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Protein

Zinc finger protein 304

Gene

ZNF304

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as transcriptional regulator and plays a role in gene silencing (PubMed:24623306, PubMed:26081979). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of several tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) by inducing trimethylation of 'Lys-27' of histone H3 (H3K27me3) (PubMed:24623306) in a Polycomb group (PcG) complexes-dependent manner. Associates at promoter regions of TSGs and mediates the recruitment of the corepressor complex containing the scaffolding protein TRIM28, methyltransferase DNMT1 and histone methyltransferase SETDB1 and/or the PcG complexes at those sites (PubMed:24623306). Transcription factor involved in the metastatic cascade process by inducing cell migration and proliferation and gain resistance to anoikis of ovarian carcinoma (OC) cells via integrin-mediated signaling pathways (PubMed:26081979). Associates with the ITGB1 promoter and positively regulates beta-1 integrin transcription expression (PubMed:26081979). Promotes angiogenesis (PubMed:26081979). Promotes tumor growth (PubMed:24623306, PubMed:26081979).2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri89 – 11123C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri115 – 13925C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri251 – 27323C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri279 – 30123C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri307 – 32923C2H2-type 5PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri335 – 35723C2H2-type 6PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri363 – 38523C2H2-type 7PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri391 – 41323C2H2-type 8PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri419 – 44123C2H2-type 9PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri447 – 46923C2H2-type 10PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri475 – 49723C2H2-type 11PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri503 – 52523C2H2-type 12PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri531 – 55323C2H2-type 13PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri559 – 58123C2H2-type 14PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri587 – 60923C2H2-type 15PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri615 – 63723C2H2-type 16PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • chromatin modification Source: UniProtKB-KW
  • integrin-mediated signaling pathway Source: UniProtKB
  • negative regulation of anoikis Source: UniProtKB
  • negative regulation of chromatin binding Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of epithelial cell proliferation Source: UniProtKB
  • positive regulation of histone H3-K27 trimethylation Source: UniProtKB
  • positive regulation of histone H3-K9 trimethylation Source: UniProtKB
  • positive regulation of methylation-dependent chromatin silencing Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • Ras protein signal transduction Source: UniProtKB
  • regulation of transcription, DNA-templated Source: GO_Central
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator

Keywords - Biological processi

Angiogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-212436. Generic Transcription Pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein 304Imported
Alternative name(s):
KRAB-containing zinc finger protein1 Publication
Gene namesi
Name:ZNF304Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:13505. ZNF304.

Subcellular locationi

  • Nucleus 1 Publication

  • Note: Associates with chromatin (PubMed:24623306).1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37791.

Polymorphism and mutation databases

BioMutaiZNF304.
DMDMi296453049.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 659659Zinc finger protein 304PRO_0000047523Add
BLAST

Post-translational modificationi

Deubiquitinated by USP28; the deubiquitination leads to the stabilization of ZNF304 from proteolytic degradation (PubMed:24623306).1 Publication

Proteomic databases

MaxQBiQ9HCX3.
PaxDbiQ9HCX3.
PRIDEiQ9HCX3.

PTM databases

PhosphoSiteiQ9HCX3.

Expressioni

Tissue specificityi

Expressed in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Expressed strongly in colorectal cancers cells (CRCs) (PubMed:24623306). Expressed strongly in ovarian carcinoma (OC) tumor cell lines compared to non-transformed ovarian epithelial cells (at protein level) (PubMed:26081979). Expressed in lymphoid tissues, thyroid, adrenal gland, prostate, pancreas and skeletal muscles (PubMed:12051768).3 Publications

Inductioni

Down-regulated during embryonic stem cells (ESCs) differentiation by retinoic acid treatment (PubMed:24623306).1 Publication

Gene expression databases

BgeeiQ9HCX3.
CleanExiHS_ZNF304.
ExpressionAtlasiQ9HCX3. baseline and differential.
GenevisibleiQ9HCX3. HS.

Organism-specific databases

HPAiHPA050531.
HPA054236.

Interactioni

Subunit structurei

Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1; leading to promoter hypermethylation and transcriptional silencing (PubMed:24623306). Probably associates with Polycomb group (PcG) complexes; leading to trimethylation of 'Lys-27' of histone H3 (H3K27me3) (PubMed:24623306). Interacts with USP28 (PubMed:24623306).1 Publication

Protein-protein interaction databases

STRINGi9606.ENSP00000282286.

Structurei

3D structure databases

ProteinModelPortaliQ9HCX3.
SMRiQ9HCX3. Positions 103-638.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 8875KRABPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 16 C2H2-type zinc fingers.PROSITE-ProRule annotation
Contains 1 KRAB domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri89 – 11123C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri115 – 13925C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri251 – 27323C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri279 – 30123C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri307 – 32923C2H2-type 5PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri335 – 35723C2H2-type 6PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri363 – 38523C2H2-type 7PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri391 – 41323C2H2-type 8PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri419 – 44123C2H2-type 9PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri447 – 46923C2H2-type 10PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri475 – 49723C2H2-type 11PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri503 – 52523C2H2-type 12PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri531 – 55323C2H2-type 13PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri559 – 58123C2H2-type 14PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri587 – 60923C2H2-type 15PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri615 – 63723C2H2-type 16PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00760000119107.
HOGENOMiHOG000234617.
HOVERGENiHBG018163.
InParanoidiQ9HCX3.
PhylomeDBiQ9HCX3.
TreeFamiTF339848.

Family and domain databases

Gene3Di3.30.160.60. 14 hits.
InterProiIPR001909. KRAB.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF01352. KRAB. 1 hit.
PF00096. zf-C2H2. 9 hits.
[Graphical view]
SMARTiSM00349. KRAB. 1 hit.
SM00355. ZnF_C2H2. 16 hits.
[Graphical view]
SUPFAMiSSF109640. SSF109640. 1 hit.
PROSITEiPS50805. KRAB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 16 hits.
PS50157. ZINC_FINGER_C2H2_2. 15 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9HCX3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAVLMDRV QSCVTFEDVF VYFSREEWEL LEEAQRFLYR DVMLENFALV
60 70 80 90 100
ATLGFWCEAE HEAPSEQSVS VEGVSQVRTA ESGLFQKAHP CEMCDPLLKD
110 120 130 140 150
ILHLAEHQGS HLTQKLCTRG LCRRRFSFSA NFYQHQKQHN GENCFRGDDG
160 170 180 190 200
GASFVKSCTV HMLGRSFTCR EEGMDLPDSS GLFQHQTTYN RVSPCRRTEC
210 220 230 240 250
MESFPHSSSL RQHQGDYDGQ MLFSCGDEGK AFLDTFTLLD SQMTHAEVRP
260 270 280 290 300
FRCLPCGNVF KEKSALINHR KIHSGEISHV CKECGKAFIH LHHLKMHQKF
310 320 330 340 350
HTGKRHYTCS ECGKAFSRKD TLVQHQRVHT GERSYDCSEC GKAYSRSSHL
360 370 380 390 400
VQHQRIHTGE RPYKCNKCGK AFSRKDTLVQ HQRFHTGERP YECSECGKFF
410 420 430 440 450
SQSSHLIEHW RIHTGARPYE CIECGKFFSH NSSLIKHRRV HTGARSYVCS
460 470 480 490 500
KCGKAFGCKD TLVQHQIIHT GARPYECSEC GKAFSRKDTL VQHQKIHTGE
510 520 530 540 550
RPYECGECGK FFSHSSNLIV HQRIHTGAKP YECNECGKCF SHNSSLILHQ
560 570 580 590 600
RVHTGARPYV CSECGKAYIS SSHLVQHKKV HTGARPYECS ECGKFFSRNS
610 620 630 640 650
GLILHQRVHT GEKPYVCSEC GKAYSRSSHL VRHQKAHTGE RAHECNSFGG

PLAASLKLV
Length:659
Mass (Da):75,047
Last modified:May 18, 2010 - v2
Checksum:i11B5263F41DB2704
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti323 – 3231V → A in CAC06610 (PubMed:12051768).Curated
Sequence conflicti334 – 3341S → P in CAC06610 (PubMed:12051768).Curated
Sequence conflicti445 – 4451R → S in CAC06610 (PubMed:12051768).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti121 – 1211L → P.
Corresponds to variant rs862708 [ dbSNP | Ensembl ].
VAR_019979
Natural varianti367 – 3671K → E.1 Publication
Corresponds to variant rs862709 [ dbSNP | Ensembl ].
VAR_033563

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ276316 mRNA. Translation: CAC06610.1.
AC005261 Genomic DNA. No translation available.
CCDSiCCDS12950.1.
RefSeqiNP_065708.2. NM_020657.3.
UniGeneiHs.287374.

Genome annotation databases

EnsembliENST00000282286; ENSP00000282286; ENSG00000131845.
ENST00000391705; ENSP00000375586; ENSG00000131845.
GeneIDi57343.
UCSCiuc010ygw.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ276316 mRNA. Translation: CAC06610.1.
AC005261 Genomic DNA. No translation available.
CCDSiCCDS12950.1.
RefSeqiNP_065708.2. NM_020657.3.
UniGeneiHs.287374.

3D structure databases

ProteinModelPortaliQ9HCX3.
SMRiQ9HCX3. Positions 103-638.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000282286.

PTM databases

PhosphoSiteiQ9HCX3.

Polymorphism and mutation databases

BioMutaiZNF304.
DMDMi296453049.

Proteomic databases

MaxQBiQ9HCX3.
PaxDbiQ9HCX3.
PRIDEiQ9HCX3.

Protocols and materials databases

DNASUi57343.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282286; ENSP00000282286; ENSG00000131845.
ENST00000391705; ENSP00000375586; ENSG00000131845.
GeneIDi57343.
UCSCiuc010ygw.3. human.

Organism-specific databases

CTDi57343.
GeneCardsiZNF304.
HGNCiHGNC:13505. ZNF304.
HPAiHPA050531.
HPA054236.
MIMi613840. gene.
neXtProtiNX_Q9HCX3.
PharmGKBiPA37791.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00760000119107.
HOGENOMiHOG000234617.
HOVERGENiHBG018163.
InParanoidiQ9HCX3.
PhylomeDBiQ9HCX3.
TreeFamiTF339848.

Enzyme and pathway databases

ReactomeiR-HSA-212436. Generic Transcription Pathway.

Miscellaneous databases

GenomeRNAii57343.
NextBioi63464.
PROiQ9HCX3.
SOURCEiSearch...

Gene expression databases

BgeeiQ9HCX3.
CleanExiHS_ZNF304.
ExpressionAtlasiQ9HCX3. baseline and differential.
GenevisibleiQ9HCX3. HS.

Family and domain databases

Gene3Di3.30.160.60. 14 hits.
InterProiIPR001909. KRAB.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF01352. KRAB. 1 hit.
PF00096. zf-C2H2. 9 hits.
[Graphical view]
SMARTiSM00349. KRAB. 1 hit.
SM00355. ZnF_C2H2. 16 hits.
[Graphical view]
SUPFAMiSSF109640. SSF109640. 1 hit.
PROSITEiPS50805. KRAB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 16 hits.
PS50157. ZINC_FINGER_C2H2_2. 15 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a KRAB-containing zinc finger protein, ZNF304, by AU-motif-directed display method and initial characterization in lymphocyte activation."
    Sabater L., Ashhab Y., Caro P., Kolkowski E.C., Pujol-Borrell R., Dominguez O.
    Biochem. Biophys. Res. Commun. 293:1066-1072(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-367, TISSUE SPECIFICITY.
    Tissue: Thymus.
  2. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype."
    Serra R.W., Fang M., Park S.M., Hutchinson L., Green M.R.
    Elife 3:E02313-E02313(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH USP28, POSSIBLE IDENTIFICATION IN A COREPRESSOR COMPLEX, CHROMATIN-BINDING, DEUBIQUITINATION BY USP28, TISSUE SPECIFICITY, INDUCTION.
  4. Cited for: FUNCTION, DNA-BINDING, TISSUE SPECIFICITY.

Entry informationi

Entry nameiZN304_HUMAN
AccessioniPrimary (citable) accession number: Q9HCX3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: May 18, 2010
Last modified: May 11, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.