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) |
|---|---|
| 2.30.30.40 : SH3 type barrels. | M00183 M00043 M00130 M00304 M00335 |
| 3.30.505.10 : SHC Adaptor Protein | M00183 M00043 M00130 M00148 M00304 M00333 M00339 M00344 T00221 |
| 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 |
|---|
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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 |
|---|---|---|---|---|---|
| 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 18291 35154 |
15422 15422 |
16761 16761 |
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| PubChem |
23930 23930 |
5957 5957 |
6022 6022 |
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| 1a0nB |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1avzC |
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Unbound | Unbound | Bound:TYR_120(chain B) | Unbound | Unbound | |
| 1azgB |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1efnA |
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Unbound | Unbound | Bound:TYR_120(chain B) | Unbound | Unbound | |
| 1efnC |
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Unbound | Unbound | Bound:TYR_120(chain D) | Unbound | Unbound | |
| 1fynA |
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Unbound | Unbound | Bound:TYR_4(chain B) | Unbound | Unbound | |
| 1m27C |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1nyfA |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1nygA |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1shfA |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1shfB |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1g83A01 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1g83B01 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1aotF |
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Unbound | Unbound | Unbound | Unbound | Bound:PTR(chain P) | |
| 1aouF |
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Unbound | Unbound | Unbound | Unbound | Bound:PTR(chain P) | |
| 1g83A02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1g83B02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| Reference for Active-site residues | ||
|---|---|---|
| resource | references | E.C. |
| Active-site residues | ||||||||||
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| PDB | Catalytic residues | Cofactor-binding residues | Modified residues | Main-chain involved in catalysis | Comment | |||||
| 1a0nB |
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| 1avzC |
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| 1azgB |
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| 1efnA |
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mutant R96I | ||||
| 1efnC |
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mutant R96I | ||||
| 1fynA |
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| 1m27C |
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| 1nyfA |
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| 1nygA |
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| 1shfA |
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| 1shfB |
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| 1g83A01 |
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| 1g83B01 |
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| 1aotF |
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mutant C97S, C98S, C104S | ||||
| 1aouF |
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| 1g83A02 |
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| 1g83B02 |
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| 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. |
| 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. ADP/ATP could be compatible with other Nucleoside diphosphate/Nucleoside triphosphate. This enzyme is composed of SH3 domain, Although the structures of SH3 and SH2 domains have been determined, |
| Created | Updated |
|---|---|
| 2004-03-03 | 2009-02-26 |