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Description:
Proto-oncogene tyrosine-protein kinase ABL1 (EC 2.7.1.112) (p150) (c-ABL) (Abelson murine leukemia viral oncogene homolog 1).
Molecular weight: 1228
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
mismatch repair( GO:0006298 )
Important dates:
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
24-JAN-2006, sequence version 4.
07-MAR-2006, entry version 88.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein ABL1_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | X16416 | CAA34438.1 | - |
| EMBL | M14752 | AAA51561.1 | - |
| EMBL | U07563 | AAB60394.1 | - |
| EMBL | U07563 | AAB60393.1 | - |
| EMBL | U07561 | AAB60393.1 | JOINED |
| EMBL | DQ145721 | AAZ38718.1 | - |
| EMBL | S69223 | AAD14034.1 | - |
| PIR | S08519 | TVHUA. | |
| PDB | 1AB2 | NMR | @=120-220. |
| PDB | 1ABL | Model | @=65-121. |
| PDB | 1AWO | NMR | @=64-120. |
| PDB | 1BBZ | X-ray | A/C/G=64-121, E=65-121. |
| PDB | 1JU5 | NMR | C=62-121. |
| PDB | 1OPL | X-ray | A/B=4-512. |
| PDB | 1ZZP | NMR | A=1007-1130. |
| PDB | 2ABL | X-ray | @=57-218. |
| PDB | 2F4J | X-ray | A=227-513. |
| IntAct | P00519 | -.1 | |
| Ensembl | ENSG00000097007 | Homo sapiens.1 | |
| HGNC | HGNC:76 | ABL1.1 | |
| MIM | 189980 | gene. | |
| MIM | 608232 | phenotype. | |
| LinkHub | P00519 | -.1 | |
| GO | GO:0005634 | C:nucleus | NAS. |
| GO | GO:0003677 | F:DNA binding | NAS. |
| GO | GO:0005515 | F:protein binding | IPI. |
| GO | GO:0004713 | F:protein-tyrosine kinase activity | TAS. |
| GO | GO:0008630 | P:DNA damage response, signal transduction re... | TAS. |
| GO | GO:0006298 | P:mismatch repair | TAS. |
| GO | GO:0006464 | P:protein modification | NAS. |
| GO | GO:0000074 | P:regulation of progression through cell cycle | TAS. |
| GO | GO:0006355 | P:regulation of transcription, DNA-dependent | TAS. |
| GO | GO:0000115 | P:S-phase-specific transcription in mitotic c... | TAS. |
| PROSITE | PS00107 | PROTEIN_KINASE_ATP | 1. |
| PROSITE | PS50011 | PROTEIN_KINASE_DOM | 1. |
| PROSITE | PS00109 | PROTEIN_KINASE_TYR | 1. |
| PROSITE | PS50001 | SH2 | 1. |
| PROSITE | PS50002 | SH3 | 1. |
Keywords:
3D-structure; Alternative splicing; ATP-binding; Chromosomal translocation; Kinase; Nucleotide-binding; Phosphorylation; Polymorphism; Proto-oncogene; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IA).
RC TISSUE=Fibroblast;
RX MEDLINE=90082420; PubMed=2687768;
RA Fainstein E., Einat M., Gokkel E., Marcelle C., Croce C.M., Gale R.P.,
RA Canaani E.;
RT "Nucleotide sequence analysis of human abl and bcr-abl cDNAs.";
RL Oncogene 4:1477-1481(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IA), AND ALTERNATIVE SPLICING.
RX MEDLINE=87028219; PubMed=3021337; DOI=10.1016/0092-8674(86)90450-2;
RA Shtivelman E., Lifshitz B., Gale R.P., Roe B.A., Canaani E.;
RT "Alternative splicing of RNAs transcribed from the human abl gene and
RT from the bcr-abl fused gene.";
RL Cell 47:277-284(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS IA AND IB).
RC TISSUE=Lung carcinoma;
RX MEDLINE=95394474; PubMed=7665185;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-706; PRO-852;
RP SER-900 AND LEU-972.
RA Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N.,
RA Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B.,
RA Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J.,
RA Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE OF 27-40.
RX MEDLINE=88065859; PubMed=2825022; DOI=10.1038/330386a0;
RA Fainstein E., Marcelle C., Rosner A., Canaani E., Gale R.P.,
RA Dreazen O., Smith S.D., Croce C.M.;
RT "A new fused transcript in Philadelphia chromosome positive acute
RT lymphocytic leukaemia.";
RL Nature 330:386-388(1987).
RN [6]
RP NUCLEOTIDE SEQUENCE OF 360-426.
RX MEDLINE=83245023; PubMed=6191223;
RA Groffen J., Heisterkamp N., Reynolds F.H. Jr., Stephenson J.R.;
RT "Homology between phosphotyrosine acceptor site of human c-abl and
RT viral oncogene products.";
RL Nature 304:167-169(1983).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 825-845.
RX MEDLINE=94142331; PubMed=7545908;
RA Inokuchi K., Futaki M., Dan K., Nomura T.;
RT "Sequence analysis of the mutation at codon 834 and the sequence
RT variation of codon 837 of c-abl gene.";
RL Leukemia 8:343-344(1994).
RN [8]
RP INTERACTION WITH SORBS1.
RX MEDLINE=21269187; PubMed=11374898; DOI=10.1006/geno.2001.6541;
RA Lin W.-H., Huang C.-J., Liu M.-W., Chang H.-M., Chen Y.-J., Tai T.-Y.,
RA Chuang L.-M.;
RT "Cloning, mapping, and characterization of the human sorbin and SH3
RT domain containing 1 (SORBS1) gene: a protein associated with c-Abl
RT during insulin signaling in the hepatoma cell line Hep3B.";
RL Genomics 74:12-20(2001).
RN [9]
RP PHOSPHORYLATION SITE SER-446, AND MUTAGENESIS OF SER-446.
RX MEDLINE=97311399; PubMed=9168116; DOI=10.1038/387516a0;
RA Baskaran R., Wood L.D., Whitaker L.L., Canman C.E., Morgan S.E.,
RA Xu Y., Barlow C., Baltimore D., Wynshaw-Boris A., Kastan M.B.,
RA Wang J.Y.;
RT "Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase
RT in response to ionizing radiation.";
RL Nature 387:516-519(1997).
RN [10]
RP PHOSPHORYLATION SITES TYR-185; TYR-226; TYR-253; TYR-257; TYR-264;
RP TYR-393; THR-394 AND TYR-469.
RX MEDLINE=22426906; PubMed=12522270; DOI=10.1073/pnas.2436191100;
RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T.,
RA Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.;
RT "Profiling of tyrosine phosphorylation pathways in human cells using
RT mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003).
RN [11]
RP STRUCTURE BY NMR OF SH2 DOMAIN.
RX MEDLINE=92370689; PubMed=1505033; DOI=10.1016/0092-8674(92)90437-H;
RA Overduin M., Rios C.B., Mayer B.J., Baltimore D., Cowburn D.;
RT "Three-dimensional solution structure of the src homology 2 domain of
RT c-abl.";
RL Cell 70:697-704(1992).
RN [12]
RP STRUCTURE BY NMR OF SH2 DOMAIN.
RX MEDLINE=93101588; PubMed=1281542;
RA Overduin M., Mayer B.J., Rios C.B., Baltimore D., Cowburn D.;
RT "Secondary structure of Src homology 2 domain of c-Abl by
RT heteronuclear NMR spectroscopy in solution.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:11673-11677(1992).
RN [13]
RP STRUCTURE BY NMR OF SH3 DOMAIN.
RX MEDLINE=96131878; PubMed=8590002; DOI=10.1016/S0969-2126(01)00243-X;
RA Gosser Y.Q., Zheng J., Overduin M., Mayer B.J., Cowburn D.;
RT "The solution structure of Abl SH3, and its relationship to SH2 in the
RT SH(32) construct.";
RL Structure 3:1075-1086(1995).
RN [14]
RP 3D-STRUCTURE MODELING OF SH3 DOMAIN.
RX MEDLINE=95199229; PubMed=7892170; DOI=10.1002/prot.340200302;
RA Pisabarro M.T., Ortiz A.R., Serrano L., Wade R.C.;
RT "Homology modeling of the Abl-SH3 domain.";
RL Proteins 20:203-215(1994).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 57-218.
RX MEDLINE=96398698; PubMed=8805596; DOI=10.1016/S0969-2126(96)00116-5;
RA Nam H.-J., Haser W.G., Roberts T.M., Frederick C.A.;
RT "Intramolecular interactions of the regulatory domains of the Bcr-Abl
RT kinase reveal a novel control mechanism.";
RL Structure 4:1105-1114(1996).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 64-121.
RX MEDLINE=98365516; PubMed=9698566; DOI=10.1006/jmbi.1998.1932;
RA Pisabarro M.T., Serrano L., Wilmanns M.;
RT "Crystal structure of the abl-SH3 domain complexed with a designed
RT high-affinity peptide ligand: implications for SH3-ligand
RT interactions.";
RL J. Mol. Biol. 281:513-521(1998).
RN [17]
RP STRUCTURE BY NMR OF 62-122 IN COMPLEX WITH CRK.
RX MEDLINE=22294994; PubMed=12384576; DOI=10.1073/pnas.212518799;
RA Donaldson L.W., Gish G., Pawson T., Kay L.E., Forman-Kay J.D.;
RT "Structure of a regulatory complex involving the Abl SH3 domain, the
RT Crk SH2 domain, and a Crk-derived phosphopeptide.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14053-14058(2002).
Feature:
CHAIN 1 1130 Proto-oncogene tyrosine-protein kinase
ABL1.
/FTId=PRO_0000088050.
DOMAIN 61 121 SH3.
DOMAIN 127 217 SH2.
DOMAIN 242 493 Protein kinase.
NP_BIND 248 256 ATP (By similarity).
MOTIF 605 609 Nuclear localization signal (Potential).
COMPBIAS 18 22 Poly-Ser.
COMPBIAS 605 609 Poly-Lys.
COMPBIAS 782 1019 Pro-rich.
COMPBIAS 897 903 Poly-Pro.
ACT_SITE 363 363 Proton acceptor (By similarity).
BINDING 271 271 ATP (By similarity).
SITE 26 27 Breakpoint for translocation to form BCR-
ABL oncogene.
MOD_RES 185 185 Phosphotyrosine.
MOD_RES 226 226 Phosphotyrosine.
MOD_RES 253 253 Phosphotyrosine.
MOD_RES 257 257 Phosphotyrosine.
MOD_RES 264 264 Phosphotyrosine.
MOD_RES 393 393 Phosphotyrosine (by autocatalysis).
MOD_RES 394 394 Phosphothreonine.
MOD_RES 446 446 Phosphoserine.
MOD_RES 469 469 Phosphotyrosine.
VARSPLIC 1 26 MLEICLKLVGCKSKKGLSSSSSCYLE -> MGQQPGKVLGD
QRRPSLPALHFIKGAGKKESSRHGGPHCNVFVEH (in
isoform IB).
/FTId=VSP_004957.
VARIANT 706 706 G -> V.
/FTId=VAR_025043.
VARIANT 852 852 T -> P.
/FTId=VAR_025044.
VARIANT 900 900 P -> S.
/FTId=VAR_025045.
VARIANT 972 972 S -> L.
/FTId=VAR_025046.
MUTAGEN 446 446 S->A: No effect on basal activity, but
abolishes IR-induced activation.
CONFLICT 140 140 L -> P (in Ref. 2).
CONFLICT 159 159 G -> S (in Ref. 2).
CONFLICT 424 425 AF -> GK (in Ref. 6).
CONFLICT 445 445 L -> R (in Ref. 2).
CONFLICT 459 459 E -> K (in Ref. 2).
CONFLICT 520 520 S -> T (in Ref. 2).
CONFLICT 719 719 A -> V (in Ref. 2).
CONFLICT 837 837 G -> E (in Ref. 1).
CONFLICT 837 837 G -> W (in Ref. 2).
CONFLICT 863 863 G -> R (in Ref. 2).
CONFLICT 894 894 R -> K (in Ref. 2).
CONFLICT 917 919 SPS -> RPG (in Ref. 2).
CONFLICT 952 952 G -> A (in Ref. 2).
CONFLICT 967 968 QS -> HP (in Ref. 2).
CONFLICT 982 982 P -> PL (in Ref. 2).
CONFLICT 1022 1022 Missing (in Ref. 2).
CONFLICT 1045 1045 R -> G (in Ref. 2).
CONFLICT 1103 1103 T -> S (in Ref. 2).
STRAND 58 58
TURN 60 61
TURN 63 64
STRAND 65 70
STRAND 72 72
STRAND 76 76
TURN 77 78
STRAND 79 79
STRAND 82 82
TURN 84 85
STRAND 87 93
TURN 95 96
STRAND 97 104
TURN 105 106
STRAND 107 112
HELIX 113 115
STRAND 116 118
TURN 119 120
HELIX 122 124
STRAND 125 125
TURN 126 127
STRAND 128 131
HELIX 134 140
TURN 141 141
STRAND 142 143
TURN 146 147
STRAND 149 153
STRAND 155 156
TURN 158 159
STRAND 161 167
TURN 168 169
STRAND 170 178
TURN 180 181
STRAND 182 182
STRAND 184 189
STRAND 191 194
HELIX 195 204
TURN 207 208
STRAND 209 211
STRAND 221 221
STRAND 226 228
STRAND 230 233
STRAND 236 236
HELIX 239 241
STRAND 242 248
HELIX 249 251
TURN 252 253
STRAND 254 261
HELIX 262 264
TURN 265 265
STRAND 266 272
STRAND 275 278
HELIX 280 292
TURN 296 297
STRAND 298 298
STRAND 301 305
STRAND 307 310
STRAND 312 316
TURN 319 320
STRAND 322 322
HELIX 323 329
STRAND 330 330
TURN 332 334
STRAND 335 335
HELIX 337 356
TURN 357 358
STRAND 359 360
STRAND 362 362
STRAND 365 365
HELIX 366 368
STRAND 369 371
HELIX 373 375
STRAND 377 379
TURN 382 383
STRAND 385 386
TURN 389 390
STRAND 393 394
TURN 397 398
HELIX 403 405
HELIX 408 413
STRAND 415 416
HELIX 418 433
TURN 434 435
STRAND 436 436
STRAND 439 440
TURN 441 442
TURN 445 447
HELIX 448 453
TURN 454 455
TURN 462 463
HELIX 466 475
TURN 476 476
STRAND 478 479
HELIX 480 482
STRAND 483 483
HELIX 486 494
TURN 495 495
STRAND 496 496
STRAND 498 500
HELIX 502 511
Comments:
-!- CATALYTIC ACTIVITY: ATP + a protein tyrosine = ADP + a protein
tyrosine phosphate.
-!- SUBUNIT: Interacts with SORBS1 following insulin stimulation.
Found in a trimolecular complex containing CDK5 and CABLES1.
Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16 (By
similarity).
-!- INTERACTION:
Q8IZP0:ABI1; NbExp=2; IntAct=EBI-375543, EBI-375446;
Q8CBW3:Abi1 (xeno); NbExp=1; IntAct=EBI-375543, EBI-375511;
P31947:SFN; NbExp=1; IntAct=EBI-375543, EBI-476295;
Q9BX66:SORBS1; NbExp=2; IntAct=EBI-375543, EBI-433642;
P63104:YWHAZ; NbExp=1; IntAct=EBI-375543, EBI-347088;
-!- SUBCELLULAR LOCATION: Cytoplasm.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=IA;
IsoId=P00519-1; Sequence=Displayed;
Name=IB;
IsoId=P00519-2; Sequence=VSP_004957;
-!- TISSUE SPECIFICITY: Widely expressed.
-!- PTM: Phosphorylated by PRKDC (By similarity). DNA damage-induced
activation of c-Abl requires the function of ATM and Ser-446
phosphorylation.
-!- DISEASE: A chromosomal aberration involving ABL1 is a cause of
chronic myeloid leukemia (CML) [MIM:608232]. Translocation
t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL
found also in acute myeloid leukemia (AML) and acute lymphoblastic
leukemia (ALL).
-!- SIMILARITY: Belongs to the Tyr protein kinase family. ABL
subfamily.
-!- SIMILARITY: Contains 1 SH2 domain.
-!- SIMILARITY: Contains 1 SH3 domain.
-!- DATABASE: NAME=Atlas Genet. Cytogenet. Oncol. Haematol.;
WWW="http://www.infobiogen.fr/services/chromcancer/Genes/ABL.html".
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Sequence length: 1130
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