transforming growth factor beta-1-induced transcript 1 protein (hydrogen peroxide-inducible clone 5 protein, Hic-5, androgen receptor-associated protein of 55 kD, TGFB1I1, ARA55)
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Function
- molecular adapter coordinating multiple protein-protein interactions at focal adhesion complex & in nucleus
- links various intracellular signaling modules to plasma membrane receptors
- regulates the Wnt & TGFB signaling pathways
- may regulate SLC6A3 & SLC6A4 targeting to plasma membrane, thus regulating their activity
- in nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid receptor, androgen receptor, mineralocorticoid receptor & progesterone receptor transcriptional activity
- role in processes of cell growth, proliferation, migration, differentiation & senescence
- zinc-dependent DNA-binding activity
- interacts with CRIP2, HSPB1, ILK, LIMS1, LIMS2, NCK2, NUDT16L1, PAK, PPARG, PTPN12, TCF3, TCF7L2 & VCL
- forms a complex with GIT1 & ARHGEF7
- interacts with androgen receptor (ligand-dependent)
- interacts with CSK, LYN, MAPK15, NR3C1, PPARG, PTK2, PTK2B, SLC6A3, SLC6A4, SMAD3, SRC & talin
- phosphorylated by gonadotropin-releasing hormone-activated SRC
Structure
- homooligomer
- contains 4 LIM zinc-binding domains
- LIM zinc-binding domains mediate glucocorticoid receptor coactivation & interaction with AR, CRIP2, ILK, LIMS1, NR3C1, PPARG, TCF3, TCF7L2, SLC6A3 & SMAD3
- LIM zinc-binding 2 & LIM zinc-binding 3 domains mediate targeting to focal adhesions & actin stress fibers
- LIM zinc-binding 3 & LIM zinc-binding 4 domains mediate interaction with TRAF4 & MAPK15.
- LIM zinc-binding 4 domain mediates interaction with HSPB1, homooligomerization & targeting to the nuclear matrix
- LIM zinc-binding 3 domain mediates interaction with PTPN12
- LD motif (leucine & aspartate-rich motif) 3 mediates interaction with GIT1 & functions as a nuclear export signal
- belongs to the paxillin family
Compartment
- cell junction, focal adhesion, nucleus
- associated with the actin cytoskeleton
- colocalizes with stress fibers
Alternative splicing
named isoforms=2
Expression
- expressed in platelets, smooth muscle & prostate stromal cells
- up-regulated by TNF-alpha & hydrogen peroxide