ABL1
entrez
25
canonical
uniprot
P00519
canonical
ensembl
ENSG00000097007
resolver
ensp
ENSP00000323315
resolver
ensp
ENSP00000361423
resolver
genesymbol
ABL1
resolver
genesymbol_syn
ABL
resolver
genesymbol_syn
JTK7
resolver
hgnc
HGNC:76
resolver
uniprot
A3KFJ3
resolver
uniprot
Q13869
resolver
uniprot
Q13870
resolver
uniprot
Q16133
resolver
uniprot
Q17R61
resolver
uniprot
Q45F09
resolver
uniprot
Q59FK4
resolver
uniprot_entry
ABL1_HUMAN
resolver
uniprot_entry
Q59FK4_HUMAN
resolver
uniprot_sec
A3KFJ3
resolver
uniprot_sec
Q13869
resolver
uniprot_sec
Q13870
resolver
uniprot_sec
Q16133
resolver
uniprot_sec
Q17R61
resolver
uniprot_sec
Q45F09
resolver
activity_regulation
ACTIVITY REGULATION: Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-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. Also stimulated by cell death inducers and DNA-damage. Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, also inhibits the tyrosine kinase activity (By similarity). Activated by 5-(1,3-diaryl-1H-pyrazol-4-yl)hydantoin, 5-[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2,4-imidazolidinedione (DPH) (PubMed:28428613). Inhibited by ABI1, whose activity is controlled by ABL1 itself through tyrosine phosphorylation. Also inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML), and by VX-680, an inhibitor that also acts on imatinib-resistant mutants (PubMed:28428613). {ECO:0000250, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:12654251, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16543148, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:28428613}.
uniprot
proteins
amino_acid_sequence
MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVNSLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESSISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAEHRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLPKDKKTNLFSALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFTPLDTADPAKSPKPSNGAGVPNGALRESGGSGFRSPHLWKKSSTLTSSRLATGEEEGGGSSSKRFLRSCSASCVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGENRSDQVTRGTVTPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGSALGTPAAAEPVTPTSKAGSGAPGGTSKGPAEESRVRRHKHSSESPGRDKGKLSRLKPAPPPPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPSQPGEGLKKPVLPATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTRVSLRKTRQPPERIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAFREAINKLENNLRELQICPATAGSGPAATQDFSKLLSSVKEISDIVQR
uniprot
proteins
disease_involvement
DISEASE: Leukemia, chronic myeloid (CML) [MIM:608232]: A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Note=A chromosomal aberration involving ABL1 has been found in patients with chronic myeloid leukemia. 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). {ECO:0000269|PubMed:3021337}.; DISEASE: Note=A chromosomal aberration involving ABL1 is found in a form of acute lymphoblastic leukemia (PubMed:15361874). Translocation t(9;9)(q34;q34) with NUP214 (PubMed:15361874). {ECO:0000269|PubMed:15361874}.; DISEASE: Congenital heart defects and skeletal malformations syndrome (CHDSKM) [MIM:617602]: An autosomal dominant disorder characterized by congenital heart disease with atrial and ventricular septal defects, variable skeletal abnormalities, and failure to thrive. Skeletal defects include pectus excavatum, scoliosis, and finger contractures. Some patient exhibit joint laxity. {ECO:0000269|PubMed:28288113}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
function
FUNCTION: Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}.
uniprot
proteins
mass_dalton
122873
uniprot
proteins
mutagenesis
MUTAGEN 735; /note="T->A: Abolishes phosphorylation. Loss of binding YWHAS and YWHAZ. Localizes to the nucleus. No effect on kinase activity."; /evidence="ECO:0000269|PubMed:15696159
uniprot
proteins
post_translational_modification
PTM: Acetylated at Lys-711 by EP300 which promotes the cytoplasmic translocation. {ECO:0000269|PubMed:16648821}.; PTM: Phosphorylation at Tyr-70 by members of the SRC family of kinases disrupts SH3 domain-based autoinhibitory interactions and intermolecular associations, such as that with ABI1, and also enhances kinase activity. Phosphorylation at Tyr-226 and Tyr-393 correlate with increased activity. DNA damage-induced activation of ABL1 requires the function of ATM and Ser-446 phosphorylation (By similarity). Phosphorylation at Ser-569 has been attributed to a CDC2-associated kinase and is coupled to cell division (By similarity). Phosphorylation at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces binding to ABI1. Phosphorylation on Thr-735 is required for binding 14-3-3 proteins for cytoplasmic translocation. Phosphorylated by PRKDC (By similarity). {ECO:0000250}.; PTM: Polyubiquitinated. Polyubiquitination of ABL1 leads to degradation. {ECO:0000269|PubMed:12475393}.
uniprot
proteins
protein_family
ABL subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10194451
uniprot
proteins
pubmed
10325413
uniprot
proteins
pubmed
10391250
uniprot
proteins
pubmed
11114745
uniprot
proteins
pubmed
11374898
uniprot
proteins
pubmed
11971963
uniprot
proteins
pubmed
12379650
uniprot
proteins
pubmed
12384576
uniprot
proteins
pubmed
12475393
uniprot
proteins
pubmed
12531427
uniprot
proteins
pubmed
12654251
uniprot
proteins
pubmed
12672821
uniprot
proteins
pubmed
12775773
uniprot
proteins
pubmed
1281542
uniprot
proteins
pubmed
15031292
uniprot
proteins
pubmed
1505033
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15302586
uniprot
proteins
pubmed
15361874
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15556646
uniprot
proteins
pubmed
15657060
uniprot
proteins
pubmed
15686624
uniprot
proteins
pubmed
15696159
uniprot
proteins
pubmed
15886098
uniprot
proteins
pubmed
16424036
uniprot
proteins
pubmed
16543148
uniprot
proteins
pubmed
16640460
uniprot
proteins
pubmed
16648821
uniprot
proteins
pubmed
16678104
uniprot
proteins
pubmed
16912036
uniprot
proteins
pubmed
16943190
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17164530
uniprot
proteins
pubmed
17306540
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17452790
uniprot
proteins
pubmed
17623672
uniprot
proteins
pubmed
18161990
uniprot
proteins
pubmed
18182299
uniprot
proteins
pubmed
18328268
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18775435
uniprot
proteins
pubmed
18945674
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19381274
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19891780
uniprot
proteins
pubmed
19906645
uniprot
proteins
pubmed
20357770
uniprot
proteins
pubmed
20417104
uniprot
proteins
pubmed
20841568
uniprot
proteins
pubmed
20861316
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
2183353
uniprot
proteins
pubmed
22810897
uniprot
proteins
pubmed
23006999
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
2542016
uniprot
proteins
pubmed
2687768
uniprot
proteins
pubmed
2825022
uniprot
proteins
pubmed
28288113
uniprot
proteins
pubmed
28428613
uniprot
proteins
pubmed
3021337
uniprot
proteins
pubmed
6191223
uniprot
proteins
pubmed
7545908
uniprot
proteins
pubmed
7665185
uniprot
proteins
pubmed
7892170
uniprot
proteins
pubmed
8590002
uniprot
proteins
pubmed
9037071
uniprot
proteins
pubmed
9144171
uniprot
proteins
pubmed
9461559
uniprot
proteins
pubmed
9698566
uniprot
proteins
sequence_length
1130
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Nucleus. Mitochondrion {ECO:0000250}. Note=Shuttles between the nucleus and cytoplasm depending on environmental signals. Sequestered into the cytoplasm through interaction with 14-3-3 proteins. Localizes to mitochondria in response to oxidative stress (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Isoform IB]: Nucleus membrane; Lipid-anchor. Note=The myristoylated c-ABL protein is reported to be nuclear.
uniprot
proteins