Q8NI51 (CTCFL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcriptional repressor CTCFL

Alternative name(s):
Brother of the regulator of imprinted sites
CCCTC-binding factor
CTCF paralog
CTCF-like protein
Cancer/testis antigen 27
Short name=CT27
Zinc finger protein CTCF-T

Gene names

Name:	CTCFL
Synonyms:	BORIS

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	663 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Testis-specific DNA binding protein responsible for insulator function, nuclear architecture and transcriptional control, which probably acts by recruiting epigenetic chromatin modifiers. Plays a key role in gene imprinting in male germline, by participating in the establishment of differential methylation at the IGF2/H19 imprinted control region (ICR). Directly binds the unmethylated H19 ICR and recruits the PRMT7 methyltransferase, leading to methylate histone H4 'Arg-3' to form H4R3sme2. This probably leads to recruit de novo DNA methyltransferases at these sites By similarity. Seems to act as tumor suppressor. In association with DNMT1 and DNMT3B, involved in activation of BAG1 gene expression by binding to its promoter. Required for dimethylation of H3 lysine 4 (H3K4me2) of MYC and BRCA1 promoters. Ref.1 Ref.5 Ref.6
Subunit structure	Interacts with histones, PRMT7 and SETD1A. Interacts (via N-terminus) with BAG6/BAT3. Ref.6
Subcellular location	Cytoplasm. Nucleus.
Tissue specificity	Testis specific. Specifically expressed in primary spermatocytes.
Developmental stage	Is up-regulated in primary spermatocytes (expression overlapping with the genome-wide erasure of methylation) to become silenced on activation of CTCF in post-meiotic germline cells (expression corresponding to DNA remethylation).
Sequence similarities	Belongs to the CTCF zinc-finger protein family. Contains 11 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Cell cycle Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Chromatin regulator Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA methylation involved in gamete generation Inferred from sequence or structural similarity. Source: UniProtKB cell cycle Inferred from electronic annotation. Source: UniProtKB-KW histone methylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.5. Source: UniProtKB regulation of gene expression by genetic imprinting Inferred from sequence or structural similarity. Source: UniProtKB regulation of histone H3-K4 methylation Inferred from mutant phenotype Ref.6. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	histone binding Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding Inferred from sequence or structural similarity. Source: UniProtKB transcription regulatory region DNA binding Inferred from direct assay Ref.5. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 663	663	Transcriptional repressor CTCFL		PRO_0000047226
Regions
	Zinc finger	257 – 279	23	C2H2-type 1
	Zinc finger	285 – 307	23	C2H2-type 2
	Zinc finger	313 – 336	24	C2H2-type 3
	Zinc finger	342 – 364	23	C2H2-type 4
	Zinc finger	370 – 392	23	C2H2-type 5
	Zinc finger	398 – 421	24	C2H2-type 6
	Zinc finger	428 – 451	24	C2H2-type 7
	Zinc finger	458 – 480	23	C2H2-type 8
	Zinc finger	486 – 508	23	C2H2-type 9
	Zinc finger	514 – 537	24	C2H2-type 10
	Zinc finger	546 – 568	23	C2H2-type 11; atypical
Natural variations
	Natural variant	50	1	E → Q. Corresponds to variant rs6070128 [ dbSNP | Ensembl ].		VAR_023213
	Natural variant	177	1	T → A. Ref.1 Corresponds to variant rs6025606 [ dbSNP | Ensembl ].		VAR_023214
	Natural variant	448	1	R → H. Corresponds to variant rs6092491 [ dbSNP | Ensembl ].		VAR_057374
	Natural variant	525	1	Q → E. Corresponds to variant rs6070122 [ dbSNP | Ensembl ].		VAR_032766
Experimental info
	Sequence conflict	613	1	Missing in AAL61541. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8NI51 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: 9351E1A85173D085	FASTA	663	75,747
	10 20 30 40 50 60 MAATEISVLS EQFTKIKELE LMPEKGLKEE EKDGVCREKD HRSPSELEAE RTSGAFQDSV 70 80 90 100 110 120 LEEEVELVLA PSEESEKYIL TLQTVHFTSE AVELQDMSLL SIQQQEGVQV VVQQPGPGLL 130 140 150 160 170 180 WLEEGPRQSL QQCVAISIQQ ELYSPQEMEV LQFHALEENV MVASEDSKLA VSLAETTGLI 190 200 210 220 230 240 KLEEEQEKNQ LLAERTKEQL FFVETMSGDE RSDEIVLTVS NSNVEEQEDQ PTAGQADAEK 250 260 270 280 290 300 AKSTKNQRKT KGAKGTFHCD VCMFTSSRMS SFNRHMKTHT SEKPHLCHLC LKTFRTVTLL 310 320 330 340 350 360 RNHVNTHTGT RPYKCNDCNM AFVTSGELVR HRRYKHTHEK PFKCSMCKYA SVEASKLKRH 370 380 390 400 410 420 VRSHTGERPF QCCQCSYASR DTYKLKRHMR THSGEKPYEC HICHTRFTQS GTMKIHILQK 430 440 450 460 470 480 HGENVPKYQC PHCATIIARK SDLRVHMRNL HAYSAAELKC RYCSAVFHER YALIQHQKTH 490 500 510 520 530 540 KNEKRFKCKH CSYACKQERH MTAHIRTHTG EKPFTCLSCN KCFRQKQLLN AHFRKYHDAN 550 560 570 580 590 600 FIPTVYKCSK CGKGFSRWIN LHRHSEKCGS GEAKSAASGK GRRTRKRKQT ILKEATKGQK 610 620 630 640 650 660 EAAKGWKEAA NGDEAAAEEA STTKGEQFPG EMFPVACRET TARVKEEVDE GVTCEMLLNT MDK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma." Loukinov D.I., Pugacheva E., Vatolin S., Pack S.D., Moon H., Chernukhin I., Mannan P., Larsson E., Kanduri C., Vostrov A.A., Cui H., Niemitz E.L., Rasko J.E.J., Docquier F.M., Kistler M., Breen J.J., Zhuang Z., Quitschke W.W. , Renkawitz R., Klenova E.M., Feinberg A.P., Ohlsson R., Morse H.C. III, Lobanenkov V.V. Proc. Natl. Acad. Sci. U.S.A. 99:6806-6811(2002) [PubMed: 12011441] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANT ALA-177. Tissue: Testis.
[2]	"The testis-specific factor CTCFL cooperates with the protein methyltransferase PRMT7 in H19 imprinting control region methylation." Jelinic P., Stehle J.-C., Shaw P. PLoS Biol. 4:E355-E355(2006) [PubMed: 17048991] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer." Klenova E.M., Morse H.C. III, Ohlsson R., Lobanenkov V.V. Semin. Cancer Biol. 12:399-414(2002) [PubMed: 12191639] [Abstract] Cited for: REVIEW.
[5]	"DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation." Sun L., Huang L., Nguyen P., Bisht K.S., Bar-Sela G., Ho A.S., Bradbury C.M., Yu W., Cui H., Lee S., Trepel J.B., Feinberg A.P., Gius D. Cancer Res. 68:2726-2735(2008) [PubMed: 18413740] [Abstract] Cited for: FUNCTION.
[6]	"BAT3 and SET1A form a complex with CTCFL/BORIS to modulate H3K4 histone dimethylation and gene expression." Nguyen P., Bar-Sela G., Sun L., Bisht K.S., Cui H., Kohn E., Feinberg A.P., Gius D. Mol. Cell. Biol. 28:6720-6729(2008) [PubMed: 18765639] [Abstract] Cited for: FUNCTION, INTERACTION WITH BAG6/BAT3 AND SETD1A.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF336042 mRNA. Translation: AAM28645.1. AY071919 mRNA. Translation: AAL61541.1. AL160176 Genomic DNA. Translation: CAI42956.1.
IPI	IPI00942274.
RefSeq	NP_542185.2. NM_080618.2.
UniGene	Hs.131543.
3D structure databases
ProteinModelPortal	Q8NI51.
SMR	Q8NI51. Positions 8-61, 227-587.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8NI51.
PTM databases
PhosphoSite	Q8NI51.
Polymorphism databases
DMDM	30172878.
Proteomic databases
PRIDE	Q8NI51.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000243914; ENSP00000243914; ENSG00000124092. ENST00000371196; ENSP00000360239; ENSG00000124092.
GeneID	140690.
KEGG	hsa:140690.
Organism-specific databases
CTD	140690.
GeneCards	GC20M056064.
H-InvDB	HIX0027672.
HGNC	HGNC:16234. CTCFL.
HPA	HPA001472.
MIM	607022. gene.
neXtProt	NX_Q8NI51.
PharmGKB	PA26999.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000063079.
InParanoid	Q8NI51.
OrthoDB	EOG4QJRN4.
PhylomeDB	Q8NI51.
Gene expression databases
ArrayExpress	Q8NI51.
Bgee	Q8NI51.
CleanEx	HS_CTCFL.
Genevestigator	Q8NI51.
GermOnline	ENSG00000124092. Homo sapiens.
Family and domain databases
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Gene3D	G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 9 hits.
Pfam	PF00096. zf-C2H2. 6 hits. [Graphical view]
SMART	SM00355. ZnF_C2H2. 11 hits. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 7 hits. PS50157. ZINC_FINGER_C2H2_2. 11 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	84239.
SOURCE	Search...

Entry information

Entry name

CTCFL_HUMAN

Accession

Primary (citable) accession number: Q8NI51
Secondary accession number(s): Q5JUG4, Q9BZ30, Q9NQJ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 23, 2003
Last sequence update:	November 30, 2010
Last modified:	January 25, 2012
This is version 90 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.