CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001783
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein kinase ABL1 
Protein Synonyms/Alias
 Abelson murine leukemia viral oncogene homolog 1; Abelson tyrosine-protein kinase 1; Proto-oncogene c-Abl; p150 
Gene Name
 ABL1 
Gene Synonyms/Alias
 ABL; JTK7 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
730EGGGSSSKRFLRSCSacetylation[1]
Reference
 [1] c-Abl acetylation by histone acetyltransferases regulates its nuclear-cytoplasmic localization.
 di Bari MG, Ciuffini L, Mingardi M, Testi R, Soddu S, Barilà D.
 EMBO Rep. 2006 Jul;7(7):727-33. [PMID: 16648821] 
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. 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. 
Sequence Annotation
 DOMAIN 61 121 SH3.
 DOMAIN 127 217 SH2.
 DOMAIN 242 493 Protein kinase.
 NP_BIND 248 256 ATP.
 NP_BIND 316 322 ATP.
 REGION 1 60 CAP.
 REGION 869 968 DNA-binding (By similarity).
 REGION 953 1130 F-actin-binding.
 MOTIF 381 405 Kinase activation loop.
 MOTIF 605 609 Nuclear localization signal 1
 MOTIF 709 715 Nuclear localization signal 2
 MOTIF 762 769 Nuclear localization signal 3
 MOTIF 1090 1100 Nuclear export signal (By similarity).
 ACT_SITE 363 363 Proton acceptor (By similarity).
 BINDING 271 271 ATP.
 MOD_RES 50 50 Phosphoserine.
 MOD_RES 70 70 Phosphotyrosine; by autocatalysis.
 MOD_RES 185 185 Phosphotyrosine.
 MOD_RES 226 226 Phosphotyrosine; by autocatalysis.
 MOD_RES 253 253 Phosphotyrosine.
 MOD_RES 257 257 Phosphotyrosine.
 MOD_RES 264 264 Phosphotyrosine.
 MOD_RES 392 392 Phosphothreonine.
 MOD_RES 393 393 Phosphotyrosine; by autocatalysis and
 MOD_RES 394 394 Phosphothreonine.
 MOD_RES 446 446 Phosphoserine (By similarity).
 MOD_RES 469 469 Phosphotyrosine.
 MOD_RES 569 569 Phosphoserine.
 MOD_RES 613 613 Phosphothreonine.
 MOD_RES 618 618 Phosphoserine; by PAK2.
 MOD_RES 619 619 Phosphoserine; by PAK2.
 MOD_RES 620 620 Phosphoserine.
 MOD_RES 659 659 Phosphoserine.
 MOD_RES 683 683 Phosphoserine.
 MOD_RES 711 711 N6-acetyllysine; by EP300.
 MOD_RES 718 718 Phosphoserine.
 MOD_RES 735 735 Phosphothreonine.
 MOD_RES 781 781 Phosphothreonine.
 MOD_RES 805 805 Phosphoserine.
 MOD_RES 809 809 Phosphoserine.
 MOD_RES 814 814 Phosphothreonine.
 MOD_RES 844 844 Phosphothreonine.
 MOD_RES 852 852 Phosphothreonine.
 MOD_RES 855 855 Phosphoserine.
 MOD_RES 917 917 Phosphoserine.
 MOD_RES 919 919 Phosphoserine.
 MOD_RES 936 936 Phosphoserine.
 MOD_RES 949 949 Phosphoserine.
 MOD_RES 977 977 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; Autophagy; Cell adhesion; Chromosomal rearrangement; Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; DNA-binding; Endocytosis; Kinase; Lipoprotein; Magnesium; Manganese; Membrane; Metal-binding; Mitochondrion; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1130 AA 
Protein Sequence
MGQQPGKVLG DQRRPSLPAL HFIKGAGKKE SSRHGGPHCN VFVEHEALQR PVASDFEPQG 60
LSEAARWNSK ENLLAGPSEN DPNLFVALYD FVASGDNTLS ITKGEKLRVL GYNHNGEWCE 120
AQTKNGQGWV PSNYITPVNS LEKHSWYHGP VSRNAAEYLL SSGINGSFLV RESESSPGQR 180
SISLRYEGRV YHYRINTASD GKLYVSSESR FNTLAELVHH HSTVADGLIT TLHYPAPKRN 240
KPTVYGVSPN YDKWEMERTD ITMKHKLGGG QYGEVYEGVW KKYSLTVAVK TLKEDTMEVE 300
EFLKEAAVMK EIKHPNLVQL LGVCTREPPF YIITEFMTYG NLLDYLRECN RQEVNAVVLL 360
YMATQISSAM EYLEKKNFIH RDLAARNCLV GENHLVKVAD FGLSRLMTGD TYTAHAGAKF 420
PIKWTAPESL AYNKFSIKSD VWAFGVLLWE IATYGMSPYP GIDLSQVYEL LEKDYRMERP 480
EGCPEKVYEL MRACWQWNPS DRPSFAEIHQ AFETMFQESS ISDEVEKELG KQGVRGAVST 540
LLQAPELPTK TRTSRRAAEH RDTTDVPEMP HSKGQGESDP LDHEPAVSPL LPRKERGPPE 600
GGLNEDERLL PKDKKTNLFS ALIKKKKKTA PTPPKRSSSF REMDGQPERR GAGEEEGRDI 660
SNGALAFTPL DTADPAKSPK PSNGAGVPNG ALRESGGSGF RSPHLWKKSS TLTSSRLATG 720
EEEGGGSSSK RFLRSCSASC VPHGAKDTEW RSVTLPRDLQ STGRQFDSST FGGHKSEKPA 780
LPRKRAGENR SDQVTRGTVT PPPRLVKKNE EAADEVFKDI MESSPGSSPP NLTPKPLRRQ 840
VTVAPASGLP HKEEAGKGSA LGTPAAAEPV TPTSKAGSGA PGGTSKGPAE ESRVRRHKHS 900
SESPGRDKGK LSRLKPAPPP PPAASAGKAG GKPSQSPSQE AAGEAVLGAK TKATSLVDAV 960
NSDAAKPSQP GEGLKKPVLP ATPKPQSAKP SGTPISPAPV PSTLPSASSA LAGDQPSSTA 1020
FIPLISTRVS LRKTRQPPER IASGAITKGV VLDSTEALCL AISRNSEQMA SHSAVLEAGK 1080
NLYTFCVSYV DSIQQMRNKF AFREAINKLE NNLRELQICP ATAGSGPAAT QDFSKLLSSV 1140
KEISDIVQR 1149 
Gene Ontology
 GO:0015629; C:actin cytoskeleton; TAS:UniProtKB.
 GO:0031252; C:cell leading edge; IEA:Compara.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
 GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
 GO:0005730; C:nucleolus; IDA:MGI.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0003785; F:actin monomer binding; TAS:UniProtKB.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0003677; F:DNA binding; NAS:UniProtKB.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0030145; F:manganese ion binding; IDA:UniProtKB.
 GO:0004515; F:nicotinate-nucleotide adenylyltransferase activity; TAS:UniProtKB.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0070064; F:proline-rich region binding; IDA:UniProtKB.
 GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
 GO:0006914; P:autophagy; IEA:UniProtKB-KW.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0007596; P:blood coagulation; TAS:Reactome.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; TAS:UniProtKB.
 GO:0006298; P:mismatch repair; TAS:ProtInc.
 GO:0042692; P:muscle cell differentiation; TAS:Reactome.
 GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Compara.
 GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
 GO:0051149; P:positive regulation of muscle cell differentiation; TAS:Reactome.
 GO:0051353; P:positive regulation of oxidoreductase activity; IDA:BHF-UCL.
 GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:2000249; P:regulation of actin cytoskeleton reorganization; TAS:UniProtKB.
 GO:0010506; P:regulation of autophagy; TAS:UniProtKB.
 GO:0030155; P:regulation of cell adhesion; TAS:UniProtKB.
 GO:0051726; P:regulation of cell cycle; IEA:Compara.
 GO:2000145; P:regulation of cell motility; TAS:UniProtKB.
 GO:0030100; P:regulation of endocytosis; TAS:UniProtKB.
 GO:2001020; P:regulation of response to DNA damage stimulus; IDA:UniProtKB.
 GO:0000115; P:regulation of transcription involved in S phase of mitotic cell cycle; TAS:ProtInc.
 GO:0042770; P:signal transduction in response to DNA damage; IDA:UniProtKB. 
Interpro
 IPR015015; F-actin_binding.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR000980; SH2.
 IPR001452; SH3_domain.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom. 
Pfam
 PF08919; F_actin_bind
 PF07714; Pkinase_Tyr
 PF00017; SH2
 PF00018; SH3_1 
SMART
 SM00808; FABD
 SM00252; SH2
 SM00326; SH3
 SM00219; TyrKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2
 PS50002; SH3 
PRINTS
 PR00401; SH2DOMAIN.
 PR00109; TYRKINASE.