Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot P42684 (ABL2_HUMAN)

Last modified November 25, 2008. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Tyrosine-protein kinase ABL2
    EC=2.7.10.2
Alternative name(s):
    Abelson murine leukemia viral oncogene homolog 2
    Abelson-related gene protein
    Tyrosine kinase ARG
Gene names
Name: ABL2
Synonyms: ABLL, ARG
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1182 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Regulates cytoskeleton remodeling during cell differentiation, cell division and cell adhesion. Localizes to dynamic actin structures, and phosphorylates CRK and CRKL, DOK1, and other proteins controlling cytoskeleton dynamics.

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

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 amino-terminal cap, and contributions from an amino-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML).

Subcellular location

Cytoplasmcytoskeleton.

Tissue specificity

Widely expressed.

Post-translational modification

Phosphorylated upon DNA damage, probably by ATM or ATR.

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.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform IB (identifier: P42684-1)

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 IA (identifier: P42684-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGQQVGRVGE...EGDKTGGSSP → MVLGTVLLPP...ASESALPDLT
Notes: Variant in position: 12:S->T (somatic mutation in a breast cancer sample). Variant in position: 42:R->H (somatic mutation in a breast cancer sample). Variant in position: 748:T->S (somatic mutation in a breast cancer sample). Variant in position: 894:K->R (somatic mutation in a breast cancer sample). Variant in position: 960:P->R (somatic mutation in a breast cancer sample). Variant in position: 63:E->Q (somatic mutation in a breast cancer sample). Variant in position: 483:R->I (somatic mutation in a lung squamous cell carcinoma).
Isoform IC (identifier: P42684-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: MGQQVGRVGE...ETGFNIFTQH → MVLGTVLLPP...ASESALPDLT
Isoform 4 (identifier: P42684-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGQQVGRVGE...EGDKTGGSSP → MVLGTVLLPP...ASESALPDLT
     688-790: Missing.
Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 11821181Tyrosine-protein kinase ABL2
PRO_0000088052

Regions

Domain107 – 16761SH3
Domain173 – 26391SH2
Domain288 – 539252Protein kinase
Nucleotide binding294 – 3029ATP By similarity
Region2 – 106105CAP
Motif658 – 6603Nuclear localization signal Potential
Compositional bias561 – 5644Poly-Ser
Compositional bias732 – 7398Poly-Gly
Compositional bias843 – 1055213Pro-rich
Compositional bias984 – 9885Poly-Pro

Sites

Active site4091Proton acceptor By similarity
Binding site3171ATP By similarity

Amino acid modifications

Modified residue711Phosphoserine
Modified residue2031Phosphoserine
Modified residue2311Phosphotyrosine By similarity
Modified residue2721Phosphotyrosine; by autocatalysis By similarity
Modified residue2991Phosphotyrosine By similarity
Modified residue3031Phosphotyrosine By similarity
Modified residue3101Phosphotyrosine
Modified residue4391Phosphotyrosine; by autocatalysis
Modified residue4401Phosphothreonine
Modified residue4921Phosphoserine By similarity
Modified residue5151Phosphotyrosine
Modified residue6201Phosphoserine
Modified residue6311Phosphoserine
Modified residue6331Phosphoserine
Modified residue6551Phosphoserine
Modified residue7831Phosphoserine
Modified residue8171Phosphoserine
Modified residue8201Phosphoserine
Modified residue9151Phosphoserine
Modified residue9361Phosphoserine
Lipidation21N-myristoyl glycine By similarity

Natural variations

Alternative sequence1 – 7373MGQQV…GGSSP → MVLGTVLLPPNSYGRDQDTS LCCLCTEASESALPDLT in isoform 4.
VSP_021307
Alternative sequence1 – 7373MGQQV…GGSSP → MVLGTVLLPPNTYGRDQDTS LCCLCTEASESALPDLT in isoform IA.
VSP_004961
Alternative sequence1 – 5252MGQQV…IFTQH → MVLGTVLLPPNSYGRDQDTS LCCLCTEASESALPDLT in isoform IC.
VSP_017112
Alternative sequence688 – 790103Missing in isoform 4.
VSP_021308
Natural variant9301K → R: dbSNP rs17277288.
VAR_029232
Natural variant9461V → M: dbSNP rs28913889.
VAR_029233
Natural variant9961P → R: dbSNP rs28913890.
VAR_029234
Natural variant10851S → N: dbSNP rs28913891.
VAR_029235
Natural variant11011T → A: dbSNP rs28913892.
VAR_029236

Experimental info

Sequence conflict343 – 3442NL → TI Ref.5
Sequence conflict9811K → R in CAD98092. Ref.2

Secondary structure

................. 1182
Helix Strand Turn

Details...

Sequences

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

Last modified November 1, 1995. Version 1.
Checksum: ED93869BC2B14FAA

FASTA1,182128,343
        10         20         30         40         50         60 
MGQQVGRVGE APGLQQPQPR GIRGSSAARP SGRRRDPAGR TTETGFNIFT QHDHFASCVE 

        70         80         90        100        110        120 
DGFEGDKTGG SSPEALHRPY GCDVEPQALN EAIRWSSKEN LLGATESDPN LFVALYDFVA 

       130        140        150        160        170        180 
SGDNTLSITK GEKLRVLGYN QNGEWSEVRS KNGQGWVPSN YITPVNSLEK HSWYHGPVSR 

       190        200        210        220        230        240 
SAAEYLLSSL INGSFLVRES ESSPGQLSIS LRYEGRVYHY RINTTADGKV YVTAESRFST 

       250        260        270        280        290        300 
LAELVHHHST VADGLVTTLH YPAPKCNKPT VYGVSPIHDK WEMERTDITM KHKLGGGQYG 

       310        320        330        340        350        360 
EVYVGVWKKY SLTVAVKTLK EDTMEVEEFL KEAAVMKEIK HPNLVQLLGV CTLEPPFYIV 

       370        380        390        400        410        420 
TEYMPYGNLL DYLRECNREE VTAVVLLYMA TQISSAMEYL EKKNFIHRDL AARNCLVGEN 

       430        440        450        460        470        480 
HVVKVADFGL SRLMTGDTYT AHAGAKFPIK WTAPESLAYN TFSIKSDVWA FGVLLWEIAT 

       490        500        510        520        530        540 
YGMSPYPGID LSQVYDLLEK GYRMEQPEGC PPKVYELMRA CWKWSPADRP SFAETHQAFE 

       550        560        570        580        590        600 
TMFHDSSISE EVAEELGRAA SSSSVVPYLP RLPILPSKTR TLKKQVENKE NIEGAQDATE 

       610        620        630        640        650        660 
NSASSLAPGF IRGAQASSGS PALPRKQRDK SPSSLLEDAK ETCFTRDRKG GFFSSFMKKR 

       670        680        690        700        710        720 
NAPTPPKRSS SFREMENQPH KKYELTGNFS SVASLQHADG FSFTPAQQEA NLVPPKCYGG 

       730        740        750        760        770        780 
SFAQRNLCND DGGGGGGSGT AGGGWSGITG FFTPRLIKKT LGLRAGKPTA SDDTSKPFPR 

       790        800        810        820        830        840 
SNSTSSMSSG LPEQDRMAMT LPRNCQRSKL QLERTVSTSS QPEENVDRAN DMLPKKSEES 

       850        860        870        880        890        900 
AAPSRERPKA KLLPRGATAL PLRTPSGDLA ITEKDPPGVG VAGVAAAPKG KEKNGGARLG 

       910        920        930        940        950        960 
MAGVPEDGEQ PGWPSPAKAA PVLPTTHNHK VPVLISPTLK HTPADVQLIG TDSQGNKFKL 

       970        980        990       1000       1010       1020 
LSEHQVTSSG DKDRPRRVKP KCAPPPPPVM RLLQHPSICS DPTEEPTALT AGQSTSETQE 

      1030       1040       1050       1060       1070       1080 
GGKKAALGAV PISGKAGRPV MPPPQVPLPT SSISPAKMAN GTAGTKVALR KTKQAAEKIS 

      1090       1100       1110       1120       1130       1140 
ADKISKEALL ECADLLSSAL TEPVPNSQLV DTGHQLLDYC SGYVDCIPQT RNKFAFREAV 

      1150       1160       1170       1180 
SKLELSLQEL QVSSAAAGVP GTNPVLNNLL SCVQEISDVV QR 

« Hide

Isoform IA [UniParc].

Checksum: 472FE7CB2CB9BE15
Show »

1,146124,574
Isoform IC [UniParc].

Checksum: 0E3923FE9EEEAFEC
Show »

1,167126,684
Isoform 4 [UniParc].

Checksum: 973C4751FD7E13F9
Show »

1,043114,159

References

« Hide 'large scale' references
[1]"The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases."
Kruh G.D., Perego R., Miki T., Aaronson S.A.
Proc. Natl. Acad. Sci. U.S.A. 87:5802-5806(1990) [PubMed: 2198571] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS IA AND IB).
[2]The German cDNA consortium
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Uterine endothelium.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y.,