EzCatDB: M00130
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DB codeM00130
RLCP classification3.103.130000.1162 : Transfer
CATH domainDomain 12.30.30.40 : SH3 type barrels.
Domain 23.30.505.10 : SHC Adaptor Protein
Domain 33.30.200.20 : Phosphorylase Kinase; domain 1
Domain 41.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
Domain 5-.-.-.-
E.C.2.7.10.2

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,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 1M00125,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 ProteinM00183,M00043,M00148,T00256,M00304,M00333,M00339,M00344,T00221

Enzyme Name
UniProtKBKEGG

P00520P00519
Protein nameTyrosine-protein kinase ABL1Tyrosine-protein kinase ABL1non-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
Abelson murine leukemia viral oncogene homolog 1
Abelson tyrosine-protein kinase 1
Proto-oncogene c-Abl
p150
EC 2.7.10.2
Abelson murine leukemia viral oncogene homolog 1
Abelson tyrosine-protein kinase 1
Proto-oncogene c-Abl
p150
RefSeqNP_001106174.1 (Protein)
NM_001112703.1 (DNA/RNA sequence)
NP_033724.2 (Protein)
NM_009594.3 (DNA/RNA sequence)
NP_005148.2 (Protein)
NM_005157.4 (DNA/RNA sequence)
NP_009297.2 (Protein)
NM_007313.2 (DNA/RNA sequence)
PfamPF08919 (F_actin_bind)
PF07714 (Pkinase_Tyr)
PF00017 (SH2)
PF00018 (SH3_1)
[Graphical view]
PF08919 (F_actin_bind)
PF07714 (Pkinase_Tyr)
PF00017 (SH2)
PF00018 (SH3_1)
[Graphical view]


UniProtKB:Accession NumberP00520P00519
Entry nameABL1_MOUSEABL1_HUMAN
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SubunitFound 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.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.
Subcellular locationCytoplasm, cytoskeleton. Nucleus. Note=The myristoylated c-ABL protein is reported to be nuclear.Cytoplasm, cytoskeleton. Nucleus. Note=The myristoylated c-ABL protein is reported to be nuclear.
CofactorMagnesium or manganese.Magnesium or manganese.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00585C00008C01167
CompoundMagnesiumATP[Protein]-L-tyrosineADP[Protein]-L-tyrosine phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidearomatic ring (only carbon atom),peptide/proteinamine group,nucleotidearomatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI18420
15422

16761

PubChem888
5957

6022

             
2ablA01UnboundUnboundUnboundUnboundUnbound
1opkA01UnboundUnboundUnboundUnboundUnbound
1oplA01UnboundUnboundUnboundUnboundUnbound
1awoAUnboundUnboundUnboundUnboundUnbound
1bbzAUnboundUnboundUnboundUnboundUnbound
1bbzCUnboundUnboundUnboundUnboundUnbound
1bbzEUnboundUnboundUnboundUnboundUnbound
1bbzGUnboundUnboundUnboundUnboundUnbound
1ju5CUnboundUnboundUnboundUnboundUnbound
1aboAUnboundUnboundUnboundUnboundUnbound
1aboBUnboundUnboundUnboundUnboundUnbound
1abqAUnboundUnboundUnboundUnboundUnbound
2ablA02UnboundUnboundUnboundUnboundUnbound
1opkA02UnboundUnboundUnboundUnboundUnbound
1oplA02UnboundUnboundUnboundUnboundUnbound
1oplB02UnboundUnboundUnboundUnboundUnbound
1opkA03UnboundUnboundUnboundUnboundUnbound
1oplA03UnboundUnboundUnboundUnboundUnbound
1oplB03UnboundUnboundUnboundUnboundUnbound
1fpuA01UnboundUnboundUnboundUnboundUnbound
1fpuB01UnboundUnboundUnboundUnboundUnbound
1iepA01UnboundUnboundUnboundUnboundUnbound
1iepB01UnboundUnboundUnboundUnboundUnbound
1m52A01UnboundUnboundUnboundUnboundUnbound
1m52B01UnboundUnboundUnboundUnboundUnbound
1opjA01UnboundUnboundUnboundUnboundUnbound
1opjB01UnboundUnboundUnboundUnboundUnbound
1opkA04UnboundUnboundUnboundUnboundUnbound
1oplA04UnboundUnboundUnboundUnboundUnbound
1oplB04UnboundUnboundUnboundUnboundUnbound
1fpuA02UnboundUnboundUnboundUnboundUnbound
1fpuB02UnboundUnboundUnboundUnboundUnbound
1iepA02UnboundUnboundUnboundUnboundUnbound
1iepB02UnboundUnboundUnboundUnboundUnbound
1m52A02UnboundUnboundUnboundUnboundUnbound
1m52B02UnboundUnboundUnboundUnboundUnbound
1opjA02UnboundUnboundUnboundUnboundUnbound
1opjB02UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P00520, P00519 & similarity with M00129
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
            
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
1fpuA02ASP 363;ARG 367
ASN 368;ASP 381(Magnesium binding)
TYR 393(auto-Phosphorylation)
 
1fpuB02ASP 363;ARG 367
ASN 368;ASP 381(Magnesium binding)
TYR 393(auto-Phosphorylation)
 
1iepA02ASP 363;ARG 367
ASN 368;ASP 381(Magnesium binding)
TYR 393(auto-Phosphorylation)
 
1iepB02ASP 363;ARG 367
ASN 368;ASP 381(Magnesium binding)
TYR 393(auto-Phosphorylation)
 
1m52A02ASP 363;ARG 367
ASN 368;ASP 381(Magnesium binding)
TYR 393(auto-Phosphorylation)
 
1m52B02ASP 363;ARG 367
ASN 368;ASP 381(Magnesium binding)
TYR 393(auto-Phosphorylation)
 
1opjA02ASP 382;ARG 386
ASN 387;ASP 400(Magnesium binding)
TYR 412(auto-Phosphorylation)
 
1opjB02ASP 382;ARG 386
ASN 387;ASP 400(Magnesium binding)
TYR 412(auto-Phosphorylation)
 


references
[1]
CommentsSTRUCTURE BY NMR OF SH2 DOMAIN.
Medline ID92370689
PubMed ID1505033
JournalCell
Year1992
Volume70
Pages697-704
AuthorsOverduin M, Rios CB, Mayer BJ, Baltimore D, Cowburn D
TitleThree-dimensional solution structure of the src homology 2 domain of c-abl.
Related PDB1ab2
Related UniProtKBP00519
[2]
CommentsSTRUCTURE BY NMR OF SH2 DOMAIN.
Medline ID93101588
PubMed ID1281542
JournalProc Natl Acad Sci U S A
Year1992
Volume89
Pages11673-7
AuthorsOverduin M, Mayer B, Rios CB, Baltimore D, Cowburn D
TitleSecondary structure of Src homology 2 domain of c-Abl by heteronuclear NMR spectroscopy in solution.
Related UniProtKBP00519
[3]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 61-121.
Medline ID95393198
PubMed ID7664083
JournalNat Struct Biol
Year1994
Volume1
Pages546-51
AuthorsMusacchio A, Saraste M, Wilmanns M
TitleHigh-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides.
Related PDB1abo,1abq
Related UniProtKBP00520
[4]
CommentsSTRUCTURE BY NMR OF SH3 DOMAIN.
Medline ID96131878
PubMed ID8590002
JournalStructure
Year1995
Volume3
Pages1075-86
AuthorsGosser YQ, Zheng J, Overduin M, Mayer BJ, Cowburn D
TitleThe solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct.
Related PDB1awo
Related UniProtKBP00519
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 57-218.
Medline ID96398698
PubMed ID8805596
JournalStructure
Year1996
Volume4
Pages1105-14
AuthorsNam HJ, Haser WG, Roberts TM, Frederick CA
TitleIntramolecular interactions of the regulatory domains of the Bcr-Abl kinase reveal a novel control mechanism.
Related PDB2abl
Related UniProtKBP00519
[6]
CommentsX-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 64-121.
Medline ID98365516
PubMed ID9698566
JournalJ Mol Biol
Year1998
Volume281
Pages513-21
AuthorsPisabarro MT, Serrano L, Wilmanns M
TitleCrystal structure of the abl-SH3 domain complexed with a designed high-affinity peptide ligand: implications for SH3-ligand interactions.
Related PDB1bbz
Related UniProtKBP00519
[7]
PubMed ID11080615
JournalCell Signal
Year2000
Volume12
Pages637-43
AuthorsAmoui M, Miller WT
TitleThe substrate specificity of the catalytic domain of Abl plays an important role in directing phosphorylation of the adaptor protein Crk.
[8]
PubMed ID10837221
JournalCurr Biol
Year2000
Volume10
Pages568-75
AuthorsKharbanda S, Kumar V, Dhar S, Pandey P, Chen C, Majumder P, Yuan ZM, Whang Y, Strauss W, Pandita TK, Weaver D, Kufe D
TitleRegulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase.
[9]
PubMed ID10964922
JournalJ Biol Chem
Year2000
Volume275
Pages35631-7
AuthorsBrasher BB, Van Etten RA
Titlec-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.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 223-515.
Medline ID20446271
PubMed ID10988075
JournalScience
Year2000
Volume289
Pages1938-42
AuthorsSchindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J
TitleStructural mechanism for STI-571 inhibition of abelson tyrosine kinase.
Related PDB1fpu
Related UniProtKBP00519
[11]
PubMed ID11781820
JournalOncogene
Year2001
Volume20
Pages8075-84
AuthorsDorey K, Engen JR, Kretzschmar J, Wilm M, Neubauer G, Schindler T, Superti-Furga G
TitlePhosphorylation and structure-based functional studies reveal a positive and a negative role for the activation loop of the c-Abl tyrosine kinase.
[12]
PubMed ID12154025
JournalCancer Res
Year2002
Volume62
Pages4236-43
AuthorsNagar B, Bornmann WG, Pellicena P, Schindler T, Veach DR, Miller WT, Clarkson B, Kuriyan J
TitleCrystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571).
Related PDB1iep,1m52
[13]
PubMed ID12384576
JournalProc Natl Acad Sci U S A
Year2002
Volume99
Pages14053-8
AuthorsDonaldson LW, Gish G, Pawson T, Kay LE, Forman-Kay JD
TitleStructure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.
Related PDB1ju5
[14]
PubMed ID12654250
JournalCell
Year2003
Volume112
Pages845-57
AuthorsHantschel O, Nagar B, Guettler S, Kretzschmar J, Dorey K, Kuriyan J, Superti-Furga G
TitleA myristoyl/phosphotyrosine switch regulates c-Abl.
[15]
PubMed ID12654251
JournalCell
Year2003
Volume112
Pages859-71
AuthorsNagar B, Hantschel O, Young MA, Scheffzek K, Veach D, Bornmann W, Clarkson B, Superti-Furga G, Kuriyan J
TitleStructural basis for the autoinhibition of c-Abl tyrosine kinase.
Related PDB1opj,1opl,1opk

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.

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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