Reviewed, UniProtKB/Swiss-Prot P00519 (ABL1_HUMAN)

Names and origin

Protein names

Recommended name:
    Proto-oncogene tyrosine-protein kinase ABL1
    EC=2.7.10.2
Alternative name(s):
    Abelson murine leukemia viral oncogene homolog 1
    c-ABL
    p150

Gene names

Name:	ABL1
Synonyms:	ABL, JTK7

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1130 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Regulates cytoskeleton remodeling during cell differentiation, cell division and cell adhesion. Localizes to dynamic actin structures, and phosphorylates CRK and CRKL, DOK1, and other proteins controlling cytoskeleton dynamics. Regulates DNA repair potentially by activating the proapoptotic pathway when the DNA damage is too severe to be repaired.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Cofactor	Magnesium or manganese.
Enzyme regulation	Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the amino-terminal cap, and contributions from an amino-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML).
Subunit structure	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 location	Cytoplasm › cytoskeleton. Nucleus. Note= The myristoylated c-ABL protein is reported to be nuclear.
Tissue specificity	Widely expressed.
Post-translational modification	Phosphorylated by PRKDC By similarity. DNA damage-induced activation of c-Abl requires the function of ATM and Ser-446 phosphorylation. Isoform IB is myristoylated on Gly-2.
Involvement in disease	A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia (CML) [MIM:608232]. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction resulting in induction of apoptosis Traceable author statement. Source: ProtInc actin cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB mismatch repair Traceable author statement. Source: ProtInc peptidyl-tyrosine phosphorylation Ref.12 Inferred from direct assay. Source: UniProtKB positive regulation of oxidoreductase activity Inferred from direct assay. Source: UniProtKB regulation of transcription during S-phase of mitotic cell cycle Traceable author statement. Source: ProtInc
Cellular component	nucleus Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Ref.12 Inferred from direct assay. Source: UniProtKB DNA binding Non-traceable author statement. Source: UniProtKB magnesium ion binding Ref.12 Inferred from direct assay. Source: UniProtKB manganese ion binding Ref.12 Inferred from direct assay. Source: UniProtKB protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein tyrosine kinase activity Ref.12 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABI1	Q8IZP0	2	EBI-375543,EBI-375446
Abi1	Q8CBW3	1	EBI-375543,EBI-375511	From a different organism.
ATM	Q13315	1	EBI-375543,EBI-495465
Bcar1	Q63767	1	EBI-375543,EBI-1176801	From a different organism.
RIN1	Q13671	3	EBI-375543,EBI-366017
SFN	P31947	1	EBI-375543,EBI-476295
SORBS1	Q9BX66	2	EBI-375543,EBI-433642
ST5	P78524	1	EBI-375543,EBI-962633
TERF1	P54274-2	1	EBI-375543,EBI-711018
YWHAZ	P63104	1	EBI-375543,EBI-347088

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform IA (identifier: P00519-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform IB (identifier: P00519-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MLEICLKLVGCKSKKGLSSSSSCYLE → MGQQPGKVLGDQRRPSLPALHFIKGAGKKESSRHGGPHCNVFVEH

Notes: Myristoylated on Gly-2.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 1130

1130

Proto-oncogene tyrosine-protein kinase ABL1

Regions

Domain

61 – 121

61

SH3

Domain

127 – 217

91

SH2

Domain

242 – 493

252

Protein kinase

Nucleotide binding

248 – 256

9

ATP By similarity

Region

1 – 60

60

CAP

Motif

605 – 609

5

Nuclear localization signal Potential

Compositional bias

18 – 22

5

Poly-Ser

Compositional bias

605 – 609

5

Poly-Lys

Compositional bias

782 – 1019

238

Pro-rich

Compositional bias

897 – 903

7

Poly-Pro

Sites

Active site

363

1

Proton acceptor By similarity

Binding site

271

1

ATP By similarity

Site

26 – 27

2

Breakpoint for translocation to form BCR-ABL oncogene

Amino acid modifications

Modified residue

185

1

Phosphotyrosine

Modified residue

226

1

Phosphotyrosine; by autocatalysis

Modified residue

253

1

Phosphotyrosine

Modified residue

257

1

Phosphotyrosine

Modified residue

264

1

Phosphotyrosine

Modified residue

393

1

Phosphotyrosine; by autocatalysis and SRC-type Tyr-kinases

Modified residue

394

1

Phosphothreonine

Modified residue

446

1

Phosphoserine By similarity

Modified residue

469

1

Phosphotyrosine

Modified residue

569

1

Phosphoserine

Modified residue

683

1

Phosphoserine

Modified residue

805

1

Phosphoserine

Modified residue

809

1

Phosphoserine

Modified residue

949

1

Phosphoserine

Natural variations

Alternative sequence

1 – 26

26

MLEIC…SCYLE → MGQQPGKVLGDQRRPSLPAL HFIKGAGKKESSRHGGPHCN VFVEH in isoform IB.

Natural variant

47

1

R → G in a lung large cell carcinoma sample; somatic mutation.

Natural variant

166

1

R → K in a melanoma sample; somatic mutation.

Natural variant

706

1

G → V

Natural variant

810

1

P → L

Natural variant

852

1

T → P

Natural variant

900

1

P → S

Natural variant

972

1

S → L

Experimental info

Sequence conflict

140

1

L → P in AAA51561. Ref.2

Sequence conflict

159

1

G → S in AAA51561. Ref.2

Sequence conflict

424 – 425

2

AF → GK Ref.6

Sequence conflict

445

1

L → R in AAA51561. Ref.2

Sequence conflict

459

1

E → K in AAA51561. Ref.2

Sequence conflict

520

1

S → T in AAA51561. Ref.2

Sequence conflict

719

1

A → V in AAA51561. Ref.2

Sequence conflict

837

1

G → E in CAA34438. Ref.1

Sequence conflict

837

1

G → W in AAA51561. Ref.2

Sequence conflict

863

1

G → R in AAA51561. Ref.2

Sequence conflict

894

1

R → K in AAA51561. Ref.2

Sequence conflict

917 – 919

3

SPS → RPG in AAA51561. Ref.2

Sequence conflict

952

1

G → A in AAA51561. Ref.2

Sequence conflict

967 – 968

2

QS → HP in AAA51561. Ref.2

Sequence conflict

982

1

P → PL in AAA51561. Ref.2

Sequence conflict

1022

1

Missing in AAA51561. Ref.2

Sequence conflict

1045

1

R → G in AAA51561. Ref.2

Sequence conflict

1103

1

T → S in AAA51561. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1130

Helix Strand Turn

Details...

Helix

49 – 53

5

Helix

58 – 60

3

Beta strand

65 – 70

6

Beta strand

87 – 93

7

Beta strand

97 – 104

8

Beta strand

107 – 112

6

Helix

113 – 115

3

Beta strand

116 – 118

3

Helix

122 – 124

3

Beta strand

128 – 131

4

Helix

134 – 140

7

Beta strand

142 – 144

3

Beta strand

148 – 153

6

Beta strand

155 – 157

3

Beta strand

161 – 167

7

Beta strand

170 – 178

9

Beta strand

184 – 187

4

Beta strand

192 – 194

3