ZNF366
Identifiers
Aliases	ZNF366, DCSCRIPT, zinc finger protein 366, DC-SCRIPT
External IDs	OMIM: 610159 MGI: 2178429 HomoloGene: 17637 GeneCards: ZNF366
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q13.2|5q13.2 Start 72,439,903 bp[1] End 72,507,410 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 D1 Start 99,321,331 bp[2] End 99,387,164 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve smooth muscle tissue appendix left ventricle lymph node subcutaneous adipose tissue muscle of leg monocyte gallbladder gastrocnemius muscle Top expressed in lung quadriceps femoris muscle muscle tissue spleen skeletal muscle tissue white adipose tissue adrenal gland cerebellum kidney heart More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding estrogen receptor binding protein binding transcription corepressor activity metal ion binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus Biological process negative regulation of transcription by RNA polymerase II negative regulation of intracellular estrogen receptor signaling pathway regulation of transcription, DNA-templated transcription, DNA-templated response to estrogen Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 167465 238803 Ensembl ENSG00000178175 ENSMUSG00000050919 UniProt Q8N895 Q6NS86 RefSeq (mRNA) NM_152625 NM_001004149 RefSeq (protein) NP_689838 NP_001004149 Location (UCSC) Chr 5: 72.44 – 72.51 Mb Chr 13: 99.32 – 99.39 Mb PubMed search [3] [4]
Wikidata
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Zinc finger protein 366, also known as DC-SCRIPT (Dendritic cell-specific transcript), is a protein that in humans is encoded by the ZNF366 gene.^[5] The ZNF366 gene was first identified in a DNA comparison study between 85 kb of Fugu rubripes sequence containing 17 genes with its homologous loci in the human draft genome.^[6]

Function

In 2006, DC-SCRIPT was isolated and characterized in human monocyte-derived dendritic cells (mo-DCs).^[7]

DC-SCRIPT contains a DNA-binding domain (11 C₂H₂ zinc (Zn) fingers), flanked by a proline-rich and an acidic region, which can interact with C-terminal-binding protein 1 (CtBP1), a global corepressor. In the immune system of both mice and humans, DC-SCRIPT was found to be specifically expressed in dendritic cells (DCs).^[8]

In COS-1 cells, DC-SCRIPT was shown to interact with the estrogen receptor DNA-binding domain (ERDBD) and represses ER activity through the association with RIP140, CtBP and histone deacetylases.^[9]

In DCs, DC-SCRIPT was found to be highly expressed in type one conventional DCs (cDC1s) under the control of PU.1.^[10] The presence of DC-SCRIPT is important for the cDC1s lineage specification via maintaining Interferon regulatory factor 8 (IRF8) expression. The DC-SCRIPT deficient cDC1s had impaired capacity to capture and present cell-associated antigens and to secrete IL-12p40.^[11]

Breast cancer

In 2010, it was shown that DC-SCRIPT can act as a coregulator of multiple nuclear receptors having opposite effects on type I vs type II NRs. DC-SCRIPT is able to repress ER and PR mediated transcription, whereas it can activate transcription mediated by RAR and PPAR. In the same study, it was shown that breast tumor tissue expresses lower levels of DC-SCRIPT than normal breast tissue from the same patient and that DC-SCRIPT mRNA expression is an independent prognostic factor for good survival of breast cancer patients with estrogen receptor- and/or progesterone receptor-positive tumors.^[12]