| 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
Human centrin 2 (HsCen2) is an EF-hand protein that plays a critical role in the centrosome duplication and separation during cell division. We studied the structural and Ca(2+)-binding properties of two C-terminal fragments of this protein: SC-HsCen2 (T94-Y172), covering two EF-hands, and LC-HsCen2 (M84-Y172), having 10 additional residues. Both fragments are highly disordered in the apo state but become better structured (although not conformationally homogeneous) in the presence of Ca(2+) and depending on the nature of the cations (K(+) or Na(+)) in the buffer. Only the longer C-terminal domain, in the Ca(2+)-saturated state and in the presence of Na(+) ions, was amenable to structure determination by nuclear magnetic resonance. The solution structure of LC-HsCen2 reveals an open two EF-hand structure, similar to the conformation of related Ca(2+)-saturated regulatory domains. Unexpectedly, the N-terminal helix segment (F86-T94) lies over the exposed hydrophobic cavity. This unusual intramolecular interaction increases considerably the Ca(2+) affinity and constitutes a useful model for the target binding.
C-terminal half of human centrin 2 behaves like a regulatory EF-hand domain.,Matei E, Miron S, Blouquit Y, Duchambon P, Durussel I, Cox JA, Craescu CT Biochemistry. 2003 Feb 18;42(6):1439-50. PMID:12578356[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
- ↑ Matei E, Miron S, Blouquit Y, Duchambon P, Durussel I, Cox JA, Craescu CT. C-terminal half of human centrin 2 behaves like a regulatory EF-hand domain. Biochemistry. 2003 Feb 18;42(6):1439-50. PMID:12578356 doi:10.1021/bi0269714
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