ID ABL1_MOUSE Reviewed; 1123 AA. AC P00520; P97896; Q61252; Q61253; Q61254; Q61255; Q61256; Q61257; AC Q61258; Q61259; Q61260; Q61261; Q6PCM5; Q8C1X4; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 15-FEB-2005, sequence version 3. DT 11-DEC-2013, entry version 182. DE RecName: Full=Tyrosine-protein kinase ABL1; DE EC=2.7.10.2; DE AltName: Full=Abelson murine leukemia viral oncogene homolog 1; DE AltName: Full=Abelson tyrosine-protein kinase 1; DE AltName: Full=Proto-oncogene c-Abl; DE AltName: Full=p150; GN Name=Abl1; Synonyms=Abl; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM I). RC TISSUE=Testis; RX PubMed=3317402; DOI=10.1073/pnas.84.23.8200; RA Oppi C., Shore S.K., Reddy E.P.; RT "Nucleotide sequence of testis-derived c-abl cDNAs: implications for RT testis-specific transcription and abl oncogene activation."; RL Proc. Natl. Acad. Sci. U.S.A. 84:8200-8204(1987). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I). RC STRAIN=ICR; TISSUE=Embryo; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IV). RC STRAIN=C57BL/6; TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-187 (ISOFORMS I; II; III AND RP IV). RX PubMed=7665185; DOI=10.1006/geno.1995.1008; RA Chissoe S.L., Bodenteich A., Wang Y.-F., Wang Y.-P., Burian D., RA Clifton S.W., Crabtree J., Freeman A., Iyer K., Jian L., Ma Y., RA McLaury H.-J., Pan H.-Q., Sarhan O.H., Toth S., Wang Z., Zhang G., RA Heisterkamp N., Groffen J., Roe B.A.; RT "Sequence and analysis of the human ABL gene, the BCR gene, and RT regions involved in the Philadelphia chromosomal translocation."; RL Genomics 27:67-82(1995). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 85-182. RX PubMed=6319018; DOI=10.1016/0092-8674(84)90228-9; RA Wang J.Y.J., Ledley F., Goff S., Lee R., Groner Y., Baltimore D.; RT "The mouse c-abl locus: molecular cloning and characterization."; RL Cell 36:349-356(1984). RN [6] RP ALTERNATIVE SPLICING. RX PubMed=3283651; RA Bernards A., Paskind M., Baltimore D.; RT "Four murine c-abl mRNAs arise by usage of two transcriptional RT promoters and alternative splicing."; RL Oncogene 2:297-304(1988). RN [7] RP PHOSPHORYLATION AT THR-547 AND SER-569. RX PubMed=2183353; DOI=10.1126/science.2183353; RA Kipreos E.T., Wang J.Y.; RT "Differential phosphorylation of c-Abl in cell cycle determined by RT cdc2 kinase and phosphatase activity."; RL Science 248:217-220(1990). RN [8] RP DISRUPTION PHENOTYPE. RX PubMed=2065352; DOI=10.1016/0092-8674(91)90011-M; RA Tybulewicz V.L., Crawford C.E., Jackson P.K., Bronson R.T., RA Mulligan R.C.; RT "Neonatal lethality and lymphopenia in mice with a homozygous RT disruption of the c-abl proto-oncogene."; RL Cell 65:1153-1163(1991). RN [9] RP DISRUPTION PHENOTYPE. RX PubMed=2065353; DOI=10.1016/0092-8674(91)90012-N; RA Schwartzberg P.L., Stall A.M., Hardin J.D., Bowdish K.S., Humaran T., RA Boast S., Harbison M.L., Robertson E.J., Goff S.P.; RT "Mice homozygous for the ablm1 mutation show poor viability and RT depletion of selected B and T cell populations."; RL Cell 65:1165-1175(1991). RN [10] RP DNA-BINDING, DOMAIN, AND PHOSPHORYLATION. RX PubMed=1566087; DOI=10.1126/science.256.5055.382; RA Kipreos E.T., Wang J.Y.; RT "Cell cycle-regulated binding of c-Abl tyrosine kinase to DNA."; RL Science 256:382-385(1992). RN [11] RP FUNCTION. RX PubMed=8194526; RA Feller S.M., Knudsen B., Hanafusa H.; RT "c-Abl kinase regulates the protein binding activity of c-Crk."; RL EMBO J. 13:2341-2351(1994). RN [12] RP FUNCTION. RX PubMed=7780740; DOI=10.1016/S0960-9822(95)00060-1; RA Mayer B.J., Hirai H., Sakai R.; RT "Evidence that SH2 domains promote processive phosphorylation by RT protein-tyrosine kinases."; RL Curr. Biol. 5:296-305(1995). RN [13] RP FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT RP SER-446, AND MUTAGENESIS OF SER-446. RX PubMed=9109492; DOI=10.1038/386732a0; RA Kharbanda S., Pandey P., Jin S., Inoue S., Bharti A., Yuan Z.-M., RA Weichselbaum R., Weaver D., Kufe D.; RT "Functional interaction between DNA-PK and c-Abl in response to DNA RT damage."; RL Nature 386:732-735(1997). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=9636171; DOI=10.1073/pnas.95.13.7457; RA Taagepera S., McDonald D., Loeb J.E., Whitaker L.L., McElroy A.K., RA Wang J.Y., Hope T.J.; RT "Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 95:7457-7462(1998). RN [15] RP IDENTIFICATION IN A TRIMOLECULAR COMPLEX WITH CDK5 AND CABLES1, AND RP INTERACTION WITH CABLES1. RC TISSUE=Brain; RX PubMed=10896159; DOI=10.1016/S0896-6273(00)81200-3; RA Zukerberg L.R., Patrick G.N., Nikolic M., Humbert S., Wu C.-L., RA Lanier L.M., Gertler F.B., Vidal M., Van Etten R.A., Tsai L.-H.; RT "Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine RT phosphorylation, kinase upregulation, and neurite outgrowth."; RL Neuron 26:633-646(2000). RN [16] RP INTERACTION WITH PSTPIP1. RX PubMed=11163214; DOI=10.1016/S1097-2765(00)00138-6; RA Cong F., Spencer S., Cote J.F., Wu Y., Tremblay M.L., Lasky L.A., RA Goff S.P.; RT "Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine RT phosphatase to the c-Abl kinase to mediate Abl dephosphorylation."; RL Mol. Cell 6:1413-1423(2000). RN [17] RP REVIEW ON FUNCTION. RX PubMed=11114745; DOI=10.1038/sj.onc.1203878; RA Wang J.Y.; RT "Regulation of cell death by the Abl tyrosine kinase."; RL Oncogene 19:5643-5650(2000). RN [18] RP INTERACTION WITH CRK, AND FUNCTION. RX PubMed=11279004; DOI=10.1074/jbc.M100095200; RA Kain K.H., Klemke R.L.; RT "Inhibition of cell migration by Abl family tyrosine kinases through RT uncoupling of Crk-CAS complexes."; RL J. Biol. Chem. 276:16185-16192(2001). RN [19] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11350980; DOI=10.1074/jbc.M101414200; RA Kumar S., Bharti A., Mishra N.C., Raina D., Kharbanda S., Saxena S., RA Kufe D.; RT "Targeting of the c-Abl tyrosine kinase to mitochondria in the RT necrotic cell death response to oxidative stress."; RL J. Biol. Chem. 276:17281-17285(2001). RN [20] RP FUNCTION. RX PubMed=11279131; DOI=10.1074/jbc.M100792200; RA Zambrano N., Bruni P., Minopoli G., Mosca R., Molino D., Russo C., RA Schettini G., Sudol M., Russo T.; RT "The beta-amyloid precursor protein APP is tyrosine-phosphorylated in RT cells expressing a constitutively active form of the Abl RT protoncogene."; RL J. Biol. Chem. 276:19787-19792(2001). RN [21] RP INTERACTION WITH ZDHHC16. RX PubMed=12021275; DOI=10.1074/jbc.M202388200; RA Li B., Cong F., Tan C.P., Wang S.X., Goff S.P.; RT "Aph2, a protein with a zf-DHHC motif, interacts with c-Abl and has RT pro-apoptotic activity."; RL J. Biol. Chem. 277:28870-28876(2002). RN [22] RP FUNCTION. RX PubMed=12107171; DOI=10.1074/jbc.M204416200; RA Cong F., Tang J., Hwang B.J., Vuong B.Q., Chu G., Goff S.P.; RT "Interaction between UV-damaged DNA binding activity proteins and the RT c-Abl tyrosine kinase."; RL J. Biol. Chem. 277:34870-34878(2002). RN [23] RP REVIEW ON FUNCTION. RX PubMed=12775773; DOI=10.1242/jcs.00622; RA Woodring P.J., Hunter T., Wang J.Y.; RT "Regulation of F-actin-dependent processes by the Abl family of RT tyrosine kinases."; RL J. Cell Sci. 116:2613-2626(2003). RN [24] RP FUNCTION, ENZYME REGULATION, INTERACTION WITH CRK, AUTOPHOSPHORYLATION RP AT TYR-226 AND TYR-393, AND MUTAGENESIS OF TYR-226; LYS-271 AND RP TYR-393. RX PubMed=12748290; DOI=10.1128/MCB.23.11.3884-3896.2003; RA Tanis K.Q., Veach D., Duewel H.S., Bornmann W.G., Koleske A.J.; RT "Two distinct phosphorylation pathways have additive effects on Abl RT family kinase activation."; RL Mol. Cell. Biol. 23:3884-3896(2003). RN [25] RP FUNCTION, ENZYME REGULATION, AND PHOSPHORYLATION. RX PubMed=14993293; DOI=10.1128/MCB.24.6.2573-2583.2004; RA Plattner R., Koleske A.J., Kazlauskas A., Pendergast A.M.; RT "Bidirectional signaling links the Abelson kinases to the platelet- RT derived growth factor receptor."; RL Mol. Cell. Biol. 24:2573-2583(2004). RN [26] RP REVIEW ON FUNCTION. RX PubMed=15686624; DOI=10.1038/sj.cr.7290261; RA Shaul Y., Ben-Yehoyada M.; RT "Role of c-Abl in the DNA damage stress response."; RL Cell Res. 15:33-35(2005). RN [27] RP FUNCTION IN REGULATION OF CELL MIGRATION, PHOSPHORYLATION, AND RP INTERACTION WITH ITGB1; HCK AND FGR. RX PubMed=19903482; DOI=10.1016/j.febslet.2009.11.009; RA Baruzzi A., Iacobucci I., Soverini S., Lowell C.A., Martinelli G., RA Berton G.; RT "c-Abl and Src-family kinases cross-talk in regulation of myeloid cell RT migration."; RL FEBS Lett. 584:15-21(2010). RN [28] RP REVIEW ON FUNCTION, AND DOMAIN. RX PubMed=20841568; DOI=10.1126/scisignal.3139re6; RA Colicelli J.; RT "ABL tyrosine kinases: evolution of function, regulation, and RT specificity."; RL Sci. Signal. 3:RE6-RE6(2010). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 61-121. RX PubMed=7664083; DOI=10.1038/nsb0894-546; RA Musacchio A., Saraste M., Wilmanns M.; RT "High-resolution crystal structures of tyrosine kinase SH3 domains RT complexed with proline-rich peptides."; RL Nat. Struct. Biol. 1:546-551(1994). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 229-515 IN COMPLEX WITH RP INHIBITOR STI-571, CATALYTIC ACTIVITY, ENZYME REGULATION, RP PHOSPHORYLATION AT TYR-393, AND ACTIVATION LOOP. RX PubMed=10988075; DOI=10.1126/science.289.5486.1938; RA Schindler T., Bornmann W., Pellicena P., Miller W.T., Clarkson B., RA Kuriyan J.; RT "Structural mechanism for STI-571 inhibition of Abelson tyrosine RT kinase."; RL Science 289:1938-1942(2000). RN [31] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 229-515, MYRISTOYLATION RP (ISOFORM IV), AND ENZYME REGULATION. RX PubMed=12654251; DOI=10.1016/S0092-8674(03)00194-6; RA Nagar B., Hantschel O., Young M.A., Scheffzek K., Veach D., RA Bornmann W., Clarkson B., Superti-Furga G., Kuriyan J.; RT "Structural basis for the autoinhibition of c-Abl tyrosine kinase."; RL Cell 112:859-871(2003). RN [32] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 229-515 OF WILD-TYPE AND RP MUTANT ILE-315 IN COMPLEX WITH INHIBITOR PPY-A. RX PubMed=17718712; DOI=10.1111/j.1747-0285.2007.00556.x; RA Zhou T., Parillon L., Li F., Wang Y., Keats J., Lamore S., Xu Q., RA Shakespeare W., Dalgarno D., Zhu X.; RT "Crystal structure of the T315I mutant of AbI kinase."; RL Chem. Biol. Drug Des. 70:171-181(2007). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 229-515 OF MUTANT ILE-315 IN RP COMPLEX WITH INHIBITOR AP24534, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=19878872; DOI=10.1016/j.ccr.2009.09.028; RA O'Hare T., Shakespeare W.C., Zhu X., Eide C.A., Rivera V.M., Wang F., RA Adrian L.T., Zhou T., Huang W.S., Xu Q., Metcalf C.A. III, Tyner J.W., RA Loriaux M.M., Corbin A.S., Wardwell S., Ning Y., Keats J.A., Wang Y., RA Sundaramoorthi R., Thomas M., Zhou D., Snodgrass J., Commodore L., RA Sawyer T.K., Dalgarno D.C., Deininger M.W., Druker B.J., Clackson T.; RT "AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, RT potently inhibits the T315I mutant and overcomes mutation-based RT resistance."; RL Cancer Cell 16:401-412(2009). RN [34] RP X-RAY CRYSTALLOGRAPHY (1.22 ANGSTROMS) OF 115-401 IN COMPLEXES WITH RP INHIBITORS AP24283 AND AP24163. RX PubMed=19895503; DOI=10.1111/j.1747-0285.2009.00905.x; RA Zhou T., Commodore L., Huang W.S., Wang Y., Sawyer T.K., RA Shakespeare W.C., Clackson T., Zhu X., Dalgarno D.C.; RT "Structural analysis of DFG-in and DFG-out dual Src-Abl inhibitors RT sharing a common vinyl purine template."; RL Chem. Biol. Drug Des. 75:18-28(2010). RN [35] RP X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 115-401 IN COMPLEX WITH RP INHIBITORS IMATINIB AND GNF-2, CATALYTIC ACTIVITY, ENZYME REGULATION, RP AUTOPHOSPHORYLATION, AND MUTAGENESIS OF PRO-112; TYR-128; TYR-139; RP SER-229; THR-315; CYS-464; PRO-465; PHE-497; GLU-505 AND VAL-506. RX PubMed=20072125; DOI=10.1038/nature08675; RA Zhang J., Adrian F.J., Jahnke W., Cowan-Jacob S.W., Li A.G., RA Iacob R.E., Sim T., Powers J., Dierks C., Sun F., Guo G.R., Ding Q., RA Okram B., Choi Y., Wojciechowski A., Deng X., Liu G., Fendrich G., RA Strauss A., Vajpai N., Grzesiek S., Tuntland T., Liu Y., Bursulaya B., RA Azam M., Manley P.W., Engen J.R., Daley G.Q., Warmuth M., Gray N.S.; RT "Targeting Bcr-Abl by combining allosteric with ATP-binding-site RT inhibitors."; RL Nature 463:501-506(2010). CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that plays a role CC in many key processes linked to cell growth and survival such as CC cytoskeleton remodeling in response to extracellular stimuli, cell CC motility and adhesion, receptor endocytosis, autophagy, DNA damage CC response and apoptosis. Coordinates actin remodeling through CC tyrosine phosphorylation of proteins controlling cytoskeleton CC dynamics like WASF3 (involved in branch formation); ANXA1 CC (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH CC (involved in signaling); or MAPT and PXN (microtubule-binding CC proteins). Phosphorylation of WASF3 is critical for the CC stimulation of lamellipodia formation and cell migration. Involved CC in the regulation of cell adhesion and motility through CC phosphorylation of key regulators of these processes such as CC BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple CC receptor tyrosine kinases and more particularly promotes CC endocytosis of EGFR, facilitates the formation of neuromuscular CC synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and CC modulates the endocytosis of activated B-cell receptor complexes. CC Other substrates which are involved in endocytosis regulation are CC the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL CC family of ubiquitin ligases that drive receptor down-regulation CC and actin remodeling. Phosphorylation of CBL leads to increased CC EGFR stability. Involved in late-stage autophagy by regulating CC positively the trafficking and function of lysosomal components. CC ABL1 targets to mitochondria in response to oxidative stress and CC thereby mediates mitochondrial dysfunction and cell death. ABL1 is CC also translocated in the nucleus where it has DNA-binding activity CC and is involved in DNA-damage response and apoptosis. Many CC substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, CC ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic CC pathway when the DNA damage is too severe to be repaired. CC Phosphorylates TP73, a primary regulator for this type of damage- CC induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-191' CC and regulates its processing in the apoptotic response to DNA CC damage. Phosphorylates PSMA7 that leads to an inhibition of CC proteasomal activity and cell cycle transition blocks. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- COFACTOR: Magnesium or manganese. CC -!- ENZYME REGULATION: Stabilized in the inactive form by an CC association between the SH3 domain and the SH2-TK linker region, CC interactions of the N-terminal cap, and contributions from an N- CC terminal myristoyl group and phospholipids. Activated by CC autophosphorylation as well as by SRC-family kinase-mediated CC phosphorylation (By similarity). Activated by RIN1 binding to the CC SH2 and SH3 domains. Also stimulated by cell death inducers and CC DNA-damage (By similarity). Phosphatidylinositol 4,5-bisphosphate CC (PIP2), a highly abundant phosphoinositide known to regulate CC cytoskeletal and membrane proteins, inhibits also the tyrosine CC kinase activity. Inhibited by imatinib mesylate (Gleevec). CC -!- SUBUNIT: Interacts with INPPL1/SHIP2. Interacts with SORBS1 CC following insulin stimulation. Found in a trimolecular complex CC containing CDK5 and CABLES1. Interacts with CABLES1 and PSTPIP1. CC Interacts with ZDHHC16. Interacts with the 14-3-3 proteins, YWHAB, CC YWHAE, YWHAG, YWHAH, SFN AND YWHAZ; the interaction with 14-3-3 CC proteins requires phosphorylation on Thr-734 and sequesters ABL1 CC into the cytoplasm. Interacts (via SH3 domain) with CASP9; the CC interaction is direct and increases in the response of cells to CC genotoxic stress and ABL1/c-Abl activation (By similarity). CC Interacts with ABI1, ABI2, BCR, CRK, FYN, LYN, PSMA7 RAD9A, RAD51, CC RAD52, TP73 and WASF3. A complex made of ABL1, CTTN and MYLK CC regulates cortical actin-based cytoskeletal rearrangement critical CC to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) CC barrier enhancement. Interacts with STX17; probably phosphorylates CC STX17 (By similarity). Interacts with ITGB1, HCK and FGR. CC -!- INTERACTION: CC Q8IZP0-4:ABI1 (xeno); NbExp=5; IntAct=EBI-8593082, EBI-8593095; CC P46527:CDKN1B (xeno); NbExp=2; IntAct=EBI-914519, EBI-519280; CC Q32MD9:Cdon; NbExp=2; IntAct=EBI-914519, EBI-7017034; CC P97465:Dok1; NbExp=4; IntAct=EBI-914519, EBI-914917; CC P28693-2:EPHB2 (xeno); NbExp=5; IntAct=EBI-914519, EBI-6725926; CC Q99M51:Nck1; NbExp=2; IntAct=EBI-914519, EBI-642202; CC P97814:Pstpip1; NbExp=5; IntAct=EBI-914519, EBI-7484574; CC P70602:Ptpn18 (xeno); NbExp=2; IntAct=EBI-914519, EBI-7484661; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Nucleus. CC Mitochondrion. Note=The myristoylated c-ABL protein is reported to CC be nuclear. Sequestered into the cytoplasm through interaction CC with 14-3-3 proteins (By similarity). Localizes to mitochondria in CC response to oxidative stress. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=I; CC IsoId=P00520-1; Sequence=Displayed; CC Name=II; CC IsoId=P00520-2; Sequence=VSP_004959; CC Name=III; CC IsoId=P00520-3; Sequence=VSP_004958; CC Name=IV; CC IsoId=P00520-4; Sequence=VSP_004960; CC -!- TISSUE SPECIFICITY: Widely expressed. CC -!- PTM: Acetylated at Lys-710 by EP300 which promotes the cytoplasmic CC translocation (By similarity). CC -!- PTM: Phosphorylation at Tyr-70 by members of the SRC family of CC kinases disrupts SH3 domain-based autoinhibitory interactions and CC intermolecular associations, such as that with ABI1, and also CC enhances kinase activity (By similarity). Phosphorylation at Tyr- CC 226 and Tyr-393 correlate with increased activity (By similarity). CC DNA damage-induced activation of ABL1 requires the function of ATM CC and Ser-446 phosphorylation. Phosphorylation at Thr-547 and Ser- CC 569 has been attributed to a CDC2-associated kinase and is coupled CC to cell division. Phosphorylation at Ser-618 and Ser-619 by PAK2 CC increases binding to CRK and reduces binding to ABI1 (By CC similarity). Phosphorylation on Thr-734 is required for binding CC 14-3-3 proteins for cytoplasmic translocation (By similarity). CC Phosphorylated by PDGFRB and PRKDC. CC -!- PTM: Polyubiquitinated. Polyubiquitination of ABL1 leads to CC degradation (By similarity). CC -!- PTM: Isoform IV is myristoylated on Gly-2. CC -!- DISRUPTION PHENOTYPE: Mutants are born with the expected Mendelian CC frequency, but fail to thrive and most die within three weeks CC after birth. Most mutants are runted, and have atrophied thymuses CC with severe thymocyte deficiency. Mutants that survive to weaning CC age are most often runted, and about half of them show CC lymphopenia. They display a major reduction in the number of pre-B CC and immature B-cell classes in bone marrow with a wide variation CC between individuals, but essentially normal mature B-cell levels. CC Mutants are highly susceptible to infections. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. ABL subfamily. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 SH2 domain. CC -!- SIMILARITY: Contains 1 SH3 domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J02995; AAA88241.1; -; mRNA. DR EMBL; AK090095; BAC41088.1; -; mRNA. DR EMBL; BC059260; AAH59260.1; -; mRNA. DR EMBL; U14721; AAB60451.1; -; Genomic_DNA. DR EMBL; U14720; AAB60451.1; JOINED; Genomic_DNA. DR EMBL; U14721; AAB60450.1; -; Genomic_DNA. DR EMBL; U14720; AAB60450.1; JOINED; Genomic_DNA. DR EMBL; U14721; AAB60448.1; -; Genomic_DNA. DR EMBL; U13835; AAB60448.1; JOINED; Genomic_DNA. DR EMBL; U14721; AAB60449.1; -; Genomic_DNA. DR EMBL; U13835; AAB60449.1; JOINED; Genomic_DNA. DR EMBL; X07539; CAA30411.1; -; Genomic_DNA. DR EMBL; X07539; CAA30412.1; -; Genomic_DNA. DR EMBL; X07540; CAA30413.1; -; Genomic_DNA. DR EMBL; X07541; CAA30414.1; -; Genomic_DNA. DR EMBL; M12263; AAA37136.1; -; mRNA. DR EMBL; M12264; AAA37137.1; -; mRNA. DR EMBL; M12265; AAA37138.1; -; mRNA. DR EMBL; M12266; AAA37134.1; -; Genomic_DNA. DR EMBL; K03228; AAA37135.1; -; mRNA. DR IPI; IPI00227806; -. DR IPI; IPI00227807; -. DR IPI; IPI00314762; -. DR IPI; IPI00453940; -. DR PIR; A39962; A39962. DR PIR; S00774; S00774. DR RefSeq; NP_001106174.1; NM_001112703.2. DR RefSeq; NP_033724.2; NM_009594.4. DR UniGene; Mm.1318; -. DR PDB; 1ABO; X-ray; 2.00 A; A/B=61-121. DR PDB; 1ABQ; X-ray; 2.80 A; A=61-121. DR PDB; 1FPU; X-ray; 2.40 A; A/B=229-515. DR PDB; 1IEP; X-ray; 2.10 A; A/B=229-515. DR PDB; 1M52; X-ray; 2.60 A; A/B=229-515. DR PDB; 1OPJ; X-ray; 1.75 A; A/B=229-515. DR PDB; 1OPK; X-ray; 1.80 A; A=27-515. DR PDB; 2HZN; X-ray; 2.70 A; A=229-515. DR PDB; 2QOH; X-ray; 1.95 A; A/B=229-515. DR PDB; 2Z60; X-ray; 1.95 A; A=229-515. DR PDB; 3DK3; X-ray; 2.02 A; A/B=233-514. DR PDB; 3DK6; X-ray; 2.02 A; A/B=233-514. DR PDB; 3DK7; X-ray; 2.01 A; A/B=233-505. DR PDB; 3IK3; X-ray; 1.90 A; A/B=229-515. DR PDB; 3K5V; X-ray; 1.74 A; A/B=229-515. DR PDB; 3KF4; X-ray; 1.90 A; A/B=229-515. DR PDB; 3KFA; X-ray; 1.22 A; A/B=229-515. DR PDB; 3MS9; X-ray; 1.80 A; A/B=229-515. DR PDB; 3MSS; X-ray; 1.95 A; A/B/C/D=229-515. DR PDB; 3OXZ; X-ray; 2.20 A; A=229-511. DR PDB; 3OY3; X-ray; 1.95 A; A/B=229-511. DR PDBsum; 1ABO; -. DR PDBsum; 1ABQ; -. DR PDBsum; 1FPU; -. DR PDBsum; 1IEP; -. DR PDBsum; 1M52; -. DR PDBsum; 1OPJ; -. DR PDBsum; 1OPK; -. DR PDBsum; 2HZN; -. DR PDBsum; 2QOH; -. DR PDBsum; 2Z60; -. DR PDBsum; 3DK3; -. DR PDBsum; 3DK6; -. DR PDBsum; 3DK7; -. DR PDBsum; 3IK3; -. DR PDBsum; 3K5V; -. DR PDBsum; 3KF4; -. DR PDBsum; 3KFA; -. DR PDBsum; 3MS9; -. DR PDBsum; 3MSS; -. DR PDBsum; 3OXZ; -. DR PDBsum; 3OY3; -. DR ProteinModelPortal; P00520; -. DR SMR; P00520; 46-511, 1017-1123. DR IntAct; P00520; 20. DR MINT; MINT-85127; -. DR BindingDB; P00520; -. DR ChEMBL; CHEMBL3099; -. DR PhosphoSite; P00520; -. DR PaxDb; P00520; -. DR PRIDE; P00520; -. DR Ensembl; ENSMUST00000028190; ENSMUSP00000028190; ENSMUSG00000026842. DR Ensembl; ENSMUST00000075759; ENSMUSP00000075167; ENSMUSG00000026842. DR GeneID; 11350; -. DR KEGG; mmu:11350; -. DR UCSC; uc008jdz.2; mouse. DR CTD; 25; -. DR MGI; MGI:87859; Abl1. DR eggNOG; COG0515; -. DR GeneTree; ENSGT00640000091347; -. DR HOVERGEN; HBG004162; -. DR KO; K06619; -. DR OMA; GAFRESG; -. DR OrthoDB; EOG7GTT2V; -. DR BRENDA; 2.7.10.2; 3474. DR Reactome; REACT_127416; Developmental Biology. DR Reactome; REACT_89750; Hemostasis. DR EvolutionaryTrace; P00520; -. DR NextBio; 278620; -. DR PRO; PR:P00520; -. DR ArrayExpress; P00520; -. DR Bgee; P00520; -. DR CleanEx; MM_ABL1; -. DR Genevestigator; P00520; -. DR GO; GO:0031252; C:cell leading edge; IDA:MGI. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; ISA:MGI. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0070064; F:proline-rich region binding; ISS:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:MGI. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IDA:MGI. DR GO; GO:0042770; P:signal transduction in response to DNA damage; ISS:UniProtKB. DR Gene3D; 3.30.505.10; -; 1. DR InterPro; IPR015015; F-actin_binding. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR Pfam; PF08919; F_actin_bind; 1. DR Pfam; PF07714; Pkinase_Tyr; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00808; FABD; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00326; SH3; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF50044; SSF50044; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS50002; SH3; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; KW ATP-binding; Autophagy; Cell adhesion; Chromosomal rearrangement; KW Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; KW DNA-binding; Endocytosis; Kinase; Lipoprotein; Magnesium; Manganese; KW Metal-binding; Mitochondrion; Myristate; Nucleotide-binding; Nucleus; KW Phosphoprotein; Proto-oncogene; Reference proteome; SH2 domain; KW SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation. FT CHAIN 1 1123 Tyrosine-protein kinase ABL1. FT /FTId=PRO_0000088051. FT DOMAIN 61 121 SH3. FT DOMAIN 127 217 SH2. FT DOMAIN 242 493 Protein kinase. FT NP_BIND 248 256 ATP (Probable). FT NP_BIND 316 322 ATP (Probable). FT REGION 1 60 CAP. FT REGION 863 961 DNA-binding. FT REGION 945 1123 F-actin-binding (By similarity). FT MOTIF 381 405 Kinase activation loop. FT MOTIF 605 609 Nuclear localization signal 1 FT (Potential). FT MOTIF 708 714 Nuclear localization signal 2 FT (Potential). FT MOTIF 761 768 Nuclear localization signal 3 FT (Potential). FT MOTIF 1083 1093 Nuclear export signal. FT COMPBIAS 18 22 Poly-Ser. FT COMPBIAS 605 609 Poly-Lys. FT COMPBIAS 804 1012 Pro-rich. FT COMPBIAS 891 897 Poly-Pro. FT ACT_SITE 363 363 Proton acceptor (By similarity). FT BINDING 271 271 ATP (By similarity). FT MOD_RES 50 50 Phosphoserine (By similarity). FT MOD_RES 70 70 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 185 185 Phosphotyrosine (By similarity). FT MOD_RES 226 226 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 253 253 Phosphotyrosine (By similarity). FT MOD_RES 257 257 Phosphotyrosine (By similarity). FT MOD_RES 264 264 Phosphotyrosine (By similarity). FT MOD_RES 392 392 Phosphothreonine (By similarity). FT MOD_RES 393 393 Phosphotyrosine; by autocatalysis and FT SRC-type Tyr-kinases. FT MOD_RES 394 394 Phosphothreonine (By similarity). FT MOD_RES 446 446 Phosphoserine. FT MOD_RES 469 469 Phosphotyrosine (By similarity). FT MOD_RES 547 547 Phosphothreonine. FT MOD_RES 569 569 Phosphoserine. FT MOD_RES 613 613 Phosphothreonine (By similarity). FT MOD_RES 618 618 Phosphoserine; by PAK2 (By similarity). FT MOD_RES 619 619 Phosphoserine; by PAK2 (By similarity). FT MOD_RES 620 620 Phosphoserine (By similarity). FT MOD_RES 658 658 Phosphoserine (By similarity). FT MOD_RES 682 682 Phosphoserine (By similarity). FT MOD_RES 710 710 N6-acetyllysine; by EP300 (By FT similarity). FT MOD_RES 717 717 Phosphoserine (By similarity). FT MOD_RES 734 734 Phosphothreonine (By similarity). FT MOD_RES 803 803 Phosphoserine (By similarity). FT MOD_RES 807 807 Phosphoserine (By similarity). FT MOD_RES 812 812 Phosphothreonine (By similarity). FT MOD_RES 844 844 Phosphothreonine (By similarity). FT MOD_RES 909 909 Phosphoserine (By similarity). FT MOD_RES 911 911 Phosphoserine (By similarity). FT MOD_RES 927 927 Phosphoserine (By similarity). FT MOD_RES 970 970 Phosphoserine (By similarity). FT VAR_SEQ 1 26 MLEICLKLVGCKSKKGLSSSSSCYLE -> MISFDLLSDEL FT HLKLLVLDV (in isoform II). FT /FTId=VSP_004959. FT VAR_SEQ 1 26 MLEICLKLVGCKSKKGLSSSSSCYLE -> MSQRWTYTKCR FT VQRDPALPFM (in isoform III). FT /FTId=VSP_004958. FT VAR_SEQ 1 26 MLEICLKLVGCKSKKGLSSSSSCYLE -> MGQQPGKVLGD FT QRRPSLPALHFIKGAGKRDSSRHGGPHCNVFVEH (in FT isoform IV). FT /FTId=VSP_004960. FT MUTAGEN 112 112 P->S: Strongly reduced inhibition by GNF- FT 2. FT MUTAGEN 128 128 Y->D: Strongly reduced inhibition by GNF- FT 2. FT MUTAGEN 139 139 Y->C: Strongly reduced inhibition by GNF- FT 2. FT MUTAGEN 226 226 Y->F: Minimal reduction in ability to FT autophosphorylate. FT MUTAGEN 229 229 S->P: Strongly reduced inhibition by GNF- FT 2. FT MUTAGEN 271 271 K->M: Loss of kinase activity. FT MUTAGEN 315 315 T->I: Loss of inhibition by imatinib. FT Loss of inhibition by GNF-2. FT MUTAGEN 393 393 Y->F: Minimal reduction in ability to FT autophosphorylate. FT MUTAGEN 446 446 S->A: No effect on basal activity, but FT abolishes ionizing radiation-induced FT activation. FT MUTAGEN 464 464 C->Y: Loss of inhibition by GNF-2. FT MUTAGEN 465 465 P->S: Loss of inhibition by GNF-2. FT MUTAGEN 497 497 F->L: Strongly reduced inhibition by GNF- FT 2. FT MUTAGEN 505 505 E->K: Loss of inhibition by GNF-2. FT MUTAGEN 506 506 V->L: Strongly reduced inhibition by GNF- FT 2. FT MUTAGEN 1083 1083 L->A: Loss of nuclear export. FT CONFLICT 184 187 LYVS -> VGDW (in Ref. 4; AAB60451/ FT AAB60450). FT CONFLICT 782 786 PPRLV -> LPGWL (in Ref. 1; AAA88241). FT CONFLICT 987 987 D -> G (in Ref. 2; BAC41088). FT STRAND 65 70 FT STRAND 76 79 FT STRAND 87 93 FT STRAND 97 103 FT STRAND 108 112 FT HELIX 113 115 FT STRAND 116 121 FT HELIX 122 124 FT STRAND 128 131 FT HELIX 134 140 FT HELIX 141 143 FT STRAND 148 153 FT STRAND 155 157 FT STRAND 161 167 FT STRAND 170 175 FT STRAND 184 187 FT STRAND 192 194 FT HELIX 195 202 FT STRAND 209 211 FT STRAND 226 228 FT STRAND 230 233 FT HELIX 239 241 FT STRAND 242 248 FT HELIX 249 251 FT STRAND 255 261 FT HELIX 262 264 FT STRAND 266 273 FT STRAND 275 278 FT HELIX 280 292 FT STRAND 301 305 FT STRAND 307 316 FT HELIX 323 329 FT TURN 332 334 FT HELIX 337 357 FT STRAND 359 362 FT HELIX 366 368 FT STRAND 369 371 FT HELIX 373 375 FT STRAND 377 379 FT HELIX 384 386 FT STRAND 390 396 FT STRAND 399 401 FT HELIX 403 405 FT HELIX 408 413 FT HELIX 418 433 FT STRAND 439 442 FT HELIX 445 447 FT HELIX 448 453 FT HELIX 466 475 FT HELIX 480 482 FT HELIX 486 509 SQ SEQUENCE 1123 AA; 122673 MW; BD48ADE8557AE95C CRC64; MLEICLKLVG CKSKKGLSSS SSCYLEEALQ RPVASDFEPQ GLSEAARWNS KENLLAGPSE NDPNLFVALY DFVASGDNTL SITKGEKLRV LGYNHNGEWC EAQTKNGQGW VPSNYITPVN SLEKHSWYHG PVSRNAAEYL LSSGINGSFL VRESESSPGQ RSISLRYEGR VYHYRINTAS DGKLYVSSES RFNTLAELVH HHSTVADGLI TTLHYPAPKR NKPTIYGVSP NYDKWEMERT DITMKHKLGG GQYGEVYEGV WKKYSLTVAV KTLKEDTMEV EEFLKEAAVM KEIKHPNLVQ LLGVCTREPP FYIITEFMTY GNLLDYLREC NRQEVSAVVL LYMATQISSA MEYLEKKNFI HRDLAARNCL VGENHLVKVA DFGLSRLMTG DTYTAHAGAK FPIKWTAPES LAYNKFSIKS DVWAFGVLLW EIATYGMSPY PGIDLSQVYE LLEKDYRMER PEGCPEKVYE LMRACWQWNP SDRPSFAEIH QAFETMFQES SISDEVEKEL GKRGTRGGAG SMLQAPELPT KTRTCRRAAE QKDAPDTPEL LHTKGLGESD ALDSEPAVSP LLPRKERGPP DGSLNEDERL LPRDRKTNLF SALIKKKKKM APTPPKRSSS FREMDGQPDR RGASEDDSRE LCNGPPALTS DAAEPTKSPK ASNGAGVPNG AFREPGNSGF RSPHMWKKSS TLTGSRLAAA EEESGMSSSK RFLRSCSASC MPHGARDTEW RSVTLPRDLP SAGKQFDSST FGGHKSEKPA LPRKRTSESR SEQVAKSTAM PPPRLVKKNE EAAEEGFKDT ESSPGSSPPS LTPKLLRRQV TASPSSGLSH KEEATKGSAS GMGTPATAEP APPSNKVGLS KASSEEMRVR RHKHSSESPG RDKGRLAKLK PAPPPPPACT GKAGKPAQSP SQEAGEAGGP TKTKCTSLAM DAVNTDPTKA GPPGEGLRKP VPPSVPKPQS TAKPPGTPTS PVSTPSTAPA PSPLAGDQQP SSAAFIPLIS TRVSLRKTRQ PPERIASGTI TKGVVLDSTE ALCLAISRNS EQMASHSAVL EAGKNLYTFC VSYVDSIQQM RNKFAFREAI NKLESNLREL QICPATASSG PAATQDFSKL LSSVKEISDI VRR //