0 A refined crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with a peptide inhibitor and detergent". Acta Crystallogr. D Biol. Crystallogr. 49 (Pt 3): 357–61. doi:10.1107/S0907444993000502. PMID 15299526.
- Hanks SK, Quinn AM (1991).  Protein kinase catalytic domain sequence database: Identification of conserved features of primary structure and classification of family members. "Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members". Meth. Enzymol. Methods in Enzymology 200: 38–62. doi:10.1016/0076-6879(91)00126-H. ISBN 978-0-12-182101-2. PMID 1956325.
- Hanks SK, Hunter T (May 1995). "Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification". FASEB J. 9 (8): 576–96. PMID 7768349.
- Scheeff ED, Bourne PE (October 2005). "Structural evolution of the protein kinase-like superfamily". PLoS Comput. Biol. 1 (5): e49. doi:10.1371/journal.pcbi.0010049. PMC 1261164. PMID 16244704.
- G. Manning, D. B. Whyte, R. Martinez, T. Hunter, S. Sudarsanam, The Protein Kinase Complement of the Human Genome, Science 6 December 2002, 298:1912-1934 doi:10.1126/science.1075762
- Hunter T, Hanks SK, Quinn AM (1988). "The protein kinase family: conserved features and deduced phylogeny of the catalytic domains". Science 241 (4861): 42–51. doi:10.1126/science.3291115. PMID 3291115.
- Manning G, Plowman GD, Hunter T, Sudarsanam S (October 2002). "Evolution of protein kinase signaling from yeast to man". Trends Biochem. Sci. 27 (10): 514–20. doi:10.1016/S0968-0004(02)02179-5. PMID 12368087.
- Stout TJ, Foster PG, Matthews DJ (2004). "High-throughput structural biology in drug discovery: protein kinases". Curr. Pharm. Des. 10 (10): 1069–82. doi:10.2174/1381612043452695. PMID 15078142.
- Li B, Liu Y, Uno T, Gray N (August 2004). "Creating chemical diversity to target protein kinases". Comb. Chem. High Throughput Screen. 7 (5): 453–72. doi:10.2174/1386207043328580. PMID 15320712.
- Hanks SK (2003). "Genomic analysis of the eukaryotic protein kinase superfamily: a perspective". Genome Biol. 4 (5): 111. doi:10.1186/gb-2003-4-5-111. PMC 156577. PMID 12734000.[dead link]
- Hunter T (1991).  Protein kinase classification. "Protein kinase classification". Meth. Enzymol. Methods in Enzymology 200: 3–37. doi:10.1016/0076-6879(91)00125-G. ISBN 978-0-12-182101-2. PMID 1835513.
- Knighton DR, Zheng JH, Ten Eyck LF, Ashford VA, Xuong NH, Taylor SS, Sowadski JM (July 1991). "Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase". Science 253 (5018): 407–14. doi:10.1126/science.1862342. PMID 1862342.
- Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (December 2002). "The protein kinase complement of the human genome". Science 298 (5600): 1912–34. doi:10.1126/science.1075762. PMID 12471243.
- Eukaryotic Linear Motif resource motif class LIG_AGCK_PIF_1
- Eukaryotic Linear Motif resource motif class LIG_AGCK_PIF_2
- Eukaryotic Linear Motif resource motif class LIG_AGCK_PIF_3
- Eukaryotic Linear Motif resource motif class LIG_MAPK_1
- Eukaryotic Linear Motif resource motif class LIG_MAPK_2
- Eukaryotic Linear Motif resource motif class MOD_CDK_1
- Eukaryotic Linear Motif resource motif class MOD_CK1_1
- Eukaryotic Linear Motif resource motif class MOD_CK2_1
- Eukaryotic Linear Motif resource motif class MOD_GSK3_1
- Eukaryotic Linear Motif resource motif class MOD_LATS_1
- Eukaryotic Linear Motif resource motif class MOD_PK_1
- Eukaryotic Linear Motif resource motif class MOD_PKA_1
- Eukaryotic Linear Motif resource motif class MOD_PKA_2
- Eukaryotic Linear Motif resource motif class MOD_PKB_1
- Eukaryotic Linear Motif resource motif class MOD_ProDKin_1
- Eukaryotic Linear Motif resource motif class MOD_TYR_DYR
Protein kinase domain Provide feedback
No Pfam abstract.
Hanks SK, Quinn AM; , Methods Enzymol 1991;200:38-62.: Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members. PUBMED:1956325 EPMC:1956325
Internal database links
|Similarity to PfamA using HHSearch:||RIO1 APH Kdo Pkinase_Tyr YrbL-PhoP_reg Kinase-like|
External database links
|PROSITE:||PDOC00100 PDOC00212 PDOC00213 PDOC00629|
|SMART:||STYKc S_TKc TyrKc|
This tab holds annotation information from the InterPro database.
InterPro entry IPR000719
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 [PUBMED:3291115]:
- 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 [PUBMED:12471243]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [PUBMED:12368087]. 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 [PUBMED:15078142], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [PUBMED:15320712].
Eukaryotic protein kinases [PUBMED:12734000, PUBMED:7768349, PUBMED:1835513, PUBMED:1956325, PUBMED:3291115] are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common with both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the catalytic domain of protein kinases. In the N-terminal extremity of the catalytic domain there is a glycine-rich stretch of residues in the vicinity of a lysine residue, which has been shown to be involved in ATP binding. In the central part of the catalytic domain there is a conserved aspartic acid residue which is important for the catalytic activity of the enzyme [PUBMED:1862342].
This entry represents the protein kinase catalytic domain found in serine/threonine-protein kinases, tyrosine-protein kinases and dual specificity protein kinases.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||ATP binding (GO:0005524)|
|protein kinase activity (GO:0004672)|
|Biological process||protein phosphorylation (GO:0006468)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
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This superfamily includes the Serine/Threonine- and Tyrosine- protein kinases as well as related kinases that act on non-protein substrates.
The clan contains the following 19 members:ABC1 APH APH_6_hur Choline_kinase DUF1679 DUF2252 EcKinase Fructosamin_kin Kdo Kinase-like PIP49_C Pkinase Pkinase_Tyr Pox_ser-thr_kin RIO1 Seadorna_VP7 UL97 WaaY YrbL-PhoP_reg
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
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Curation and family details
|Number in seed:||54|
|Number in full:||114309|
|Average length of the domain:||237.60 aa|
|Average identity of full alignment:||20 %|
|Average coverage of the sequence by the domain:||40.43 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||20|
|Download:||download the raw HMM for this family|
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There are 21 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Pkinase domain has been found. There are 2311 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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