Q9P0U4 (CXXC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CpG-binding protein

Alternative name(s):
CXXC-type zinc finger protein 1
PHD finger and CXXC domain-containing protein 1

Gene names

Name:	CXXC1
Synonyms:	CFP1, CGBP, PCCX1, PHF18

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	656 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional activator that exhibits a unique DNA binding specificity for CpG unmethylated motifs with a preference for CpGG. Ref.16
Subunit structure	Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1 HCFC1 and DPY30. Interacts with SETD1A. Ref.9 Ref.10 Ref.11 Ref.12
Subcellular location	Nucleus speckle. Note: Associated with euchromatin. During mitosis, excluded from condensed chromosomes. Ref.8 Ref.10
Tissue specificity	Ubiquitous.
Domain	The acidic domain carries the potential to activate transcription. Ref.7
Post-translational modification	May be regulated by proteolysis.
Sequence similarities	Contains 1 CXXC-type zinc finger. Contains 1 PHD-type zinc finger.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome histone H3-K4 methylation Inferred from direct assay Ref.10. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.1. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Set1C/COMPASS complex Inferred from direct assay Ref.11Ref.12. Source: UniProtKB nuclear matrix Inferred from electronic annotation. Source: Compara nuclear speck Inferred from direct assay. Source: LIFEdb
Molecular_function	unmethylated CpG binding Inferred from direct assay Ref.1. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9P0U4-1)

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: Q9P0U4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     340-340: K → KVMER

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 656

656

CpG-binding protein

PRO_0000079743

Regions

Zinc finger

28 – 76

49

PHD-type

Zinc finger

160 – 209

50

CXXC-type

Coiled coil

422 – 474

53

Potential

Compositional bias

256 – 317

62

Asp/Glu-rich (acidic)

Compositional bias

321 – 359

39

Arg/Lys-rich (basic)

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.15

Modified residue

6

1

Phosphoserine Ref.15

Modified residue

19

1

Phosphoserine Ref.15

Modified residue

227

1

Phosphothreonine Ref.13

Natural variations

Alternative sequence

340

1

K → KVMER in isoform 2.

VSP_040132

Experimental info

Mutagenesis

169

1

C → A: Complete loss of DNA binding activity. No effect on localization in nuclear speckles. Ref.7

Mutagenesis

208

1

C → A: Complete loss of DNA binding activity. No effect on localization in nuclear speckles. Ref.7

Sequence conflict

117

1

D → N in AAF37799. Ref.1

Sequence conflict

175

1

C → R in BAG37400. Ref.4

Sequence conflict

235

1

P → S in BAG37400. Ref.4

Sequence conflict

302

1

H → N in AAF37799. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

656

Helix Strand Turn

Details...

Beta strand

170 – 172

3

Helix

173 – 176

4

Beta strand

182 – 184

3

Helix

185 – 189

5

Helix

191 – 193

3

Helix

204 – 206

3

Turn

209 – 211

3

Helix

214 – 216

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 27, 2002. Version 2. Checksum: 6D2376E449905A18	FASTA	656	75,712
	10 20 30 40 50 60 MEGDGSDPEP PDAGEDSKSE NGENAPIYCI CRKPDINCFM IGCDNCNEWF HGDCIRITEK 70 80 90 100 110 120 MAKAIREWYC RECREKDPKL EIRYRHKKSR ERDGNERDSS EPRDEGGGRK RPVPDPDLQR 130 140 150 160 170 180 RAGSGTGVGA MLARGSASPH KSSPQPLVAT PSQHHQQQQQ QIKRSARMCG ECEACRRTED 190 200 210 220 230 240 CGHCDFCRDM KKFGGPNKIR QKCRLRQCQL RARESYKYFP SSLSPVTPSE SLPRPRRPLP 250 260 270 280 290 300 TQQQPQPSQK LGRIREDEGA VASSTVKEPP EATATPEPLS DEDLPLDPDL YQDFCAGAFD 310 320 330 340 350 360 DHGLPWMSDT EESPFLDPAL RKRAVKVKHV KRREKKSEKK KEERYKRHRQ KQKHKDKWKH 370 380 390 400 410 420 PERADAKDPA SLPQCLGPGC VRPAQPSSKY CSDDCGMKLA ANRIYEILPQ RIQQWQQSPC 430 440 450 460 470 480 IAEEHGKKLL ERIRREQQSA RTRLQEMERR FHELEAIILR AKQQAVREDE ESNEGDSDDT 490 500 510 520 530 540 DLQIFCVSCG HPINPRVALR HMERCYAKYE SQTSFGSMYP TRIEGATRLF CDVYNPQSKT 550 560 570 580 590 600 YCKRLQVLCP EHSRDPKVPA DEVCGCPLVR DVFELTGDFC RLPKRQCNRH YCWEKLRRAE 610 620 630 640 650 VDLERVRVWY KLDELFEQER NVRTAMTNRA GLLALMLHQT IQHDPLTTDL RSSADR
	Isoform 2 [UniParc]. Checksum: 502AD163711D50E7	FASTA	660	76,227
	10 20 30 40 50 60 MEGDGSDPEP PDAGEDSKSE NGENAPIYCI CRKPDINCFM IGCDNCNEWF HGDCIRITEK 70 80 90 100 110 120 MAKAIREWYC RECREKDPKL EIRYRHKKSR ERDGNERDSS EPRDEGGGRK RPVPDPDLQR 130 140 150 160 170 180 RAGSGTGVGA MLARGSASPH KSSPQPLVAT PSQHHQQQQQ QIKRSARMCG ECEACRRTED 190 200 210 220 230 240 CGHCDFCRDM KKFGGPNKIR QKCRLRQCQL RARESYKYFP SSLSPVTPSE SLPRPRRPLP 250 260 270 280 290 300 TQQQPQPSQK LGRIREDEGA VASSTVKEPP EATATPEPLS DEDLPLDPDL YQDFCAGAFD 310 320 330 340 350 360 DHGLPWMSDT EESPFLDPAL RKRAVKVKHV KRREKKSEKK VMERKEERYK RHRQKQKHKD 370 380 390 400 410 420 KWKHPERADA KDPASLPQCL GPGCVRPAQP SSKYCSDDCG MKLAANRIYE ILPQRIQQWQ 430 440 450 460 470 480 QSPCIAEEHG KKLLERIRRE QQSARTRLQE MERRFHELEA IILRAKQQAV REDEESNEGD 490 500 510 520 530 540 SDDTDLQIFC VSCGHPINPR VALRHMERCY AKYESQTSFG SMYPTRIEGA TRLFCDVYNP 550 560 570 580 590 600 QSKTYCKRLQ VLCPEHSRDP KVPADEVCGC PLVRDVFELT GDFCRLPKRQ CNRHYCWEKL 610 620 630 640 650 660 RRAEVDLERV RVWYKLDELF EQERNVRTAM TNRAGLLALM LHQTIQHDPL TTDLRSSADR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a mammalian transcriptional activator that binds unmethylated CpG motifs and shares a CXXC domain with DNA methyltransferase, human trithorax, and methyl-CpG binding domain protein 1." Voo K.S., Carlone D.L., Jacobsen B.M., Flodin A., Skalnik D.G. Mol. Cell. Biol. 20:2108-2121(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"PCCX1, a novel DNA-binding protein with PHD finger and CXXC domain, is regulated by proteolysis." Fujino T., Hasegawa M., Shibata S., Kishimoto T., Imai S., Takano T. Biochem. Biophys. Res. Commun. 271:305-310(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DNA-BINDING.
[3]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S. Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Cervix, Colon and Skin.
[7]	"Identification and characterization of the DNA binding domain of CpG-binding protein." Lee J.-H., Voo K.S., Skalnik D.G. J. Biol. Chem. 276:44669-44676(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING DOMAIN, MUTAGENESIS OF CYS-169 AND CYS-208.
[8]	"CpG-binding protein is a nuclear matrix- and euchromatin-associated protein localized to nuclear speckles containing human trithorax. Identification of nuclear matrix targeting signals." Lee J.-H., Skalnik D.G. J. Biol. Chem. 277:42259-42267(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"CpG-binding protein (CXXC finger protein 1) is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of the yeast Set1/COMPASS complex." Lee J.-H., Skalnik D.G. J. Biol. Chem. 280:41725-41731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE SET1 COMPLEX.
[10]	"Identification and characterization of the human Set1B histone H3-Lys4 methyltransferase complex." Lee J.-H., Tate C.M., You J.-S., Skalnik D.G. J. Biol. Chem. 282:13419-13428(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN THE SET1 COMPLEX.
[11]	"Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A Histone H3-Lys4 methyltransferase complex to transcription start sites of transcribed human genes." Lee J.H., Skalnik D.G. Mol. Cell. Biol. 28:609-618(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN SET1 COMPLEX, INTERACTION WITH SETD1A.
[12]	"Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS." Wu M., Wang P.F., Lee J.S., Martin-Brown S., Florens L., Washburn M., Shilatifard A. Mol. Cell. Biol. 28:7337-7344(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN SET1 COMPLEX.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-227, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6 AND SER-19, MASS SPECTROMETRY.
[16]	"The structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain." Xu C., Bian C., Lam R., Dong A., Min J. Nat. Commun. 2:227-227(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 161-222 IN COMPLEX WITH DNA, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF149758 mRNA. Translation: AAF37799.1.
AB031069 mRNA. Translation: BAA96307.1.
AL136862 mRNA. Translation: CAB66796.1.
AK314886 mRNA. Translation: BAG37400.1.
AC090246 Genomic DNA. No translation available.
BC014940 mRNA. Translation: AAH14940.1.
BC015733 mRNA. Translation: AAH15733.1.
BC029922 mRNA. Translation: AAH29922.1.

IPI

IPI00292445.
IPI00641026.

RefSeq

NP_001095124.1. NM_001101654.1.
NP_055408.2. NM_014593.3.

UniGene

Hs.180933.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3QMB	X-ray	2.06	A	161-222	[»]
3QMC	X-ray	2.10	A	161-222	[»]
3QMD	X-ray	1.90	A	161-222	[»]
3QMG	X-ray	2.30	A	161-222	[»]
3QMH	X-ray	2.50	A	161-222	[»]
3QMI	X-ray	2.10	A	161-222	[»]

ProteinModelPortal

Q9P0U4.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9P0U4. 3 interactions.

STRING

9606.ENSP00000390475.

PTM databases

PhosphoSite

Q9P0U4.

Polymorphism databases

DMDM

20138037.

Proteomic databases

PaxDb

Q9P0U4.

PRIDE

Q9P0U4.

Protocols and materials databases

DNASU

30827.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000285106; ENSP00000285106; ENSG00000154832.
ENST00000412036; ENSP00000390475; ENSG00000154832.

GeneID

30827.

KEGG

hsa:30827.

UCSC

uc002leq.4. human.
uc002ler.4. human.

Organism-specific databases

CTD

30827.

GeneCards

GC18M047808.

HGNC

HGNC:24343. CXXC1.

HPA

HPA044511.

MIM

609150. gene.

neXtProt

NX_Q9P0U4.

PharmGKB

PA134908762.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG246725.

HOGENOM

HOG000116258.

HOVERGEN

HBG051274.

InParanoid

Q9P0U4.

KO

K14960.

OMA

YESQASF.

OrthoDB

EOG4229JQ.

PhylomeDB

Q9P0U4.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

Bgee

Q9P0U4.

CleanEx

HS_CXXC1.

Genevestigator

Q9P0U4.

GermOnline

ENSG00000154832. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR022056. CpG-bd_C.
IPR019786. Zinc_finger_PHD-type_CS.
IPR002857. Znf_CXXC.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Pfam

PF00628. PHD. 1 hit.
PF12269. zf-CpG_bind_C. 1 hit.
PF02008. zf-CXXC. 1 hit.
[Graphical view]

SMART

SM00249. PHD. 1 hit.
[Graphical view]

SUPFAM

SSF57903. FYVE_PHD_ZnF. 1 hit.

PROSITE

PS51058. ZF_CXXC. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

CXXC1. human.

EvolutionaryTrace

Q9P0U4.

GenomeRNAi

30827.

NextBio

52928.

SOURCE

Search...

Entry information

Entry name

CXXC1_HUMAN

Accession

Primary (citable) accession number: Q9P0U4
Secondary accession number(s): B2RC03 , Q8N2W4, Q96BC8, Q9P2V7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	March 27, 2002
Last modified:	May 1, 2013
This is version 113 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.