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4704  structures 7104  species 73  interactions 349448  sequences 9546  architectures

Family: Pkinase (PF00069)

Summary: Protein kinase domain

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This is the Wikipedia entry entitled "Protein kinase domain". More...

Protein kinase domain Edit Wikipedia article

Protein kinase domain
PDB 1apm EBI.jpg
Structure of the catalytic subunit of cAMP-dependent protein kinase.[1]
Identifiers
Symbol Pkinase
Pfam PF00069
InterPro IPR000719
SMART TyrKc
PROSITE PDOC00100
SCOP 1apm
SUPERFAMILY 1apm
OPM superfamily 417
OPM protein 2w5a
CDD cd00180

The protein kinase domain is a structurally conserved protein domain containing the catalytic function of protein kinases.[2][3][4] 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.[5]

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.[6]

Function

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.[7] Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins.

Structure

The catalytic subunits of protein kinases are highly conserved, and several structures have been solved,[8] leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases.[9]

Eukaryotic protein kinases[2][3][10][11] 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.[12]

Examples

The following is a list of human proteins containing the protein kinase domain:[13]

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; 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; VEGFR; VRK1; VRK2; VRK3; WEE1; WEE2; WNK1; WNK2; WNK3; WNK4; YES1; ZAK; ZAP70;

References

  1. ^ 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. 49 (Pt 3): 357–61. doi:10.1107/S0907444993000502. PMID 15299526. 
  2. ^ a b Hanks SK, Quinn AM (1991). "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. 
  3. ^ a b 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. 
  4. ^ 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 Freely accessible. PMID 16244704. 
  5. ^ 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
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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 Freely accessible. PMID 12734000. Archived from the original on 24 January 2013. 
  11. ^ Hunter T (1991). "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. 
  12. ^ 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. 
  13. ^ 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. 

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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Literature references

  1. 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

  2. Hanks SK, Hunter T; , FASEB J 1995;9:576-596.: Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. PUBMED:7768349 EPMC:7768349

  3. Hunter T, Plowman GD; , Trends Biochem Sci 1997;22:18-22.: The protein kinases of budding yeast: six score and more. PUBMED:9020587 EPMC:9020587

Internal database links

SCOOP: ABC1 APH Choline_kinase DUF1679 EcKinase EF-hand_1 EF-hand_5 EF-hand_6 EF-hand_7 EF-hand_8 Fructosamin_kin FTA2 Haspin_kinase HNOBA Kdo Kinase-like PIP49_C Pkinase_C Pkinase_fungal Pkinase_Tyr Pox_ser-thr_kin RIO1 Seadorna_VP7 WaaY YrbL-PhoP_reg YukC
Similarity to PfamA using HHSearch: RIO1 APH Kdo Pkinase_Tyr Haspin_kinase FTA2 Kinase-like Pkinase_fungal

External database links

HOMSTRAD: kinase TyrKc
PRINTS: PR00109
PROSITE: PDOC00100 PDOC00212 PDOC00213 PDOC00629
PROSITE profile: PS50011
SCOP: 1apm
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 domain containing the catalytic function of protein kinases [PUBMED:1956325]. This domain is found in serine/threonine-protein kinases, tyrosine-protein kinases and dual specificity protein kinases.

Gene Ontology

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)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan PKinase (CL0016), which has the following description:

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 38 members:

ABC1 AceK Act-Frag_cataly Alpha_kinase APH APH_6_hur Choline_kinase CotH DUF1679 DUF2252 DUF4135 EcKinase Fam20C Fructosamin_kin FTA2 Haspin_kinase HipA_C Ins_P5_2-kin IPK IucA_IucC Kdo Kinase-like Kinase-PolyVal KIND Pan3_PK PI3_PI4_kinase PIP49_C PIP5K Pkinase Pkinase_fungal Pkinase_Tyr Pox_ser-thr_kin RIO1 Seadorna_VP7 UL97 WaaY YrbL-PhoP_reg YukC

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(38)		 Full
(349448)		 Representative proteomes UniProt
(551127)		 NCBI
(986456)		 Meta
(4445)
RP15
(96458)		 RP35
(201494)		 RP55
(284786)		 RP75
(343869)
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PP/heatmap 1                

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, — not available.

Format an alignment

  Seed
(38)		 Full
(349448)		 Representative proteomes UniProt
(551127)		 NCBI
(986456)		 Meta
(4445)
RP15
(96458)		 RP35
(201494)		 RP55
(284786)		 RP75
(343869)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(38)		 Full
(349448)		 Representative proteomes UniProt
(551127)		 NCBI
(986456)		 Meta
(4445)
RP15
(96458)		 RP35
(201494)		 RP55
(284786)		 RP75
(343869)
Raw Stockholm Download     Download             Download  
Gzipped Download     Download             Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Unknown
Previous IDs: pkinase;
Type: Domain
Sequence Ontology: SO:0000417
Author: Sonnhammer ELL
Number in seed: 38
Number in full: 349448
Average length of the domain: 241.50 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 38.16 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 31.6 31.6
Trusted cut-off 31.6 31.6
Noise cut-off 31.5 31.5
Model length: 264
Family (HMM) version: 25
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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Structures

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 4704 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 sequence.

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