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A-kinase anchor protein 13; AKAP-13; AKAP-Lbc; breast cancer nuclear receptor-binding auxiliary protein; guanine nucleotide exchange factor Lbc; human thyroid-anchoring protein 31; lymphoid blast crisis oncogene; LBC oncogene; non-oncogenic Rho GTPase-specific GTP exchange factor; protein kinase A-anchoring protein 13; p47 (AKAP13, BRX, HT31, LBC)
Function:
- anchors cAMP-dependent protein kinase (PKA)
- acts as an adapter protein to selectively couple G alpha-13 & Rho
- augments gene activation by the estrogen receptor (element-specific, ligand-dependent)
- activates estrogen receptor beta by a p38 MAPK-dependent pathway
- isoform 6 stimulates exchange activity on Rho proteins in vitro, but not on CDC42, Ras or Rac
- may bind Ca+2
- binds cAMP-dependent protein kinase (PKA) & to the RII-alpha regulatory subunit of PKA
- interacts with ESR1, ESR2, THRA, PPARA, RHOA & NME2
Structure:
- both the DH & PH domains are required for transforming activity
- contains 1 DH (DBL-homology) domain
- contains 1 PH domain
- contains 1 phorbol-ester/DAG-type Zn+2 finger
Compartment:
- isoform 2: cytoplasm
- isoform 3: cytoplasm, nucleus
- isoform 6: cytoplasm
- isoform 7: membrane
Alternative splicing: named isoforms=7
Expression:
- isoform 3 & isoform 6
- expressed in hematopoietic cells, skeletal muscle, lung, heart, estrogen- responsive reproductive tissues, including breast ductal epithelium
- also found in testis & breast cancer cell lines
- isoform 6 is not found in brain, placenta, liver, pancreas or kidney
- isoform 7 is expressed in myeloid & lymphoid lineages, a variety of epithelial tissues & skeletal muscle
- isoform 2
- predominantly expressed in the heart
- lower expression in lung, placenta, kidney, pancreas, skeletal muscle & liver
General
guanine nucleotide exchange factor (GDP/GTP dissociation stimulator, guanine nucleotide-releasing factor/protein, GNEF, GNDS, GDS)
phosphoprotein
zinc finger protein
Properties
SIZE: entity length = 2813 aa
MW = 308 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: binding site
SITE: 494-516
FOR-BINDING-OF: RII
Ser phosphorylation site {S983}
serine-rich region {1471-1474}
MOTIF: serine residue (SEVERAL)
glutamate-rich region {1534-1537}
MOTIF: glutamate residue (SEVERAL)
Ser phosphorylation site {S1559}
Ser phosphorylation site {S1642}
Ser phosphorylation site {S1645}
Ser phosphorylation site {S1647}
coiled coil {1758-1790}
Zinc finger
NAME: Zinc finger
SITE: 1791-1838
EFFECTOR-BOUND: Zn+2
Ser phosphorylation site {S1876}
Ser phosphorylation site {S1895}
ESR1 interaction {1919-2813}
MOTIF: Ser phosphorylation site {S1929}
Ser phosphorylation site {S1932}
Dbl homology domain {1994-2191}
PH domain {2231-2333}
coiled coil {2345-2381}
Ser phosphorylation site {S2398}
Ser phosphorylation site {S2402}
coiled coil {2568-2683}
Ser phosphorylation site {S2703}
Ser phosphorylation site {S2709}
Ser phosphorylation site {S2728}
lysine-rich region {2778-2790}
MOTIF: lysine residue (SEVERAL)
Database Correlations
OMIM 604686
UniProt Q12802
PFAM correlations
Entrez Gene 11214
Kegg hsa:11214
References
UniProt :accession Q12802