Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MTJ1/ERdj1 and its human homologue HTJ1 are membrane proteins that interact with the molecular chaperone BiP through their J-domain. HTJ1 also contains a C-terminal cytosolic region of unknown function that consists of two SANT domains separated by a spacer region. We recently showed that the second SANT domain of HTJ1 (SANT2) binds to alpha1-antichymotrypsin and alters its serpin activity [B. Kroczynska, C.M. Evangelista, S.S. Samant, E.C. Elguindi, S.Y. Blond, The SANT2 domain of the murine tumor cell DnaJ-like protein 1 human homologue interacts with alpha1-antichymotrypsin and kinetically interferes with its serpin inhibitory activity, J. Biol. Chem. 279 (2004) 11432-11443]. Here, we identified a new variant of human inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) that also interacts with the SANT2 domain of HTJ1. Biochemical, mutagenesis, and fluorescence studies demonstrate that SANT2 binds to a carboxyl-terminal fragment that corresponds to the last third of the new ITIH4 isoform sequence (residues 588-930). ITIH4 and MTJ1 co-immunoprecipitate from total liver protein extracts and SANT2 protects the ITIH4(588-930) recombinant fragment from being processed by kallikrein in vitro. This work reveals that the SANT2 domain of HTJ1 is a genuine protein-protein interaction module.
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PMID:BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-trypsin inhibitor heavy chain 4. 1627 2

The results of recent studies indicate that inflammatory responses occurring in the early stages of equine laminitis lead to downstream events that eventually result in failure of the bond between the hoof wall and the distal phalanx. In order to gain further insights into the molecular mechanisms involved in the development of laminitis, an equine-specific cDNA microarray consisting of transcripts for more that 3000 genes was used to assess temporal changes in gene expression in laminar tissues at 1.5, 3 and 12 h after administration of either a laminitis-inducing agent (black walnut heartwood extract; BWHE) or an equal volume of water (control). As early as 1.5 h after BWHE administration, pro-inflammatory genes associated with leukocyte activation and emigration, including MCP-3/CCL7, MCP-1/CCL2, IP-10/CXCL10 and ICAM-1 were up-regulated. At both 1.5 and 3h after administration of BWHE, expression of B-cell specific transcripts (e.g., Ig-gamma 3, Ig-gamma 1 and lambda-light chain) were decreased in the laminar tissues. At the onset of Obel grade 1 lameness in horses administered BWHE, other genes involved in inflammatory processes (e.g., serum amyloid A, calgranulin C and NFAT-activation molecule 1), regulation of inflammation (e.g., inter-alpha-trypsin inhibitor, BiP/GRP78 [Ig binding protein], L-plastin, serpin and nexin-1), antioxidant responses (e.g., superoxide dismutase), matrix turnover (e.g., MMP-9 and TIMP-1), and anti-microbial responses (e.g., serotransferrin, beta-defensin-1 and elafin) were up-regulated. These results provide convincing evidence that genes associated with inflammation, activation and extravasation of leukocytes, antimicrobial activities, and destruction of the lamellar basement membrane are induced during the early stages of development of laminitis in response to administration of BWHE.
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PMID:Temporal aspects of laminar gene expression during the developmental stages of equine laminitis. 1912 42