| Structural highlights
Function
[CHP1_RAT] Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription. Involved in the constitutive exocytic membrane traffic. Mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is also required for the targeting and fusion of transcytotic vesicles (TCV) with the plasma membrane. Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Affects the pH sensitivity of SLC9A1/NHE1 by increasing its sensitivity at acidic pH. Required for the stabilization and localization of SLC9A1/NHE1 at the plasma membrane. Inhibits serum- and GTPase-stimulated Na(+)/H(+) exchange. Plays a role as an inhibitor of ribosomal RNA transcription by repressing the nucleolar UBF1 transcriptional activity. May sequester UBF1 in the nucleoplasm and limit its translocation to the nucleolus. Associates to the ribosomal gene promoter. Acts as a negative regulator of the calcineurin/NFAT signaling pathway. Inhibits NFAT nuclear translocation and transcriptional activity by suppressing the calcium-dependent calcineurin phosphatase activity. Also negatively regulates the kinase activity of the apoptosis-induced kinase STK17B. Inhibits both STK17B auto- and substrate-phosphorylations in a calcium-dependent manner.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Calcineurin B homologous protein 1 (CHP1), also known as p22, is a calcium-binding EF-hand protein that plays a role in membrane trafficking. It binds to multiple effector proteins, including Na(+)/H(+) exchangers, a serine/threonine kinase, and calcineurin, potentially modulating their function. The crystal structure of calcium-bound CHP1 from rat has been determined at 2.2 Angstroms of resolution. The molecule has a compact alpha-helical structure containing four EF-hands. The overall folding topology of the protein is similar to that of the regulatory B subunit of calcineurin and to that of calcium- and integrin-binding protein. The calcium ion is coordinated in typical fashion in the third and fourth EF-hands, but the first and second EF-hands contain no calcium ion. The first EF-hand is maintained by internal interactions, and the second EF-hand is stabilized by hydrophobic interactions. CHP1 contains a hydrophobic pocket on the opposite side of the protein to the EF-hands that has been implicated in ligand binding.
Structural characterization of calcineurin B homologous protein 1.,Naoe Y, Arita K, Hashimoto H, Kanazawa H, Sato M, Shimizu T J Biol Chem. 2005 Sep 16;280(37):32372-8. Epub 2005 Jun 29. PMID:15987692[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Barroso MR, Bernd KK, DeWitt ND, Chang A, Mills K, Sztul ES. A novel Ca2+-binding protein, p22, is required for constitutive membrane traffic. J Biol Chem. 1996 Apr 26;271(17):10183-7. PMID:8626580
- ↑ Kuwahara H, Kamei J, Nakamura N, Matsumoto M, Inoue H, Kanazawa H. The apoptosis-inducing protein kinase DRAK2 is inhibited in a calcium-dependent manner by the calcium-binding protein CHP. J Biochem. 2003 Aug;134(2):245-50. PMID:12966074
- ↑ Andrade J, Pearce ST, Zhao H, Barroso M. Interactions among p22, glyceraldehyde-3-phosphate dehydrogenase and microtubules. Biochem J. 2004 Dec 1;384(Pt 2):327-36. PMID:15312048 doi:http://dx.doi.org/10.1042/BJ20040622
- ↑ Andrade J, Zhao H, Titus B, Timm Pearce S, Barroso M. The EF-hand Ca2+-binding protein p22 plays a role in microtubule and endoplasmic reticulum organization and dynamics with distinct Ca2+-binding requirements. Mol Biol Cell. 2004 Feb;15(2):481-96. Epub 2003 Dec 2. PMID:14657246 doi:http://dx.doi.org/10.1091/mbc.E03-07-0500
- ↑ Jimenez-Vidal M, Srivastava J, Putney LK, Barber DL. Nuclear-localized calcineurin homologous protein CHP1 interacts with upstream binding factor and inhibits ribosomal RNA synthesis. J Biol Chem. 2010 Nov 19;285(47):36260-6. doi: 10.1074/jbc.M110.165555. Epub 2010, Aug 18. PMID:20720019 doi:http://dx.doi.org/10.1074/jbc.M110.165555
- ↑ Matsushita M, Tanaka H, Mitsui K, Kanazawa H. Dual functional significance of calcineurin homologous protein 1 binding to Na(+)/H(+) exchanger isoform 1. Am J Physiol Cell Physiol. 2011 Aug;301(2):C280-8. doi:, 10.1152/ajpcell.00404.2010. Epub 2011 May 4. PMID:21543739 doi:http://dx.doi.org/10.1152/ajpcell.00404.2010
- ↑ Naoe Y, Arita K, Hashimoto H, Kanazawa H, Sato M, Shimizu T. Structural characterization of calcineurin B homologous protein 1. J Biol Chem. 2005 Sep 16;280(37):32372-8. Epub 2005 Jun 29. PMID:15987692 doi:10.1074/jbc.M503390200
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