DB code: M00130

RLCP classification 3.103.130000.1162 : Transfer
CATH domain 2.30.30.40 : SH3 type barrels.
3.30.505.10 : SHC Adaptor Protein
3.30.200.20 : Phosphorylase Kinase; domain 1
1.10.510.10 : Transferase(Phosphotransferase); domain 1 Catalytic domain
-.-.-.- :
E.C. 2.7.10.2
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1 M00125 M00124 M00131 T00224 M00127 M00129 M00132 M00136 M00196 M00197 M00198 M00304 M00323 M00325 M00326 M00327 M00328 M00329 M00330 M00331 M00332 M00333 M00335 M00339 M00344
2.30.30.40 : SH3 type barrels. M00183 M00043 T00256 M00304 M00335
3.30.200.20 : Phosphorylase Kinase; domain 1 M00125 M00124 M00131 T00224 M00127 M00129 M00132 M00136 M00196 M00197 M00198 M00304 M00323 M00325 M00326 M00327 M00328 M00329 M00330 M00331 M00332 M00333 M00335 M00339 M00344 D00298
3.30.505.10 : SHC Adaptor Protein M00183 M00043 M00148 T00256 M00304 M00333 M00339 M00344 T00221

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P00520 Tyrosine-protein kinase ABL1
EC 2.7.10.2
Abelson murine leukemia viral oncogene homolog 1
Abelson tyrosine-protein kinase 1
Proto-oncogene c-Abl
p150
NP_001106174.1 (Protein)
NM_001112703.1 (DNA/RNA sequence)
NP_033724.2 (Protein)
NM_009594.3 (DNA/RNA sequence)
PF08919 (F_actin_bind)
PF07714 (Pkinase_Tyr)
PF00017 (SH2)
PF00018 (SH3_1)
[Graphical View]
P00519 Tyrosine-protein kinase ABL1
EC 2.7.10.2
Abelson murine leukemia viral oncogene homolog 1
Abelson tyrosine-protein kinase 1
Proto-oncogene c-Abl
p150
NP_005148.2 (Protein)
NM_005157.4 (DNA/RNA sequence)
NP_009297.2 (Protein)
NM_007313.2 (DNA/RNA sequence)
PF08919 (F_actin_bind)
PF07714 (Pkinase_Tyr)
PF00017 (SH2)
PF00018 (SH3_1)
[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
P00520 ABL1_MOUSE ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Found in a trimolecular complex containing CDK5 and CABLES1. Interacts with CABLES1. Interacts with SORBS1 following insulin stimulation. Interacts with INPPL1/SHIP2 (By similarity). Interacts with PSTPIP1. Interacts with ZDHHC16. Cytoplasm, cytoskeleton. Nucleus. Note=The myristoylated c-ABL protein is reported to be nuclear. Magnesium or manganese.
P00519 ABL1_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Interacts with SORBS1 following insulin stimulation. Found in a trimolecular complex containing CDK5 and CABLES1. Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16 (By similarity). Interacts with INPPL1/SHIP2. Cytoplasm, cytoskeleton. Nucleus. Note=The myristoylated c-ABL protein is reported to be nuclear. Magnesium or manganese.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00585 C00008 C01167
E.C.
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
 18420
 		15422
 15422
 		16761
 16761
PubChem 888
 888
 		5957
 5957
 		6022
 6022
2ablA01 Unbound Unbound Unbound Unbound Unbound
1opkA01 Unbound Unbound Unbound Unbound Unbound
1oplA01 Unbound Unbound Unbound Unbound Unbound
1awoA Unbound Unbound Unbound Unbound Unbound
1bbzA Unbound Unbound Unbound Unbound Unbound
1bbzC Unbound Unbound Unbound Unbound Unbound
1bbzE Unbound Unbound Unbound Unbound Unbound
1bbzG Unbound Unbound Unbound Unbound Unbound
1ju5C Unbound Unbound Unbound Unbound Unbound
1aboA Unbound Unbound Unbound Unbound Unbound
1aboB Unbound Unbound Unbound Unbound Unbound
1abqA Unbound Unbound Unbound Unbound Unbound
2ablA02 Unbound Unbound Unbound Unbound Unbound
1opkA02 Unbound Unbound Unbound Unbound Unbound
1oplA02 Unbound Unbound Unbound Unbound Unbound
1oplB02 Unbound Unbound Unbound Unbound Unbound
1opkA03 Unbound Unbound Unbound Unbound Unbound
1oplA03 Unbound Unbound Unbound Unbound Unbound
1oplB03 Unbound Unbound Unbound Unbound Unbound
1fpuA01 Unbound Unbound Unbound Unbound Unbound
1fpuB01 Unbound Unbound Unbound Unbound Unbound
1iepA01 Unbound Unbound Unbound Unbound Unbound
1iepB01 Unbound Unbound Unbound Unbound Unbound
1m52A01 Unbound Unbound Unbound Unbound Unbound
1m52B01 Unbound Unbound Unbound Unbound Unbound
1opjA01 Unbound Unbound Unbound Unbound Unbound
1opjB01 Unbound Unbound Unbound Unbound Unbound
1opkA04 Unbound Unbound Unbound Unbound Unbound
1oplA04 Unbound Unbound Unbound Unbound Unbound
1oplB04 Unbound Unbound Unbound Unbound Unbound
1fpuA02 Unbound Unbound Unbound Unbound Unbound
1fpuB02 Unbound Unbound Unbound Unbound Unbound
1iepA02 Unbound Unbound Unbound Unbound Unbound
1iepB02 Unbound Unbound Unbound Unbound Unbound
1m52A02 Unbound Unbound Unbound Unbound Unbound
1m52B02 Unbound Unbound Unbound Unbound Unbound
1opjA02 Unbound Unbound Unbound Unbound Unbound
1opjB02 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00520, P00519 & similarity with M00129

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
2ablA01
1opkA01
1oplA01
1awoA
1bbzA
1bbzC
1bbzE
1bbzG
1ju5C
1aboA
1aboB
1abqA
2ablA02
1opkA02
1oplA02
1oplB02
1opkA03
1oplA03
1oplB03
1fpuA01
1fpuB01
1iepA01
1iepB01
1m52A01
1m52B01
1opjA01
1opjB01
1opkA04 ;ARG 386 ASN 387;ASP 400(Magnesium binding) TYR 412(auto-Phosphorylation) mutant D382N
1oplA04 ;ARG 386 ASN 387;ASP 400(Magnesium binding) TYR 412(auto-Phosphorylation) mutant D382N
1oplB04 ;ARG 386 ASN 387;ASP 400(Magnesium binding) TYR 412(auto-Phosphorylation) mutant D382N
1fpuA02 ASP 363;ARG 367 ASN 368;ASP 381(Magnesium binding) TYR 393(auto-Phosphorylation)
1fpuB02 ASP 363;ARG 367 ASN 368;ASP 381(Magnesium binding) TYR 393(auto-Phosphorylation)
1iepA02 ASP 363;ARG 367 ASN 368;ASP 381(Magnesium binding) TYR 393(auto-Phosphorylation)
1iepB02 ASP 363;ARG 367 ASN 368;ASP 381(Magnesium binding) TYR 393(auto-Phosphorylation)
1m52A02 ASP 363;ARG 367 ASN 368;ASP 381(Magnesium binding) TYR 393(auto-Phosphorylation)
1m52B02 ASP 363;ARG 367 ASN 368;ASP 381(Magnesium binding) TYR 393(auto-Phosphorylation)
1opjA02 ASP 382;ARG 386 ASN 387;ASP 400(Magnesium binding) TYR 412(auto-Phosphorylation)
1opjB02 ASP 382;ARG 386 ASN 387;ASP 400(Magnesium binding) TYR 412(auto-Phosphorylation)

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

References
[1]
Resource
Comments STRUCTURE BY NMR OF SH2 DOMAIN.
Medline ID 92370689
PubMed ID 1505033
Journal Cell
Year 1992
Volume 70
Pages 697-704
Authors Overduin M, Rios CB, Mayer BJ, Baltimore D, Cowburn D
Title Three-dimensional solution structure of the src homology 2 domain of c-abl.
Related PDB 1ab2
Related UniProtKB P00519
[2]
Resource
Comments STRUCTURE BY NMR OF SH2 DOMAIN.
Medline ID 93101588
PubMed ID 1281542
Journal Proc Natl Acad Sci U S A
Year 1992
Volume 89
Pages 11673-7
Authors Overduin M, Mayer B, Rios CB, Baltimore D, Cowburn D
Title Secondary structure of Src homology 2 domain of c-Abl by heteronuclear NMR spectroscopy in solution.
Related PDB
Related UniProtKB P00519
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 61-121.
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 1abo 1abq
Related UniProtKB P00520
[4]
Resource
Comments STRUCTURE BY NMR OF SH3 DOMAIN.
Medline ID 96131878
PubMed ID 8590002
Journal Structure
Year 1995
Volume 3
Pages 1075-86
Authors Gosser YQ, Zheng J, Overduin M, Mayer BJ, Cowburn D
Title The solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct.
Related PDB 1awo
Related UniProtKB P00519
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 57-218.
Medline ID 96398698
PubMed ID 8805596
Journal Structure
Year 1996
Volume 4
Pages 1105-14
Authors Nam HJ, Haser WG, Roberts TM, Frederick CA
Title Intramolecular interactions of the regulatory domains of the Bcr-Abl kinase reveal a novel control mechanism.
Related PDB 2abl
Related UniProtKB P00519
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 64-121.
Medline ID 98365516
PubMed ID 9698566
Journal J Mol Biol
Year 1998
Volume 281
Pages 513-21
Authors Pisabarro MT, Serrano L, Wilmanns M
Title Crystal structure of the abl-SH3 domain complexed with a designed high-affinity peptide ligand: implications for SH3-ligand interactions.
Related PDB 1bbz
Related UniProtKB P00519
[7]
Resource
Comments
Medline ID
PubMed ID 11080615
Journal Cell Signal
Year 2000
Volume 12
Pages 637-43
Authors Amoui M, Miller WT
Title The substrate specificity of the catalytic domain of Abl plays an important role in directing phosphorylation of the adaptor protein Crk.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10837221
Journal Curr Biol
Year 2000
Volume 10
Pages 568-75
Authors Kharbanda S, Kumar V, Dhar S, Pandey P, Chen C, Majumder P, Yuan ZM, Whang Y, Strauss W, Pandita TK, Weaver D, Kufe D
Title Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10964922
Journal J Biol Chem
Year 2000
Volume 275
Pages 35631-7
Authors Brasher BB, Van Etten RA
Title c-Abl has high intrinsic tyrosine kinase activity that is stimulated by mutation of the Src homology 3 domain and by autophosphorylation at two distinct regulatory tyrosines.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 223-515.
Medline ID 20446271
PubMed ID 10988075
Journal Science
Year 2000
Volume 289
Pages 1938-42
Authors Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J
Title Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.
Related PDB 1fpu
Related UniProtKB P00519
[11]
Resource
Comments
Medline ID
PubMed ID 11781820
Journal Oncogene
Year 2001
Volume 20
Pages 8075-84
Authors Dorey K, Engen JR, Kretzschmar J, Wilm M, Neubauer G, Schindler T, Superti-Furga G
Title Phosphorylation and structure-based functional studies reveal a positive and a negative role for the activation loop of the c-Abl tyrosine kinase.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12154025
Journal Cancer Res
Year 2002
Volume 62
Pages 4236-43
Authors Nagar B, Bornmann WG, Pellicena P, Schindler T, Veach DR, Miller WT, Clarkson B, Kuriyan J
Title Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571).
Related PDB 1iep 1m52
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12384576
Journal Proc Natl Acad Sci U S A
Year 2002
Volume 99
Pages 14053-8
Authors Donaldson LW, Gish G, Pawson T, Kay LE, Forman-Kay JD
Title Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.
Related PDB 1ju5
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 12654250
Journal Cell
Year 2003
Volume 112
Pages 845-57
Authors Hantschel O, Nagar B, Guettler S, Kretzschmar J, Dorey K, Kuriyan J, Superti-Furga G
Title A myristoyl/phosphotyrosine switch regulates c-Abl.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 12654251
Journal Cell
Year 2003
Volume 112
Pages 859-71
Authors Nagar B, Hantschel O, Young MA, Scheffzek K, Veach D, Bornmann W, Clarkson B, Superti-Furga G, Kuriyan J
Title Structural basis for the autoinhibition of c-Abl tyrosine kinase.
Related PDB 1opj 1opl 1opk
Related UniProtKB

Comments
The E.C. was transferred from 2.7.1.112 to 2.7.10.2.
This enzyme is composed of the N-terminal poly-Ser region, SH3 domain, SH2 domain, protein kinase domain, nuclear localization signal region with poly-Lys, and Pro-rich domain.
The PDB structure, 2abl, corresponds to the SH3 and SH2 domains, whilst the structure, 1fpu, corresponds to the kinase domain. (1opk and 1opl cover from the SH3 domain to the kinase domain.) The structures of the C-terminal domains have not been determined yet.
Altough the catalytic mechanism of this enzyme has not been discussed yet, it can be similar to that of its homologous enzymes (see M00129) due to the complete conservation of active site residues.

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