DegronMD - P00519(ABL1)

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. 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 acts also 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. 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:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. View more >>

GO - Biological processes (BP): actin cytoskeleton organization [GO:0030036]; actin filament branching [GO:0090135]; actin filament polymerization [GO:0030041]; activated T cell proliferation [GO:0050798]; activation of protein kinase C activity [GO:1990051]; alpha-beta T cell differentiation [GO:0046632]; associative learning [GO:0008306]; autophagy [GO:0006914]; B-1 B cell homeostasis [GO:0001922]; B cell proliferation involved in immune response [GO:0002322]; B cell receptor signaling pathway [GO:0050853]; Bergmann glial cell differentiation [GO:0060020]; cellular protein modification process [GO:0006464]; cellular response to DNA damage stimulus [GO:0006974]; cellular response to dopamine [GO:1903351]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to oxidative stress [GO:0034599]; cellular response to transforming growth factor beta stimulus [GO:0071560]; cerebellum morphogenesis [GO:0021587]; circulatory system development [GO:0072359]; collateral sprouting [GO:0048668]; DNA conformation change [GO:0071103]; DNA damage induced protein phosphorylation [GO:0006975]; endocytosis [GO:0006897]; endothelial cell migration [GO:0043542]; epidermal growth factor receptor signaling pathway [GO:0007173]; establishment of protein localization [GO:0045184]; Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096]; glomerular visceral epithelial cell apoptotic process [GO:1903210]; integrin-mediated signaling pathway [GO:0007229]; intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630]; microspike assembly [GO:0030035]; mismatch repair [GO:0006298]; mitochondrial depolarization [GO:0051882]; mitotic cell cycle [GO:0000278]; negative regulation of BMP signaling pathway [GO:0030514]; negative regulation of cell-cell adhesion [GO:0022408]; negative regulation of cellular senescence [GO:2000773]; negative regulation of endothelial cell apoptotic process [GO:2000352]; negative regulation of ERK1 and ERK2 cascade [GO:0070373]; negative regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043124]; negative regulation of long-term synaptic potentiation [GO:1900272]; negative regulation of mitotic cell cycle [GO:0045930]; negative regulation of phospholipase C activity [GO:1900275]; negative regulation of protein serine/threonine kinase activity [GO:0071901]; negative regulation of ubiquitin-protein transferase activity [GO:0051444]; neural tube closure [GO:0001843]; neuroepithelial cell differentiation [GO:0060563]; neuromuscular process controlling balance [GO:0050885]; neuropilin signaling pathway [GO:0038189]; peptidyl-tyrosine autophosphorylation [GO:0038083]; peptidyl-tyrosine phosphorylation [GO:0018108]; platelet-derived growth factor receptor-beta signaling pathway [GO:0035791]; positive regulation of actin cytoskeleton reorganization [GO:2000251]; positive regulation of actin filament binding [GO:1904531]; positive regulation of apoptotic process [GO:0043065]; positive regulation of blood vessel branching [GO:1905555]; positive regulation of cell migration involved in sprouting angiogenesis [GO:0090050]; positive regulation of cytosolic calcium ion concentration [GO:0007204]; positive regulation of dendrite development [GO:1900006]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of extracellular matrix organization [GO:1903055]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of focal adhesion assembly [GO:0051894]; positive regulation of hydrogen peroxide-mediated programmed cell death [GO:1901300]; positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123]; positive regulation of interferon-gamma production [GO:0032729]; positive regulation of interleukin-2 production [GO:0032743]; positive regulation of microtubule binding [GO:1904528]; positive regulation of mitotic cell cycle [GO:0045931]; positive regulation of neuron apoptotic process [GO:0043525]; positive regulation of osteoblast proliferation [GO:0033690]; positive regulation of oxidoreductase activity [GO:0051353]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of release of sequestered calcium ion into cytosol [GO:0051281]; positive regulation of stress fiber assembly [GO:0051496]; positive regulation of substrate adhesion-dependent cell spreading [GO:1900026]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of vasoconstriction [GO:0045907]; positive regulation of Wnt signaling pathway, planar cell polarity pathway [GO:2000096]; post-embryonic development [GO:0009791]; protein autophosphorylation [GO:0046777]; protein phosphorylation [GO:0006468]; regulation of actin cytoskeleton organization [GO:0032956]; regulation of actin cytoskeleton reorganization [GO:2000249]; regulation of apoptotic process [GO:0042981]; regulation of autophagy [GO:0010506]; regulation of axon extension [GO:0030516]; regulation of Cdc42 protein signal transduction [GO:0032489]; regulation of cell adhesion [GO:0030155]; regulation of cell cycle [GO:0051726]; regulation of cell motility [GO:2000145]; regulation of endocytosis [GO:0030100]; regulation of hematopoietic stem cell differentiation [GO:1902036]; regulation of microtubule polymerization [GO:0031113]; regulation of modification of synaptic structure [GO:1905244]; regulation of response to DNA damage stimulus [GO:2001020]; regulation of T cell differentiation [GO:0045580]; regulation of transcription, DNA-templated [GO:0006355]; response to endoplasmic reticulum stress [GO:0034976]; response to epinephrine [GO:0071871]; response to oxidative stress [GO:0006979]; response to xenobiotic stimulus [GO:0009410]; signal transduction in response to DNA damage [GO:0042770]; spleen development [GO:0048536]; substrate adhesion-dependent cell spreading [GO:0034446]; T cell receptor signaling pathway [GO:0050852]; thymus development [GO:0048538]; transitional one stage B cell differentiation [GO:0002333] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

Choose a PDB ID:
Open in full screen with detailed sequence annotations

Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.K106N	TCGA-09-2051	OV	TCGA	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.0556
p.M643I	TCGA-13-1404	OV	TCGA	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation rewiring degron network	0.25
p.R535H	TCGA-AX-A063	UCEC	TCGA	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation blocking phosphorylation signal	0.6389
p.R636H	TCGA-AX-A1C9	UCEC	TCGA	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation rewiring degron network	0.0556
p.P548S	TCGA-AX-A2HD	UCEC	TCGA	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation altering degron motif	0.6752
p.R552S	TCGA-BA-A6DD	HNSC	TCGA	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation rewiring degron network	0.2778
p.T123I	TCGA-DY-A0XA	READ	TCGA	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.2778
p.V130L	TCGA-EV-5903	KIRP	TCGA	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.0833
p.G116W	TCGA-FI-A2F4	UCEC	TCGA	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation altering degron motif	0.7825
p.V534I	TCGA-HU-8602	STAD	TCGA	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation rewiring degron network	0.1667
p.P647R	TCGA-XF-A9T6	BLCA	TCGA	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation altering degron motif	0.7512
p.S642G	DO234462	ESAD	ICGC	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation blocking phosphorylation signal	0.6667
p.R533S	DO44452	HNSC	ICGC	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation rewiring degron network	0.1389
p.V111L	DO20890	KIRP	ICGC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.1944
p.V119F	DO228976	LICA	ICGC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation altering degron motif	0.5957
p.E549Q	DO45454	LUSC	ICGC	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation altering degron motif	0.6744
p.P131S	DO46657	PAAD	ICGC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.0556
p.P131S	SIDM00482	Chronic Myelogenous Leukemia	GDSC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.0556
p.P131S	RPMI-8866	haematopoietic and lymphoid tissue	COSMIC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.0556
p.P551L	DO37415	SKCM	ICGC	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation rewiring degron network	0.3056
p.G653D	SIDM01278	Colorectal Carcinoma	GDSC	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation altering degron motif	0.7198
p.R649H	SIDM01092	B-Cell Non-Hodgkin's Lymphoma	GDSC	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation altering degron motif	0.8244
p.R649H	RF-48	stomach	COSMIC	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation altering degron motif	0.8244
p.K106E	SIDM01028	Esophageal Squamous Cell Carcinoma	GDSC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.0556
p.K106E	KYSE-410	oesophagus	COSMIC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.0556
p.E546K	SIDM00598	Squamous Cell Lung Carcinoma	GDSC	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation altering degron motif	0.7022
p.E546K	HARA	lung	COSMIC	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation altering degron motif	0.7022
p.N115S	SIDM00394	Cervical Carcinoma	GDSC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation blocking phosphorylation signal	0.75
p.N115S	SIDM00488	Colorectal Carcinoma	GDSC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation blocking phosphorylation signal	0.75
p.N115S	SIDM01551	Gastric Carcinoma	GDSC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation blocking phosphorylation signal	0.75
p.N115S	SIDM01494	Glioblastoma	GDSC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation blocking phosphorylation signal	0.75
p.N115S	SISO	cervix	COSMIC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation blocking phosphorylation signal	0.75
p.N115S	CaR-1	large intestine	COSMIC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation blocking phosphorylation signal	0.75
p.K550N	SIDM01776	Plasma Cell Myeloma	GDSC	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation altering degron motif	0.6918
p.R658Q	SIDM01378	Ovarian Carcinoma	GDSC	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation substituting flanking lysine	0.3056
p.R639Q	ACH-000646	Ovarian Cancer	CCLE	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation rewiring degron network	0.1389
p.H552R	ACH-000914	Lymphoma	CCLE	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation rewiring degron network	0.2778
p.H552R	HT	haematopoietic and lymphoid tissue	COSMIC	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation rewiring degron network	0.2778
p.P662L	ACH-000919	Gastric Cancer	CCLE	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation rewiring degron network	0.0833
p.P662L	ACH-002041	Thyroid Cancer	CCLE	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation rewiring degron network	0.0833
p.P662L	IM-95	stomach	COSMIC	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation rewiring degron network	0.0833
p.K531N	ACH-001162	Myeloma	CCLE	EHRDTTDVPEM	DEG_COP1_1	540:550	Mutation substituting flanking lysine	0.1944
p.A647D	ACH-001603	Neuroblastoma	CCLE	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation altering degron motif	0.6682
p.A647D	NH-12	autonomic ganglia	COSMIC	LAFTPLDT	DEG_SCF_FBW7_1	646:653	Mutation altering degron motif	0.6682
p.P112S	ACH-002302	Leukemia	CCLE	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.2222
p.P112S	RPMI-8866	haematopoietic and lymphoid tissue	COSMIC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation rewiring degron network	0.2222
p.C119G	MDA-MB-436	breast	COSMIC	ITPVNS	DEG_SCF_FBW7_1	116:121	Mutation altering degron motif	0.76

DegronMD: protein-targeted degradation, mutation and drug response to degrons

ABL1

UniProt ID: P00519

Entrez ID: 25

Protein name: 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)

External links: UniprotKB HGNC RefSeq COSMIC

Data table is loading....

Kaplan plot for ABL1 in