DB code: T00256

CATH domain 2.30.30.40 : SH3 type barrels.
3.30.505.10 : SHC Adaptor Protein
-.-.-.- :
E.C. 2.7.10.2
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.30.505.10 : SHC Adaptor Protein M00183 M00043 M00130 M00148 M00304 M00333 M00339 M00344 T00221
2.30.30.40 : SH3 type barrels. M00183 M00043 M00130 M00304 M00335

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P06241 Tyrosine-protein kinase Fyn
EC 2.7.10.2
Proto-oncogene Syn
Proto-oncogene c-Fyn
Src-like kinase
SLK
p59-Fyn
NP_002028.1 (Protein)
NM_002037.5 (DNA/RNA sequence)
NP_694592.1 (Protein)
NM_153047.3 (DNA/RNA sequence)
NP_694593.1 (Protein)
NM_153048.3 (DNA/RNA sequence)
PF07714 (Pkinase_Tyr)
PF00017 (SH2)
PF00018 (SH3_1)
[Graphical View]

KEGG enzyme name
SYN
Tck
TEC
TNK1
Tsk
TXK
TYK2
TYK3
YES1
YK2
ZAP70
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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P06241 FYN_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Associates through its SH3 domain, to the p85 subunit of phosphatidylinositol 3-kinase. Interacts with the FYN-binding protein (FYB). Interacts with phosphorylated TOM1L1. Interacts with CD79A upon activation of the B-cell antigen receptor which increases FYN activity (By similarity). Interacts with PAG1. Interacts (via SH3 domain) with HEV ORF3 protein. Cell membrane. Note=Present and active in lipid rafts. Present in cell body and along the process of mature and developing oligodendroyctes. Manganese.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00034 C00002 C00585 C00008 C01167
E.C.
Compound Manganese ATP [Protein]-L-tyrosine ADP [Protein]-L-tyrosine phosphate
Type heavy metal 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 18291
35154
15422
16761
PubChem 23930
5957
6022
1a0nB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1avzC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:TYR_120(chain B) Unbound Unbound
1azgB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1efnA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:TYR_120(chain B) Unbound Unbound
1efnC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:TYR_120(chain D) Unbound Unbound
1fynA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:TYR_4(chain B) Unbound Unbound
1m27C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1nyfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1nygA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1shfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1shfB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1g83A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1g83B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1aotF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:PTR(chain P)
1aouF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:PTR(chain P)
1g83A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1g83B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound 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
1a0nB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1avzC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1azgB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1efnA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant R96I
1efnC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant R96I
1fynA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1m27C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nyfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nygA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1shfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1shfB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1g83A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1g83B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1aotF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant C97S, C98S, C104S
1aouF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1g83A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1g83B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

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

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF SH3 DOMAIN.
Medline ID 93327750
PubMed ID 7687536
Journal EMBO J
Year 1993
Volume 12
Pages 2617-24
Authors Noble ME, Musacchio A, Saraste M, Courtneidge SA, Wierenga RK
Title Crystal structure of the SH3 domain in human Fyn; comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and spectrin.
Related PDB 1shf
Related UniProtKB P06241
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 80-141.
Medline ID 95393198
PubMed ID 7664083
Journal Nat Struct Biol
Year 1994
Volume 1
Pages 546-51
Authors Musacchio A, Saraste M, Wilmanns M
Title High-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides.
Related PDB 1fyn
Related UniProtKB P06241
[3]
Resource
Comments
Medline ID
PubMed ID 7589480
Journal FEBS Lett
Year 1995
Volume 373
Pages 265-8
Authors Hane M, Lowin B, Peitsch M, Becker K, Tschopp J
Title Interaction of peptides derived from the Fas ligand with the Fyn-SH3 domain.
Related PDB
Related UniProtKB
[4]
Resource
Comments STRUCTURE BY NMR.
Medline ID 97121261
PubMed ID 8961927
Journal Biochemistry
Year 1996
Volume 35
Pages 15646-53
Authors Renzoni DA, Pugh DJ, Siligardi G, Das P, Morton CJ, Rossi C, Waterfield MD, Campbell ID, Ladbury JE
Title Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase.
Related PDB 1a0n 1azg
Related UniProtKB P06241
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 84-140 IN COMPLEX WITH NEF.
Medline ID 96279837
PubMed ID 8681387
Journal Cell
Year 1996
Volume 85
Pages 931-42
Authors Lee CH, Saksela K, Mirza UA, Chait BT, Kuriyan J
Title Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain.
Related PDB 1efn
Related UniProtKB P06241
[6]
Resource
Comments
Medline ID
PubMed ID 8626429
Journal J Biol Chem
Year 1996
Volume 271
Pages 6333-41
Authors Collette Y, Dutartre H, Benziane A, Ramos-Morales, Benarous R, Harris M, Olive D
Title Physical and functional interaction of Nef with Lck. HIV-1 Nef-induced T-cell signaling defects.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8599760
Journal Nat Struct Biol
Year 1996
Volume 3
Pages 340-5
Authors Grzesiek S, Bax A, Clore GM, Gronenborn AM, Hu JS, Kaufman J, Palmer I, Stahl SJ, Wingfield PT
Title The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase.
Related PDB
Related UniProtKB
[8]
Resource
Comments STRUCTURE BY NMR OF SH3 DOMAIN.
Medline ID 96399716
PubMed ID 8805554
Journal Structure
Year 1996
Volume 4
Pages 705-14
Authors Morton CJ, Pugh DJ, Brown EL, Kahmann JD, Renzoni DA, Campbell ID
Title Solution structure and peptide binding of the SH3 domain from human Fyn.
Related PDB 1nyf 1nyg
Related UniProtKB P06241
[9]
Resource
Comments
Medline ID
PubMed ID 9317120
Journal J Immunol
Year 1997
Volume 159
Pages 3220-9
Authors Marengere LE, Okkenhaug K, Clavreul A, Couez D, Gibson S, Mills GB, Mak TW, Rottapel R
Title The SH3 domain of Itk/Emt binds to proline-rich sequences in the cytoplasmic domain of the T cell costimulatory receptor CD28.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9351809
Journal Structure
Year 1997
Volume 5
Pages 1361-72
Authors Arold S, Franken P, Strub MP, Hoh F, Benichou S, Benarous R, Dumas C
Title The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling.
Related PDB 1avz
Related UniProtKB
[11]
Resource
Comments STRUCTURE BY NMR OF SH2 DOMAIN.
Medline ID 98035454
PubMed ID 9351806
Journal Structure
Year 1997
Volume 5
Pages 1313-23
Authors Mulhern TD, Shaw GL, Morton CJ, Day AJ, Campbell ID
Title The SH2 domain from the tyrosine kinase Fyn in complex with a phosphotyrosyl peptide reveals insights into domain stability and binding specificity.
Related PDB 1aot 1aou
Related UniProtKB P06241
[12]
Resource
Comments
Medline ID
PubMed ID 9750131
Journal Anal Biochem
Year 1998
Volume 262
Pages 185-92
Authors Ohba T, Ishino M, Aoto H, Sasaki T
Title Dot far-western blot analysis of relative binding affinities of the Src homology 3 domains of Efs and its related proteins.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9656992
Journal Virology
Year 1998
Volume 246
Pages 45-52
Authors Karn T, Hock B, Holtrich U, Adamski M, Strebhardt K, Rubsamen-Waigmann H
Title Nef proteins of distinct HIV-1 or -2 isolates differ in their binding properties for HCK: isolation of a novel Nef binding factor with characteristics of an adaptor protein.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 10430626
Journal J Exp Med
Year 1999
Volume 190
Pages 375-84
Authors Holdorf AD, Green JM, Levin SD, Denny MF, Straus DB, Link V, Changelian PS, Allen PM, Shaw AS
Title Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 10394361
Journal Mol Cell
Year 1999
Volume 3
Pages 729-39
Authors Fackler OT, Luo W, Geyer M, Alberts AS, Peterlin BM
Title Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10660579
Journal J Biol Chem
Year 2000
Volume 275
Pages 4171-6
Authors Collette Y, Arold S, Picard C, Janvier K, Benichou S, Benarous R, Olive D, Dumas C
Title HIV-2 and SIV nef proteins target different Src family SH3 domains than does HIV-1 Nef because of a triple amino acid substitution.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11278857
Journal J Biol Chem
Year 2001
Volume 276
Pages 17199-205
Authors Arold ST, Ulmer TS, Mulhern TD, Werner JM, Ladbury JE, Campbell ID, Noble ME
Title The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases.
Related PDB 1g83
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 11149959
Journal Proc Natl Acad Sci U S A
Year 2001
Volume 98
Pages 705-10
Authors Nitabach MN, Llamas DA, Araneda RC, Intile JL, Thompson IJ, Zhou YI, Holmes TC
Title A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 12121645
Journal Structure
Year 2002
Volume 10
Pages 901-11
Authors Ulmer TS, Werner JM, Campbell ID
Title SH3-SH2 domain orientation in Src kinases: NMR studies of Fyn.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 12545173
Journal Nat Cell Biol
Year 2003
Volume 5
Pages 149-54
Authors Latour S, Roncagalli R, Chen R, Bakinowski M, Shi X, Schwartzberg PL, Davidson D, Veillette A
Title Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulation.
Related PDB
Related UniProtKB

Comments
The E.C. was transferred from 2.7.1.112 to 2.7.10.2.
ADP/ATP could be compatible with other Nucleoside diphosphate/Nucleoside triphosphate.
This enzyme is composed of SH3 domain, SH2 domain and protein kinase domain.
Although the structures of SH3 and SH2 domains have been determined, the catalytic domain of this enzyme has not been solved.

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