CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001784
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 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
902PPPACTGKAGKPAQSacetylation[1]
Reference
 [1] Tip60-mediated acetylation activates transcription independent apoptotic activity of Abl.
 Jiang Z, Kamath R, Jin S, Balasubramani M, Pandita TK, Rajasekaran B.
 Mol Cancer. 2011 Jul 22;10:88. [PMID: 21781306] 
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-191' 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. 
Sequence Annotation
 DOMAIN 61 121 SH3.
 DOMAIN 127 217 SH2.
 DOMAIN 242 493 Protein kinase.
 NP_BIND 248 256 ATP (Probable).
 NP_BIND 316 322 ATP (Probable).
 REGION 1 60 CAP.
 REGION 863 961 DNA-binding.
 REGION 945 1123 F-actin-binding (By similarity).
 MOTIF 381 405 Kinase activation loop.
 MOTIF 605 609 Nuclear localization signal 1
 MOTIF 708 714 Nuclear localization signal 2
 MOTIF 761 768 Nuclear localization signal 3
 MOTIF 1083 1093 Nuclear export signal.
 ACT_SITE 363 363 Proton acceptor (By similarity).
 BINDING 271 271 ATP (By similarity).
 MOD_RES 50 50 Phosphoserine (By similarity).
 MOD_RES 70 70 Phosphotyrosine; by autocatalysis (By
 MOD_RES 185 185 Phosphotyrosine (By similarity).
 MOD_RES 226 226 Phosphotyrosine; by autocatalysis (By
 MOD_RES 253 253 Phosphotyrosine (By similarity).
 MOD_RES 257 257 Phosphotyrosine (By similarity).
 MOD_RES 264 264 Phosphotyrosine (By similarity).
 MOD_RES 392 392 Phosphothreonine (By similarity).
 MOD_RES 393 393 Phosphotyrosine; by autocatalysis and
 MOD_RES 394 394 Phosphothreonine (By similarity).
 MOD_RES 446 446 Phosphoserine.
 MOD_RES 469 469 Phosphotyrosine (By similarity).
 MOD_RES 547 547 Phosphothreonine.
 MOD_RES 569 569 Phosphoserine.
 MOD_RES 613 613 Phosphothreonine (By similarity).
 MOD_RES 618 618 Phosphoserine; by PAK2 (By similarity).
 MOD_RES 619 619 Phosphoserine; by PAK2 (By similarity).
 MOD_RES 620 620 Phosphoserine (By similarity).
 MOD_RES 658 658 Phosphoserine (By similarity).
 MOD_RES 682 682 Phosphoserine (By similarity).
 MOD_RES 710 710 N6-acetyllysine; by EP300 (By
 MOD_RES 717 717 Phosphoserine (By similarity).
 MOD_RES 734 734 Phosphothreonine (By similarity).
 MOD_RES 803 803 Phosphoserine (By similarity).
 MOD_RES 807 807 Phosphoserine (By similarity).
 MOD_RES 812 812 Phosphothreonine (By similarity).
 MOD_RES 844 844 Phosphothreonine (By similarity).
 MOD_RES 909 909 Phosphoserine (By similarity).
 MOD_RES 911 911 Phosphoserine (By similarity).
 MOD_RES 927 927 Phosphoserine (By similarity).
 MOD_RES 970 970 Phosphoserine (By similarity).  
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; Metal-binding; Mitochondrion; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1123 AA 
Protein Sequence
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 NKPTIYGVSP NYDKWEMERT 240
DITMKHKLGG GQYGEVYEGV WKKYSLTVAV KTLKEDTMEV EEFLKEAAVM KEIKHPNLVQ 300
LLGVCTREPP FYIITEFMTY GNLLDYLREC NRQEVSAVVL LYMATQISSA MEYLEKKNFI 360
HRDLAARNCL VGENHLVKVA DFGLSRLMTG DTYTAHAGAK FPIKWTAPES LAYNKFSIKS 420
DVWAFGVLLW EIATYGMSPY PGIDLSQVYE LLEKDYRMER PEGCPEKVYE LMRACWQWNP 480
SDRPSFAEIH QAFETMFQES SISDEVEKEL GKRGTRGGAG SMLQAPELPT KTRTCRRAAE 540
QKDAPDTPEL LHTKGLGESD ALDSEPAVSP LLPRKERGPP DGSLNEDERL LPRDRKTNLF 600
SALIKKKKKM APTPPKRSSS FREMDGQPDR RGASEDDSRE LCNGPPALTS DAAEPTKSPK 660
ASNGAGVPNG AFREPGNSGF RSPHMWKKSS TLTGSRLAAA EEESGMSSSK RFLRSCSASC 720
MPHGARDTEW RSVTLPRDLP SAGKQFDSST FGGHKSEKPA LPRKRTSESR SEQVAKSTAM 780
PPPRLVKKNE EAAEEGFKDT ESSPGSSPPS LTPKLLRRQV TASPSSGLSH KEEATKGSAS 840
GMGTPATAEP APPSNKVGLS KASSEEMRVR RHKHSSESPG RDKGRLAKLK PAPPPPPACT 900
GKAGKPAQSP SQEAGEAGGP TKTKCTSLAM DAVNTDPTKA GPPGEGLRKP VPPSVPKPQS 960
TAKPPGTPTS PVSTPSTAPA PSPLAGDQQP SSAAFIPLIS TRVSLRKTRQ PPERIASGTI 1020
TKGVVLDSTE ALCLAISRNS EQMASHSAVL EAGKNLYTFC VSYVDSIQQM RNKFAFREAI 1080
NKLESNLREL QICPATASSG PAATQDFSKL LSSVKEISDI VRR 1123 
Gene Ontology
 GO:0031252; C:cell leading edge; IDA:MGI.
 GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; ISA:MGI.
 GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
 GO:0005730; C:nucleolus; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0030145; F:manganese ion binding; IDA:UniProtKB.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC.
 GO:0070064; F:proline-rich region binding; ISS:UniProtKB.
 GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0030036; P:actin cytoskeleton organization; IDA:UniProtKB.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0006914; P:autophagy; IEA:UniProtKB-KW.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0006975; P:DNA damage induced protein phosphorylation; IEA:Compara.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
 GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IEA:Compara.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:MGI.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:0051353; P:positive regulation of oxidoreductase activity; IEA:Compara.
 GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
 GO:0051726; P:regulation of cell cycle; IDA:MGI.
 GO:2001020; P:regulation of response to DNA damage stimulus; IEA:Compara.
 GO:0042770; P:signal transduction in response to DNA damage; ISS: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.