ABL1 (基因名), Tyrosine-protein kinase ABL1 (蛋白名), ABL1_HUMAN.
Human ABL1/ Tyrosine-protein kinase ABL1 Recombinant Protein
Abelson murine leukemia viral oncogene homolog 1, Abelson tyrosine-protein kinase 1, Proto-oncogene c-Abl, p150, ABL, JTK7
>90% by SDS-PAGE
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50mM NaH2PO4, 500mM NaCl Buffer with 500mM Imidazole, 10%glycerol(PH8.0)
Store at -20°C. (Avoid repeated freezing and thawing.)
Interacts with SORBS1 following insulin stimulation. Found in a trimolecular complex containing CDK5 and CABLES1. Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16, ITGB1 and HCK (By similarity). Interacts with STX17; probably phosphorylates STX17. Interacts with INPPL1/SHIP2. Interacts with the 14-3-3 proteins, YWHAB, YWHAE, YWHAG, YWHAH, SFN AND YWHAZ; the interaction with 14-3-3 proteins requires phosphorylation on Thr-735 and, sequesters ABL1 into the cytoplasm. Interacts with ABI1, ABI2, BCR, CRK, FGR, FYN, HCK, LYN, PSMA7 RAD9A, RAD51, RAD52, TP73 and WASF3. A complex made of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Interacts (via SH3 domain) with CASP9; the interaction is direct and increases in the response of cells to genotoxic stress and ABL1/c-Abl activation. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases.
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.
Isoform IB Nucleus membrane Lipid-anchor The myristoylated c-ABL protein is reported to be nuclear.
MLEICLKLVG | CKSKKGLSSS | SSCYLEEALQ | RPVASDFEPQ | GLSEAARWNS |
KENLLAGPSE | NDPNLFVALY | DFVASGDNTL | SITKGEKLRV | LGYNHNGEWC |
EAQTKNGQGW | VPSNYITPVN | SLEKHSWYHG | PVSRNAAEYL | LSSGINGSFL |
VRESESSPGQ | RSISLRYEGR | VYHYRINTAS | DGKLYVSSES | RFNTLAELVH |
HHSTVADGLI | TTLHYPAPKR | NKPTVYGVSP | NYDKWEMERT | DITMKHKLGG |
GQYGEVYEGV | WKKYSLTVAV | KTLKEDTMEV | EEFLKEAAVM | KEIKHPNLVQ |
LLGVCTREPP | FYIITEFMTY | GNLLDYLREC | NRQEVNAVVL | LYMATQISSA |
MEYLEKKNFI | HRDLAARNCL | VGENHLVKVA | DFGLSRLMTG | DTYTAHAGAK |
FPIKWTAPES | LAYNKFSIKS | DVWAFGVLLW | EIATYGMSPY | PGIDLSQVYE |
LLEKDYRMER | PEGCPEKVYE | LMRACWQWNP | SDRPSFAEIH | QAFETMFQES |
SISDEVEKEL | GKQGVRGAVS | TLLQAPELPT | KTRTSRRAAE | HRDTTDVPEM |
PHSKGQGESD | PLDHEPAVSP | LLPRKERGPP | EGGLNEDERL | LPKDKKTNLF |
SALIKKKKKT | APTPPKRSSS | FREMDGQPER | RGAGEEEGRD | ISNGALAFTP |
LDTADPAKSP | KPSNGAGVPN | GALRESGGSG | FRSPHLWKKS | STLTSSRLAT |
GEEEGGGSSS | KRFLRSCSAS | CVPHGAKDTE | WRSVTLPRDL | QSTGRQFDSS |
TFGGHKSEKP | ALPRKRAGEN | RSDQVTRGTV | TPPPRLVKKN | EEAADEVFKD |
IMESSPGSSP | PNLTPKPLRR | QVTVAPASGL | PHKEEAGKGS | ALGTPAAAEP |
VTPTSKAGSG | APGGTSKGPA | EESRVRRHKH | SSESPGRDKG | KLSRLKPAPP |
PPPAASAGKA | GGKPSQSPSQ | EAAGEAVLGA | KTKATSLVDA | VNSDAAKPSQ |
PGEGLKKPVL | PATPKPQSAK | PSGTPISPAP | VPSTLPSASS | ALAGDQPSST |
AFIPLISTRV | SLRKTRQPPE | RIASGAITKG | VVLDSTEALC | LAISRNSEQM |
ASHSAVLEAG | KNLYTFCVSY | VDSIQQMRNK | FAFREAINKL | ENNLRELQIC |
PATAGSGPAA | TQDFSKLLSS | VKEISDIVQR |
"Cbl-associated protein is tyrosine phosphorylated by c-Abl and c-Src kinases."
"Allosteric inhibition of the nonMyristoylated c-Abl tyrosine kinase by phosphopeptides derived from Abi1/Hssh3bp1."
"Interaction between c-Abl and Arg tyrosine kinases and proteasome subunit PSMA7 regulates proteasome degradation."
"c-Abl acetylation by histone acetyltransferases regulates its nuclear-cytoplasmic localization."
"JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of c-Abl in the apoptotic response to DNA damage."
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