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P00520 (ABL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 186. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase ABL1

EC=2.7.10.2
Alternative name(s):
Abelson murine leukemia viral oncogene homolog 1
Abelson tyrosine-protein kinase 1
Proto-oncogene c-Abl
p150
Gene names
Name:Abl1
Synonyms:Abl
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1123 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.11 Ref.12 Ref.13 Ref.18 Ref.19 Ref.20 Ref.22 Ref.24 Ref.25 Ref.27 Ref.33

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.30 Ref.33 Ref.35

Cofactor

Magnesium or manganese.

Enzyme regulation

Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation By similarity. Activated by RIN1 binding to the SH2 and SH3 domains. Also stimulated by cell death inducers and DNA-damage By similarity. Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits also the tyrosine kinase activity. Inhibited by imatinib mesylate (Gleevec). Ref.13 Ref.24 Ref.25 Ref.30 Ref.31 Ref.35

Subunit structure

Interacts with INPPL1/SHIP2. Interacts with SORBS1 following insulin stimulation. Found in a trimolecular complex containing CDK5 and CABLES1. Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16. 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-734 and sequesters ABL1 into the cytoplasm. 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 By similarity. Interacts with ABI1, ABI2, BCR, CRK, FYN, 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 with STX17; probably phosphorylates STX17 By similarity. Interacts with ITGB1, HCK and FGR. Ref.15 Ref.16 Ref.18 Ref.21 Ref.24 Ref.27

Subcellular location

Cytoplasmcytoskeleton. Nucleus. Mitochondrion. Note: The myristoylated c-ABL protein is reported to be nuclear. Sequestered into the cytoplasm through interaction with 14-3-3 proteins By similarity. Localizes to mitochondria in response to oxidative stress. Ref.13 Ref.14 Ref.19

Tissue specificity

Widely expressed.

Post-translational modification

Acetylated at Lys-710 by EP300 which promotes the cytoplasmic translocation By similarity.

Phosphorylation at Tyr-70 by members of the SRC family of kinases disrupts SH3 domain-based autoinhibitory interactions and intermolecular associations, such as that with ABI1, and also enhances kinase activity By similarity. Phosphorylation at Tyr-226 and Tyr-393 correlate with increased activity By similarity. DNA damage-induced activation of ABL1 requires the function of ATM and Ser-446 phosphorylation. Phosphorylation at Thr-547 and Ser-569 has been attributed to a CDC2-associated kinase and is coupled to cell division. Phosphorylation at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces binding to ABI1 By similarity. Phosphorylation on Thr-734 is required for binding 14-3-3 proteins for cytoplasmic translocation By similarity. Phosphorylated by PDGFRB and PRKDC. Ref.7 Ref.10 Ref.13 Ref.24 Ref.25 Ref.27 Ref.30 Ref.35

Polyubiquitinated. Polyubiquitination of ABL1 leads to degradation By similarity.

Isoform IV is myristoylated on Gly-2.

Disruption phenotype

Mutants are born with the expected Mendelian frequency, but fail to thrive and most die within three weeks after birth. Most mutants are runted, and have atrophied thymuses with severe thymocyte deficiency. Mutants that survive to weaning age are most often runted, and about half of them show lymphopenia. They display a major reduction in the number of pre-B and immature B-cell classes in bone marrow with a wide variation between individuals, but essentially normal mature B-cell levels. Mutants are highly susceptible to infections. Ref.8 Ref.9

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Biological processApoptosis
Autophagy
Cell adhesion
DNA damage
DNA repair
Endocytosis
   Cellular componentCytoplasm
Cytoskeleton
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
   DiseaseProto-oncogene
   DomainSH2 domain
SH3 domain
   LigandATP-binding
DNA-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMAcetylation
Lipoprotein
Myristate
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage induced protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

DNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

actin cytoskeleton organization

Inferred from direct assay Ref.18. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

autophagy

Inferred from electronic annotation. Source: UniProtKB-KW

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to DNA damage stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of protein serine/threonine kinase activity

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 11390389Ref.13. Source: UniProtKB

platelet-derived growth factor receptor signaling pathway

Inferred from direct assay PubMed 20417104. Source: MGI

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of oxidoreductase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell cycle

Inferred from direct assay PubMed 11809706. Source: MGI

regulation of response to DNA damage stimulus

Inferred from electronic annotation. Source: Ensembl

signal transduction in response to DNA damage

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell leading edge

Inferred from direct assay PubMed 20417104. Source: MGI

cytoplasm

Inferred from direct assay Ref.14. Source: UniProtKB

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from sequence alignment PubMed 17101133. Source: MGI

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleolus

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.14. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from direct assay Ref.13. Source: UniProtKB

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

kinase activity

Inferred from direct assay PubMed 12379650. Source: MGI

magnesium ion binding

Inferred from direct assay Ref.13. Source: UniProtKB

manganese ion binding

Inferred from direct assay Ref.13. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

proline-rich region binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction PubMed 8438166. Source: MGI

protein kinase activity

Inferred from direct assay PubMed 12672821. Source: MGI

protein tyrosine kinase activity

Inferred from direct assay PubMed 11390389PubMed 15657060Ref.13. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ABI1Q8IZP0-45EBI-8593082,EBI-8593095From a different organism.
CDKN1BP465272EBI-914519,EBI-519280From a different organism.
CdonQ32MD92EBI-914519,EBI-7017034
Dok1P974654EBI-914519,EBI-914917
EPHB2P28693-25EBI-914519,EBI-6725926From a different organism.
Nck1Q99M512EBI-914519,EBI-642202
Pstpip1P978145EBI-914519,EBI-7484574
Ptpn18P706022EBI-914519,EBI-7484661From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform I (identifier: P00520-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform II (identifier: P00520-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MLEICLKLVGCKSKKGLSSSSSCYLE → MISFDLLSDELHLKLLVLDV
Isoform III (identifier: P00520-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MLEICLKLVGCKSKKGLSSSSSCYLE → MSQRWTYTKCRVQRDPALPFM
Isoform IV (identifier: P00520-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MLEICLKLVGCKSKKGLSSSSSCYLE → MGQQPGKVLGDQRRPSLPALHFIKGAGKRDSSRHGGPHCNVFVEH

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11231123Tyrosine-protein kinase ABL1
PRO_0000088051

Regions

Domain61 – 12161SH3
Domain127 – 21791SH2
Domain242 – 493252Protein kinase
Nucleotide binding248 – 2569ATP Probable
Nucleotide binding316 – 3227ATP Probable
Region1 – 6060CAP
Region863 – 96199DNA-binding
Region945 – 1123179F-actin-binding By similarity
Motif381 – 40525Kinase activation loop
Motif605 – 6095Nuclear localization signal 1 Potential
Motif708 – 7147Nuclear localization signal 2 Potential
Motif761 – 7688Nuclear localization signal 3 Potential
Motif1083 – 109311Nuclear export signal
Compositional bias18 – 225Poly-Ser
Compositional bias605 – 6095Poly-Lys
Compositional bias804 – 1012209Pro-rich
Compositional bias891 – 8977Poly-Pro

Sites

Active site3631Proton acceptor By similarity
Binding site2711ATP By similarity

Amino acid modifications

Modified residue501Phosphoserine By similarity
Modified residue701Phosphotyrosine; by autocatalysis By similarity
Modified residue1851Phosphotyrosine By similarity
Modified residue2261Phosphotyrosine; by autocatalysis By similarity
Modified residue2531Phosphotyrosine By similarity
Modified residue2571Phosphotyrosine By similarity
Modified residue2641Phosphotyrosine By similarity
Modified residue3921Phosphothreonine By similarity
Modified residue3931Phosphotyrosine; by autocatalysis and SRC-type Tyr-kinases Ref.24 Ref.30
Modified residue3941Phosphothreonine By similarity
Modified residue4461Phosphoserine Ref.13
Modified residue4691Phosphotyrosine By similarity
Modified residue5471Phosphothreonine Ref.7
Modified residue5691Phosphoserine Ref.7
Modified residue6131Phosphothreonine By similarity
Modified residue6181Phosphoserine; by PAK2 By similarity
Modified residue6191Phosphoserine; by PAK2 By similarity
Modified residue6201Phosphoserine By similarity
Modified residue6581Phosphoserine By similarity
Modified residue6821Phosphoserine By similarity
Modified residue7101N6-acetyllysine; by EP300 By similarity
Modified residue7171Phosphoserine By similarity
Modified residue7341Phosphothreonine By similarity
Modified residue8031Phosphoserine By similarity
Modified residue8071Phosphoserine By similarity
Modified residue8121Phosphothreonine By similarity
Modified residue8441Phosphothreonine By similarity
Modified residue9091Phosphoserine By similarity
Modified residue9111Phosphoserine By similarity
Modified residue9271Phosphoserine By similarity
Modified residue9701Phosphoserine By similarity

Natural variations

Alternative sequence1 – 2626MLEIC…SCYLE → MISFDLLSDELHLKLLVLDV in isoform II.
VSP_004959
Alternative sequence1 – 2626MLEIC…SCYLE → MSQRWTYTKCRVQRDPALPF M in isoform III.
VSP_004958
Alternative sequence1 – 2626MLEIC…SCYLE → MGQQPGKVLGDQRRPSLPAL HFIKGAGKRDSSRHGGPHCN VFVEH in isoform IV.
VSP_004960

Experimental info

Mutagenesis1121P → S: Strongly reduced inhibition by GNF-2. Ref.35
Mutagenesis1281Y → D: Strongly reduced inhibition by GNF-2. Ref.35
Mutagenesis1391Y → C: Strongly reduced inhibition by GNF-2. Ref.35
Mutagenesis2261Y → F: Minimal reduction in ability to autophosphorylate. Ref.24
Mutagenesis2291S → P: Strongly reduced inhibition by GNF-2. Ref.35
Mutagenesis2711K → M: Loss of kinase activity. Ref.24
Mutagenesis3151T → I: Loss of inhibition by imatinib. Loss of inhibition by GNF-2. Ref.35
Mutagenesis3931Y → F: Minimal reduction in ability to autophosphorylate. Ref.24
Mutagenesis4461S → A: No effect on basal activity, but abolishes ionizing radiation-induced activation. Ref.13
Mutagenesis4641C → Y: Loss of inhibition by GNF-2. Ref.35
Mutagenesis4651P → S: Loss of inhibition by GNF-2. Ref.35
Mutagenesis4971F → L: Strongly reduced inhibition by GNF-2. Ref.35
Mutagenesis5051E → K: Loss of inhibition by GNF-2. Ref.35
Mutagenesis5061V → L: Strongly reduced inhibition by GNF-2. Ref.35
Mutagenesis10831L → A: Loss of nuclear export.
Sequence conflict184 – 1874LYVS → VGDW in AAB60451. Ref.4
Sequence conflict184 – 1874LYVS → VGDW in AAB60450. Ref.4
Sequence conflict782 – 7865PPRLV → LPGWL in AAA88241. Ref.1
Sequence conflict9871D → G in BAC41088. Ref.2

Secondary structure

............................................................................................. 1123
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform I [UniParc].

Last modified February 15, 2005. Version 3.
Checksum: BD48ADE8557AE95C

FASTA1,123122,673
        10         20         30         40         50         60 
MLEICLKLVG CKSKKGLSSS SSCYLEEALQ RPVASDFEPQ GLSEAARWNS KENLLAGPSE 

        70         80         90        100        110        120 
NDPNLFVALY DFVASGDNTL SITKGEKLRV LGYNHNGEWC EAQTKNGQGW VPSNYITPVN 

       130        140        150        160        170        180 
SLEKHSWYHG PVSRNAAEYL LSSGINGSFL VRESESSPGQ RSISLRYEGR VYHYRINTAS 

       190        200        210        220        230        240 
DGKLYVSSES RFNTLAELVH HHSTVADGLI TTLHYPAPKR NKPTIYGVSP NYDKWEMERT 

       250        260        270        280        290        300 
DITMKHKLGG GQYGEVYEGV WKKYSLTVAV KTLKEDTMEV EEFLKEAAVM KEIKHPNLVQ 

       310        320        330        340        350        360 
LLGVCTREPP FYIITEFMTY GNLLDYLREC NRQEVSAVVL LYMATQISSA MEYLEKKNFI 

       370        380        390        400        410        420 
HRDLAARNCL VGENHLVKVA DFGLSRLMTG DTYTAHAGAK FPIKWTAPES LAYNKFSIKS 

       430        440        450        460        470        480 
DVWAFGVLLW EIATYGMSPY PGIDLSQVYE LLEKDYRMER PEGCPEKVYE LMRACWQWNP 

       490        500        510        520        530        540 
SDRPSFAEIH QAFETMFQES SISDEVEKEL GKRGTRGGAG SMLQAPELPT KTRTCRRAAE 

       550        560        570        580        590        600 
QKDAPDTPEL LHTKGLGESD ALDSEPAVSP LLPRKERGPP DGSLNEDERL LPRDRKTNLF 

       610        620        630        640        650        660 
SALIKKKKKM APTPPKRSSS FREMDGQPDR RGASEDDSRE LCNGPPALTS DAAEPTKSPK 

       670        680        690        700        710        720 
ASNGAGVPNG AFREPGNSGF RSPHMWKKSS TLTGSRLAAA EEESGMSSSK RFLRSCSASC 

       730        740        750        760        770        780 
MPHGARDTEW RSVTLPRDLP SAGKQFDSST FGGHKSEKPA LPRKRTSESR SEQVAKSTAM 

       790        800        810        820        830        840 
PPPRLVKKNE EAAEEGFKDT ESSPGSSPPS LTPKLLRRQV TASPSSGLSH KEEATKGSAS 

       850        860        870        880        890        900 
GMGTPATAEP APPSNKVGLS KASSEEMRVR RHKHSSESPG RDKGRLAKLK PAPPPPPACT 

       910        920        930        940        950        960 
GKAGKPAQSP SQEAGEAGGP TKTKCTSLAM DAVNTDPTKA GPPGEGLRKP VPPSVPKPQS 

       970        980        990       1000       1010       1020 
TAKPPGTPTS PVSTPSTAPA PSPLAGDQQP SSAAFIPLIS TRVSLRKTRQ PPERIASGTI 

      1030       1040       1050       1060       1070       1080 
TKGVVLDSTE ALCLAISRNS EQMASHSAVL EAGKNLYTFC VSYVDSIQQM RNKFAFREAI 

      1090       1100       1110       1120 
NKLESNLREL QICPATASSG PAATQDFSKL LSSVKEISDI VRR 

« Hide

Isoform II [UniParc].

Checksum: 002F9D346307028A
Show »

FASTA1,117122,179
Isoform III [UniParc].

Checksum: AB3B4510AE8C5C38
Show »

FASTA1,118122,480
Isoform IV [UniParc].

Checksum: 7A9DB9E772EAF05F
Show »

FASTA1,142124,769

References

« Hide 'large scale' references
[1]"Nucleotide sequence of testis-derived c-abl cDNAs: implications for testis-specific transcription and abl oncogene activation."
Oppi C., Shore S.K., Reddy E.P.
Proc. Natl. Acad. Sci. U.S.A. 84:8200-8204(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM I).
Tissue: Testis.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I).
Strain: ICR.
Tissue: Embryo.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IV).
Strain: C57BL/6.
Tissue: Brain.
[4]"Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation."
Chissoe S.L., Bodenteich A., Wang Y.-F., Wang Y.-P., Burian D., Clifton S.W., Crabtree J., Freeman A., Iyer K., Jian L., Ma Y., McLaury H.-J., Pan H.-Q., Sarhan O.H., Toth S., Wang Z., Zhang G., Heisterkamp N., Groffen J., Roe B.A.
Genomics 27:67-82(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-187 (ISOFORMS I; II; III AND IV).
[5]"The mouse c-abl locus: molecular cloning and characterization."
Wang J.Y.J., Ledley F., Goff S., Lee R., Groner Y., Baltimore D.
Cell 36:349-356(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 85-182.
[6]"Four murine c-abl mRNAs arise by usage of two transcriptional promoters and alternative splicing."
Bernards A., Paskind M., Baltimore D.
Oncogene 2:297-304(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[7]"Differential phosphorylation of c-Abl in cell cycle determined by cdc2 kinase and phosphatase activity."
Kipreos E.T., Wang J.Y.
Science 248:217-220(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-547 AND SER-569.
[8]"Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene."
Tybulewicz V.L., Crawford C.E., Jackson P.K., Bronson R.T., Mulligan R.C.
Cell 65:1153-1163(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[9]"Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populations."
Schwartzberg P.L., Stall A.M., Hardin J.D., Bowdish K.S., Humaran T., Boast S., Harbison M.L., Robertson E.J., Goff S.P.
Cell 65:1165-1175(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[10]"Cell cycle-regulated binding of c-Abl tyrosine kinase to DNA."
Kipreos E.T., Wang J.Y.
Science 256:382-385(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, DOMAIN, PHOSPHORYLATION.
[11]"c-Abl kinase regulates the protein binding activity of c-Crk."
Feller S.M., Knudsen B., Hanafusa H.
EMBO J. 13:2341-2351(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Evidence that SH2 domains promote processive phosphorylation by protein-tyrosine kinases."
Mayer B.J., Hirai H., Sakai R.
Curr. Biol. 5:296-305(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Functional interaction between DNA-PK and c-Abl in response to DNA damage."
Kharbanda S., Pandey P., Jin S., Inoue S., Bharti A., Yuan Z.-M., Weichselbaum R., Weaver D., Kufe D.
Nature 386:732-735(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-446, MUTAGENESIS OF SER-446.
[14]"Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase."
Taagepera S., McDonald D., Loeb J.E., Whitaker L.L., McElroy A.K., Wang J.Y., Hope T.J.
Proc. Natl. Acad. Sci. U.S.A. 95:7457-7462(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[15]"Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth."
Zukerberg L.R., Patrick G.N., Nikolic M., Humbert S., Wu C.-L., Lanier L.M., Gertler F.B., Vidal M., Van Etten R.A., Tsai L.-H.
Neuron 26:633-646(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A TRIMOLECULAR COMPLEX WITH CDK5 AND CABLES1, INTERACTION WITH CABLES1.
Tissue: Brain.
[16]"Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation."
Cong F., Spencer S., Cote J.F., Wu Y., Tremblay M.L., Lasky L.A., Goff S.P.
Mol. Cell 6:1413-1423(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PSTPIP1.
[17]"Regulation of cell death by the Abl tyrosine kinase."
Wang J.Y.
Oncogene 19:5643-5650(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[18]"Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes."
Kain K.H., Klemke R.L.
J. Biol. Chem. 276:16185-16192(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CRK, FUNCTION.
[19]"Targeting of the c-Abl tyrosine kinase to mitochondria in the necrotic cell death response to oxidative stress."
Kumar S., Bharti A., Mishra N.C., Raina D., Kharbanda S., Saxena S., Kufe D.
J. Biol. Chem. 276:17281-17285(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[20]"The beta-amyloid precursor protein APP is tyrosine-phosphorylated in cells expressing a constitutively active form of the Abl protoncogene."
Zambrano N., Bruni P., Minopoli G., Mosca R., Molino D., Russo C., Schettini G., Sudol M., Russo T.
J. Biol. Chem. 276:19787-19792(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[21]"Aph2, a protein with a zf-DHHC motif, interacts with c-Abl and has pro-apoptotic activity."
Li B., Cong F., Tan C.P., Wang S.X., Goff S.P.
J. Biol. Chem. 277:28870-28876(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZDHHC16.
[22]"Interaction between UV-damaged DNA binding activity proteins and the c-Abl tyrosine kinase."
Cong F., Tang J., Hwang B.J., Vuong B.Q., Chu G., Goff S.P.
J. Biol. Chem. 277:34870-34878(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[23]"Regulation of F-actin-dependent processes by the Abl family of tyrosine kinases."
Woodring P.J., Hunter T., Wang J.Y.
J. Cell Sci. 116:2613-2626(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[24]"Two distinct phosphorylation pathways have additive effects on Abl family kinase activation."
Tanis K.Q., Veach D., Duewel H.S., Bornmann W.G., Koleske A.J.
Mol. Cell. Biol. 23:3884-3896(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, INTERACTION WITH CRK, AUTOPHOSPHORYLATION AT TYR-226 AND TYR-393, MUTAGENESIS OF TYR-226; LYS-271 AND TYR-393.
[25]"Bidirectional signaling links the Abelson kinases to the platelet-derived growth factor receptor."
Plattner R., Koleske A.J., Kazlauskas A., Pendergast A.M.
Mol. Cell. Biol. 24:2573-2583(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION.
[26]"Role of c-Abl in the DNA damage stress response."
Shaul Y., Ben-Yehoyada M.
Cell Res. 15:33-35(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[27]"c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration."
Baruzzi A., Iacobucci I., Soverini S., Lowell C.A., Martinelli G., Berton G.
FEBS Lett. 584:15-21(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF CELL MIGRATION, PHOSPHORYLATION, INTERACTION WITH ITGB1; HCK AND FGR.
[28]"ABL tyrosine kinases: evolution of function, regulation, and specificity."
Colicelli J.
Sci. Signal. 3:RE6-RE6(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, DOMAIN.
[29]"High-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides."
Musacchio A., Saraste M., Wilmanns M.
Nat. Struct. Biol. 1:546-551(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 61-121.
[30]"Structural mechanism for STI-571 inhibition of Abelson tyrosine kinase."
Schindler T., Bornmann W., Pellicena P., Miller W.T., Clarkson B., Kuriyan J.
Science 289:1938-1942(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 229-515 IN COMPLEX WITH INHIBITOR STI-571, CATALYTIC ACTIVITY, ENZYME REGULATION, PHOSPHORYLATION AT TYR-393, ACTIVATION LOOP.
[31]"Structural basis for the autoinhibition of c-Abl tyrosine kinase."
Nagar B., Hantschel O., Young M.A., Scheffzek K., Veach D., Bornmann W., Clarkson B., Superti-Furga G., Kuriyan J.
Cell 112:859-871(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 229-515, MYRISTOYLATION (ISOFORM IV), ENZYME REGULATION.
[32]"Crystal structure of the T315I mutant of AbI kinase."
Zhou T., Parillon L., Li F., Wang Y., Keats J., Lamore S., Xu Q., Shakespeare W., Dalgarno D., Zhu X.
Chem. Biol. Drug Des. 70:171-181(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 229-515 OF WILD-TYPE AND MUTANT ILE-315 IN COMPLEX WITH INHIBITOR PPY-A.
[33]"AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance."
O'Hare T., Shakespeare W.C., Zhu X., Eide C.A., Rivera V.M., Wang F., Adrian L.T., Zhou T., Huang W.S., Xu Q., Metcalf C.A. III, Tyner J.W., Loriaux M.M., Corbin A.S., Wardwell S., Ning Y., Keats J.A., Wang Y. expand/collapse author list , Sundaramoorthi R., Thomas M., Zhou D., Snodgrass J., Commodore L., Sawyer T.K., Dalgarno D.C., Deininger M.W., Druker B.J., Clackson T.
Cancer Cell 16:401-412(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 229-515 OF MUTANT ILE-315 IN COMPLEX WITH INHIBITOR AP24534, CATALYTIC ACTIVITY, FUNCTION.
[34]"Structural analysis of DFG-in and DFG-out dual Src-Abl inhibitors sharing a common vinyl purine template."
Zhou T., Commodore L., Huang W.S., Wang Y., Sawyer T.K., Shakespeare W.C., Clackson T., Zhu X., Dalgarno D.C.
Chem. Biol. Drug Des. 75:18-28(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.22 ANGSTROMS) OF 115-401 IN COMPLEXES WITH INHIBITORS AP24283 AND AP24163.
[35]"Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors."
Zhang J., Adrian F.J., Jahnke W., Cowan-Jacob S.W., Li A.G., Iacob R.E., Sim T., Powers J., Dierks C., Sun F., Guo G.R., Ding Q., Okram B., Choi Y., Wojciechowski A., Deng X., Liu G., Fendrich G. expand/collapse author list , Strauss A., Vajpai N., Grzesiek S., Tuntland T., Liu Y., Bursulaya B., Azam M., Manley P.W., Engen J.R., Daley G.Q., Warmuth M., Gray N.S.
Nature 463:501-506(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 115-401 IN COMPLEX WITH INHIBITORS IMATINIB AND GNF-2, CATALYTIC ACTIVITY, ENZYME REGULATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF PRO-112; TYR-128; TYR-139; SER-229; THR-315; CYS-464; PRO-465; PHE-497; GLU-505 AND VAL-506.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02995 mRNA. Translation: AAA88241.1.
AK090095 mRNA. Translation: BAC41088.1.
BC059260 mRNA. Translation: AAH59260.1.
U14721, U14720 Genomic DNA. Translation: AAB60451.1.
U14721, U14720 Genomic DNA. Translation: AAB60450.1.
U14721, U13835 Genomic DNA. Translation: AAB60448.1.
U14721, U13835 Genomic DNA. Translation: AAB60449.1.
X07539 Genomic DNA. Translation: CAA30411.1.
X07539 Genomic DNA. Translation: CAA30412.1.
X07540 Genomic DNA. Translation: CAA30413.1.
X07541 Genomic DNA. Translation: CAA30414.1.
M12263 mRNA. Translation: AAA37136.1.
M12264 mRNA. Translation: AAA37137.1.
M12265 mRNA. Translation: AAA37138.1.
M12266 Genomic DNA. Translation: AAA37134.1.
K03228 mRNA. Translation: AAA37135.1.
PIRA39962.
S00774.
RefSeqNP_001106174.1. NM_001112703.2.
NP_001269974.1. NM_001283045.1.
NP_001269975.1. NM_001283046.1.
NP_033724.2. NM_009594.4.
UniGeneMm.1318.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ABOX-ray2.00A/B61-121[»]
1ABQX-ray2.80A61-121[»]
1FPUX-ray2.40A/B229-515[»]
1IEPX-ray2.10A/B229-515[»]
1M52X-ray2.60A/B229-515[»]
1OPJX-ray1.75A/B229-515[»]
1OPKX-ray1.80A27-515[»]
2HZNX-ray2.70A229-515[»]
2QOHX-ray1.95A/B229-515[»]
2Z60X-ray1.95A229-515[»]
3DK3X-ray2.02A/B233-514[»]
3DK6X-ray2.02A/B233-514[»]
3DK7X-ray2.01A/B233-505[»]
3IK3X-ray1.90A/B229-515[»]
3K5VX-ray1.74A/B229-515[»]
3KF4X-ray1.90A/B229-515[»]
3KFAX-ray1.22A/B229-515[»]
3MS9X-ray1.80A/B229-515[»]
3MSSX-ray1.95A/B/C/D229-515[»]
3OXZX-ray2.20A229-511[»]
3OY3X-ray1.95A/B229-511[»]
ProteinModelPortalP00520.
SMRP00520. Positions 46-511, 1017-1123.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid197906. 19 interactions.
IntActP00520. 20 interactions.
MINTMINT-85127.

Chemistry

BindingDBP00520.
ChEMBLCHEMBL3099.

PTM databases

PhosphoSiteP00520.

Proteomic databases

PaxDbP00520.
PRIDEP00520.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000028190; ENSMUSP00000028190; ENSMUSG00000026842. [P00520-1]
ENSMUST00000075759; ENSMUSP00000075167; ENSMUSG00000026842. [P00520-4]
GeneID11350.
KEGGmmu:11350.
UCSCuc008jdz.2. mouse. [P00520-1]

Organism-specific databases

CTD25.
MGIMGI:87859. Abl1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00640000091347.
HOVERGENHBG004162.
KOK06619.
OMAGAFRESG.
OrthoDBEOG7GTT2V.
TreeFamTF105081.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.
ReactomeREACT_188576. Developmental Biology.

Gene expression databases

ArrayExpressP00520.
BgeeP00520.
CleanExMM_ABL1.
GenevestigatorP00520.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR015015. F-actin_binding.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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.
[Graphical view]
PfamPF08919. F_actin_bind. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTSM00808. FABD. 1 hit.
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00520.
NextBio278620.
PROP00520.
SOURCESearch...

Entry information

Entry nameABL1_MOUSE
AccessionPrimary (citable) accession number: P00520
Secondary accession number(s): P97896 expand/collapse secondary AC list , Q61252, Q61253, Q61254, Q61255, Q61256, Q61257, Q61258, Q61259, Q61260, Q61261, Q6PCM5, Q8C1X4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 15, 2005
Last modified: April 16, 2014
This is version 186 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot