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breakpoint cluster region protein P160 (p160BCR)
Protein product of BCR-gene (breakpoint cluster region) gene that forms a chimeric gene with abl in the Philadelphia chromosome associated with chronic myelogenous leukemia (CML).
Function:
- GTPase-activating protein for RAC1 & CDC42
- promotes exchange of RAC or CDC42-bound GDP by GTP, thereby activating them
- displays serine/threonine kinase activity
- interacts with PDZK1
- may interact with CCPG1
- autophosphorylated
ATP + a protein ADP + a phosphoprotein
Structure:
- homotetramer
- region involved in binding to ABL1 SH2-domain is rich in Ser & needs to be Ser/Thr phosphorylated prior to SH2 binding; this region is essential for the activation of the ABL1 tyrosine kinase & transforming potential of the chimeric BCR-ABL oncogene
- DH domain is involved in interaction with CCPG1
- contains 1 C2 domain contains 1 DH (DBL-homology) domain contains 1 PH domain contains 1 Rho-GAP domain
Alternative splicing: named isoforms=2
Pathology:
- chromosomal translocation t(9;22)(q34.1;q11) involving BCR with ABL1 is a cause of chronic myeloid leukemia translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) & acute lymphoblastic leukemia (ALL))
Related
guanine nucleotide exchange factor (GDP/GTP dissociation stimulator, guanine nucleotide-releasing factor/protein, GNEF, GNDS, GDS)
Specific
p210 bcr/abl
General
oligomerizing protein
rho GTPase-activating protein (rho-GAP)
serine/threonine kinase
Properties
SIZE: MW = 160 kD
STATE: active state
MOTIF: Kinase {1-426}
MOTIF: Tyr phosphorylation site {Y177}
Binding to ABL SH2 {197-385}
Thr phosphorylation site {T310}
Breakpoint {426-427}
Ser phosphorylation site {S459}
Ser phosphorylation site {S463}
Dbl homology domain {498-691}
MOTIF: Tyr phosphorylation site {Y591}
Tyr phosphorylation site {Y644}
PH domain {708-866}
MOTIF: leucine residue {824-827} (4)
C2 domain {870-1002}
MOTIF: binding site
FOR-BINDING-OF: phospholipid
Ca+2-binding site
rho-GAP domain
NAME: rho-GAP domain
SITE: 1054-1248
Ser phosphorylation site {S1264}
Database Correlations
OMIM correlations
UniProt P11274
PFAM correlations
Entrez Gene 613
References
- Maru Y, Witte ON.
The BCR gene encodes a novel serine/threonine kinase activity
within a single exon.
Cell. 1991 Nov 1;67(3):459-68.
PMID: 1657398
- Musacchio A, Gibson T, Rice P, Thompson J, Saraste M.
The PH domain: a common piece in the structural patchwork of
signalling proteins.
Trends Biochem Sci. 1993 Sep;18(9):343-8. Review.
PMID: 8236453
- Atlas of Genetics & cytogenetics in oncology & Haematology
http://atlasgeneticsoncology.org/Genes/BCR.html