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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)
Function:
1) molecular adapter coordinating multiple protein-protein interactions at focal adhesion complex & in nucleus
2) links various intracellular signaling modules to plasma membrane receptors
3) regulates the Wnt & TGFB signaling pathways
4) may regulate SLC6A3 & SLC6A4 targeting to plasma membrane, thus regulating their activity
5) in nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid receptor, androgen receptor, mineralocorticoid receptor & progesterone receptor transcriptional activity
6) role in processes of cell growth, proliferation, migration, differentiation & senescence
7) zinc-dependent DNA-binding activity
8) interacts with CRIP2, HSPB1, ILK, LIMS1, LIMS2, NCK2, NUDT16L1, PAK, PPARG, PTPN12, TCF3, TCF7L2 & VCL
9) forms a complex with GIT1 & ARHGEF7
10) interacts with androgen receptor (ligand-dependent)
11) interacts with CSK, LYN, MAPK15, NR3C1, PPARG, PTK2, PTK2B, SLC6A3, SLC6A4, SMAD3, SRC & talin
12) 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
General
adhesion protein
cytoskeletal protein
phosphoprotein
Properties
SIZE: MW = 50 kD
entity length = 461 aa
COMPARTMENT: cell nucleus
MOTIF: interaction with PTK2B {1-240}
MOTIF: transcriptional activation domain
SITE: 1-200
LD motif 1 {3-15}
Tyr phosphorylation site {Y38}
Tyr phosphorylation site {Y60}
Ser phosphorylation site {S68}
PTK2 interaction {83-136}
LD motif 2 {92-104}
LD motif 3 {157-168}
LD motif 4 {203-215}
LIM domain {226-285}
MOTIF: cysteine residue (6)
histidine residue
Zn+2-binding site
LIM domain {286-343}
MOTIF: cysteine residue (6)
histidine residue
Zn+2-binding site
LIM domain {344-403}
MOTIF: cysteine residue (6)
histidine residue
Zn+2-binding site
LIM domain {404-461}
MOTIF: cysteine residue (6)
histidine residue
Zn+2-binding site
Database Correlations
OMIM 602353
UniProt O43294
Pfam PF00412
References
UniProt :accession O43294