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Showing Protein E3 ubiquitin-protein ligase CHFR (HMDBP09295)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 4 metabolites
Identification
HMDB Protein ID HMDBP09295
Secondary Accession Numbers
  • 15125
Name E3 ubiquitin-protein ligase CHFR
Synonyms
  1. Checkpoint with forkhead and RING finger domains protein
  2. RING finger protein 196
Gene Name CHFR
Protein Type Enzyme
Biological Properties
General Function Involved in protein binding
Specific Function E3 ubiquitin-protein ligase that functions in the antephase checkpoint by actively delaying passage into mitosis in response to microtubule poisons. Acts in early prophase before chromosome condensation, when the centrosome move apart from each other along the periphery of the nucleus. Probably involved in signaling the presence of mitotic stress caused by microtubule poisons by mediating the 'Lys-48'-linked ubiquitination of target proteins, leading to their degradation by the proteasome. Promotes the ubiquitination and subsequent degradation of AURKA and PLK1. Probably acts as a tumor suppressor, possibly by mediating the polyubiquitination of HDAC1, leading to its degradation. May also promote the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation, but are rather involved in signaling cellular stress
Pathways Not Available
Reactions Not Available
GO Classification
Function
ion binding
cation binding
metal ion binding
binding
transition metal ion binding
zinc ion binding
protein binding
Cellular Location
  1. Nucleus
  2. PML body
Gene Properties
Chromosome Location Chromosome:1
Locus 12q24.33
SNPs CHFR
Gene Sequence 
>1995 bp
ATGGAGCGGCCCGAGGAAGGCAAGCAGTCGCCGCCGCCGCAGCCCTGGGGACGGCTCCTG
CGTCTGGGCGCGGAGGAGGGCGAGCCGCACGTCCTCCTGAGGAAGCGGGAGTGGACCATC
GGGCGGAGACGAGGTTGCGACCTTTCCTTCCCCAGCAATAAACTGGTCTCTGGAGATCAC
TGTAGAATTGTAGTGGATGAAAAATCAGGTCAGGTGACACTGGAAGATACCAGCACCAGT
GGAACAGTGATTAACAAGCTGAAGGTTGTTAAGAAGCAGACATGCCCTTTACAGACTGGG
GATGTCATCTACTTGGTGTACAGGAAGAATGAACCGGAACACAACGTGGCATACCTCTAT
GAATCTTTAAGTGAAAAGCAAGGCATGACACAAGAATCCTTTGAAGCTAACAAGGAAAAT
GTGTTCCATGGGACCAAAGATACCTCAGGTGCAGGTGCAGGGCGAGGGGCCGATCCCCGG
GTCCCTCCGTCGTCGCCCGCCACTCAGGTGTGCTTTGAGGAACCACAGCCATCAACATCG
ACGTCAGACCTCTTCCCCACAGCCTCGGCCTCTTCCACGGAGCCTTCTCCTGCAGGGCGA
GAGCGTTCCTCCAGTTGTGGGTCTGGGGGTGGTGGCATCTCCCCTAAAGGAAGTGGTCCC
TCTGTGGCAAGTGATGAAGTCTCCAGCTTTGCCTCAGCTCTCCCAGACAGAAAGACTGCG
TCCTTTTCGTCGTTGGAACCCCAGGATCAGGAGGATTTGGAGCCCGTGAAGAAGAAAATG
AGAGGAGATGGGGACCTTGACCTGAACGGGCAGTTGTTGGTCGCACAACCGCGTAGAAAT
GCCCAAACCGTCCACGAGGACGTCAGAGCAGCGGCTGGGAAGCCAGACAAGATGGAGGAG
ACGCTGACATGCATCATCTGCCAGGACCTGCTGCACGACTGCGTGAGTTTGCAGCCCTGC
ATGCACACGTTCTGCGCGGCTTGCTACTCGGGCTGGATGGAGCGCTCGTCCCTGTGTCCT
ACCTGCCGCTGTCCCGTGGAGCGGATCTGTAAAAACCACATCCTCAACAACCTCGTGGAA
GCATACCTCATCCAGCATCCAGACAAGAGTCGCAGTGAAGAAGATGTGCAAAGTATGGAT
GCCAGGAATAAAATCACTCAAGACATGCTGCAGCCCAAAGTCAGGCGGTCTTTTTCTGAT
GAAGAAGGGAGTTCAGAGGACCTGCTGGAGCTGTCAGACGTTGACAGTGAGTCCTCAGAC
ATTAGCCAGCCATACGTCGTGTGCCGGCAGTGTCCTGAGTACAGAAGGCAGGCGGCGCAG
CCTCCCCACTGCCCAGCACCCGAGGGCGAGCCAGGAGCCCCACAGGCCCTGGGGGATGCA
CCCTCCACGTCCGTCAGCCTGACGACAGCAGTCCAGGATTACGTGTGCCCTCTGCAAGGA
AGCCACGCCCTGTGCACCTGCTGCTTCCAGCCCATGCCCGACCGGAGAGCGGAGCGCGAG
CAGGACCCGCGTGTCGCCCCTCAGCAGTGTGCGGTCTGCCTGCAGCCTTTCTGCCACCTG
TACTGGGGCTGCACCCGGACCGGCTGCTACGGCTGCCTGGCCCCGTTTTGTGAGCTCAAC
CTGGGTGACAAGTGTCTGGACGGCGTGCTGAACAACAACAGCTACGAGTCAGACATCCTG
AAGAATTACCTGGCAACCAGAGGTTTGACATGGAAAAACATGTTGACCGAGAGCCTCGTG
GCTCTCCAGCGGGGAGTGTTTCTGCTGTCTGATTACAGAGTCACGGGAGACACCGTTCTG
TGTTACTGCTGTGGCCTGCGCAGCTTCCGTGAGCTGACCTATCAGTATCGGCAGAACATT
CCTGCTTCCGAGTTGCCAGTGGCCGTAACATCCCGTCCTGACTGCTACTGGGGCCGTAAC
TGCCGCACTCAGGTGAAAGCTCACCACGCCATGAAATTCAATCATATCTGTGAACAGACA
AGGTTCAAAAACTAA
Protein Properties
Number of Residues 664
Molecular Weight 73385.8
Theoretical pI 5.9
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>E3 ubiquitin-protein ligase CHFR
MERPEEGKQSPPPQPWGRLLRLGAEEGEPHVLLRKREWTIGRRRGCDLSFPSNKLVSGDH
CRIVVDEKSGQVTLEDTSTSGTVINKLKVVKKQTCPLQTGDVIYLVYRKNEPEHNVAYLY
ESLSEKQGMTQESFEANKENVFHGTKDTSGAGAGRGADPRVPPSSPATQVCFEEPQPSTS
TSDLFPTASASSTEPSPAGRERSSSCGSGGGGISPKGSGPSVASDEVSSFASALPDRKTA
SFSSLEPQDQEDLEPVKKKMRGDGDLDLNGQLLVAQPRRNAQTVHEDVRAAAGKPDKMEE
TLTCIICQDLLHDCVSLQPCMHTFCAACYSGWMERSSLCPTCRCPVERICKNHILNNLVE
AYLIQHPDKSRSEEDVQSMDARNKITQDMLQPKVRRSFSDEEGSSEDLLELSDVDSESSD
ISQPYVVCRQCPEYRRQAAQPPHCPAPEGEPGAPQALGDAPSTSVSLTTAVQDYVCPLQG
SHALCTCCFQPMPDRRAEREQDPRVAPQQCAVCLQPFCHLYWGCTRTGCYGCLAPFCELN
LGDKCLDGVLNNNSYESDILKNYLATRGLTWKNMLTESLVALQRGVFLLSDYRVTGDTVL
CYCCGLRSFRELTYQYRQNIPASELPVAVTSRPDCYWGRNCRTQVKAHHAMKFNHICEQT
RFKN
GenBank ID Protein 239048792
UniProtKB/Swiss-Prot ID Q96EP1
UniProtKB/Swiss-Prot Entry Name CHFR_HUMAN
PDB IDs
GenBank Gene ID NM_001161344.1
GeneCard ID CHFR
GenAtlas ID CHFR
HGNC ID HGNC:20455
References
General References
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  5. Bothos J, Summers MK, Venere M, Scolnick DM, Halazonetis TD: The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains. Oncogene. 2003 Oct 16;22(46):7101-7. [PubMed:14562038 ]
  6. Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC: Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins. Nature. 2008 Jan 3;451(7174):81-5. doi: 10.1038/nature06420. [PubMed:18172500 ]
  7. Oh YM, Kwon YE, Kim JM, Bae SJ, Lee BK, Yoo SJ, Chung CH, Deshaies RJ, Seol JH: Chfr is linked to tumour metastasis through the downregulation of HDAC1. Nat Cell Biol. 2009 Mar;11(3):295-302. doi: 10.1038/ncb1837. Epub 2009 Feb 1. [PubMed:19182791 ]
  8. Scolnick DM, Halazonetis TD: Chfr defines a mitotic stress checkpoint that delays entry into metaphase. Nature. 2000 Jul 27;406(6794):430-5. [PubMed:10935642 ]
  9. Kang D, Chen J, Wong J, Fang G: The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition. J Cell Biol. 2002 Jan 21;156(2):249-59. Epub 2002 Jan 21. [PubMed:11807090 ]
  10. Chaturvedi P, Sudakin V, Bobiak ML, Fisher PW, Mattern MR, Jablonski SA, Hurle MR, Zhu Y, Yen TJ, Zhou BB: Chfr regulates a mitotic stress pathway through its RING-finger domain with ubiquitin ligase activity. Cancer Res. 2002 Mar 15;62(6):1797-801. [PubMed:11912157 ]
  11. Mizuno K, Osada H, Konishi H, Tatematsu Y, Yatabe Y, Mitsudomi T, Fujii Y, Takahashi T: Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers. Oncogene. 2002 Apr 4;21(15):2328-33. [PubMed:11948416 ]
  12. Corn PG, Summers MK, Fogt F, Virmani AK, Gazdar AF, Halazonetis TD, El-Deiry WS: Frequent hypermethylation of the 5' CpG island of the mitotic stress checkpoint gene Chfr in colorectal and non-small cell lung cancer. Carcinogenesis. 2003 Jan;24(1):47-51. [PubMed:12538348 ]
  13. Toyota M, Sasaki Y, Satoh A, Ogi K, Kikuchi T, Suzuki H, Mita H, Tanaka N, Itoh F, Issa JP, Jair KW, Schuebel KE, Imai K, Tokino T: Epigenetic inactivation of CHFR in human tumors. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7818-23. Epub 2003 Jun 16. [PubMed:12810945 ]
  14. Satoh A, Toyota M, Itoh F, Sasaki Y, Suzuki H, Ogi K, Kikuchi T, Mita H, Yamashita T, Kojima T, Kusano M, Fujita M, Hosokawa M, Endo T, Tokino T, Imai K: Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in gastric cancer. Cancer Res. 2003 Dec 15;63(24):8606-13. [PubMed:14695171 ]
  15. Shtivelman E: Promotion of mitosis by activated protein kinase B after DNA damage involves polo-like kinase 1 and checkpoint protein CHFR. Mol Cancer Res. 2003 Nov;1(13):959-69. [PubMed:14638868 ]
  16. Erson AE, Petty EM: CHFR-associated early G2/M checkpoint defects in breast cancer cells. Mol Carcinog. 2004 Jan;39(1):26-33. [PubMed:14694445 ]
  17. Daniels MJ, Marson A, Venkitaraman AR: PML bodies control the nuclear dynamics and function of the CHFR mitotic checkpoint protein. Nat Struct Mol Biol. 2004 Nov;11(11):1114-21. Epub 2004 Oct 3. [PubMed:15467728 ]
  18. Fukuda T, Kondo Y, Nakagama H: The anti-proliferative effects of the CHFR depend on the forkhead associated domain, but not E3 ligase activity mediated by ring finger domain. PLoS One. 2008 Mar 12;3(3):e1776. doi: 10.1371/journal.pone.0001776. [PubMed:18335050 ]
  19. Stavridi ES, Huyen Y, Loreto IR, Scolnick DM, Halazonetis TD, Pavletich NP, Jeffrey PD: Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate. Structure. 2002 Jul;10(7):891-9. [PubMed:12121644 ]
  20. Mariatos G, Bothos J, Zacharatos P, Summers MK, Scolnick DM, Kittas C, Halazonetis TD, Gorgoulis VG: Inactivating mutations targeting the chfr mitotic checkpoint gene in human lung cancer. Cancer Res. 2003 Nov 1;63(21):7185-9. [PubMed:14612512 ]