Q96EP1 (CHFR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase CHFR
EC=6.3.2.-

Alternative name(s):
Checkpoint with forkhead and RING finger domains protein
RING finger protein 196

Gene names

Name:	CHFR
Synonyms:	RNF196

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	664 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.1 Ref.6 Ref.7 Ref.13 Ref.14 Ref.16 Ref.18
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with HDAC1 and HDAC2. Interacts with PML (with sumoylated form of PML). Ref.13 Ref.15 Ref.18
Subcellular location	Nucleus › PML body Ref.7 Ref.15 Ref.16.
Tissue specificity	Ubiquitous. Ref.1
Developmental stage	Weakly expressed in G1 phase, and highly expressed during S phase. Ref.7
Domain	The PBZ-type zinc finger (also named CYR) mediates non-covalent poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is dependent on the presence of zinc and is required for its function in antephase checkpoint. Ref.16 Ref.17 The FHA domain plays a key role in the anti-proliferative properties of the protein and is involved in initiating a cell cycle arrest at G2/M. The FHA domain may be required to interact with phosphorylated proteins. Ref.16 Ref.17
Post-translational modification	Poly-ADP-ribosylated. In addition to binding non covalently poly(ADP-ribose) via its PBZ-type zinc finger, the protein is also covalently poly-ADP-ribosylated by PARP1. Ref.16 Autoubiquitinated; may regulate its cellular level. Phosphorylated upon DNA damage, probably by ATM or ATR By similarity. Phosphorylated by PKB. Phosphorylation may affect its E3 ligase activity. Ref.12 Ref.13
Miscellaneous	CHFR is silenced in many primary cancers because of CpG methylation and deacetylated histones on its promoter region. This however raises the question of whether CHFR silencing is a consequence or a cause of primary cancers.
Sequence similarities	Belongs to the CHFR family. Contains 1 FHA domain. Contains 1 PBZ-type zinc finger. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	ADP-ribosylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic cell cycle checkpoint Inferred from mutant phenotype Ref.16Ref.18. Source: UniProtKB modification-dependent protein catabolic process Inferred from direct assay Ref.18. Source: UniProtKB protein polyubiquitination Inferred from direct assay Ref.18. Source: UniProtKB
Cellular component	PML body Inferred from direct assay Ref.15. Source: UniProtKB
Molecular function	nucleotide binding Inferred from direct assay Ref.16. Source: UniProtKB protein binding Inferred from physical interaction Ref.15Ref.16Ref.18. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.16Ref.18. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96EP1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96EP1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     135-146: Missing.

Isoform 3 (identifier: Q96EP1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     136-206: ANKENVFHGT...PAGRERSSSC → MVPCCVAQAGLKLLGSSDPPTLASQSIVIT

Isoform 4 (identifier: Q96EP1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     470-470: Missing.

Isoform 5 (identifier: Q96EP1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     115-207: NVAYLYESLS...AGRERSSSCG → R

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 664

664

E3 ubiquitin-protein ligase CHFR

PRO_0000055872

Regions

Domain

38 – 89

52

FHA

Zinc finger

304 – 343

40

RING-type

Zinc finger

633 – 655

23

PBZ-type

Amino acid modifications

Modified residue

130

1

Phosphothreonine By similarity

Modified residue

386

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

115 – 207

93

NVAYL…SSSCG → R in isoform 5.

VSP_038126

Alternative sequence

135 – 146

12

Missing in isoform 2.

VSP_009349

Alternative sequence

136 – 206

71

ANKEN…RSSSC → MVPCCVAQAGLKLLGSSDPP TLASQSIVIT in isoform 3.

VSP_009350

Alternative sequence

470

1

Missing in isoform 4.

VSP_038127

Natural variant

166

1

P → L in a patient with non small cell lung carcinomas; homozygous. Ref.20

VAR_017582

Natural variant

202

1

R → P in a patient with non small cell lung carcinomas. Ref.20

VAR_017583

Natural variant

270

1

G → R. Ref.8

VAR_017584

Natural variant

497

1

A → V Common polymorphism. Ref.4 Ref.8
Corresponds to variant rs2306541 [ dbSNP | Ensembl ].

VAR_017585

Natural variant

536

1

F → S in a patient with non small cell lung carcinomas. Ref.20

VAR_017586

Natural variant

580

1

V → M Common polymorphism. Ref.1 Ref.2 Ref.8
Corresponds to variant rs2306536 [ dbSNP | Ensembl ].

VAR_017587

Experimental info

Mutagenesis

39

1

T → A: Abolishes phosphorylation but not autoubiquitination; when associated with A-205. Ref.12

Mutagenesis

205

1

S → A: Abolishes phosphorylation but not autoubiquitination; when associated with A-39. Ref.12

Mutagenesis

306

1

I → A: Abolishes autoubiquitination. Does not affect phosphorylation. Ref.6 Ref.18

Mutagenesis

332

1

W → A: Abolishes autoubiquitination in vitro. Ref.6

Mutagenesis

632

1

R → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1. Ref.16

Mutagenesis

635

1

C → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-641. Ref.16

Mutagenesis

641

1

C → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-635. Ref.16

Mutagenesis

642

1

R → A: Impairs poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1. Ref.16

Mutagenesis

644

1

Q → A: Impairs poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1. Ref.16

Sequence conflict

256

1

V → E in BAA91817. Ref.2

Sequence conflict

462

1

S → P in BAA91817. Ref.2

Sequence conflict

599

1

V → A in BAG65178. Ref.2

Sequence conflict

617

1

R → Q in BAA91817. Ref.2

Secondary structure

1

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664

Helix Strand Turn

Details...

Beta strand

17 – 21

5

Beta strand

26 – 28

3

Beta strand

31 – 33

3

Beta strand

35 – 43

9

Beta strand

46 – 49

4

Beta strand

61 – 65

5

Turn

67 – 69

3

Beta strand

72 – 76

5

Beta strand

78 – 80

3

Beta strand

82 – 90

9

Beta strand

92 – 97

6

Beta strand

102 – 106

5

Helix

112 – 114

3

Beta strand

116 – 123

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 2, 2004. Version 2. Checksum: 141A1E7FEFAE36A2	FASTA	664	73,386
	10 20 30 40 50 60 MERPEEGKQS PPPQPWGRLL RLGAEEGEPH VLLRKREWTI GRRRGCDLSF PSNKLVSGDH 70 80 90 100 110 120 CRIVVDEKSG QVTLEDTSTS GTVINKLKVV KKQTCPLQTG DVIYLVYRKN EPEHNVAYLY 130 140 150 160 170 180 ESLSEKQGMT QESFEANKEN VFHGTKDTSG AGAGRGADPR VPPSSPATQV CFEEPQPSTS 190 200 210 220 230 240 TSDLFPTASA SSTEPSPAGR ERSSSCGSGG GGISPKGSGP SVASDEVSSF ASALPDRKTA 250 260 270 280 290 300 SFSSLEPQDQ EDLEPVKKKM RGDGDLDLNG QLLVAQPRRN AQTVHEDVRA AAGKPDKMEE 310 320 330 340 350 360 TLTCIICQDL LHDCVSLQPC MHTFCAACYS GWMERSSLCP TCRCPVERIC KNHILNNLVE 370 380 390 400 410 420 AYLIQHPDKS RSEEDVQSMD ARNKITQDML QPKVRRSFSD EEGSSEDLLE LSDVDSESSD 430 440 450 460 470 480 ISQPYVVCRQ CPEYRRQAAQ PPHCPAPEGE PGAPQALGDA PSTSVSLTTA VQDYVCPLQG 490 500 510 520 530 540 SHALCTCCFQ PMPDRRAERE QDPRVAPQQC AVCLQPFCHL YWGCTRTGCY GCLAPFCELN 550 560 570 580 590 600 LGDKCLDGVL NNNSYESDIL KNYLATRGLT WKNMLTESLV ALQRGVFLLS DYRVTGDTVL 610 620 630 640 650 660 CYCCGLRSFR ELTYQYRQNI PASELPVAVT SRPDCYWGRN CRTQVKAHHA MKFNHICEQT RFKN
	Isoform 2 [UniParc]. Checksum: 572F2CE6D1743D80	FASTA	652	72,031
	10 20 30 40 50 60 MERPEEGKQS PPPQPWGRLL RLGAEEGEPH VLLRKREWTI GRRRGCDLSF PSNKLVSGDH 70 80 90 100 110 120 CRIVVDEKSG QVTLEDTSTS GTVINKLKVV KKQTCPLQTG DVIYLVYRKN EPEHNVAYLY 130 140 150 160 170 180 ESLSEKQGMT QESFDTSGAG AGRGADPRVP PSSPATQVCF EEPQPSTSTS DLFPTASASS 190 200 210 220 230 240 TEPSPAGRER SSSCGSGGGG ISPKGSGPSV ASDEVSSFAS ALPDRKTASF SSLEPQDQED 250 260 270 280 290 300 LEPVKKKMRG DGDLDLNGQL LVAQPRRNAQ TVHEDVRAAA GKPDKMEETL TCIICQDLLH 310 320 330 340 350 360 DCVSLQPCMH TFCAACYSGW MERSSLCPTC RCPVERICKN HILNNLVEAY LIQHPDKSRS 370 380 390 400 410 420 EEDVQSMDAR NKITQDMLQP KVRRSFSDEE GSSEDLLELS DVDSESSDIS QPYVVCRQCP 430 440 450 460 470 480 EYRRQAAQPP HCPAPEGEPG APQALGDAPS TSVSLTTAVQ DYVCPLQGSH ALCTCCFQPM 490 500 510 520 530 540 PDRRAEREQD PRVAPQQCAV CLQPFCHLYW GCTRTGCYGC LAPFCELNLG DKCLDGVLNN 550 560 570 580 590 600 NSYESDILKN YLATRGLTWK NMLTESLVAL QRGVFLLSDY RVTGDTVLCY CCGLRSFREL 610 620 630 640 650 TYQYRQNIPA SELPVAVTSR PDCYWGRNCR TQVKAHHAMK FNHICEQTRF KN
	Isoform 3 [UniParc]. Checksum: B747CD23B74368E7	FASTA	623	69,192
	10 20 30 40 50 60 MERPEEGKQS PPPQPWGRLL RLGAEEGEPH VLLRKREWTI GRRRGCDLSF PSNKLVSGDH 70 80 90 100 110 120 CRIVVDEKSG QVTLEDTSTS GTVINKLKVV KKQTCPLQTG DVIYLVYRKN EPEHNVAYLY 130 140 150 160 170 180 ESLSEKQGMT QESFEMVPCC VAQAGLKLLG SSDPPTLASQ SIVITGSGGG GISPKGSGPS 190 200 210 220 230 240 VASDEVSSFA SALPDRKTAS FSSLEPQDQE DLEPVKKKMR GDGDLDLNGQ LLVAQPRRNA 250 260 270 280 290 300 QTVHEDVRAA AGKPDKMEET LTCIICQDLL HDCVSLQPCM HTFCAACYSG WMERSSLCPT 310 320 330 340 350 360 CRCPVERICK NHILNNLVEA YLIQHPDKSR SEEDVQSMDA RNKITQDMLQ PKVRRSFSDE 370 380 390 400 410 420 EGSSEDLLEL SDVDSESSDI SQPYVVCRQC PEYRRQAAQP PHCPAPEGEP GAPQALGDAP 430 440 450 460 470 480 STSVSLTTAV QDYVCPLQGS HALCTCCFQP MPDRRAEREQ DPRVAPQQCA VCLQPFCHLY 490 500 510 520 530 540 WGCTRTGCYG CLAPFCELNL GDKCLDGVLN NNSYESDILK NYLATRGLTW KNMLTESLVA 550 560 570 580 590 600 LQRGVFLLSD YRVTGDTVLC YCCGLRSFRE LTYQYRQNIP ASELPVAVTS RPDCYWGRNC 610 620 RTQVKAHHAM KFNHICEQTR FKN
	Isoform 4 [UniParc]. Checksum: 302207777755B60C	FASTA	663	73,315
	10 20 30 40 50 60 MERPEEGKQS PPPQPWGRLL RLGAEEGEPH VLLRKREWTI GRRRGCDLSF PSNKLVSGDH 70 80 90 100 110 120 CRIVVDEKSG QVTLEDTSTS GTVINKLKVV KKQTCPLQTG DVIYLVYRKN EPEHNVAYLY 130 140 150 160 170 180 ESLSEKQGMT QESFEANKEN VFHGTKDTSG AGAGRGADPR VPPSSPATQV CFEEPQPSTS 190 200 210 220 230 240 TSDLFPTASA SSTEPSPAGR ERSSSCGSGG GGISPKGSGP SVASDEVSSF ASALPDRKTA 250 260 270 280 290 300 SFSSLEPQDQ EDLEPVKKKM RGDGDLDLNG QLLVAQPRRN AQTVHEDVRA AAGKPDKMEE 310 320 330 340 350 360 TLTCIICQDL LHDCVSLQPC MHTFCAACYS GWMERSSLCP TCRCPVERIC KNHILNNLVE 370 380 390 400 410 420 AYLIQHPDKS RSEEDVQSMD ARNKITQDML QPKVRRSFSD EEGSSEDLLE LSDVDSESSD 430 440 450 460 470 480 ISQPYVVCRQ CPEYRRQAAQ PPHCPAPEGE PGAPQALGDA PSTSVSLTTV QDYVCPLQGS 490 500 510 520 530 540 HALCTCCFQP MPDRRAEREQ DPRVAPQQCA VCLQPFCHLY WGCTRTGCYG CLAPFCELNL 550 560 570 580 590 600 GDKCLDGVLN NNSYESDILK NYLATRGLTW KNMLTESLVA LQRGVFLLSD YRVTGDTVLC 610 620 630 640 650 660 YCCGLRSFRE LTYQYRQNIP ASELPVAVTS RPDCYWGRNC RTQVKAHHAM KFNHICEQTR FKN
	Isoform 5 [UniParc]. Checksum: C3CFDEF89A9C85B7	FASTA	572	63,873
	10 20 30 40 50 60 MERPEEGKQS PPPQPWGRLL RLGAEEGEPH VLLRKREWTI GRRRGCDLSF PSNKLVSGDH 70 80 90 100 110 120 CRIVVDEKSG QVTLEDTSTS GTVINKLKVV KKQTCPLQTG DVIYLVYRKN EPEHRSGGGG 130 140 150 160 170 180 ISPKGSGPSV ASDEVSSFAS ALPDRKTASF SSLEPQDQED LEPVKKKMRG DGDLDLNGQL 190 200 210 220 230 240 LVAQPRRNAQ TVHEDVRAAA GKPDKMEETL TCIICQDLLH DCVSLQPCMH TFCAACYSGW 250 260 270 280 290 300 MERSSLCPTC RCPVERICKN HILNNLVEAY LIQHPDKSRS EEDVQSMDAR NKITQDMLQP 310 320 330 340 350 360 KVRRSFSDEE GSSEDLLELS DVDSESSDIS QPYVVCRQCP EYRRQAAQPP HCPAPEGEPG 370 380 390 400 410 420 APQALGDAPS TSVSLTTAVQ DYVCPLQGSH ALCTCCFQPM PDRRAEREQD PRVAPQQCAV 430 440 450 460 470 480 CLQPFCHLYW GCTRTGCYGC LAPFCELNLG DKCLDGVLNN NSYESDILKN YLATRGLTWK 490 500 510 520 530 540 NMLTESLVAL QRGVFLLSDY RVTGDTVLCY CCGLRSFREL TYQYRQNIPA SELPVAVTSR 550 560 570 PDCYWGRNCR TQVKAHHAMK FNHICEQTRF KN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Chfr defines a mitotic stress checkpoint that delays entry into metaphase." Scolnick D.M., Halazonetis T.D. Nature 406:430-435(2000) [PubMed: 10935642] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, VARIANT MET-580.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4), VARIANT MET-580. Tissue: Teratocarcinoma, Testis and Trachea.
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT VAL-497. Tissue: Placenta.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 359-664. Tissue: Testis.
[6]	"The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition." Kang D., Chen J., Wong J., Fang G. J. Cell Biol. 156:249-259(2002) [PubMed: 11807090] [Abstract] Cited for: FUNCTION, AUTOUBIQUITINATION, MUTAGENESIS OF ILE-306 AND TRP-332.
[7]	"Chfr regulates a mitotic stress pathway through its RING-finger domain with ubiquitin ligase activity." Chaturvedi P., Sudakin V., Bobiak M.L., Fisher P.W., Mattern M.R., Jablonski S.A., Hurle M.R., Zhu Y., Yen T.J., Zhou B.-B. Cancer Res. 62:1797-1801(2002) [PubMed: 11912157] [Abstract] Cited for: FUNCTION, AUTOUBIQUITINATION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[8]	"Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers." Mizuno K., Osada H., Konishi H., Tatematsu Y., Yatabe Y., Mitsudomi T., Fujii Y., Takahashi T. Oncogene 21:2328-2333(2002) [PubMed: 11948416] [Abstract] Cited for: VARIANTS ARG-270; VAL-497 AND MET-580, SILENCING IN PRIMARY CANCERS.
[9]	"Frequent hypermethylation of the 5' CpG island of the mitotic stress checkpoint gene Chfr in colorectal and non-small cell lung cancer." Corn P.G., Summers M.K., Fogt F., Virmani A.K., Gazdar A.F., Halazonetis T.D., El-Deiry W.S. Carcinogenesis 24:47-51(2003) [PubMed: 12538348] [Abstract] Cited for: SILENCING IN PRIMARY CANCERS.
[10]	"Epigenetic inactivation of CHFR in human tumors." Toyota M., Sasaki Y., Satoh A., Ogi K., Kikuchi T., Suzuki H., Mita H., Tanaka N., Itoh F., Issa J.-P.J., Jair K.-W., Schuebel K.E., Imai K., Tokino T. Proc. Natl. Acad. Sci. U.S.A. 100:7818-7823(2003) [PubMed: 12810945] [Abstract] Cited for: SILENCING IN PRIMARY CANCERS.
[11]	"Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in gastric cancer." 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. Cancer Res. 63:8606-8613(2003) [PubMed: 14695171] [Abstract] Cited for: SILENCING IN PRIMARY CANCERS.
[12]	"Promotion of mitosis by activated protein kinase B after DNA damage involves polo-like kinase 1 and checkpoint protein CHFR." Shtivelman E. Mol. Cancer Res. 1:959-969(2003) [PubMed: 14638868] [Abstract] Cited for: PHOSPHORYLATION, MUTAGENESIS OF THR-39 AND SER-205.
[13]	"The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains." Bothos J., Summers M.K., Venere M., Scolnick D.M., Halazonetis T.D. Oncogene 22:7101-7107(2003) [PubMed: 14562038] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBE2V2, PHOSPHORYLATION.
[14]	"CHFR-associated early G2/M checkpoint defects in breast cancer cells." Erson A.E., Petty E.M. Mol. Carcinog. 39:26-33(2004) [PubMed: 14694445] [Abstract] Cited for: FUNCTION.
[15]	"PML bodies control the nuclear dynamics and function of the CHFR mitotic checkpoint protein." Daniels M.J., Marson A., Venkitaraman A.R. Nat. Struct. Mol. Biol. 11:1114-1121(2004) [PubMed: 15467728] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PML.
[16]	"Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins." Ahel I., Ahel D., Matsusaka T., Clark A.J., Pines J., Boulton S.J., West S.C. Nature 451:81-85(2008) [PubMed: 18172500] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DOMAIN PBZ-TYPE, POLY-ADP-RIBOSYLATION, ADP-RIBOSE-BINDING, MUTAGENESIS OF ARG-632; CYS-635; CYS-641; ARG-642 AND GLN-644.
[17]	"The anti-proliferative effects of the CHFR depend on the forkhead associated domain, but not E3 ligase activity mediated by ring finger domain." Fukuda T., Kondo Y., Nakagama H. PLoS ONE 3:E1776-E1776(2008) [PubMed: 18335050] [Abstract] Cited for: DOMAIN FHA.
[18]	"Chfr is linked to tumour metastasis through the downregulation of HDAC1." Oh Y.M., Kwon Y.E., Kim J.M., Bae S.J., Lee B.K., Yoo S.J., Chung C.H., Deshaies R.J., Seol J.H. Nat. Cell Biol. 11:295-302(2009) [PubMed: 19182791] [Abstract] Cited for: FUNCTION, INTERACTION WITH HDAC1 AND HDAC2, AUTOUBIQUITINATION, MUTAGENESIS OF ILE-306.
[19]	"Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate." Stavridi E.S., Huyen Y., Loreto I.R., Scolnick D.M., Halazonetis T.D., Pavletich N.P., Jeffrey P.D. Structure 10:891-899(2002) [PubMed: 12121644] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 14-128.
[20]	"Inactivating mutations targeting the chfr mitotic checkpoint gene in human lung cancer." Mariatos G., Bothos J., Zacharatos P., Summers M.K., Scolnick D.M., Kittas C., Halazonetis T.D., Gorgoulis V.G. Cancer Res. 63:7185-7189(2003) [PubMed: 14612512] [Abstract] Cited for: VARIANTS LEU-166; PRO-202 AND SER-536.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF170724 mRNA. Translation: AAF91084.1.
AK001658 mRNA. Translation: BAA91817.1.
AK027687 mRNA. Translation: BAB55297.1.
AK302785 mRNA. Translation: BAG63989.1.
AK304333 mRNA. Translation: BAG65178.1.
AC127070 Genomic DNA. No translation available.
BC012072 mRNA. Translation: AAH12072.1.
AL137561 mRNA. Translation: CAB70812.1.

IPI

IPI00023513.
IPI00397548.
IPI00796680.
IPI00930659.
IPI00953641.

PIR

T46399.

RefSeq

NP_001154816.1. NM_001161344.1.
NP_001154817.1. NM_001161345.1.
NP_001154818.1. NM_001161346.1.
NP_001154819.1. NM_001161347.1.
NP_060693.2. NM_018223.2.

UniGene

Hs.720197.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LGP	X-ray	2.00	A	14-128	[»]
1LGQ	X-ray	2.10	A/B	14-124	[»]
2XOC	X-ray	1.89	A/B	407-663	[»]
2XOY	X-ray	2.60	A/B	407-664	[»]
2XOZ	X-ray	2.37	A/B	407-664	[»]
2XP0	X-ray	1.98	A/B	394-664	[»]

ProteinModelPortal

Q96EP1.

SMR

Q96EP1. Positions 14-125, 294-369, 424-663.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96EP1. 15 interactions.

MINT

MINT-1381330.

STRING

Q96EP1.

PTM databases

PhosphoSite

Q96EP1.

Polymorphism databases

DMDM

41688511.

Proteomic databases

PRIDE

Q96EP1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000266880; ENSP00000266880; ENSG00000072609.
ENST00000443047; ENSP00000416431; ENSG00000072609.

GeneID

55743.

KEGG

hsa:55743.

UCSC

uc001uld.1. human.
uc001ule.1. human.
uc001ulf.1. human.

Organism-specific databases

CTD

55743.

GeneCards

GC12M133416.

HGNC

HGNC:20455. CHFR.

MIM

605209. gene.

neXtProt

NX_Q96EP1.

PharmGKB

PA134898949.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15533.

GeneTree

ENSGT00400000022306.

HOGENOM

HBG446387.

HOVERGEN

HBG048005.

InParanoid

Q96EP1.

OMA

DVIYVVY.

OrthoDB

EOG43FGWJ.

PhylomeDB

Q96EP1.

Gene expression databases

ArrayExpress

Q96EP1.

Bgee

Q96EP1.

CleanEx

HS_CHFR.

Genevestigator

Q96EP1.

GermOnline

ENSG00000072609. Homo sapiens.

Family and domain databases

InterPro

IPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Gene3D

G3DSA:2.60.200.20. FHA. 1 hit.
G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.

KO

K10644.

Pfam

PF00498. FHA. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]

SMART

SM00240. FHA. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

SUPFAM

SSF49879. SMAD_FHA. 1 hit.

PROSITE

PS50006. FHA_DOMAIN. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

60707.

SOURCE

Search...

Entry information

Entry name

CHFR_HUMAN

Accession

Primary (citable) accession number: Q96EP1
Secondary accession number(s): A6NEN5 , B4DZ77, B4E2L6, Q96SL3, Q9NRT4, Q9NT32, Q9NVD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	February 2, 2004
Last modified:	January 25, 2012
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.