SMART: TyrKc domain annotation

TyrKc Tyrosine kinase, catalytic domain

SMART accession number:	SM00219
Description:	Phosphotransferases. Tyrosine-specific kinase subfamily.
Interpro abstract (IPR020635):	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)]. 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 [(PUBMED:12471243)]: 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 [(PUBMED:19275641)]. 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 [(PUBMED:16700535)]. 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 [(PUBMED:15845350)].
GO process:	protein phosphorylation (GO:0006468)
GO function:	protein tyrosine kinase activity (GO:0004713)
Family alignment:	View or

There are 4546 TyrKc domains in 4544 proteins in SMART's nrdb database.

Click on the following links for more information.

Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a TyrKc domain in a specific node, click on it.

This tree shows only several representative species. The complete taxonomic breakdown of all proteins with TyrKc domain is also avaliable.

Useful shortcuts: Expand all nodes or Collapse tree
Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes
Cellular role (predicted cellular role)
Binding / catalysis: tyrosine-specific phosphotransferase
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Stapleton D, Balan I, Pawson T, Sicheri F
- The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization.
- Nat Struct Biol. 1999; 6: 44-9
- Display abstract
- The sterile alpha motif (SAM) domain is a novel protein module of approximately 70 amino acids that is found in a variety of signaling molecules including tyrosine and serine/threonine protein kinases, cytoplasmic scaffolding and adaptor proteins, regulators of lipid metabolism, and GTPases as well as members of the ETS family of transcription factors. The SAM domain can potentially function as a protein interaction module through the ability to homo- and hetero-oligomerize with other SAM domains. This functional property elicits the oncogenic activation of chimeric proteins arising from translocation of the SAM domain of TEL to coding regions of the betaPDGF receptor, Abl, JAK2 protein kinase and the AML1 transcription factor. Here we describe the 2.0 A X-ray crystal structure of a SAM domain homodimer from the intracellular region of the EphA4 receptor tyrosine kinase. The structure reveals a mode of dimerization that we predict is shared amongst the SAM domains of the Eph receptor tyrosine kinases and possibly other SAM domain containing proteins. These data indicate a mechanism through which an independently folding protein module can form homophilic complexes that regulate signaling events at the membrane and in the nucleus.
- Thanos CD, Goodwill KE, Bowie JU
- Oligomeric structure of the human EphB2 receptor SAM domain.
- Science. 1999; 283: 833-6
- Display abstract
- The sterile alpha motif (SAM) domain is a protein interaction module that is present in diverse signal-transducing proteins. SAM domains are known to form homo- and hetero-oligomers. The crystal structure of the SAM domain from an Eph receptor tyrosine kinase, EphB2, reveals two large interfaces. In one interface, adjacent monomers exchange amino-terminal peptides that insert into a hydrophobic groove on each neighbor. A second interface is composed of the carboxyl-terminal helix and a nearby loop. A possible oligomer, constructed from a combination of these binding modes, may provide a platform for the formation of larger protein complexes.
- Williams JC, Wierenga RK, Saraste M
- Insights into Src kinase functions: structural comparisons.
- Trends Biochem Sci. 1998; 23: 179-84
- Display abstract
- Recent structures of Src tyrosine kinases reveal complex mechanisms for regulation of enzymatic activity. The regulatory SH3 and SH2 domains bind to the back of the catalytic kinase domain via a linker region that joins the SH2 domain to the catalytic domain. Members of a subgroup of the Src kinase family show distinct features in this linker and in the loops that interact with it. Hydrophobicity of key residues in this region is important for intramolecular regulation. The kinases Abl, Btk and Csk seem to have the same molecular architecture as Src. Structural comparisons between serine/threonine and tyrosine kinases indicate a specific twisting mechanism involving the N- and C-terminal lobes of the catalytic domain. This motion could provide insights into the various mechanisms used to regulate kinase activity.
- Sicheri F, Moarefi I, Kuriyan J
- Crystal structure of the Src family tyrosine kinase Hck.
- Nature. 1997; 385: 602-9
- Display abstract
- The crystal structure of the haematopoietic cell kinase Hck has been determined at 2.6/2.9 A resolution. Inhibition of enzymatic activity is a consequence of intramolecular interactions of the enzyme's Src-homology domains SH2 and SH3, with concomitant displacement of elements of the catalytic domain. The conformation of the active site has similarities with that of inactive cyclin-dependent protein kinases.
- Xu W, Harrison SC, Eck MJ
- Three-dimensional structure of the tyrosine kinase c-Src.
- Nature. 1997; 385: 595-602
- Display abstract
- The structure of a large fragment of the c-Src tyrosine kinase, comprising the regulatory and kinase domains and the carboxy-terminal tall, has been determined at 1.7 A resolution in a closed, inactive state. Interactions among domains, stabilized by binding of the phosphorylated tail to the SH2 domain, lock the molecule in a conformation that simultaneously disrupts the kinase active site and sequesters the binding surfaces of the SH2 and SH3 domains. The structure shows how appropriate cellular signals, or transforming mutations in v-Src, could break these interactions to produce an open, active kinase.
- Mohammadi M, Schlessinger J, Hubbard SR
- Structure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism.
- Cell. 1996; 86: 577-87
- Display abstract
- The crystal structure of the tyrosine kinase domain of fibroblast growth factor receptor 1 (FGFR1K) has been determined in its unliganded form to 2.0 angstroms resolution and in complex with with an ATP analog to 2.3 angstrosms A resolution. Several features distinguish the structure of FGFR1K from that of the tyrosine kinase domain of the insulin receptor. Residues in the activation loop of FGFR1K appear to interfere with substrate peptide binding but not with ATP binding, revealing a second and perhaps more general autoinhibitory mechanism for receptor tyrosine kinases. In addition, a dimeric form of FGFR1K observed in the crystal structure may provide insights into the molecular mechanisms by which FGF receptors are activated. Finally, the structure provides a basis for rationalizing the effects of kinase mutations in FGF receptors that lead to developmental disorders in nematodes and humans.
- Hanks SK, Hunter T
- Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification.
- FASEB J. 1995; 9: 576-96
- Display abstract
- The eukaryotic protein kinases make up a large superfamily of homologous proteins. They are related by virtue of their kinase domains (also known as catalytic domains), which consist of approximately 250-300 amino acid residues. The kinase domains that define this group of enzymes contain 12 conserved subdomains that fold into a common catalytic core structure, as revealed by the 3-dimensional structures of several protein-serine kinases. There are two main subdivisions within the superfamily: the protein-serine/threonine kinases and the protein-tyrosine kinases. 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.
- Liu D, Bienkowska J, Petosa C, Collier RJ, Fu H, Liddington R
- Crystal structure of the zeta isoform of the 14-3-3 protein.
- Nature. 1995; 376: 191-4
- Display abstract
- The 14-3-3 family of proteins have recently been identified as regulatory elements in intracellular signalling pathways: 14-3-3 proteins bind to oncogene and proto-oncogene products, including c-Raf-1 (refs 2-5), c-Bcr (ref. 6) and polyomavirus middle-T antigen; overexpression of 14-3-3 activates Raf kinase in yeast and induces meiotic maturation in Xenopus oocytes. Here we report the crystal structure of the major isoform of mammalian 14-3-3 proteins at 2.9 A resolution. Each subunit of the dimeric protein consists of a bundle of nine antiparallel helices that form a palisade around an amphipathic groove. The groove is large enough to accommodate a tenth helix, and we propose that binding to an amphipathic helix represents a general mechanism for the interaction of 14-3-3 with diverse cellular proteins. The residues in the dimer interface and the putative ligand-binding surface are invariant among vertebrates, yeast and plants, suggesting a conservation of structure and function throughout the 14-3-3 family.
- Owen DJ, Noble ME, Garman EF, Papageorgiou AC, Johnson LN
- Two structures of the catalytic domain of phosphorylase kinase: an active protein kinase complexed with substrate analogue and product.
- Structure. 1995; 3: 467-82
- Display abstract
- BACKGROUND: Control of intracellular events by protein phosphorylation is promoted by specific protein kinases. All the known protein kinase possess a common structure that defines a catalytically competent entity termed the 'kinase catalytic core'. Within this common structural framework each kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by association with other proteins. Structural studies of phosphorylase kinase (Phk), the major substrate of which is glycogen phosphorylase, may be expected to shed light on its regulation. RESULTS: We report two crystal structures of the catalytic core (residues 1-298; Phk gamma trnc) of the gamma-subunit of rabbit muscle phosphorylase kinase: the binary complex with Mn2+/beta-gamma-imidoadenosine 5'-triphosphate (AMPPNP) to a resolution of 2.6 A and the binary complex with Mg2+/ADP to a resolution of 3.0 A. The structures were solved by molecular replacement using the cAMP-dependent protein kinase (cAPK) as a model. CONCLUSIONS: The overall structure of Phk gamma trnc is similar to that of the catalytic core of other protein kinases. It consists of two domians joined on one edge by a 'hinge', with the catalytic site located in the cleft between the domains. Phk gamma trnc is constitutively active, and lacks the need for an activatory phosphorylation event that is essential for many kinases. The structure exhibits an essentially 'closed' conformation of the domains which is similar to that of cAPK complexed with substrates. The phosphorylated residue that is located at the domain interface in many protein kinases and that is believed to stabilize an active conformation is substituted by a glutamate in Phk gamma trnc. The glutamate, in a similar manner to the phosphorylated residue in other protein kinases, interacts with an arginine adjacent to the catalytic aspartate but does not participate in interdomain contacts. The interactions between the enzyme and the nucleotide product of its activity, Mg2+/ADP, explain the inhibitory properties of the nucleotides that are observed in kinetic studies.
- Hubbard SR, Wei L, Ellis L, Hendrickson WA
- Crystal structure of the tyrosine kinase domain of the human insulin receptor.
- Nature. 1994; 372: 746-54
- Display abstract
- The X-ray crystal structure of the tyrosine kinase domain of the human insulin receptor has been determined by multiwavelength anomalous diffraction phasing and refined to 2.1 A resolution. The structure reveals the determinants of substrate preference for tyrosine rather than serine or threonine and a novel autoinhibition mechanism whereby one of the tyrosines that is autophosphorylated in response to insulin, Tyr 1,162, is bound in the active site.
- Taylor SS, Radzio-Andzelm E
- Three protein kinase structures define a common motif.
- Structure. 1994; 2: 345-55
- Display abstract
- Structural comparisons between cAMP-dependent protein kinase, cyclin-dependent kinase 2 and mitogen-activated protein kinase reveal which features are common to the protein kinase family and which are enzyme-specific.
- Knighton DR et al.
- Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.
- Science. 1991; 253: 407-14
- Display abstract
- The crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase complexed with a 20-amino acid substrate analog inhibitor has been solved and partially refined at 2.7 A resolution to an R factor of 0.212. The magnesium adenosine triphosphate (MgATP) binding site was located by difference Fourier synthesis. The enzyme structure is bilobal with a deep cleft between the lobes. The cleft is filled by MgATP and a portion of the inhibitor peptide. The smaller lobe, consisting mostly of amino-terminal sequence, is associated with nucleotide binding, and its largely antiparallel beta sheet architecture constitutes an unusual nucleotide binding motif. The larger lobe is dominated by helical structure with a single beta sheet at the domain interface. This lobe is primarily involved in peptide binding and catalysis. Residues 40 through 280 constitute a conserved catalytic core that is shared by more than 100 protein kinases. Most of the invariant amino acids in this conserved catalytic core are clustered at the sites of nucleotide binding and catalysis.
Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the TyrKc domain.

Protein	Disease
TGF-beta receptor type-2 (P37173) (SMART)	OMIM:190182: Colon cancer ; Colorectal cancer, hereditary nonpolyposis, type 6 OMIM:114500: Esophageal cancer OMIM:133239:
Phosphorylase b kinase gamma catalytic chain, testis/liver isoform (P15735) (SMART)	OMIM:172471: Glycogenosis, hepatic, autosomal
Rhodopsin kinase (Q15835) (SMART)	OMIM:180381: Oguchi disease-2 OMIM:258100:
Tyrosine-protein kinase BTK (Q06187) (SMART)	OMIM:300300: Agammaglobulinemia, type 1, X-linked ; ?XLA and isolated growth hormone deficiency OMIM:307200:
Insulin receptor subunit beta (P06213) (SMART)	OMIM:147670: Leprechaunism OMIM:246200: Rabson-Mendenhall syndrome OMIM:262190: Diabetes mellitus, insulin-resistant, with acanthosis nigricans
Tyrosine-protein kinase ZAP-70 (P43403) (SMART)	OMIM:176947: Selective T-cell defect
Serine/threonine-protein kinase receptor R3 (P37023) (SMART)	OMIM:601284: Hereditary hemorrhagic telangiectasia-2 OMIM:600376:
High affinity nerve growth factor receptor (P04629) (SMART)	OMIM:191315: Insensitivity to pain, congenital, with anhidrosis OMIM:256800: Medullary thyroid carcinoma, familial OMIM:155240:
Retinal guanylyl cyclase 1 (Q02846) (SMART)	OMIM:601777: Cone dystrophy, progressive OMIM:600179: Leber congenital amaurosis, type I OMIM:204000: Cone-rod dystrophy 6 OMIM:601777:
Ribosomal protein S6 kinase alpha-3 (P51812) (SMART)	OMIM:300075: Coffin-Lowry syndrome OMIM:303600: Mental retardation, X-linked nonspecific, type 19
Protein kinase C gamma type (P05129) (SMART)	OMIM:176980: PROTEIN KINASE C, GAMMA; PRKCG
Fibroblast growth factor receptor 3 (P22607) (SMART)	OMIM:134934: Achondroplasia OMIM:100800: Hypochondroplasia OMIM:146000: Thanatophoric dysplasia, types I and II OMIM:187600: Crouzon syndrome with acanthosis nigricans ; Muencke syndrome OMIM:602849: OMIM:600593: Craniosynostosis, Adelaide type
Proto-oncogene tyrosine-protein kinase receptor Ret (P07949) (SMART)	OMIM:164761: Multiple endocrine neoplasia IIA OMIM:171400: Medullary thyroid carcinoma OMIM:155240: Multiple endocrine neoplasia IIB OMIM:162300: Hirschsprung disease OMIM:142623: OMIM:188550: Thyroid papillary carcinoma
Serine/threonine-protein kinase 11 (Q15831) (SMART)	OMIM:602216: Peutz-Jeghers syndrome OMIM:175200:
Cell division protein kinase 4 (P11802) (SMART)	OMIM:123829: Melanoma
Angiopoietin-1 receptor (Q02763) (SMART)	OMIM:600221: Venous malformations, multiple cutaneous and mucosal OMIM:600195:
Hepatocyte growth factor receptor (P08581) (SMART)	OMIM:164860: Renal cell carcinoma, papillary, familial and sporadic OMIM:605074: Hepatocellular carcinoma, childhood type OMIM:114550:
Mast/stem cell growth factor receptor (P10721) (SMART)	OMIM:164920: Piebaldism ; Mast cell leukemia ; Mastocytosis with associated hematologic disorder ; Germ cell tumors OMIM:273300:

Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

3D Structures of TyrKc domains in PDB

PDB code	Main view	Title
1ad5		Src family kinase hck-amp-pnp complex
1agw		Crystal structure of the tyrosine kinase domain of fibroblast growth factor receptor 1 in complex with su4984 inhibitor
1byg		Kinase domain of human c-terminal src kinase (csk) in complex with inhibitor staurosporine
1fgi		Crystal structure of the tyrosine kinase domain of fibroblast growth factor receptor 1 in complex with su5402 inhibitor
1fgk		Crystal structure of the tyrosine kinase domain of fibroblast growth factor receptor 1
1fmk		Crystal structure of human tyrosine-protein kinase c-src
1fpu		Crystal structure of abl kinase domain in complex with a small molecule inhibitor
1fvr		Tie2 kinase domain
1gag		Crystal structure of the insulin receptor kinase in complex with a bisubstrate inhibitor
1gjo		The fgfr2 tyrosine kinase domain
1i44		Crystallographic studies of an activation loop mutant of the insulin receptor tyrosine kinase
1iep		Crystal structure of the c-abl kinase domain in complex with sti-571.
1ir3		Phosphorylated insulin receptor tyrosine kinase in complex with peptide substrate and atp analog
1irk		Crystal structure of the tyrosine kinase domain of the human insulin receptor
1jpa		Crystal structure of unphosphorylated ephb2 receptor tyrosine kinase and juxtamembrane region
1jqh		Igf-1 receptor kinase domain
1k2p		Crystal structure of bruton's tyrosine kinase domain
1k3a		Structure of the insulin-like growth factor 1 receptor kinase
1k9a		Crystal structure analysis of full-length carboxyl-terminal src kinase at 2.5 a resolution
1ksw		Structure of human c-src tyrosine kinase (thr338gly mutant) in complex with n6-benzyl adp
1luf		Crystal structure of the musk tyrosine kinase: insights into receptor autoregulation
1m14		Tyrosine kinase domain from epidermal growth factor receptor
1m17		Epidermal growth factor receptor tyrosine kinase domain with 4-anilinoquinazoline inhibitor erlotinib
1m52		Crystal structure of the c-abl kinase domain in complex with pd173955
1m7n		Crystal structure of unactivated apo insulin-like growth factor-1 receptor kinase domain
1mp8		Crystal structure of focal adhesion kinase (fak)
1mqb		Crystal structure of ephrin a2 (epha2) receptor protein kinase
1oec		Fgfr2 kinase domain
1opj		Structural basis for the auto-inhibition of c-abl tyrosine kinase
1opk		Structural basis for the auto-inhibition of c-abl tyrosine kinase
1opl		Structural basis for the auto-inhibition of c-abl tyrosine kinase
1p14		Crystal structure of a catalytic-loop mutant of the insulin receptor tyrosine kinase
1p4o		Structure of apo unactivated igf-1r kinase domain at 1.5a resolution.
1pkg		Structure of a c-kit kinase product complex
1qcf		Crystal structure of hck in complex with a src family- selective tyrosine kinase inhibitor
1qpc		Structural analysis of the lymphocyte-specific kinase lck in complex with non-selective and src family selective kinase inhibitors
1qpd		Structural analysis of the lymphocyte-specific kinase lck in complex with non-selective and src family selective kinase inhibitors
1qpe		Structural analysis of the lymphocyte-specific kinase lck in complex with non-selective and src family selective kinase inhibitors
1qpj		Crystal structure of the lymphocyte-specific kinase lck in complex with staurosporine.
1r0p		Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with the microbial alkaloid k-252a
1r1w		Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met
1rjb		Crystal structure of flt3
1rqq		Crystal structure of the insulin receptor kinase in complex with the sh2 domain of aps
1sm2		Crystal structure of the phosphorylated interleukin-2 tyrosine kinase catalytic domain
1snu		Crystal structure of the unphosphorylated interleukin-2 tyrosine kinase catalytic domain
1snx		Crystal structure of apo interleukin-2 tyrosine kinase catalytic domain
1t45		Structural basis for the autoinhibition and sti-571 inhibition of c-kit tyrosine kinase
1t46		Structural basis for the autoinhibition and sti-571 inhibition of c-kit tyrosine kinase
1u46		Crystal structure of the unphosphorylated kinase domain of the tyrosine kinase ack1
1u4d		Structure of the ack1 kinase domain bound to debromohymenialdisine
1u54		Crystal structures of the phosphorylated and unphosphorylated kinase domains of the cdc42-associated tyrosine kinase ack1 bound to amp-pcp
1u59		Crystal structure of the zap-70 kinase domain in complex with staurosporine
1vr2		Human vascular endothelial growth factor receptor 2 (kdr) kinase domain
1xba		Crystal structure of apo syk tyrosine kinase domain
1xbb		Crystal structure of the syk tyrosine kinase domain with gleevec
1xbc		Crystal structure of the syk tyrosine kinase domain with staurosporin
1xkk		Egfr kinase domain complexed with a quinazoline inhibitor- gw572016
1y57		Structure of unphosphorylated c-src in complex with an inhibitor
1y6a		Crystal structure of vegfr2 in complex with a 2-anilino-5- aryl-oxazole inhibitor
1y6b		Crystal structure of vegfr2 in complex with a 2-anilino-5- aryl-oxazole inhibitor
1yi6		C-term tail segment of human tyrosine kinase (258-533)
1yoj		Crystal structure of src kinase domain
1yol		Crystal structure of src kinase domain in complex with cgp77675
1yom		Crystal structure of src kinase domain in complex with purvalanol a
1yvj		Crystal structure of the jak3 kinase domain in complex with a staurosporine analogue
1ywn		Vegfr2 in complex with a novel 4-amino-furo[2,3-d]pyrimidine
2auh		Crystal structure of the grb14 bps region in complex with the insulin receptor tyrosine kinase
2b4s		Crystal structure of a complex between ptp1b and the insulin receptor tyrosine kinase
2b7a		The structural basis of janus kinase 2 inhibition by a potent and specific pan-janus kinase inhibitor
2bdf		Src kinase in complex with inhibitor ap23451
2bdj		Src kinase in complex with inhibitor ap23464
2c0i		Src family kinase hck with bound inhibitor a-420983
2c0o		Src family kinase hck with bound inhibitor a-770041
2c0t		Src family kinase hck with bound inhibitor a-641359
2dq7		Crystal structure of fyn kinase domain complexed with staurosporine
2e2b		Crystal structure of the c-abl kinase domain in complex with inno-406
2eb2		Crystal structure of mutated egfr kinase domain (g719s)
2eb3		Crystal structure of mutated egfr kinase domain (l858r) in complex with amppnp
2etm		Crystal structure of focal adhesion kinase domain complexed with 7h-pyrrolo [2,3-d] pyrimidine derivative
2f4j		Structure of the kinase domain of an imatinib-resistant abl mutant in complex with the aurora kinase inhibitor vx-680
2fgi		Crystal structure of the tyrosine kinase domain of fgf receptor 1 in complex with inhibitor pd173074
2fo0		Organization of the sh3-sh2 unit in active and inactive forms of the c-abl tyrosine kinase
2g15		Structural characterization of autoinhibited c-met kinase
2g1t		A src-like inactive conformation in the abl tyrosine kinase domain
2g2f		A src-like inactive conformation in the abl tyrosine kinase domain
2g2h		A src-like inactive conformation in the abl tyrosine kinase domain
2g2i		A src-like inactive conformation in the abl tyrosine kinase domain
2gqg		X-ray crystal structure of dasatinib (bms-354825) bound to activated abl kinase domain
2gs2		Crystal structure of the active egfr kinase domain
2gs6		Crystal structure of the active egfr kinase domain in complex with an atp analog-peptide conjugate
2gs7		Crystal structure of the inactive egfr kinase domain in complex with amp-pnp
2gsf		The human epha3 receptor tyrosine kinase and juxtamembrane region
2h8h		Src kinase in complex with a quinazoline inhibitor
2hck		Src family kinase hck-quercetin complex
2hel		Crystal structure of a mutant epha4 kinase domain (y742a)
2hen		Crystal structure of the ephb2 receptor kinase domain in complex with adp
2hiw		Crystal structure of inactive conformation abl kinase catalytic domain complexed with type ii inhibitor
2hk5		Hck kinase in complex with lck targetted inhibitor pg-
2hwo		Crystal structure of src kinase domain in complex with covalent inhibitor
2hwp		Crystal structure of src kinase domain in complex with covalent inhibitor pd168393
2hyy		Human abl kinase domain in complex with imatinib (sti571, glivec)
2hz0		Abl kinase domain in complex with nvp-aeg082
2hz4		Abl kinase domain unligated and in complex with tetrahydrostaurosporine
2hzi		Abl kinase domain in complex with pd180970
2hzn		Abl kinase domain in complex with nvp-afg210
2i0v		C-fms tyrosine kinase in complex with a quinolone inhibitor
2i0y		Cfms tyrosine kinase (fgf kid) in complex with an arylamide inhibitor
2i1m		Cfms tyrosine kinase (tie2 kid) in complex with an arylamide inhibitor
2ijm		Crystal structure of focal adhesion kinase domain with 2 molecules in the asymmetric unit complexed with adp and atp
2itn		Crystal structure of egfr kinase domain g719s mutation in complex with amp-pnp
2ito		Crystal structure of egfr kinase domain g719s mutation in complex with iressa
2itp		Crystal structure of egfr kinase domain g719s mutation in complex with aee788
2itq		Crystal structure of egfr kinase domain g719s mutation in complex with afn941
2itt		Crystal structure of egfr kinase domain l858r mutation in complex with aee788
2itu		Crystal structure of egfr kinase domain l858r mutation in complex with afn941
2itv		Crystal structure of egfr kinase domain l858r mutation in complex with amp-pnp
2itw		Crystal structure of egfr kinase domain in complex with afn941
2itx		Crystal structure of egfr kinase domain in complex with amp- pnp
2ity		Crystal structure of egfr kinase domain in complex with iressa
2itz		Crystal structure of egfr kinase domain l858r mutation in complex with iressa
2ivs		Crystal structure of non-phosphorylated ret tyrosine kinase domain
2ivt		Crystal structure of phosphorylated ret tyrosine kinase domain
2ivu		Crystal structure of phosphorylated ret tyrosine kinase domain complexed with the inhibitor zd6474
2ivv		Crystal structure of phosphorylated ret tyrosine kinase domain complexed with the inhibitor pp1
2j0j		Crystal structure of a fragment of focal adhesion kinase containing the ferm and kinase domains.
2j0k		Crystal structure of a fragment of focal adhesion kinase containing the ferm and kinase domains.
2j0l		Crystal structure of a the active conformation of the kinase domain of focal adhesion kinase with a phosphorylated activation loop.
2j0m		Crystal structure a two-chain complex between the ferm and kinase domains of focal adhesion kinase.
2j5e		Crystal structure of egfr kinase domain in complex with an irreversible inhibitor 13-jab
2j5f		Crystal structure of egfr kinase domain in complex with an irreversible inhibitor 34-jab
2j6m		Crystal structure of egfr kinase domain in complex with aee788
2jit		Crystal structure of egfr kinase domain t790m mutation
2jiu		Crystal structure of egfr kinase domain t790m mutation in complex with aee788
2jiv		Crystal structure of egfr kinase domain t790m mutation in compex with hki-272
2jkk		Focal adhesion kinase catalytic domain in complex with bis- anilino pyrimidine inhibitor
2jkm		Focal adhesion kinase catalytic domain in complex with bis- anilino pyrimidine inhibitor
2jko		Focal adhesion kinase catalytic domain in complex with bis- anilino pyrimidine inhibitor
2jkq		Focal adhesion kinase catalytic domain in complex with bis- anilino pyrimidine inhibitor
2of2		Crystal structure of furanopyrimidine 8 bound to lck
2of4		Crystal structure of furanopyrimidine 1 bound to lck
2ofu		X-ray crystal structure of 2-aminopyrimidine carbamate 43 bound to lck
2ofv		Crystal structure of aminoquinazoline 1 bound to lck
2og8		Crystal structure of aminoquinazoline 36 bound to lck
2ogv		Crystal structure of the autoinhibited human c-fms kinase domain
2oh4		Crystal structure of vegfr2 with a benzimidazole-urea inhibitor
2oiq		Crystal structure of chicken c-src kinase domain in complex with the cancer drug imatinib.
2oj9		Structure of igf-1r kinase domain complexed with a benzimidazole inhibitor
2oo8		Synthesis, structural analysis, and sar studies of triazine derivatives as potent, selective tie-2 inhibitors
2osc		Synthesis, structural analysis, and sar studies of triazine derivatives as potent, selective tie-2 inhibitors
2ozo		Autoinhibited intact human zap-70
2p0c		Catalytic domain of the proto-oncogene tyrosine-protein kinase mer
2p2h		Crystal structure of the vegfr2 kinase domain in complex with a pyridinyl-triazine inhibitor
2p2i		Crystal structure of the vegfr2 kinase domain in complex with a nicotinamide inhibitor
2p4i		Evolution of a highly selective and potent 2-(pyridin-2-yl)- 1,3,5-triazine tie-2 kinase inhibitor
2pl0		Lck bound to imatinib
2psq		Crystal structure of unphosphorylated unactivated wild type fgf receptor 2 (fgfr2) kinase domain
2ptk		Chicken src tyrosine kinase
2pvf		Crystal structure of tyrosine phosphorylated activated fgf receptor 2 (fgfr2) kinase domain in complex with atp analog and substrate peptide
2pvy		Crystal strucure of fgf receptor 2 (fgfr2) kinase domain harboring the pathogenic k659n mutation responsible for an unclassified craniosynostosis syndrome.
2pwl		Crystal strucure of fgf receptor 2 (fgfr2) kinase domain harboring the pathogenic n549h mutation responsible for crouzon syndrome.
2py3		Crystal strucure of fgf receptor 2 (fgfr2) kinase domain harboring the pathogenic e565g mutation responsible for pfeiffer syndrome
2pz5		Crystal strucure of fgf receptor 2 (fgfr2) kinase domain harboring the pathogenic n549t mutation responsible for pfeiffer syndrome
2pzp		Crystal strucure of fgf receptor 2 (fgfr2) kinase domain harboring the pathogenic k526e mutation responsible for crouzon syndrome
2pzr		Crystal strucure of fgf receptor 2 (fgfr2) kinase domain harboring the pathogenic k641r mutation responsible for pfeiffer syndrome
2q0b		Crystal strucure of fgf receptor 2 (fgfr2) kinase domain harboring the pathogenic e565a mutation responsible for pfeiffer syndrome
2qi8		Crystal structure of drug resistant src kinase domain
2qlq		Crystal structure of src kinase domain with covalent inhibitor rl3
2qo2		Human epha3 kinase and juxtamembrane region, dephosphorylated, apo structure
2qo7		Human epha3 kinase and juxtamembrane region, dephosphorylated, amp-pnp bound
2qo9		Human epha3 kinase and juxtamembrane region, phosphorylated, amp-pnp bound
2qob		Human epha3 kinase domain, base structure
2qoc		Human epha3 kinase domain, phosphorylated, amp-pnp bound structure
2qod		Human epha3 kinase and juxtamembrane region, y602f mutant
2qof		Human epha3 kinase and juxtamembrane region, y596f mutant
2qoh		Crystal structure of abl kinase bound with ppy-a
2qoi		Human epha3 kinase and juxtamembrane region, y596f:y602f double mutant
2qok		Human epha3 kinase and juxtamembrane region, y596f:y602f:s768a triple mutant
2qol		Human epha3 kinase and juxtamembrane region, y596:y602:s768g triple mutant
2qon		Human epha3 kinase and juxtamembrane region, y596f:y602f:y742a triple mutant
2qoo		Human epha3 kinase and juxtamembrane region, y596f:y602f:y742f triple mutant
2qoq		Human epha3 kinase and juxtamembrane region, base, amp-pnp bound structure
2qq7		Crystal structure of drug resistant src kinase domain with irreversible inhibitor
2qu5		Crystal structure of the vegfr2 kinase domain in complex with a benzimidazole inhibitor
2qu6		Crystal structure of the vegfr2 kinase domain in complex with a benzoxazole inhibitor
2r2p		Kinase domain of human ephrin type-a receptor 5 (epha5)
2r4b		Erbb4 kinase domain complexed with a thienopyrimidine inhibitor
2rei		Kinase domain of human ephrin type-a receptor 7 (epha7)
2rf9		Crystal structure of the complex between the egfr kinase domain and a mig6 peptide
2rfd		Crystal structure of the complex between the egfr kinase domain and a mig6 peptide
2rfe		Crystal structure of the complex between the egfr kinase domain and a mig6 peptide
2rfn		X-ray structure of c-met with inhibitor.
2rfs		X-ray structure of su11274 bound to c-met
2rgp		Structure of egfr in complex with hydrazone, a potent dual inhibitor
2rl5		Crystal structure of the vegfr2 kinase domain in complex with a 2,3-dihydro-1,4-benzoxazine inhibitor
2src		Crystal structure of human tyrosine-protein kinase c-src, in complex with amp-pnp
2v7a		Crystal structure of the t315i abl mutant in complex with the inhibitor pha-739358
2vwu		Ephb4 kinase domain inhibitor complex
2vwv		Ephb4 kinase domain inhibitor complex
2vww		Ephb4 kinase domain inhibitor complex
2vwx		Ephb4 kinase domain inhibitor complex
2vwy		Ephb4 kinase domain inhibitor complex
2vwz		Ephb4 kinase domain inhibitor complex
2vx0		Ephb4 kinase domain inhibitor complex
2vx1		Ephb4 kinase domain inhibitor complex
2w1i		Structure determination of aurora kinase in complex with inhibitor
2wd1		Human c-met kinase in complex with azaindole inhibitor
2wgj		X-ray structure of pf-02341066 bound to the kinase domain of c-met
2wqb		Structure of the tie2 kinase domain in complex with a thiazolopyrimidine inhibitor
2z60		Crystal structure of the t315i mutant of abl kinase bound with ppy-a
2z8c		Phosphorylated insulin receptor tyrosine kinase in complex with (4-{[5-carbamoyl-4-(3-methylanilino)pyrimidin-2- yl]amino}phenyl)acetic acid
2zm1		Crystal structure of imidazo pyrazin 1 bound to the kinase domain of human lck, (auto-phosphorylated on tyr394)
2zm3		Complex structure of insulin-like growth factor receptor and isoquinolinedione inhibitor
2zm4		Crystal structure of imidazo quinoxaline 1 bound to the kinase domain of human lck, activated form (auto- phosphorylated on tyr394)
2zv7		Lyn tyrosine kinase domain, apo form
2zv8		Lyn tyrosine kinase domain-amp-pnp complex
2zv9		Lyn tyrosine kinase domain-pp2 complex
2zva		Lyn tyrosine kinase domain-dasatinib complex
2zyb		Crystal structure of phenylimidazo pyrazin 2 bound to the kinase domain of human lck, (auto-phosphorylated on tyr394)
3b2t		Structure of phosphotransferase
3b2w		Crystal structure of pyrimidine amide 11 bound to lck
3b8q		Crystal structure of the vegfr2 kinase domain in complex with a naphthamide inhibitor
3b8r		Crystal structure of the vegfr2 kinase domain in complex with a naphthamide inhibitor
3bbt		Crystal structure of the erbb4 kinase in complex with lapatinib
3bbw		Crystal structure of the erbb4 kinase in its inactive conformation
3bce		Crystal structure of the erbb4 kinase
3be2		Crystal structure of the vegfr2 kinase domain in complex with a benzamide inhibitor
3bea		Cfms tyrosine kinase (tie2 kid) in complex with a pyrimidinopyridone inhibitor
3bel		X-ray structure of egfr in complex with oxime inhibitor
3bkb		Crystal structure of human feline sarcoma viral oncogene homologue (v-fes)
3bpr		Crystal structure of catalytic domain of the proto-oncogene tyrosine-protein kinase mer in complex with inhibitor c52
3brb		Crystal structure of catalytic domain of the proto-oncogene tyrosine-protein kinase mer in complex with adp
3bu3		Crystal structure of the insulin receptor kinase in complex with irs2 krlb peptide
3bu5		Crystal structure of the insulin receptor kinase in complex with irs2 krlb peptide and atp
3bu6		Crystal structure of the insulin receptor kinase in complex with irs2 krlb phosphopeptide
3bym		X-ray co-crystal structure aminobenzimidazole triazine 1 bound to lck
3byo		X-ray co-crystal structure of 2-amino-6-phenylpyrimido[5', 4':5,6]pyrimido[1,2-a]benzimidazol-5(6h)-one 25 bound to lck
3bys		Co-crystal structure of lck and aminopyrimidine amide 10b
3byu		Co-crystal structure of lck and aminopyrimidine reverse amide 23
3bz3		Crystal structure analysis of focal adhesion kinase with a methanesulfonamide diaminopyrimidine inhibitor
3c1x		Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with a pyrrolotriazine based inhibitor
3c4f		Fgfr tyrosine kinase domain in complex with 3-(3- methoxybenzyl)-7-azaindole
3c7q		Structure of vegfr2 kinase domain in complex with bibf1120
3cbl		Crystal structure of human feline sarcoma viral oncogene homologue (v-fes) in complex with staurosporine and a consensus peptide
3cc6		Crystal structure of kinase domain of protein tyrosine kinase 2 beta (ptk2b)
3ccn		X-ray structure of c-met with triazolopyridazine inhibitor.
3cd3		Crystal structure of phosphorylated human feline sarcoma viral oncogene homologue (v-fes) in complex with staurosporine and a consensus peptide
3cd8		X-ray structure of c-met with triazolopyridazine inhibitor.
3ce3		Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with a pyrrolopyridinepyridone based inhibitor
3cjf		Crystal structure of vegfr2 in complex with a 3,4,5- trimethoxy aniline containing pyrimidine
3cjg		Crystal structure of vegfr2 in complex with a 3,4,5- trimethoxy aniline containing pyrimidine
3cly		Crystal structure of fgf receptor 2 (fgfr2) kinase domains trapped in trans-phosphorylation reaction
3cp9		Crystal structure of the vegfr2 kinase domain in complex with a pyridone inhibitor
3cpb		Crystal structure of the vegfr2 kinase domain in complex with a bisamide inhibitor
3cpc		Crystal structure of the vegfr2 kinase domain in complex with a pyridone inhibitor
3cs9		Human abl kinase in complex with nilotinib
3cth		Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with a aminopyridine based inhibitor
3ctj		Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with a aminopyridine based inhibitor
3d7t		Structural basis for the recognition of c-src by its inactivator csk
3d7u		Structural basis for the recognition of c-src by its inactivator csk
3d94		Crystal structure of the insulin-like growth factor-1 receptor kinase in complex with pqip
3dk3		Crystal structure of mutant abl kinase domain in complex with small molecule fragment
3dk6		Crystal structure of mutant abl kinase domain in complex with small molecule fragment
3dk7		Crystal structure of mutant abl kinase domain in complex with small molecule fragment
3dkc		Sgx clone 5698a65kfg1h1
3dkf		Sgx clone 5698a65kfg1h1
3dkg		Sgx clone 5698a109kfg1h1
3dko		Complex between the kinase domain of human ephrin type-a receptor 7 (epha7) and inhibitor alw-ii-49-7
3dpk		Cfms tyrosine kinase in complex with a pyridopyrimidinone inhibitor
3dqw		C-src kinase domain thr338ile mutant in complex with atpgs
3dqx		Chicken c-src kinase domain in complex with atpgs
3dtc		Crystal structure of mixed-lineage kinase mlk1 complexed with compound 16
3dtw		Crystal structure of the vegfr2 kinase domain in complex with a benzisoxazole inhibitor
3dzq		Human epha3 kinase domain in complex with inhibitor awl-ii- 38.3
3e62		Fragment based discovery of jak-2 inhibitors
3e63		Fragment based discovery of jak-2 inhibitors
3e64		Fragment based discovery of jak-2 inhibitors
3efj		Structure of c-met with pyrimidone inhibitor 7
3efk		Structure of c-met with pyrimidone inhibitor 50
3efl		Crystal structure of the vegfr2 kinase domain in complex with motesanib
3ekk		Insulin receptor kinase complexed with an inhibitor
3ekn		Insulin receptor kinase complexed with an inhibitor
3el7		Crystal structure of c-src in complex with pyrazolopyrimidine 3
3el8		Crystal structure of c-src in complex with pyrazolopyrimidine 5
3emg		Discovery and sar of novel 4-thiazolyl-2- phenylaminopyrimidines as potent inhibitors of spleen tyrosine kinase (syk)
3en4		Targeted polypharmacology: crystal structure of the c-src kinase domain in complex with pp121, a multitargeted kinase inhibitor
3en5		Targeted polypharmacology: crystal structure of the c-src kinase domain in complex with pp494, a multitargeted kinase inhibitor
3en6		Targeted polypharmacology: crystal structure of the c-src kinase domain in complex with pp102, a multitargeted kinase inhibitor
3en7		Targeted polypharmacology: crystal structure of the c-src kinase domain in complex with s1, a multitargeted kinase inhibitor
3eqp		Crystal structure of ack1 with compound t95
3eqr		Crystal structure of ack1 with compound t74
3et7		Crystal structure of pyk2 complexed with pf-2318841
3eta		Kinase domain of insulin receptor complexed with a pyrrolo pyridine inhibitor
3ewh		Crystal structure of the vegfr2 kinase domain in complex with a pyridyl-pyrimidine benzimidazole inhibitor
3eyg		Crystal structures of jak1 and jak2 inhibitor complexes
3eyh		Crystal structures of jak1 and jak2 inhibitor complexes
3f3t		Kinase domain of csrc in complex with inhibitor rl38 (type iii)
3f3u		Kinase domain of csrc in complex with inhibitor rl37 (type iii)
3f3v		Kinase domain of csrc in complex with inhibitor rl45 (type ii)
3f3w		Drug resistant csrc kinase domain in complex with inhibitor rl45 (type ii)
3f5p		Complex structure of insulin-like growth factor receptor and 3-cyanoquinoline inhibitor
3f66		Human c-met kinase in complex with quinoxaline inhibitor
3f6x		C-src kinase domain in complex with small molecule inhibitor
3f82		Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with n- (4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4- ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3- carboxamide
3fqe		Crystal structure of spleen tyrosine kinase complexed with ym193306
3fqh		Crystal structure of spleen tyrosine kinase complexed with a 2-substituted 7-azaindole
3fqs		Crystal structure of spleen tyrosine kinase complexed with r406
3fup		Crystal structures of jak1 and jak2 inhibitor complexes
3fxx		Human epha3 kinase and juxtamembrane region bound to substrate kqwdnye[ptyr]iw
3fy2		Human epha3 kinase and juxtamembrane region bound to substrate kqwdnyefiw
3fzo		Crystal structure of pyk2-apo, proline-rich tyrosine kinase
3fzp		Crystal structure of pyk2 complexed with atpgs
3fzr		Crystal structure of pyk2 complexed with pf-431396
3fzs		Crystal structure of pyk2 complexed with birb796
3fzt		Crystal structure of pyk2 complexed with pf-4618433
3g0e		Kit kinase domain in complex with sunitinib
3g0f		Kit kinase domain mutant d816h in complex with sunitinib
3g5d		Kinase domain of csrc in complex with dasatinib
3g6g		Equally potent inhibition of c-src and abl by compounds that recognize inactive kinase conformations
3g6h		Src thr338ile inhibited in the dfg-asp-out conformation
3geq		Structural basis for the chemical rescue of src kinase activity
3gop		Crystal structure of the egf receptor juxtamembrane and kinase domains
3gqi		Crystal structure of activated receptor tyrosine kinase in complex with substrates
3gql		Crystal structure of activated receptor tyrosine kinase in complex with substrates
3gt8		Crystal structure of the inactive egfr kinase domain in complex with amp-pnp
3gvu		The crystal structure of human abl2 in complex with gleevec
3h3c		Crystal structure of pyk2 in complex with sulfoximine- substituted trifluoromethylpyrimidine analog
3hmi		The crystal structure of human abl2 in complex with 5-amino- 3-{[4-(aminosulfonyl)phenyl]amino}-n-(2,6-difluorophenyl)- 1h-1,2,4-triazole-1-carbothioamide
3hng		Crystal structure of vegfr1 in complex with n-(4- chlorophenyl)-2-((pyridin-4-ylmethyl)amino)benzamide
3ik3		Ap24534, a pan-bcr-abl inhibitor for chronic myeloid leukemia, potently inhibits the t315i mutant and overcomes mutation-based resistance
3io7		2-aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of jak2
3iok		2-aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of jak2
3kck		A novel chemotype of kinase inhibitors
3lck		The kinase domain of human lymphocyte kinase (lck), activated form (auto-phosphorylated on tyr394)

Links (links to other resources describing this domain)
BLOCKS RECEPTOR_TYR_KIN_V_1
PFAM pkinase
INTERPRO IPR020635