P00519

※ Protein Information

Tag	Content
UniProt Accession	ABL1_HUMAN; P00519;
Entrez ID	25
GenBank Protein ID	NM_005157.5; NM_007313.2;
GenBank Nucleotide ID	NP_005148.2; NP_009297.2;
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)
Gene Name	ABL1; ABL; JTK7
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	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 (microt(view all) Functional Description 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).
Sequence (Fasta)	MLEICLKLVG CKSKKGLSSS SSCYLEEALQ RPVASDFEPQ GLSEAARWNS KENLLAGPSE 60 NDPNLFVALY DFVASGDNTL SITKGEKLRV LGYNHNGEWC EAQTKNGQGW VPSNYITPVN 120 SLEKHSWYHG PVSRNAAEYL LSSGINGSFL VRESESSPGQ RSISLRYEGR VYHYRINTAS 180 DGKLYVSSES RFNTLAELVH HHSTVADGLI TTLHYPAPKR NKPTVYGVSP NYDKWEMERT 240 DITMKHKLGG GQYGEVYEGV WKKYSLTVAV KTLKEDTMEV EEFLKEAAVM KEIKHPNLVQ 300 LLGVCTREPP FYIITEFMTY GNLLDYLREC NRQEVNAVVL LYMATQISSA MEYLEKKNFI 360 HRDLAARNCL VGENHLVKVA DFGLSRLMTG DTYTAHAGAK FPIKWTAPES LAYNKFSIKS 420 DVWAFGVLLW EIATYGMSPY PGIDLSQVYE LLEKDYRMER PEGCPEKVYE LMRACWQWNP 480 SDRPSFAEIH QAFETMFQES SISDEVEKEL GKQGVRGAVS TLLQAPELPT KTRTSRRAAE 540 HRDTTDVPEM PHSKGQGESD PLDHEPAVSP LLPRKERGPP EGGLNEDERL LPKDKKTNLF 600 SALIKKKKKT APTPPKRSSS FREMDGQPER RGAGEEEGRD ISNGALAFTP LDTADPAKSP 660 KPSNGAGVPN GALRESGGSG FRSPHLWKKS STLTSSRLAT GEEEGGGSSS KRFLRSCSAS 720 CVPHGAKDTE WRSVTLPRDL QSTGRQFDSS TFGGHKSEKP ALPRKRAGEN RSDQVTRGTV 780 TPPPRLVKKN EEAADEVFKD IMESSPGSSP PNLTPKPLRR QVTVAPASGL PHKEEAGKGS 840 ALGTPAAAEP VTPTSKAGSG APGGTSKGPA EESRVRRHKH SSESPGRDKG KLSRLKPAPP 900 PPPAASAGKA GGKPSQSPSQ EAAGEAVLGA KTKATSLVDA VNSDAAKPSQ PGEGLKKPVL 960 PATPKPQSAK PSGTPISPAP VPSTLPSASS ALAGDQPSST AFIPLISTRV SLRKTRQPPE 1020 RIASGAITKG VVLDSTEALC LAISRNSEQM ASHSAVLEAG KNLYTFCVSY VDSIQQMRNK 1080 FAFREAINKL ENNLRELQIC PATAGSGPAA TQDFSKLLSS VKEISDIVQR 1131 Fasta Sequence >P00519\|ABL1; ABL; JTK7\|Homo sapiens (Human) MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVNSLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESSISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAEHRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLPKDKKTNLFSALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFTPLDTADPAKSPKPSNGAGVPNGALRESGGSGFRSPHLWKKSSTLTSSRLATGEEEGGGSSSKRFLRSCSASCVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGENRSDQVTRGTVTPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGSALGTPAAAEPVTPTSKAGSGAPGGTSKGPAEESRVRRHKHSSESPGRDKGKLSRLKPAPPPPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPSQPGEGLKKPVLPATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTRVSLRKTRQPPERIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAFREAINKLENNLRELQICPATAGSGPAATQDFSKLLSSVKEISDIVQR

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Tyrosine Phosphorylation	Leukemia		U	Y257	17164333
1	[Reference]: Elevated in drug resistant leukemias with T315I mutations in Abl, and is associated with increased oncogenicity

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	CML, ALL, T-ALL
CTD (Curated) (count: 13) (view all)	MESH:D000230 ; Adenocarcinoma MESH:D001848 ; Bone Diseases, Developmental MESH:D001943 ; Breast Neoplasms MESH:D063646 ; Carcinogenesis MESH:D004938 ; Esophageal Neoplasms MESH:D005183 ; Failure to Thrive MESH:D006330 ; Heart Defects, Congenital MESH:D015464 ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive MESH:D008113 ; Liver Neoplasms MESH:D009139 ; Musculoskeletal Abnormalities MESH:D009374 ; Neoplasms, Experimental MESH:D011230 ; Precancerous Conditions MESH:D054198 ; Precursor Cell Lymphoblastic Leukemia-Lymphoma
DisGeNet (Curated) (count: 20) (view all)	C0001418; Adenocarcinoma C0014859; Esophageal Neoplasms C0015672; Fatigue C0015967; Fever C0023473; Myeloid Leukemia, Chronic C0023518; Leukocytosis C0023903; Liver neoplasms C0027022; Myeloproliferative disease C0027659; Neoplasms, Experimental C0032927; Precancerous Conditions C0038002; Splenomegaly C0040034; Thrombocytopenia C0232462; Decrease in appetite C0392386; Decreased platelet count C0596263; Carcinogenesis C0836924; Thrombocytosis C0857460; Increased number of platelets C1458155; Mammary Neoplasms C1961102; Precursor Cell Lymphoblastic Leukemia Lymphoma C4025736; Abnormality of basophils
GWASdb (count: 18) (view all)	rs2789764; Urinary metabolites; kidney disease rs4740363; Neutrophil count; hematopoietic system disease\|Human immunodeficiency virus infectious disease rs4740366; Neutrophil count; hematopoietic system disease\|Human immunodeficiency virus infectious disease rs4740203; Lymphocyte counts; asthma\|leukemia\|lymphoma\|lymphopenia\|cardiovascular system disease rs4740203; Neutrophil count; hematopoietic system disease\|Human immunodeficiency virus infectious disease rs11244146; Personality dimensions; personality disorder rs2260323; Coronary heart disease; coronary artery disease rs2855190; Personality dimensions; personality disorder rs2855190; Age-related macular degeneration; age related macular degeneration rs6597642; Personality dimensions; personality disorder rs1800609; Personality dimensions; personality disorder rs1800609; Coronary heart disease; coronary artery disease rs3824400; Personality dimensions; personality disorder rs6597645; Response to amphetamines; amphetamine abuse rs3808816; Multiple complex diseases; Null rs4740376; Response to amphetamines; amphetamine abuse rs2070997; Response to amphetamines; amphetamine abuse rs4740377; Multiple complex diseases; Null

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 106) (view all)	1011 PLISTRVSLRKTRQP dbPAF 1064 LEAGKNLYTFCVSYV dbPAF 1070 LYTFCVSYVDSIQQM dbPAF 1106 ICPATAGSGPAATQD dbPAF 1111 AGSGPAATQDFSKLL dbPAF 113 NGQGWVPSNYITPVN dbPAF 115 QGWVPSNYITPVNSL dbPAF 117 WVPSNYITPVNSLEK dbPAF 128 SLEKHSWYHGPVSRN dbPAF 139 VSRNAAEYLLSSGIN dbPAF 142 NAAEYLLSSGINGSF dbPAF 154 GSFLVRESESSPGQR dbPAF 167 QRSISLRYEGRVYHY dbPAF 172 LRYEGRVYHYRINTA dbPAF 174 YEGRVYHYRINTASD dbPAF 178 VYHYRINTASDGKLY dbPAF 180 HYRINTASDGKLYVS dbPAF 185 TASDGKLYVSSESRF dbPAF 187 SDGKLYVSSESRFNT dbPAF 215 GLITTLHYPAPKRNK dbPAF 224 APKRNKPTVYGVSPN dbPAF 226 KRNKPTVYGVSPNYD dbPAF 229 KPTVYGVSPNYDKWE dbPAF 232 VYGVSPNYDKWEMER dbPAF 243 EMERTDITMKHKLGG dbPAF 253 HKLGGGQYGEVYEGV dbPAF 257 GGQYGEVYEGVWKKY dbPAF 264 YEGVWKKYSLTVAVK dbPAF 265 EGVWKKYSLTVAVKT dbPAF 267 VWKKYSLTVAVKTLK dbPAF 306 VQLLGVCTREPPFYI dbPAF 312 CTREPPFYIITEFMT dbPAF 320 IITEFMTYGNLLDYL dbPAF 389 FGLSRLMTGDTYTAH dbPAF 392 SRLMTGDTYTAHAGA dbPAF 393 RLMTGDTYTAHAGAK dbPAF 394 LMTGDTYTAHAGAKF dbPAF 406 AKFPIKWTAPESLAY dbPAF 413 TAPESLAYNKFSIKS dbPAF 417 SLAYNKFSIKSDVWA dbPAF 43 DFEPQGLSEAARWNS dbPAF 446 PYPGIDLSQVYELLE dbPAF 456 YELLEKDYRMERPEG dbPAF 469 EGCPEKVYELMRACW dbPAF 50 SEAARWNSKENLLAG dbPAF 532 APELPTKTRTSRRAA dbPAF 535 LPTKTRTSRRAAEHR dbPAF 559 HSKGQGESDPLDHEP dbPAF 569 LDHEPAVSPLLPRKE dbPAF 59 ENLLAGPSENDPNLF dbPAF 597 LLPKDKKTNLFSALI dbPAF 601 DKKTNLFSALIKKKK dbPAF 610 LIKKKKKTAPTPPKR dbPAF 613 KKKKTAPTPPKRSSS dbPAF 618 APTPPKRSSSFREMD dbPAF 619 PTPPKRSSSFREMDG dbPAF 620 TPPKRSSSFREMDGQ dbPAF 642 EEEGRDISNGALAFT dbPAF 649 SNGALAFTPLDTADP dbPAF 653 LAFTPLDTADPAKSP dbPAF 659 DTADPAKSPKPSNGA dbPAF 676 PNGALRESGGSGFRS dbPAF 679 ALRESGGSGFRSPHL dbPAF 683 SGGSGFRSPHLWKKS dbPAF 690 SPHLWKKSSTLTSSR dbPAF 691 PHLWKKSSTLTSSRL dbPAF 692 HLWKKSSTLTSSRLA dbPAF 696 KSSTLTSSRLATGEE dbPAF 70 PNLFVALYDFVASGD dbPAF 700 LTSSRLATGEEEGGG dbPAF 708 GEEEGGGSSSKRFLR dbPAF 709 EEEGGGSSSKRFLRS dbPAF 710 EEGGGSSSKRFLRSC dbPAF 716 SSKRFLRSCSASCVP dbPAF 718 KRFLRSCSASCVPHG dbPAF 733 AKDTEWRSVTLPRDL dbPAF 735 DTEWRSVTLPRDLQS dbPAF 75 ALYDFVASGDNTLSI dbPAF 751 GRQFDSSTFGGHKSE dbPAF 781 QVTRGTVTPPPRLVK dbPAF 79 FVASGDNTLSITKGE dbPAF 804 VFKDIMESSPGSSPP dbPAF 805 FKDIMESSPGSSPPN dbPAF 808 IMESSPGSSPPNLTP dbPAF 809 MESSPGSSPPNLTPK dbPAF 814 GSSPPNLTPKPLRRQ dbPAF 823 KPLRRQVTVAPASGL dbPAF 828 QVTVAPASGLPHKEE dbPAF 844 GKGSALGTPAAAEPV dbPAF 852 PAAAEPVTPTSKAGS dbPAF 854 AAEPVTPTSKAGSGA dbPAF 855 AEPVTPTSKAGSGAP dbPAF 859 TPTSKAGSGAPGGTS dbPAF 884 RHKHSSESPGRDKGK dbPAF 915 GKAGGKPSQSPSQEA dbPAF 917 AGGKPSQSPSQEAAG dbPAF 919 GKPSQSPSQEAAGEA dbPAF 93 EKLRVLGYNHNGEWC dbPAF 935 LGAKTKATSLVDAVN dbPAF 936 GAKTKATSLVDAVNS dbPAF 943 SLVDAVNSDAAKPSQ dbPAF 949 NSDAAKPSQPGEGLK dbPAF 963 KKPVLPATPKPQSAK dbPAF 968 PATPKPQSAKPSGTP dbPAF 977 KPSGTPISPAPVPST dbPAF 989 PSTLPSASSALAGDQ dbPAF
Acetylation (count: 1)	711 EGGGSSSKRFLRSCS PLMD

PTM

Modification Sites

Phosphorylation
(count: 106)
(view all)

1011      PLISTRVSLRKTRQP     dbPAF
1064      LEAGKNLYTFCVSYV     dbPAF
1070      LYTFCVSYVDSIQQM     dbPAF
1106      ICPATAGSGPAATQD     dbPAF
1111      AGSGPAATQDFSKLL     dbPAF
113       NGQGWVPSNYITPVN     dbPAF

Acetylation
(count: 1)

711 EGGGSSSKRFLRSCS PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

O60674	P00519	HPRD
P00519	P00533	MINT
P00519	P04626	MINT
P00519	P04637	HPRD
P00519	P05107	MINT
P00519	P05412	HPRD
P00519	P06400	HPRD
P00519	P06493	HPRD
P00519	P08047	IntAct
P00519	P10721	HPRD
P00519	P12931	IntAct; MINT;HPRD
P00519	P15498	MINT
P00519	P15941	MINT;HPRD
P00519	P16220	HPRD
P00519	P19174	IntAct; MINT
P00519	P20936	HPRD
P00519	P21860	MINT
P00519	P22681	MINT;HPRD
P00519	P23458	HPRD
P00519	P27986	IntAct; MINT;HPRD
P00519	P31947	IntAct;HPRD
P00519	P35222	MINT
P00519	P38398	MINT
P00519	P43403	HPRD
P00519	P46108	DIP; IntAct; MINT;HPRD
P00519	P46109	MINT;HPRD
P00519	P46527	HPRD
P00519	P46937	HPRD
P00519	P56945	HPRD
P00519	Q03135	HPRD
P00519	Q05655	MINT
P00519	Q06187	HPRD
P00519	Q06830	MINT
P00519	Q13315	DIP; IntAct;HPRD
P00519	Q15303	MINT
P00519	Q9H5I1	IntAct; MINT
P00519	Q9Y2J2	IntAct
P00519	Q9Y4K3	HPRD

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction