|
CATH domain | Related DB codes (homologues) |
---|
1.10.510.10 : Transferase(Phosphotransferase); domain 1 | M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344 | 2.30.30.40 : SH3 type barrels. | M00183,M00043,M00130,T00256,M00335 | 3.30.200.20 : Phosphorylase Kinase; domain 1 | M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344,D00298 | 3.30.505.10 : SHC Adaptor Protein | M00183,M00043,M00130,M00148,T00256,M00333,M00339,M00344,T00221 |
UniProtKB:Accession Number | P32577 | P41241 | P41240 |
---|
Entry name | CSK_RAT | CSK_MOUSE | CSK_HUMAN |
---|
Activity | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. |
---|
Subunit | Homodimer (via SH3-domain). Interacts with PTPN8. Interacts with phosphorylated SIT1, PAG1, LIME1 and TGFB1I1, these interactions serve to recruit CSK to the membrane where it can phosphorylate and inhibit Src-family kinases. Interacts with SRCIN1. Interacts with RHOH (By similarity). | Homodimer (via SH3-domain). Interacts with PTPN8. Interacts with phosphorylated SIT1, PAG1, LIME1 and TGFB1I1, these interactions serve to recruit CSK to the membrane where it can phosphorylate and inhibit Src-family kinases. Interacts with SRCIN1. Interacts with RHOH (By similarity). | Homodimer (via SH3-domain). Interacts with PTPN8 (By similarity). Interacts with phosphorylated SIT1, PAG1, LIME1 and TGFB1I1, these interactions serve to recruit CSK to the membrane where it can phosphorylate and inhibit Src-family kinases. Interacts with SRCIN1. Interacts with RHOH. |
---|
Subcellular location | Cytoplasm (By similarity). Cell membrane (By similarity). Note: Mainly cytoplasmic, also present in lipid rafts (By similarity). | Cytoplasm. Cell membrane. Note: Mainly cytoplasmic, also present in lipid rafts. | Cytoplasm (By similarity). Cell membrane (By similarity). Note: Mainly cytoplasmic, also present in lipid rafts (By similarity). |
---|
Cofactor |
|
|
|
---|
Compound table: links to PDB-related databases & PoSSuM |
---|
| Cofactors | Substrates | Products |
---|
KEGG-id | C00305 | C00002 | C00585 | C00008 | C01167 |
---|
Compound | Magnesium | ATP | [protein]-L-tyrosine | ADP | [protein]-L-tyrosine phosphate |
---|
Type | divalent metal (Ca2+, Mg2+) | amine group,nucleotide | aromatic ring (only carbon atom),peptide/protein | amine group,nucleotide | aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion |
---|
ChEBI | 18420
| 15422
|
| 16761
|
|
---|
PubChem | 888
| 5957
|
| 6022
|
|
---|
| | | | | | | | | | | | |
---|
1k9aA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aB01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aC01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aD01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aE01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aF01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1jegA00 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1cskA00 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1cskB00 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1cskC00 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1cskD00 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aB02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aC02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aD02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aE02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aF02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
3eacA00 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
3eazA00 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aA03 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aB03 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aC03 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aD03 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aE03 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aF03 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1bygA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
3d7tA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
3d7uA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
3d7uC01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aA04 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aB04 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aC04 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aD04 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aE04 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1k9aF04 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1bygA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
3d7tA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
3d7uA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
3d7uC02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
---|
[6] | FIG.4 |
| [8] | Figure 2 |
| [34] | Figure 7, p.344-345 |
|
references | [1] |
---|
Comments | FUNCTION IN PHOSPHORYLATION OF LYN AND FYN. |
---|
PubMed ID | 1722201 |
---|
Journal | J Biol Chem |
---|
Year | 1991 |
---|
Volume | 266 |
---|
Pages | 24249-52 |
---|
Authors | Okada M, Nada S, Yamanashi Y, Yamamoto T, Nakagawa H |
---|
Title | CSK: a protein-tyrosine kinase involved in regulation of src family kinases. |
---|
[2] |
---|
Comments | X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-71. |
---|
PubMed ID | 7511113 |
---|
Journal | FEBS Lett |
---|
Year | 1994 |
---|
Volume | 341 |
---|
Pages | 79-85 |
---|
Authors | Borchert TV, Mathieu M, Zeelen JP, Courtneidge SA, Wierenga RK |
---|
Title | The crystal structure of human CskSH3: structural diversity near the RT-Src and n-Src loop. |
---|
Related PDB | 1csk |
---|
Related UniProtKB | P41240 |
---|
[3] |
---|
PubMed ID | 7527038 |
---|
Journal | J Biol Chem |
---|
Year | 1994 |
---|
Volume | 269 |
---|
Pages | 30880-7 |
---|
Authors | Cole PA, Burn P, Takacs B, Walsh CT |
---|
Title | Evaluation of the catalytic mechanism of recombinant human Csk (C-terminal Src kinase) using nucleotide analogs and viscosity effects. |
---|
[4] |
---|
PubMed ID | 7518562 |
---|
Journal | Mol Cell Biol |
---|
Year | 1994 |
---|
Volume | 14 |
---|
Pages | 5402-11 |
---|
Authors | Howell BW, Cooper JA |
---|
Title | Csk suppression of Src involves movement of Csk to sites of Src activity. |
---|
[5] |
---|
PubMed ID | 7513429 |
---|
Journal | Proc Natl Acad Sci U S A |
---|
Year | 1994 |
---|
Volume | 91 |
---|
Pages | 3984-8 |
---|
Authors | Sabe H, Hata A, Okada M, Nakagawa H, Hanafusa H |
---|
Title | Analysis of the binding of the Src homology 2 domain of Csk to tyrosine-phosphorylated proteins in the suppression and mitotic activation of c-Src. |
---|
[6] |
---|
PubMed ID | 7673185 |
---|
Journal | J Biol Chem |
---|
Year | 1995 |
---|
Volume | 270 |
---|
Pages | 22105-8 |
---|
Authors | Cole PA, Grace MR, Phillips RS, Burn P, Walsh CT |
---|
Title | The role of the catalytic base in the protein tyrosine kinase Csk. |
---|
[7] |
---|
PubMed ID | 9048573 |
---|
Journal | Biochemistry |
---|
Year | 1997 |
---|
Volume | 36 |
---|
Pages | 1874-81 |
---|
Authors | Grace MR, Walsh CT, Cole PA |
---|
Title | Divalent ion effects and insights into the catalytic mechanism of protein tyrosine kinase Csk. |
---|
[8] |
---|
Journal | J Am Chem Soc |
---|
Year | 1998 |
---|
Volume | 120 |
---|
Pages | 9851-8 |
---|
Authors | Kim K, Cole PA |
---|
Title | Kinetic analysis of a protein tyrosine kinase reaction transition state in the forward and reverse directions. |
---|
[9] |
---|
PubMed ID | 10395732 |
---|
Journal | Arch Biochem Biophys |
---|
Year | 1999 |
---|
Volume | 367 |
---|
Pages | 167-72 |
---|
Authors | Sun G, Budde RJ |
---|
Title | Mutations in the N-terminal regulatory region reduce the catalytic activity of Csk, but do not affect its recognition of Src. |
---|
[10] |
---|
PubMed ID | 10460171 |
---|
Journal | Biochemistry |
---|
Year | 1999 |
---|
Volume | 38 |
---|
Pages | 11147-55 |
---|
Authors | Sondhi D, Cole PA |
---|
Title | Domain interactions in protein tyrosine kinase Csk. |
---|
[11] |
---|
PubMed ID | 9878439 |
---|
Journal | J Mol Biol |
---|
Year | 1999 |
---|
Volume | 285 |
---|
Pages | 713-25 |
---|
Authors | Lamers MB, Antson AA, Hubbard RE, Scott RK, Williams DH |
---|
Title | Structure of the protein tyrosine kinase domain of C-terminal Src kinase (CSK) in complex with staurosporine. |
---|
Related PDB | 1byg |
---|
Related UniProtKB | P41240 |
---|
[12] |
---|
PubMed ID | 10918051 |
---|
Journal | J Biol Chem |
---|
Year | 2000 |
---|
Volume | 275 |
---|
Pages | 29183-6 |
---|
Authors | Takeuchi S, Takayama Y, Ogawa A, Tamura K, Okada M |
---|
Title | Transmembrane phosphoprotein Cbp positively regulates the activity of the carboxyl-terminal Src kinase, Csk. |
---|
[13] |
---|
Comments | INTERACTION WITH PAG1. |
---|
PubMed ID | 10790433 |
---|
Journal | J Exp Med |
---|
Year | 2000 |
---|
Volume | 191 |
---|
Pages | 1591-604 |
---|
Authors | Brdicka T, Pavlistova D, Leo A, Bruyns E, Korinek V, Angelisova P, Scherer J, Shevchenko A, Hilgert I, Cerny J, Drbal K, Kuramitsu Y, Kornacker B, Horejsi V, Schraven B |
---|
Title | Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. |
---|
[14] |
---|
Comments | INTERACTION WITH PAG1. |
---|
PubMed ID | 10801129 |
---|
Journal | Nature |
---|
Year | 2000 |
---|
Volume | 404 |
---|
Pages | 999-1003 |
---|
Authors | Kawabuchi M, Satomi Y, Takao T, Shimonishi Y, Nada S, Nagai K, Tarakhovsky A, Okada M |
---|
Title | Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases. |
---|
[15] |
---|
PubMed ID | 11551213 |
---|
Journal | Biochemistry |
---|
Year | 2001 |
---|
Volume | 40 |
---|
Pages | 11149-55 |
---|
Authors | Shaffer J, Sun G, Adams JA |
---|
Title | Nucleotide release and associated conformational changes regulate function in the COOH-terminal Src kinase, Csk. |
---|
[16] |
---|
Comments | PHOSPHORYLATION AT SER-364 BY PKA, MUTAGENESIS OF SER-364. |
---|
PubMed ID | 11181701 |
---|
Journal | J Exp Med |
---|
Year | 2001 |
---|
Volume | 193 |
---|
Pages | 497-507 |
---|
Authors | Vang T, Torgersen KM, Sundvold V, Saxena M, Levy FO, Skalhegg BS, Hansson V, Mustelin T, Tasken K |
---|
Title | Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor. |
---|
[17] |
---|
PubMed ID | 11724538 |
---|
Journal | J Mol Biol |
---|
Year | 2001 |
---|
Volume | 314 |
---|
Pages | 129-38 |
---|
Authors | Shekhtman A, Ghose R, Wang D, Cole PA, Cowburn D |
---|
Title | Novel mechanism of regulation of the non-receptor protein tyrosine kinase Csk: insights from NMR mapping studies and site-directed mutagenesis. |
---|
[18] |
---|
Comments | STRUCTURE BY NMR OF 1-83. |
---|
PubMed ID | 11685249 |
---|
Journal | Nat Struct Biol |
---|
Year | 2001 |
---|
Volume | 8 |
---|
Pages | 998-1004 |
---|
Authors | Ghose R, Shekhtman A, Goger MJ, Ji H, Cowburn D |
---|
Title | A novel, specific interaction involving the Csk SH3 domain and its natural ligand. |
---|
Related PDB | 1jeg |
---|
Related UniProtKB | P41241 |
---|
[19] |
---|
PubMed ID | 11884384 |
---|
Journal | J Biol Chem |
---|
Year | 2002 |
---|
Volume | 277 |
---|
Pages | 14351-4 |
---|
Authors | Ogawa A, Takayama Y, Sakai H, Chong KT, Takeuchi S, Nakagawa A, Nada S, Okada M, Tsukihara T |
---|
Title | Structure of the carboxyl-terminal Src kinase, Csk. |
---|
Related PDB | 1k9a |
---|
Related UniProtKB | P32577 |
---|
[20] |
---|
PubMed ID | 12417200 |
---|
Journal | J Mol Biol |
---|
Year | 2002 |
---|
Volume | 323 |
---|
Pages | 871-81 |
---|
Authors | Hamuro Y, Wong L, Shaffer J, Kim JS, Stranz DD, Jennings PA, Woods VL Jr, Adams JA |
---|
Title | Phosphorylation driven motions in the COOH-terminal Src kinase, CSK, revealed through enhanced hydrogen-deuterium exchange and mass spectrometry (DXMS). |
---|
[21] |
---|
PubMed ID | 12600271 |
---|
Journal | Biochem J |
---|
Year | 2003 |
---|
Volume | 372 |
---|
Pages | 271-8 |
---|
Authors | Yaqub S, Abrahamsen H, Zimmerman B, Kholod N, Torgersen KM, Mustelin T, Herberg FW, Tasken K, Vang T |
---|
Title | Activation of C-terminal Src kinase (Csk) by phosphorylation at serine-364 depends on the Csk-Src homology 3 domain. |
---|
[22] |
---|
PubMed ID | 12686554 |
---|
Journal | J Biol Chem |
---|
Year | 2003 |
---|
Volume | 278 |
---|
Pages | 24072-7 |
---|
Authors | Lin X, Lee S, Sun G |
---|
Title | Functions of the activation loop in Csk protein-tyrosine kinase. |
---|
[23] |
---|
PubMed ID | 15504335 |
---|
Journal | Biochem Biophys Res Commun |
---|
Year | 2004 |
---|
Volume | 324 |
---|
Pages | 1155-64 |
---|
Authors | Roskoski R Jr |
---|
Title | Src protein-tyrosine kinase structure and regulation. |
---|
[24] |
---|
PubMed ID | 15312765 |
---|
Journal | J Mol Biol |
---|
Year | 2004 |
---|
Volume | 341 |
---|
Pages | 93-106 |
---|
Authors | Wong L, Lieser S, Chie-Leon B, Miyashita O, Aubol B, Shaffer J, Onuchic JN, Jennings PA, Woods VL Jr, Adams JA |
---|
Title | Dynamic coupling between the SH2 domain and active site of the COOH terminal Src kinase, Csk. |
---|
[25] |
---|
PubMed ID | 15683240 |
---|
Journal | Biochemistry |
---|
Year | 2005 |
---|
Volume | 44 |
---|
Pages | 1561-7 |
---|
Authors | Lin X, Ayrapetov MK, Lee S, Parang K, Sun G |
---|
Title | Probing the communication between the regulatory and catalytic domains of a protein tyrosine kinase, Csk. |
---|
[26] |
---|
Comments | REVIEW. |
---|
PubMed ID | 16243715 |
---|
Journal | Growth Factors |
---|
Year | 2005 |
---|
Volume | 23 |
---|
Pages | 233-44 |
---|
Authors | Chong YP, Mulhern TD, Cheng HC |
---|
Title | C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK)--endogenous negative regulators of Src-family protein kinases. |
---|
[27] |
---|
PubMed ID | 15623523 |
---|
Journal | J Biol Chem |
---|
Year | 2005 |
---|
Volume | 280 |
---|
Pages | 7769-76 |
---|
Authors | Lieser SA, Shindler C, Aubol BE, Lee S, Sun G, Adams JA |
---|
Title | Phosphoryl transfer step in the C-terminal Src kinase controls Src recognition. |
---|
[28] |
---|
PubMed ID | 16002086 |
---|
Journal | J Mol Biol |
---|
Year | 2005 |
---|
Volume | 351 |
---|
Pages | 131-43 |
---|
Authors | Wong L, Lieser SA, Miyashita O, Miller M, Tasken K, Onuchic JN, Adams JA, Woods VL Jr, Jennings PA |
---|
Title | Coupled motions in the SH2 and kinase domains of Csk control Src phosphorylation. |
---|
[29] |
---|
PubMed ID | 17018524 |
---|
Journal | J Biol Chem |
---|
Year | 2006 |
---|
Volume | 281 |
---|
Pages | 38004-12 |
---|
Authors | Lieser SA, Shaffer J, Adams JA |
---|
Title | SRC tail phosphorylation is limited by structural changes in the regulatory tyrosine kinase Csk. |
---|
[30] |
---|
PubMed ID | 16483606 |
---|
Journal | J Mol Biol |
---|
Year | 2006 |
---|
Volume | 357 |
---|
Pages | 1263-73 |
---|
Authors | Lin X, Wang Y, Ahmadibeni Y, Parang K, Sun G |
---|
Title | Structural basis for domain-domain communication in a protein tyrosine kinase, the C-terminal Src kinase. |
---|
[31] |
---|
PubMed ID | 17137590 |
---|
Journal | J Mol Biol |
---|
Year | 2007 |
---|
Volume | 365 |
---|
Pages | 1460-8 |
---|
Authors | Mills JE, Whitford PC, Shaffer J, Onuchic JN, Adams JA, Jennings PA |
---|
Title | A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity. |
---|
[32] |
---|
PubMed ID | 18614016 |
---|
Journal | Cell |
---|
Year | 2008 |
---|
Volume | 134 |
---|
Pages | 124-34 |
---|
Authors | Levinson NM, Seeliger MA, Cole PA, Kuriyan J |
---|
Title | Structural basis for the recognition of c-Src by its inactivator Csk. |
---|
Related PDB | 3d7t,3d7u |
---|
Related UniProtKB | P41240 |
---|
[33] |
---|
PubMed ID | 19244618 |
---|
Journal | J Mol Biol |
---|
Year | 2009 |
---|
Volume | 386 |
---|
Pages | 1066-77 |
---|
Authors | Huang K, Wang YH, Brown A, Sun G |
---|
Title | Identification of N-terminal lobe motifs that determine the kinase activity of the catalytic domains and regulatory strategies of Src and Csk protein tyrosine kinases. |
---|
[34] |
---|
PubMed ID | 20476842 |
---|
Journal | Growth Factors |
---|
Year | 2010 |
---|
Volume | 28 |
---|
Pages | 329-50 |
---|
Authors | Ia KK, Mills RD, Hossain MI, Chan KC, Jarasrassamee B, Jorissen RN, Cheng HC |
---|
Title | Structural elements and allosteric mechanisms governing regulation and catalysis of CSK-family kinases and their inhibition of Src-family kinases. |
---|
comments | This enzyme is a nonreceptor tyrosine kinase, whose catalytic domain is homologous to that of proto-oncogene tyrosine-protein kinase ABL1 (M00130 in EzCatDB). This enzyme is composed of SH2 domain, SH3 domain and catalytic domain. Unlike other homologous enzymes, this enzyme is not regulated by autophosphorylation of its activation loop and does not have a phosphorylation site in the C-terminus. According to the literature, this enzyme is involved in the regulation of the Src family tyrosine kinases (SFKs), which are also homologous to this enzyme. This enzyme phosphorylate the C-terminal tail of SFKs, which could repress the activity of those enzymes. Src is one of SFKs.
|
created | updated |
---|
2012-05-22 | 2013-01-28 |
|
|