DB code: M00148

CATH domain 3.30.505.10 : SHC Adaptor Protein
1.10.930.10 : Syk Kinase; Chain A, domain 2
3.30.505.10 : SHC Adaptor Protein
-.-.-.- :
-.-.-.- :
E.C. 2.7.10.2
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.930.10 : Syk Kinase; Chain A, domain 2 M00333
3.30.505.10 : SHC Adaptor Protein M00183 M00043 M00130 T00256 M00304 M00333 M00339 M00344 T00221

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P43405 Tyrosine-protein kinase SYK
EC 2.7.10.2
Spleen tyrosine kinase
p72-Syk
NP_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)
PF07714 (Pkinase_Tyr)
PF00017 (SH2)
[Graphical View]

KEGG enzyme name
non-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P43405 KSYK_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Interacts 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.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00002 C00585 C00008 C01167
E.C.
Compound ATP [Protein]-L-tyrosine ADP [Protein]-L-tyrosine phosphate
Type 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 15422
 15422
 		16761
 16761
PubChem 5957
 5957
 		6022
 6022
1a81A01 Unbound Unbound Unbound Unbound
1a81C01 Unbound Unbound Unbound Unbound
1a81E01 Unbound Unbound Unbound Unbound
1a81G01 Unbound Unbound Unbound Unbound
1a81I01 Unbound Unbound Unbound Unbound
1a81K01 Unbound Unbound Unbound Unbound
1a81A02 Unbound Unbound Unbound Unbound
1a81C02 Unbound Unbound Unbound Unbound
1a81E02 Unbound Unbound Unbound Unbound
1a81G02 Unbound Unbound Unbound Unbound
1a81I02 Unbound Unbound Unbound Unbound
1a81K02 Unbound Unbound Unbound Unbound
1a81A03 Unbound Unbound Unbound Unbound
1a81C03 Unbound Unbound Unbound Unbound
1a81E03 Unbound Unbound Unbound Unbound
1a81G03 Unbound Unbound Unbound Unbound
1a81I03 Unbound Unbound Unbound Unbound
1a81K03 Unbound Unbound Unbound Unbound
1csyA Unbound Unbound Unbound Unbound
1cszA Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1a81A01
1a81C01
1a81E01
1a81G01
1a81I01
1a81K01
1a81A02
1a81C02
1a81E02
1a81G02
1a81I02
1a81K02
1a81A03
1a81C03
1a81E03
1a81G03
1a81I03
1a81K03
1csyA
1cszA

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments
Medline ID
PubMed ID 8580068
Journal Int Immunol
Year 1995
Volume 7
Pages 1701-8
Authors Wienands J, Freuler F, Baumann G
Title Tyrosine-phosphorylated forms of Ig beta, CD22, TCR zeta and HOSS are major ligands for tandem SH2 domains of Syk.
Related PDB
Related UniProtKB
[2]
Resource
Comments STRUCTURE BY NMR OF 163-265.
Medline ID 96131877
PubMed ID 8590001
Journal Structure
Year 1995
Volume 3
Pages 1061-73
Authors Narula SS, Yuan RW, Adams SE, Green OM, Green J, Philips TB, Zydowsky LD, Botfield MC, Hatada M, Laird ER, et al
Title Solution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide.
Related PDB 1csy 1csz
Related UniProtKB P43405
[3]
Resource
Comments
Medline ID
PubMed ID 8611520
Journal Biochemistry
Year 1996
Volume 35
Pages 5327-32
Authors Ruzzene M, Brunati AM, Marin O, Donella-Deana A, Pinna LA
Title SH2 domains mediate the sequential phosphorylation of HS1 protein by p72syk and Src-related protein tyrosine kinases.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8628292
Journal Mol Cell Biol
Year 1996
Volume 16
Pages 2255-63
Authors Northrop JP, Pustelnik MJ, Lu AT, Grove JR
Title Characterization of the roles of SH2 domain-containing proteins in T-lymphocyte activation by using dominant negative SH2 domains.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9548930
Journal Biochemistry
Year 1998
Volume 37
Pages 5481-6
Authors Qin S, Kurosaki T, Yamamura H
Title Differential regulation of oxidative and osmotic stress induced Syk activation by both autophosphorylation and SH2 domains.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9422724
Journal J Biol Chem
Year 1998
Volume 273
Pages 729-35
Authors Ottinger EA, Botfield MC, Shoelson SE
Title Tandem SH2 domains confer high specificity in tyrosine kinase signaling.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 9-262.
Medline ID 98365517
PubMed ID 9698567
Journal J Mol Biol
Year 1998
Volume 281
Pages 523-37
Authors Futterer K, Wong J, Grucza RA, Chan AC, Waksman G
Title Structural 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 PDB 1a81
Related UniProtKB P43405
[8]
Resource
Comments
Medline ID
PubMed ID 10213605
Journal Biochemistry
Year 1999
Volume 38
Pages 5024-33
Authors Grucza RA, Futterer K, Chan AC, Waksman G
Title Thermodynamic study of the binding of the tandem-SH2 domain of the Syk kinase to a dually phosphorylated ITAM peptide: evidence for two conformers.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10955995
Journal Biochemistry
Year 2000
Volume 39
Pages 10072-81
Authors Grucza RA, Bradshaw JM, Mitaxov V, Waksman G
Title Role 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.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11828442
Journal Chembiochem
Year 2001
Volume 2
Pages 171-9
Authors Ruijtenbeek R, Kruijtzer JA, van de Wiel W, Fischer MJ, Fluck M, Redegeld FA, Liskamp RM, Nijkamp FP
Title Peptoid - peptide hybrids that bind Syk SH2 domains involved in signal transduction.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11741491
Journal J Med Chem
Year 2001
Volume 44
Pages 4737-40
Authors Niimi 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
Title Design and synthesis of non-peptidic inhibitors for the Syk C-terminal SH2 domain based on structure-based in-silico screening.
Related PDB
Related UniProtKB

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.

Created Updated
2004-03-03 2009-02-26