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Conserved domains on  [gi|56119141|ref|NP_001007799|]
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tyrosine-protein kinase BTK [Rattus norvegicus]

Protein Classification

SH2_Tec_Btk and PTKc_Btk_Bmx domain-containing protein (domain architecture ID 10100792)

protein containing domains PH_Btk, SH3_BTK, SH2_Tec_Btk, and PTKc_Btk_Bmx

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
398-653 0e+00

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


:

Pssm-ID: 173657  Cd Length: 256  Bit Score: 534.84  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 398 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEY 477
Cdd:cd05113   1 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMKLSHEKLVQLYGVCTKQRPIYIVTEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 478 MANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVG 557
Cdd:cd05113  81 MSNGCLLNYLREHGKRFQPSQLLEMCKDVCEGMAYLESKQFIHRDLAARNCLVDDQGCVKVSDFGLSRYVLDDEYTSSVG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 558 SKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSCWHE 637
Cdd:cd05113 161 SKFPVRWSPPEVLLYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFNNSETVEKVSQGLRLYRPHLASEKVYAIMYSCWHE 240
                       250
                ....*....|....*.
gi 56119141 638 KADERPSFKILLSNIL 653
Cdd:cd05113 241 KAEERPTFQQLLSSIE 256
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
275-379 4.48e-68

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198260  Cd Length: 106  Bit Score: 220.48  E-value: 4.48e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 275 DSIEMYEWYSKHMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSTGEPQGVIRHYVVCSTPQSQYYLAEKHLFS 354
Cdd:cd10397   1 DSLEMYEWYSKNMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSAGDPQGVIRHYVVCSTPQSQYYLAEKHLFS 80
                        90       100
                ....*....|....*....|....*
gi 56119141 355 TIPELINYHQHNSAGLISRLKYPVS 379
Cdd:cd10397  81 TIPELINYHQHNAAGLISRLKYPVS 105
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
6-167 3.31e-62

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 269944  Cd Length: 140  Bit Score: 205.93  E-value: 3.31e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141   6 LESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERgrRGSKKGSIDVEKITCVETVVPEknPPPERqipvprge 85
Cdd:cd01238   1 LEGLLVKRSQGKKRFGPVNYKERWFVLTKSSLSYYEGDGEK--RGKEKGSIDLSKVRCVEEVKDE--AFFER-------- 68
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141  86 essemeqisiierfPYPFQVVYDEGPLYVFSPTEELRKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMG 165
Cdd:cd01238  69 --------------KYPFQVVYDDYTLYVFAPSEEDRDEWIAALRKVCRNNSNLHDKYHPGFWTGGKWSCCGQTSKSAPG 134

                ..
gi 56119141 166 CQ 167
Cdd:cd01238 135 CQ 136
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
218-272 2.16e-33

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212839  Cd Length: 55  Bit Score: 123.40  E-value: 2.16e-33
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 56119141 218 KKVVALYDYMPMNANDLQLRKGEEYFILEESNLPWWRARDKNGQEGYIPSNYVTE 272
Cdd:cd11906   1 KKVVALYDYTPMNAQDLQLRKGEEYVILEESNLPWWRARDKNGREGYIPSNYVTE 55
 
Name Accession Description Interval E-value
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
398-653 0e+00

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657  Cd Length: 256  Bit Score: 534.84  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 398 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEY 477
Cdd:cd05113   1 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMKLSHEKLVQLYGVCTKQRPIYIVTEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 478 MANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVG 557
Cdd:cd05113  81 MSNGCLLNYLREHGKRFQPSQLLEMCKDVCEGMAYLESKQFIHRDLAARNCLVDDQGCVKVSDFGLSRYVLDDEYTSSVG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 558 SKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSCWHE 637
Cdd:cd05113 161 SKFPVRWSPPEVLLYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFNNSETVEKVSQGLRLYRPHLASEKVYAIMYSCWHE 240
                       250
                ....*....|....*.
gi 56119141 638 KADERPSFKILLSNIL 653
Cdd:cd05113 241 KAEERPTFQQLLSSIE 256
Pkinase_Tyr pfam07714
Protein tyrosine kinase;
403-652 7.47e-133

Protein tyrosine kinase;


Pssm-ID: 311583  Cd Length: 258  Bit Score: 394.94  E-value: 7.47e-133
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141   403 LTFLKELGTGQFGVVKYGKWRG-----QYDVAIKMIREGSMSED--EFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIIT 475
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGdgegtKIKVAVKTLKEGADEEEreDFLEEASIMKKLSHPNIVRLLGVCTQGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141   476 EYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYV-LDDEYTS 554
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKGKLTLPDLLQMALQIAKGMEYLESKNFVHRDLAARNCLVTENLVVKISDFGLSRDIyDDDYYRK 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141   555 SVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSC 634
Cdd:pfam07714 161 RGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMTQC 240
                         250
                  ....*....|....*...
gi 56119141   635 WHEKADERPSFKILLSNI 652
Cdd:pfam07714 241 WAYDPEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
403-650 3.71e-129

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581  Cd Length: 257  Bit Score: 385.35  E-value: 3.71e-129
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    403 LTFLKELGTGQFGVVKYGKWRG-----QYDVAIKMIREGSMSED--EFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIIT 475
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKGkggkkKVEVAVKTLKEDASEQQieEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    476 EYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSS 555
Cdd:smart00219  81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYRK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    556 VGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSCW 635
Cdd:smart00219 161 RGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCW 240
                          250
                   ....*....|....*
gi 56119141    636 HEKADERPSFKILLS 650
Cdd:smart00219 241 AEDPEDRPTFSELVE 255
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
275-379 4.48e-68

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198260  Cd Length: 106  Bit Score: 220.48  E-value: 4.48e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 275 DSIEMYEWYSKHMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSTGEPQGVIRHYVVCSTPQSQYYLAEKHLFS 354
Cdd:cd10397   1 DSLEMYEWYSKNMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSAGDPQGVIRHYVVCSTPQSQYYLAEKHLFS 80
                        90       100
                ....*....|....*....|....*
gi 56119141 355 TIPELINYHQHNSAGLISRLKYPVS 379
Cdd:cd10397  81 TIPELINYHQHNAAGLISRLKYPVS 105
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
6-167 3.31e-62

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944  Cd Length: 140  Bit Score: 205.93  E-value: 3.31e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141   6 LESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERgrRGSKKGSIDVEKITCVETVVPEknPPPERqipvprge 85
Cdd:cd01238   1 LEGLLVKRSQGKKRFGPVNYKERWFVLTKSSLSYYEGDGEK--RGKEKGSIDLSKVRCVEEVKDE--AFFER-------- 68
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141  86 essemeqisiierfPYPFQVVYDEGPLYVFSPTEELRKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMG 165
Cdd:cd01238  69 --------------KYPFQVVYDDYTLYVFAPSEEDRDEWIAALRKVCRNNSNLHDKYHPGFWTGGKWSCCGQTSKSAPG 134

                ..
gi 56119141 166 CQ 167
Cdd:cd01238 135 CQ 136
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
218-272 2.16e-33

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212839  Cd Length: 55  Bit Score: 123.40  E-value: 2.16e-33
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 56119141 218 KKVVALYDYMPMNANDLQLRKGEEYFILEESNLPWWRARDKNGQEGYIPSNYVTE 272
Cdd:cd11906   1 KKVVALYDYTPMNAQDLQLRKGEEYVILEESNLPWWRARDKNGREGYIPSNYVTE 55
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
280-369 5.94e-24

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585  Cd Length: 84  Bit Score: 98.07  E-value: 5.94e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    280 YEWYSKHMTRSQAEQLLKQEGkEGGFIVRDS-SKAGKYTVSVFAKstgepqGVIRHYVVCSTPQSQYYLAEKHLFSTIPE 358
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEG-DGDFLVRDSeSSPGDYVLSVRVK------GKVKHYRIRRNEDGKFYLEGGRKFPSLVE 73
                           90
                   ....*....|.
gi 56119141    359 LINYHQHNSAG 369
Cdd:smart00252  74 LVEHYQKNSLG 84
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
404-611 1.37e-23

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 223589  Cd Length: 384  Bit Score: 103.28  E-value: 1.37e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 404 TFLKELGTGQFGVVKYGKwrGQYDVAIKMIREGSMSEDE----FIEEAKVMMNLSHEK-LVQLYGVCTKQRPIFIITEYM 478
Cdd:COG0515   3 RILRKLGEGSFGEVYLAR--DRKLVALKVLAKKLESKSKeverFLREIQILASLNHPPnIVKLYDFFQDEGSLYLVMEYV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 479 ANGCLLNYLREM--RHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQG-VVKVSDFGLSRYVLDDEYTSS 555
Cdd:COG0515  81 DGGSLEDLLKKIgrKGPLSESEALFILAQILSALEYLHSKGIIHRDIKPENILLDRDGrVVKLIDFGLAKLLPDPGSTSS 160
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 56119141 556 VGSKFPV-----RWSPPEVLMYSKF---SSKSDIWAFGVLMWEIySLGKIPYERFTNSETAEHI 611
Cdd:COG0515 161 IPALPSTsvgtpGYMAPEVLLGLSLayaSSSSDIWSLGITLYEL-LTGLPPFEGEKNSSATSQT 223
SH2 pfam00017
SH2 domain;
282-363 1.47e-23

SH2 domain;


Pssm-ID: 278446  Cd Length: 77  Bit Score: 96.51  E-value: 1.47e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141   282 WYSKHMTRSQAEQLLKQEGKEGGFIVRDS-SKAGKYTVSVFAkstgepQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELI 360
Cdd:pfam00017   1 WYHGKISREEAERLLLNGKPDGTFLVRESeSTPGGYTLSVRD------DGKVKHYKIQSTDNGGYYISGGVKFSSLAELV 74

                  ...
gi 56119141   361 NYH 363
Cdd:pfam00017  75 EHY 77
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
395-614 8.31e-20

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289  Cd Length: 329  Bit Score: 91.03  E-value: 8.31e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141  395 SWEIdpKDLTFLKELGTGQFGVVKYGKWR--GQYdVAIKMIREGSM----SEDEFIEEAKVMMNLSHEKLVQLYGVCTKQ 468
Cdd:PTZ00263  14 SWKL--SDFEMGETLGTGSFGRVRIAKHKgtGEY-YAIKCLKKREIlkmkQVQHVAQEKSILMELSHPFIVNMMCSFQDE 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141  469 RPIFIITEYMANGCLLNYLREMrHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVL 548
Cdd:PTZ00263  91 NRVYFLLEFVVGGELFTHLRKA-GRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVP 169
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 56119141  549 DDEYTsSVGSKfpvRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSlGKIPYERFTNSETAEHIAQG 614
Cdd:PTZ00263 170 DRTFT-LCGTP---EYLAPEVIQSKGHGKAVDWWTMGVLLYEFIA-GYPPFFDDTPFRIYEKILAG 230
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
216-271 1.24e-17

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620  Cd Length: 56  Bit Score: 79.12  E-value: 1.24e-17
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 56119141    216 ELKKVVALYDYMPMNANDLQLRKGEEYFILEESNLPWWRARDKNGQEGYIPSNYVT 271
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56
BTK smart00107
Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and ...
136-171 1.29e-16

Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains (but not all PH domains are followed by BTK motifs). The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 128417  Cd Length: 36  Bit Score: 75.88  E-value: 1.29e-16
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 56119141    136 NSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILEN 171
Cdd:smart00107   1 NNNLLQKYHPSFWVDGKWLCCQQSEKNAPGCTPYEA 36
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
221-267 8.45e-16

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organisation. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 278447  Cd Length: 47  Bit Score: 73.76  E-value: 8.45e-16
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 56119141   221 VALYDYMPMNANDLQLRKGEEYFILEESNLPWWRARDKNGQEGYIPS 267
Cdd:pfam00018   1 VALYDYTAREPDELSFKKGDVIIVLEKSDDGWWKGRLKGGGEGLIPS 47
BTK pfam00779
BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found ...
142-167 1.07e-10

BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains. The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 307086  Cd Length: 26  Bit Score: 58.70  E-value: 1.07e-10
                          10        20
                  ....*....|....*....|....*.
gi 56119141   142 KYHPCFWIDGQYLCCSQTAKNAMGCQ 167
Cdd:pfam00779   1 KYHPGAFRGGKWLCCKQTDKNAPGCS 26
 
Name Accession Description Interval E-value
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
398-653 0e+00

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657  Cd Length: 256  Bit Score: 534.84  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 398 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEY 477
Cdd:cd05113   1 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMKLSHEKLVQLYGVCTKQRPIYIVTEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 478 MANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVG 557
Cdd:cd05113  81 MSNGCLLNYLREHGKRFQPSQLLEMCKDVCEGMAYLESKQFIHRDLAARNCLVDDQGCVKVSDFGLSRYVLDDEYTSSVG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 558 SKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSCWHE 637
Cdd:cd05113 161 SKFPVRWSPPEVLLYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFNNSETVEKVSQGLRLYRPHLASEKVYAIMYSCWHE 240
                       250
                ....*....|....*.
gi 56119141 638 KADERPSFKILLSNIL 653
Cdd:cd05113 241 KAEERPTFQQLLSSIE 256
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
398-653 0e+00

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637  Cd Length: 256  Bit Score: 523.16  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 398 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEY 477
Cdd:cd05059   1 IDPSELTFLKELGSGQFGVVHLGKWRGKIDVAIKMIREGAMSEDDFIEEAKVMMKLSHPNLVQLYGVCTKQRPIFIVTEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 478 MANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVG 557
Cdd:cd05059  81 MANGCLLNYLRERKGKLGTEWLLDMCSDVCEAMEYLESNGFIHRDLAARNCLVGEDNVVKVSDFGLARYVLDDQYTSSQG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 558 SKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSCWHE 637
Cdd:cd05059 161 TKFPVKWAPPEVFDYSRFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVESVSAGYRLYRPKLAPTEVYTIMYSCWHE 240
                       250
                ....*....|....*.
gi 56119141 638 KADERPSFKILLSNIL 653
Cdd:cd05059 241 KPEDRPAFKKLLSQLT 256
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
398-657 8.24e-142

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685  Cd Length: 260  Bit Score: 418.11  E-value: 8.24e-142
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 398 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEY 477
Cdd:cd05114   1 INPSELTFMKELGSGLFGVVRLGKWRAQYKVAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 478 MANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVG 557
Cdd:cd05114  81 MENGCLLNYLRQRRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDDQYTSSSG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 558 SKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSCWHE 637
Cdd:cd05114 161 AKFPVKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHE 240
                       250       260
                ....*....|....*....|
gi 56119141 638 KADERPSFKILLSNILDVMD 657
Cdd:cd05114 241 KPEGRPTFADLLRTITEIAE 260
Pkinase_Tyr pfam07714
Protein tyrosine kinase;
403-652 7.47e-133

Protein tyrosine kinase;


Pssm-ID: 311583  Cd Length: 258  Bit Score: 394.94  E-value: 7.47e-133
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141   403 LTFLKELGTGQFGVVKYGKWRG-----QYDVAIKMIREGSMSED--EFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIIT 475
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGdgegtKIKVAVKTLKEGADEEEreDFLEEASIMKKLSHPNIVRLLGVCTQGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141   476 EYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYV-LDDEYTS 554
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKGKLTLPDLLQMALQIAKGMEYLESKNFVHRDLAARNCLVTENLVVKISDFGLSRDIyDDDYYRK 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141   555 SVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSC 634
Cdd:pfam07714 161 RGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMTQC 240
                         250
                  ....*....|....*...
gi 56119141   635 WHEKADERPSFKILLSNI 652
Cdd:pfam07714 241 WAYDPEDRPTFSELVEDL 258
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
398-649 2.54e-129

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243  Cd Length: 256  Bit Score: 385.84  E-value: 2.54e-129
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 398 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEY 477
Cdd:cd05112   1 IHPSELTLVQEIGSGQFGLVWLGYWLEKRKVAIKTIREGAMSEEDFIEEAQVMMKLSHPKLVQLYGVCTERSPICLVFEF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 478 MANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVG 557
Cdd:cd05112  81 MEHGCLSDYLRAQRGKFSQETLLGMCLDVCEGMAYLESSNVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDDQYTSSTG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 558 SKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSCWHE 637
Cdd:cd05112 161 TKFPVKWSSPEVFSFSKYSSKSDVWSFGVLMWEVFSEGKTPYENRSNSEVVETINAGFRLYKPRLASQSVYELMQHCWKE 240
                       250
                ....*....|..
gi 56119141 638 KADERPSFKILL 649
Cdd:cd05112 241 RPEDRPSFSLLL 252
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
403-650 3.71e-129

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581  Cd Length: 257  Bit Score: 385.35  E-value: 3.71e-129
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    403 LTFLKELGTGQFGVVKYGKWRG-----QYDVAIKMIREGSMSED--EFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIIT 475
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKGkggkkKVEVAVKTLKEDASEQQieEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    476 EYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSS 555
Cdd:smart00219  81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYRK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    556 VGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSCW 635
Cdd:smart00219 161 RGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCW 240
                          250
                   ....*....|....*
gi 56119141    636 HEKADERPSFKILLS 650
Cdd:smart00219 241 AEDPEDRPTFSELVE 255
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
403-649 3.66e-127

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568  Cd Length: 258  Bit Score: 379.97  E-value: 3.66e-127
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    403 LTFLKELGTGQFGVVKYGKWRG-----QYDVAIKMIREGSMSED--EFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIIT 475
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKGkgdgkEVEVAVKTLKEDASEQQieEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    476 EYMANGCLLNYLREMRHRF-QTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTS 554
Cdd:smart00221  81 EYMPGGDLLDYLRKNRPKElSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141    555 SVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIMYSC 634
Cdd:smart00221 161 VKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQC 240
                          250
                   ....*....|....*
gi 56119141    635 WHEKADERPSFKILL 649
Cdd:smart00221 241 WAEDPEDRPTFSELV 255
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
407-650 3.85e-117

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623  Cd Length: 262  Bit Score: 354.54  E-value: 3.85e-117
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 407 KELGTGQFGVVKYGKWRGQ----YDVAIKMIREGSMSED--EFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMAN 480
Cdd:cd00192   1 KKLGEGAFGEVYKGKLKGGdgktVDVAVKTLKEDASESErkDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 481 GCLLNYLREMRHRFQ--------TQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYV-LDDE 551
Cdd:cd00192  81 GDLLDFLRKSRPVFPspepstlsLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIyDDDY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 552 YTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKIPYERFTNSETAEHIAQGLRLYRPHLASDRVYTIM 631
Cdd:cd00192 161 YRKKTGGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYELM 240
                       250
                ....*....|....*....
gi 56119141 632 YSCWHEKADERPSFKILLS 650
Cdd:cd00192 241 LSCWQLDPEDRPTFSELVE 259
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
407-650 3.20e-108

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630  Cd Length: 248  Bit Score: 330.78  E-value: 3.20e-108
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 407 KELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNY 486
Cdd:cd05034   1 KKLGAGQFGEVWMGVWNGTTKVAVKTLKPGTMSPEAFLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSKGSLLDY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56119141 487 LREMRHRFQT-QQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGS