CXXC4_HUMAN
ID CXXC4_HUMAN Reviewed; 198 AA.
AC Q9H2H0;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=CXXC-type zinc finger protein 4;
DE AltName: Full=Inhibition of the Dvl and axin complex protein;
GN Name=CXXC4; Synonyms=IDAX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11113207; DOI=10.1128/mcb.21.1.330-342.2001;
RA Hino S., Kishida S., Michiue T., Fukui A., Sakamoto I., Takada S.,
RA Asashima M., Kikuchi A.;
RT "Inhibition of the Wnt signaling pathway by Idax, a novel Dvl-binding
RT protein.";
RL Mol. Cell. Biol. 21:330-342(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5] {ECO:0007744|PDB:5VC9}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 133-180 IN COMPLEX WITH CPG DNA,
RP FUNCTION, DOMAIN CXXC-TYPE ZINC-FINGER, AND ZINC-BINDING.
RX PubMed=29276034; DOI=10.1016/j.str.2017.11.022;
RA Xu C., Liu K., Lei M., Yang A., Li Y., Hughes T.R., Min J.;
RT "DNA Sequence Recognition of Human CXXC Domains and Their Structural
RT Determinants.";
RL Structure 26:85-95.e3(2018).
CC -!- FUNCTION: Acts as a negative regulator of the Wnt signaling pathway via
CC its interaction with DVL1 (By similarity). Binds preferentially to DNA
CC containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH
CC (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-
CC CpG (PubMed:29276034). {ECO:0000250|UniProtKB:Q6NXI8,
CC ECO:0000269|PubMed:29276034}.
CC -!- SUBUNIT: Interacts with the PDZ domain of DVL1.
CC {ECO:0000250|UniProtKB:Q9EQC9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9EQC9}.
CC -!- DOMAIN: The CXXC zinc finger mediates binding to CpG-DNA.
CC {ECO:0000269|PubMed:29276034}.
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DR EMBL; AF272159; AAG42072.1; -; mRNA.
DR EMBL; AC093628; AAY40933.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX06175.1; -; Genomic_DNA.
DR EMBL; BC119751; AAI19752.1; -; mRNA.
DR EMBL; BC119752; AAI19753.1; -; mRNA.
DR PDB; 5VC9; X-ray; 2.10 A; C/F=133-180.
DR PDBsum; 5VC9; -.
DR AlphaFoldDB; Q9H2H0; -.
DR SMR; Q9H2H0; -.
DR IntAct; Q9H2H0; 7.
DR STRING; 9606.ENSP00000378248; -.
DR iPTMnet; Q9H2H0; -.
DR PhosphoSitePlus; Q9H2H0; -.
DR BioMuta; CXXC4; -.
DR DMDM; 74752605; -.
DR MassIVE; Q9H2H0; -.
DR PaxDb; Q9H2H0; -.
DR PeptideAtlas; Q9H2H0; -.
DR PRIDE; Q9H2H0; -.
DR ProteomicsDB; 80549; -.
DR GeneCards; CXXC4; -.
DR HGNC; HGNC:24593; CXXC4.
DR MIM; 611645; gene.
DR neXtProt; NX_Q9H2H0; -.
DR PharmGKB; PA134992016; -.
DR eggNOG; ENOG502QQVJ; Eukaryota.
DR InParanoid; Q9H2H0; -.
DR PhylomeDB; Q9H2H0; -.
DR TreeFam; TF326617; -.
DR PathwayCommons; Q9H2H0; -.
DR Reactome; R-HSA-5368598; Negative regulation of TCF-dependent signaling by DVL-interacting proteins.
DR SignaLink; Q9H2H0; -.
DR ChiTaRS; CXXC4; human.
DR Pharos; Q9H2H0; Tbio.
DR PRO; PR:Q9H2H0; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q9H2H0; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; IPI:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0007352; P:zygotic specification of dorsal/ventral axis; ISS:BHF-UCL.
DR InterPro; IPR040388; CXXC4/CXXC5.
DR InterPro; IPR002857; Znf_CXXC.
DR PANTHER; PTHR13419; PTHR13419; 1.
DR Pfam; PF02008; zf-CXXC; 1.
DR PROSITE; PS51058; ZF_CXXC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; DNA-binding; Metal-binding; Reference proteome;
KW Wnt signaling pathway; Zinc; Zinc-finger.
FT CHAIN 1..198
FT /note="CXXC-type zinc finger protein 4"
FT /id="PRO_0000317542"
FT ZN_FING 132..173
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034"
FT REGION 114..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 161..166
FT /note="Interaction with DVL1"
FT /evidence="ECO:0000250|UniProtKB:Q9EQC9"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:5VC9"
FT BINDING 142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:5VC9"
FT BINDING 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:5VC9"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:5VC9"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:5VC9"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:5VC9"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:5VC9"
FT BINDING 172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:5VC9"
FT HELIX 143..146
FT /evidence="ECO:0007829|PDB:5VC9"
FT HELIX 155..158
FT /evidence="ECO:0007829|PDB:5VC9"
FT HELIX 160..163
FT /evidence="ECO:0007829|PDB:5VC9"
FT TURN 168..170
FT /evidence="ECO:0007829|PDB:5VC9"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:5VC9"
SQ SEQUENCE 198 AA; 20978 MW; 9D9F7FAD11A9B759 CRC64;
MHHRNDSQRL GKAGCPPEPS LQMANTNFLS TLSPEHCRPL AGECMNKLKC GAAEAEIMNL
PERVGTFSAI PALGGISLPP GVIVMTALHS PAAASAAVTD SAFQIANLAD CPQNHSSSSS
SSSGGAGGAN PAKKKRKRCG VCVPCKRLIN CGVCSSCRNR KTGHQICKFR KCEELKKKPG
TSLERTPVPS AEAFRWFF
