UniProtKB - Q9HCX3 (ZN304_HUMAN)
Protein
Zinc finger protein 304
Gene
ZNF304
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 89 – 111 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 115 – 139 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 251 – 273 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 279 – 301 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 307 – 329 | C2H2-type 5PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 335 – 357 | C2H2-type 6PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 363 – 385 | C2H2-type 7PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 391 – 413 | C2H2-type 8PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 419 – 441 | C2H2-type 9PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 447 – 469 | C2H2-type 10PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 475 – 497 | C2H2-type 11PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 503 – 525 | C2H2-type 12PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 531 – 553 | C2H2-type 13PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 559 – 581 | C2H2-type 14PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 587 – 609 | C2H2-type 15PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 615 – 637 | C2H2-type 16PROSITE-ProRule annotationAdd BLAST | 23 |
GO - Molecular functioni
- DNA binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- promoter-specific chromatin binding Source: UniProtKB
GO - Biological processi
- angiogenesis Source: UniProtKB-KW
- chromatin organization 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 by RNA polymerase II Source: UniProtKB
- Ras protein signal transduction Source: UniProtKB
Keywordsi
Molecular function | Activator, Chromatin regulator, DNA-binding |
Biological process | Angiogenesis, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-HSA-212436 Generic Transcription Pathway |
Names & Taxonomyi
Protein namesi | Recommended name: Zinc finger protein 304ImportedAlternative name(s): KRAB-containing zinc finger protein1 Publication |
Gene namesi | Name:ZNF304Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:13505 ZNF304 |
MIMi | 613840 gene |
neXtProti | NX_Q9HCX3 |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 57343 |
OpenTargetsi | ENSG00000131845 |
PharmGKBi | PA37791 |
Miscellaneous databases
Pharosi | Q9HCX3 |
Polymorphism and mutation databases
BioMutai | ZNF304 |
DMDMi | 296453049 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000047523 | 1 – 659 | Zinc finger protein 304Add BLAST | 659 |
Post-translational modificationi
Deubiquitinated by USP28; the deubiquitination leads to the stabilization of ZNF304 from proteolytic degradation (PubMed:24623306).1 Publication
Proteomic databases
MassIVEi | Q9HCX3 |
MaxQBi | Q9HCX3 |
PaxDbi | Q9HCX3 |
PeptideAtlasi | Q9HCX3 |
PRIDEi | Q9HCX3 |
ProteomicsDBi | 81804 |
PTM databases
iPTMneti | Q9HCX3 |
PhosphoSitePlusi | Q9HCX3 |
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
Bgeei | ENSG00000131845 Expressed in 211 organ(s), highest expression level in secondary oocyte |
ExpressionAtlasi | Q9HCX3 baseline and differential |
Genevisiblei | Q9HCX3 HS |
Organism-specific databases
HPAi | HPA050531 |
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 PublicationProtein-protein interaction databases
BioGridi | 121493, 3 interactors |
CORUMi | Q9HCX3 |
STRINGi | 9606.ENSP00000375586 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 14 – 88 | KRABPROSITE-ProRule annotationAdd BLAST | 75 |
Sequence similaritiesi
Belongs to the krueppel C2H2-type zinc-finger protein family.Curated
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 89 – 111 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 115 – 139 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 251 – 273 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 279 – 301 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 307 – 329 | C2H2-type 5PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 335 – 357 | C2H2-type 6PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 363 – 385 | C2H2-type 7PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 391 – 413 | C2H2-type 8PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 419 – 441 | C2H2-type 9PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 447 – 469 | C2H2-type 10PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 475 – 497 | C2H2-type 11PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 503 – 525 | C2H2-type 12PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 531 – 553 | C2H2-type 13PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 559 – 581 | C2H2-type 14PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 587 – 609 | C2H2-type 15PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 615 – 637 | C2H2-type 16PROSITE-ProRule annotationAdd BLAST | 23 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG1721 Eukaryota COG5048 LUCA |
GeneTreei | ENSGT00940000161016 |
HOGENOMi | HOG000234617 |
InParanoidi | Q9HCX3 |
KOi | K09228 |
OrthoDBi | 1318335at2759 |
PhylomeDBi | Q9HCX3 |
TreeFami | TF339848 |
Family and domain databases
CDDi | cd07765 KRAB_A-box, 1 hit |
InterProi | View protein in InterPro IPR001909 KRAB IPR036051 KRAB_dom_sf IPR036236 Znf_C2H2_sf IPR013087 Znf_C2H2_type |
Pfami | View protein in Pfam PF01352 KRAB, 1 hit PF00096 zf-C2H2, 11 hits |
SMARTi | View protein in SMART SM00349 KRAB, 1 hit SM00355 ZnF_C2H2, 16 hits |
SUPFAMi | SSF109640 SSF109640, 1 hit SSF57667 SSF57667, 10 hits |
PROSITEi | View protein in PROSITE PS50805 KRAB, 1 hit PS00028 ZINC_FINGER_C2H2_1, 16 hits PS50157 ZINC_FINGER_C2H2_2, 15 hits |
i Sequence
Sequence statusi: Complete.
Q9HCX3-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 323 | V → A in CAC06610 (PubMed:12051768).Curated | 1 | |
Sequence conflicti | 334 | S → P in CAC06610 (PubMed:12051768).Curated | 1 | |
Sequence conflicti | 445 | R → S in CAC06610 (PubMed:12051768).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019979 | 121 | L → P. Corresponds to variant dbSNP:rs862708Ensembl. | 1 | |
Natural variantiVAR_033563 | 367 | K → E1 PublicationCorresponds to variant dbSNP:rs862709Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ276316 mRNA Translation: CAC06610.1 AC005261 Genomic DNA No translation available. |
CCDSi | CCDS12950.1 |
RefSeqi | NP_065708.2, NM_020657.3 |
Genome annotation databases
GeneIDi | 57343 |
KEGGi | hsa:57343 |
UCSCi | uc010ygw.3 human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ276316 mRNA Translation: CAC06610.1 AC005261 Genomic DNA No translation available. |
CCDSi | CCDS12950.1 |
RefSeqi | NP_065708.2, NM_020657.3 |
3D structure databases
SMRi | Q9HCX3 |
ModBasei | Search... |
Protein-protein interaction databases
BioGridi | 121493, 3 interactors |
CORUMi | Q9HCX3 |
STRINGi | 9606.ENSP00000375586 |
PTM databases
iPTMneti | Q9HCX3 |
PhosphoSitePlusi | Q9HCX3 |
Polymorphism and mutation databases
BioMutai | ZNF304 |
DMDMi | 296453049 |
Proteomic databases
MassIVEi | Q9HCX3 |
MaxQBi | Q9HCX3 |
PaxDbi | Q9HCX3 |
PeptideAtlasi | Q9HCX3 |
PRIDEi | Q9HCX3 |
ProteomicsDBi | 81804 |
Protocols and materials databases
DNASUi | 57343 |
Genome annotation databases
GeneIDi | 57343 |
KEGGi | hsa:57343 |
UCSCi | uc010ygw.3 human |
Organism-specific databases
CTDi | 57343 |
DisGeNETi | 57343 |
GeneCardsi | ZNF304 |
HGNCi | HGNC:13505 ZNF304 |
HPAi | HPA050531 |
MIMi | 613840 gene |
neXtProti | NX_Q9HCX3 |
OpenTargetsi | ENSG00000131845 |
PharmGKBi | PA37791 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1721 Eukaryota COG5048 LUCA |
GeneTreei | ENSGT00940000161016 |
HOGENOMi | HOG000234617 |
InParanoidi | Q9HCX3 |
KOi | K09228 |
OrthoDBi | 1318335at2759 |
PhylomeDBi | Q9HCX3 |
TreeFami | TF339848 |
Enzyme and pathway databases
Reactomei | R-HSA-212436 Generic Transcription Pathway |
Miscellaneous databases
GenomeRNAii | 57343 |
Pharosi | Q9HCX3 |
PROi | PR:Q9HCX3 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000131845 Expressed in 211 organ(s), highest expression level in secondary oocyte |
ExpressionAtlasi | Q9HCX3 baseline and differential |
Genevisiblei | Q9HCX3 HS |
Family and domain databases
CDDi | cd07765 KRAB_A-box, 1 hit |
InterProi | View protein in InterPro IPR001909 KRAB IPR036051 KRAB_dom_sf IPR036236 Znf_C2H2_sf IPR013087 Znf_C2H2_type |
Pfami | View protein in Pfam PF01352 KRAB, 1 hit PF00096 zf-C2H2, 11 hits |
SMARTi | View protein in SMART SM00349 KRAB, 1 hit SM00355 ZnF_C2H2, 16 hits |
SUPFAMi | SSF109640 SSF109640, 1 hit SSF57667 SSF57667, 10 hits |
PROSITEi | View protein in PROSITE PS50805 KRAB, 1 hit PS00028 ZINC_FINGER_C2H2_1, 16 hits PS50157 ZINC_FINGER_C2H2_2, 15 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ZN304_HUMAN | |
Accessioni | Q9HCX3Primary (citable) accession number: Q9HCX3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 19, 2002 |
Last sequence update: | May 18, 2010 | |
Last modified: | October 16, 2019 | |
This is version 159 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - SIMILARITY comments
Index of protein domains and families - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot