EzCatDB: M00148
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DB codeM00148
CATH domainDomain 13.30.505.10 : SHC Adaptor Protein
Domain 21.10.930.10 : Syk Kinase; Chain A, domain 2
Domain 33.30.505.10 : SHC Adaptor Protein
Domain 4-.-.-.-
Domain 5-.-.-.-
E.C.2.7.10.2

CATH domainRelated DB codes (homologues)
1.10.930.10 : Syk Kinase; Chain A, domain 2M00333
3.30.505.10 : SHC Adaptor ProteinM00183,M00043,M00130,T00256,M00304,M00333,M00339,M00344,T00221

Enzyme Name
UniProtKBKEGG

P43405
Protein nameTyrosine-protein kinase SYKnon-specific protein-tyrosine kinase
ABL
ABL1
ABL2
ABLL
ACK1
ACK2
AGMX1
ARG
ATK
ATP:protein-tyrosine O-phosphotransferase (ambiguous)
BLK
Bmk
BMX
BRK
Bruton's tyrosine kinase
Bsk
BTK
BTKL
CAKb
Cdgip
CHK
CSK
CTK
CYL
cytoplasmic protein tyrosine kinase
EMT
ETK
Fadk
FAK
FAK2
FER
Fert1/2
FES
FGR
focal adhesion kinase
FPS
FRK
FYN
HCK
HCTK
HYL
IMD1
ITK
IYK
JAK1
JAK2
JAK3
Janus kinase 1
Janus kinase 2
Janus kinase 3
JTK1
JTK9
L-JAK
LCK
LSK
LYN
MATK
Ntk
p60c-src protein tyrosine kinase
PKB
protein-tyrosine kinase (ambiguous)
PSCTK
PSCTK1
PSCTK2
PSCTK4
PSCTK5
PTK2
PTK2B
PTK6
PYK2
RAFTK
RAK
Rlk
Sik
SLK
SRC
SRC2
SRK
SRM
SRMS
STD
SYK
SYN
Tck
TEC
TNK1
Tsk
TXK
TYK2
TYK3
YES1
YK2
ZAP70
SynonymsEC 2.7.10.2
Spleen tyrosine kinase
p72-Syk
RefSeqNP_001128524.1 (Protein)
NM_001135052.2 (DNA/RNA sequence)
NP_001167638.1 (Protein)
NM_001174167.1 (DNA/RNA sequence)
NP_001167639.1 (Protein)
NM_001174168.1 (DNA/RNA sequence)
NP_003168.2 (Protein)
NM_003177.5 (DNA/RNA sequence)
PfamPF07714 (Pkinase_Tyr)
PF00017 (SH2)
[Graphical view]


UniProtKB:Accession NumberP43405
Entry nameKSYK_HUMAN
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SubunitInteracts with CBL and SLA when it is phosphorylated. The interaction with SLA may link it to CBL, leading to its destruction. Interacts with phosphorylated NFAM1 (By similarity). Interacts with Epstein-Barr virus LMP2A. Interacts through its SH2 domains with the phosphorylated ITAM domain of CD79A which stimulates SYK autophosphorylation and activation. Interacts with FCRL3.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00002C00585C00008C01167
CompoundATP[Protein]-L-tyrosineADP[Protein]-L-tyrosine phosphate
Typeamine group,nucleotidearomatic ring (only carbon atom),peptide/proteinamine group,nucleotidearomatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI15422

16761

PubChem5957

6022

            
1a81A01UnboundUnboundUnboundUnbound
1a81C01UnboundUnboundUnboundUnbound
1a81E01UnboundUnboundUnboundUnbound
1a81G01UnboundUnboundUnboundUnbound
1a81I01UnboundUnboundUnboundUnbound
1a81K01UnboundUnboundUnboundUnbound
1a81A02UnboundUnboundUnboundUnbound
1a81C02UnboundUnboundUnboundUnbound
1a81E02UnboundUnboundUnboundUnbound
1a81G02UnboundUnboundUnboundUnbound
1a81I02UnboundUnboundUnboundUnbound
1a81K02UnboundUnboundUnboundUnbound
1a81A03UnboundUnboundUnboundUnbound
1a81C03UnboundUnboundUnboundUnbound
1a81E03UnboundUnboundUnboundUnbound
1a81G03UnboundUnboundUnboundUnbound
1a81I03UnboundUnboundUnboundUnbound
1a81K03UnboundUnboundUnboundUnbound
1csyAUnboundUnboundUnboundUnbound
1cszAUnboundUnboundUnboundUnbound

Active-site residues
pdb
        
1a81A01
1a81C01
1a81E01
1a81G01
1a81I01
1a81K01
1a81A02
1a81C02
1a81E02
1a81G02
1a81I02
1a81K02
1a81A03
1a81C03
1a81E03
1a81G03
1a81I03
1a81K03
1csyA
1cszA


references
[1]
PubMed ID8580068
JournalInt Immunol
Year1995
Volume7
Pages1701-8
AuthorsWienands J, Freuler F, Baumann G
TitleTyrosine-phosphorylated forms of Ig beta, CD22, TCR zeta and HOSS are major ligands for tandem SH2 domains of Syk.
[2]
CommentsSTRUCTURE BY NMR OF 163-265.
Medline ID96131877
PubMed ID8590001
JournalStructure
Year1995
Volume3
Pages1061-73
AuthorsNarula SS, Yuan RW, Adams SE, Green OM, Green J, Philips TB, Zydowsky LD, Botfield MC, Hatada M, Laird ER, et al
TitleSolution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide.
Related PDB1csy,1csz
Related UniProtKBP43405
[3]
PubMed ID8611520
JournalBiochemistry
Year1996
Volume35
Pages5327-32
AuthorsRuzzene M, Brunati AM, Marin O, Donella-Deana A, Pinna LA
TitleSH2 domains mediate the sequential phosphorylation of HS1 protein by p72syk and Src-related protein tyrosine kinases.
[4]
PubMed ID8628292
JournalMol Cell Biol
Year1996
Volume16
Pages2255-63
AuthorsNorthrop JP, Pustelnik MJ, Lu AT, Grove JR
TitleCharacterization of the roles of SH2 domain-containing proteins in T-lymphocyte activation by using dominant negative SH2 domains.
[5]
PubMed ID9548930
JournalBiochemistry
Year1998
Volume37
Pages5481-6
AuthorsQin S, Kurosaki T, Yamamura H
TitleDifferential regulation of oxidative and osmotic stress induced Syk activation by both autophosphorylation and SH2 domains.
[6]
PubMed ID9422724
JournalJ Biol Chem
Year1998
Volume273
Pages729-35
AuthorsOttinger EA, Botfield MC, Shoelson SE
TitleTandem SH2 domains confer high specificity in tyrosine kinase signaling.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 9-262.
Medline ID98365517
PubMed ID9698567
JournalJ Mol Biol
Year1998
Volume281
Pages523-37
AuthorsFutterer K, Wong J, Grucza RA, Chan AC, Waksman G
TitleStructural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide.
Related PDB1a81
Related UniProtKBP43405
[8]
PubMed ID10213605
JournalBiochemistry
Year1999
Volume38
Pages5024-33
AuthorsGrucza RA, Futterer K, Chan AC, Waksman G
TitleThermodynamic study of the binding of the tandem-SH2 domain of the Syk kinase to a dually phosphorylated ITAM peptide: evidence for two conformers.
[9]
PubMed ID10955995
JournalBiochemistry
Year2000
Volume39
Pages10072-81
AuthorsGrucza RA, Bradshaw JM, Mitaxov V, Waksman G
TitleRole of electrostatic interactions in SH2 domain recognition: salt-dependence of tyrosyl-phosphorylated peptide binding to the tandem SH2 domain of the Syk kinase and the single SH2 domain of the Src kinase.
[10]
PubMed ID11828442
JournalChembiochem
Year2001
Volume2
Pages171-9
AuthorsRuijtenbeek R, Kruijtzer JA, van de Wiel W, Fischer MJ, Fluck M, Redegeld FA, Liskamp RM, Nijkamp FP
TitlePeptoid - peptide hybrids that bind Syk SH2 domains involved in signal transduction.
[11]
PubMed ID11741491
JournalJ Med Chem
Year2001
Volume44
Pages4737-40
AuthorsNiimi T, Orita M, Okazawa-Igarashi M, Sakashita H, Kikuchi K, Ball E, Ichikawa A, Yamagiwa Y, Sakamoto S, Tanaka A, Tsukamoto S, Fujita S, Tatsuta K, Maeda Y, Chikauchi K
TitleDesign and synthesis of non-peptidic inhibitors for the Syk C-terminal SH2 domain based on structure-based in-silico screening.

comments
The E.C. was transferred from 2.7.1.112 to 2.7.10.2.
This enzyme is composed of the two N-terminal SH2 domains, the linker region inserted between the SH2 domains, another linker domain, and the C-terminal protein kinase domain.
The tertiary structures of the N-terminal SH2 domains and the linker region have been determined. However, the structure of the catalytic domain has not been determined yet.

createdupdated
2004-03-032009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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