The Protein Kinase Complement of the Human Genome

  title={The Protein Kinase Complement of the Human Genome},
  author={Gerard Manning and David B. Whyte and Raquel Martinez and Tony Hunter and Sucha Sudarsanam},
  pages={1912 - 1934}
We have catalogued the protein kinase complement of the human genome (the "kinome") using public and proprietary genomic, complementary DNA, and expressed sequence tag (EST) sequences. [] Key Result We identify 518 putative protein kinase genes, of which 71 have not previously been reported or described as kinases, and we extend or correct the protein sequences of 56 more kinases.

Bioinformatic prediction and analysis of eukaryotic protein kinases in the rat genome.

Eukaryotic protein kinases, containing a conserved catalytic domain, represent one of the largest superfamilies of the eukaryotic proteins and play distinct roles in cell signaling and diseases. Near

Systematic analysis of human kinase genes: a large number of genes and alternative splicing events result in functional and structural diversity

The predicted human kinome was extended by identifiying both additional genes and potential splice variants, resulting in a varied panorama where functionality may be searched at the gene and protein level.

ProKinO: An Ontology for Integrative Analysis of Protein Kinases in Cancer

ProKinO is described, aprotein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on protein kinases, and presents an integrated framework for large-scale integrative analysis of protein kinase data.

A genomic perspective of protein kinases in Plasmodium falciparum

A genome‐wide analysis for protein kinase encoded in the Plasmodium falciparum genome is described, revealing a new subfamily of protein kinases having limited sequence similarity with previously known subfamilies.

A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage

This analysis explored the sequence of the human genome to define the composition of the PTP family and discovered one novel human PTP gene and defined chromosomal loci and exon structure of the additional 37 genes encoding known PTP transcripts.

The Janus Kinase Protein Family

The near-completion of sequencing of the human genome has identified 518 protein kinase genes, representing 1.7% of all human genes. Protein kinases form one of the largest protein families in human,

The mouse kinome: discovery and comparative genomics of all mouse protein kinases.

The full protein kinase (PK) complement (kinome) of mouse is determined, which includes many novel kinases and corrections or extensions to >150 published sequences, and links 163 kinases to mutant phenotypes and unlocks the use of mouse genetics to determine functions of orthologous human kinases.

Building a human kinase gene repository: bioinformatics, molecular cloning, and functional validation.

The mining of public databases to collect the sequence information of all identified human kinase genes and the cloning of the corresponding ORFs is described, which will facilitate the functional assaying of this important gene family in phenotypic screens and their use in biochemical and structural studies.



The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification 1

  • S. HanksT. Hunter
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1995
The eukaryotic protein kinases make up a large superfamily of homologous proteins, and a classification scheme can be founded on a kinase domain phylogeny, which reveals families of enzymes that have related substrate specificities and modes of regulation.

WNK1, a Novel Mammalian Serine/Threonine Protein Kinase Lacking the Catalytic Lysine in Subdomain II*

Mutation of this lysine residue to methionine eliminates WNK1 activity, consistent with the conclusion that it is required for catalysis, and indicates that W NK1 belongs to a novel family of serine/threonine protein kinases.

Extensive genomic duplication during early chordate evolution

A systematic and objective analysis of the draft human genome sequence is reported to identify paralogous chromosomal regions (paralogons) formed during chordate evolution and to estimate the ages of duplicate genes.

Complex Effects of Naturally Occurring Mutations in the JAK3 Pseudokinase Domain: Evidence for Interactions between the Kinase and Pseudokinase Domains

It is concluded that the JAK3 pseudokinase domain is essential forJAK3 function by regulating its catalytic activity and autophosphorylation and proposed a model in which this occurs via intramolecular interaction with the kinase domain.

Identification and Characterization of a Haploid Germ Cell-specific Nuclear ProteinKinase (Haspin) in Spermatid Nuclei and Its Effects on Somatic Cells*

We have cloned the entire coding region of a mouse germ cell-specific cDNA encoding a unique protein kinase whose catalytic domain contains only three consensus subdomains (I–III) instead of the

The Sequence of the Human Genome

Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems are indicated.

KSR: a MAPK scaffold of the Ras pathway?

The model now emerging is that KSR acts as a scaffolding protein that coordinates the assembly of a membrane-localized, multiprotein MAP kinase complex, a vital step in Ras-mediated signal transduction, and while Kinase Suppressor of Ras may be its name, phosphorylation may not be its game.

The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18 within the mdm-2 binding site of the p53 tumour suppressor protein

The human VRK1 protein is an upstream regulator of p53 that belongs to a new signalling pathway that phosphorylates acidic proteins, and basic proteins such as histone 2b and myelin basic protein.

Cyclin C/CDK8 is a novel CTD kinase associated with RNA polymerase II.

It is demonstrated that the cyclin C/CDK8 complex associates with the large subunit of RNA polymerase II in vivo, implicating a potential role for cyclin B/CDB8 in regulating its activities and retaining potent CTD kinase activity.