| Structural highlights
Function
[CETN2_HUMAN] Plays a fundamental role in microtubule-organizing center structure and function. Required for centriole duplication and correct spindle formation. Has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CEP110.[1] [2] [3] [4] [5] [6] Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with RAD23B appears to stabilize XPC. In vitro, stimulates DNA binding of the XPC:RAD23B dimer.[7] [8] [9] [10] [11] [12] The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair.[13] [14] [15] [16] [17] [18]
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
Centrins are well-conserved calcium binding proteins from the EF-hand superfamily implicated in various cellular functions, such as centrosome duplication, DNA repair, and nuclear mRNA export. The intrinsic molecular flexibility and the self-association tendency make difficult the structural characterization of the integral protein. In this paper we report the solution structure, the Ca2+ binding properties, and the intermolecular interactions of the N-terminal domain of two human centrin isoforms, HsCen1 and HsCen2. In the absence of Ca2+, the N-terminal construct of HsCen2 revealed a compact core conformation including four almost antiparallel alpha-helices and a short antiparallel beta-sheet, very similar to the apo state structure of other calcium regulatory EF-hand domains. The first 25 residues show a highly irregular and dynamic structure. The three-dimensional model for the N-terminal domain of HsCen1, based on the high sequence conservation and NMR spectroscopic data, shows very close structural properties. Ca2+ titration of the apo-N-terminal domain of HsCen1 and HsCen2, monitored by NMR spectroscopy, revealed a very weak affinity (10(2)-10(3) M(-1)), suggesting that the cellular role of this domain is not calcium dependent. Isothermal calorimetric titrations showed that an 18-residue peptide, derived from the N-terminal unstructured fragment, has a significant affinity (approximately 10(5) M(-1)) for the isolated C-terminal domain, suggesting an active role in the self-assembly of centrin molecules.
The N-terminal domain of human centrin 2 has a closed structure, binds calcium with a very low affinity, and plays a role in the protein self-assembly.,Yang A, Miron S, Duchambon P, Assairi L, Blouquit Y, Craescu CT Biochemistry. 2006 Jan 24;45(3):880-9. PMID:16411764[19]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lee VD, Huang B. Molecular cloning and centrosomal localization of human caltractin. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11039-43. PMID:8248209
- ↑ Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. J Biol Chem. 2001 Jun 1;276(22):18665-72. Epub 2001 Feb 27. PMID:11279143 doi:10.1074/jbc.M100855200
- ↑ Salisbury JL, Suino KM, Busby R, Springett M. Centrin-2 is required for centriole duplication in mammalian cells. Curr Biol. 2002 Aug 6;12(15):1287-92. PMID:12176356
- ↑ Nishi R, Okuda Y, Watanabe E, Mori T, Iwai S, Masutani C, Sugasawa K, Hanaoka F. Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein. Mol Cell Biol. 2005 Jul;25(13):5664-74. PMID:15964821 doi:10.1128/MCB.25.13.5664-5674.2005
- ↑ Bunick CG, Miller MR, Fuller BE, Fanning E, Chazin WJ. Biochemical and structural domain analysis of xeroderma pigmentosum complementation group C protein. Biochemistry. 2006 Dec 19;45(50):14965-79. PMID:17154534 doi:10.1021/bi061370o
- ↑ Tsang WY, Spektor A, Luciano DJ, Indjeian VB, Chen Z, Salisbury JL, Sanchez I, Dynlacht BD. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell. 2006 Aug;17(8):3423-34. Epub 2006 Jun 7. PMID:16760425 doi:10.1091/mbc.E06-04-0371
- ↑ Lee VD, Huang B. Molecular cloning and centrosomal localization of human caltractin. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11039-43. PMID:8248209
- ↑ Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. J Biol Chem. 2001 Jun 1;276(22):18665-72. Epub 2001 Feb 27. PMID:11279143 doi:10.1074/jbc.M100855200
- ↑ Salisbury JL, Suino KM, Busby R, Springett M. Centrin-2 is required for centriole duplication in mammalian cells. Curr Biol. 2002 Aug 6;12(15):1287-92. PMID:12176356
- ↑ Nishi R, Okuda Y, Watanabe E, Mori T, Iwai S, Masutani C, Sugasawa K, Hanaoka F. Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein. Mol Cell Biol. 2005 Jul;25(13):5664-74. PMID:15964821 doi:10.1128/MCB.25.13.5664-5674.2005
- ↑ Bunick CG, Miller MR, Fuller BE, Fanning E, Chazin WJ. Biochemical and structural domain analysis of xeroderma pigmentosum complementation group C protein. Biochemistry. 2006 Dec 19;45(50):14965-79. PMID:17154534 doi:10.1021/bi061370o
- ↑ Tsang WY, Spektor A, Luciano DJ, Indjeian VB, Chen Z, Salisbury JL, Sanchez I, Dynlacht BD. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell. 2006 Aug;17(8):3423-34. Epub 2006 Jun 7. PMID:16760425 doi:10.1091/mbc.E06-04-0371
- ↑ Lee VD, Huang B. Molecular cloning and centrosomal localization of human caltractin. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11039-43. PMID:8248209
- ↑ Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. J Biol Chem. 2001 Jun 1;276(22):18665-72. Epub 2001 Feb 27. PMID:11279143 doi:10.1074/jbc.M100855200
- ↑ Salisbury JL, Suino KM, Busby R, Springett M. Centrin-2 is required for centriole duplication in mammalian cells. Curr Biol. 2002 Aug 6;12(15):1287-92. PMID:12176356
- ↑ Nishi R, Okuda Y, Watanabe E, Mori T, Iwai S, Masutani C, Sugasawa K, Hanaoka F. Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein. Mol Cell Biol. 2005 Jul;25(13):5664-74. PMID:15964821 doi:10.1128/MCB.25.13.5664-5674.2005
- ↑ Bunick CG, Miller MR, Fuller BE, Fanning E, Chazin WJ. Biochemical and structural domain analysis of xeroderma pigmentosum complementation group C protein. Biochemistry. 2006 Dec 19;45(50):14965-79. PMID:17154534 doi:10.1021/bi061370o
- ↑ Tsang WY, Spektor A, Luciano DJ, Indjeian VB, Chen Z, Salisbury JL, Sanchez I, Dynlacht BD. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell. 2006 Aug;17(8):3423-34. Epub 2006 Jun 7. PMID:16760425 doi:10.1091/mbc.E06-04-0371
- ↑ Yang A, Miron S, Duchambon P, Assairi L, Blouquit Y, Craescu CT. The N-terminal domain of human centrin 2 has a closed structure, binds calcium with a very low affinity, and plays a role in the protein self-assembly. Biochemistry. 2006 Jan 24;45(3):880-9. PMID:16411764 doi:10.1021/bi051397s
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