Zinc Finger Protein 821, also known as ZNF821, is a protein encoded by the ZNF821 gene. This gene is located on the 16th chromosome and is expressed highly in the testes, moderately expressed in the brain and low expression in 23 other tissues. The protein encoded is 412 amino acids long with 2 Zinc Finger motifs (C2H2 type) and a 23 amino acid long STPR domain.
Gene
Locus ZNF821 is located at 16q22.2 on the minus strand, it is composed of 35,657 bases spanning from base 71,893,583 to 71,929,239. ZNF821 has 8 exons and is located in the same neighborhood as 4 other genes, ATXNL1, IST1, PKD1L3, AP1G1.
Transcriptional Regulation Transcription of ZNF821 is handled by the promoter GXP_9784938 which is 539 bases long and located from base 71,884,046 to 71,884,585. The promoter region begins 404 base pairs upstream of the beginning of transcription. Several transcription factors with scores greater than 0.9 are predicted to regulate ZNF821 expression. Transcription factorAbbreviationBinding SiteStrandMyeloid zinc finger proteinMZF1GTGGGGATCCG +Cyclin D binding myb-like transcription factorDMTFCACCCCTAGGCCCGA -Early growth response 2EGRFGAGAGGGGGTGCCTGCGGC +Human acute myelogenous leukemia factorsHAMLAGCTGTGGTTGGGGG +C2H2 zinc finger transcription factors 2ZF02GACTTGAGCTACCACCCCATTCT -Hypoxia-response elementsHIFFCCATCCCACCGCAAATGTGCAGGTC -Ets variant 1ETSFCACGTCCAGGAAGGTCTGGGG +Homeobox transcription factor NanogHOXFACCCGGGAATGGGCGAGGC +GLIS family zinc finger 3GLIFCGCTCCGCCCCCCAAGG -GTF2I-like repeat 4 of GTF3GUCECGGGATTGGGC +zinc finger protein with KRAB and SCAN domains 12ZF07GGAGCCCCTCCTCTCCA +Myc associated zinc finger proteinMAZFGTCTCGGGGAGAGGAGTCCGGGGCGGGTGTT -Zinc finger and BTB domain containing 14 VF5FCGGTCCGCGCGCGGCCC + , -Transcription factor II B (TFIIB) recognition elementTF2BCCGCGCC -Zinc finger protein 37 alpha ZF37CCTCCCCCT -E2F transcription factor 1E2FFCGCGCGAGGGCGGCGGG -Cas-interacting zinc finger CIZFGTAGAAAAAGG -Sma- and Mad-related proteinsSMADTCTGTCTGTCT +SRY (sex determining region Y)-box 6SORYCAGACAGACAGACGACAACCGAAACAGGCAG -
Expression ZNF821 is highly expressed in the testes, almost 2.5 times as much as in the brain, the next most highly expressed in tissue. Expression in the brain is primarily during fetal development, with lower levels of expression occurring in the cerebellum. There are low levels of expression in most other tissues.
mRNA
Variants and Isoforms ZNF821 has 7 different transcript variants and 4 isoforms. Variant 1 Isoform 1 is the second longest and but most abundant of all the variants and isoforms. While variant 2 is longer, it contains one fewer exon. Variant 1, Isoform 1 is 1987 bases long with a 5' UTR 415 bases long and a 3' UTR 433 bases long. VariantIsoformLength# of Exons1119878212005732189474218796531853764195987417227
Protein
Characteristics The protein encoded by the ZNF821 gene is 412 amino acids long with a calculated molecular weight of ~ 47 kDa and a predicted isoelectric point of 6.14. Compared to the rest of the human proteome, there are decreased amounts of Isoleucine and Tyrosine residues as well as increased levels of Arginine residues.
Structure
ZNF821 protein contains two C2H2 Zinc Finger motifs (spanning amino acids 120-140 and 152–172, respectively) and an STPR (one-score-and-three-amino acid peptide repeat) domain (spanning amino acids 223–314) containing a bipartite nuclear localization signal. This STPR domain is a double-stranded DNA-binding domain with similar traits to the silkworm FMBP-1 STPR domain and is thought to be responsible for the nuclear localization of the ZNF821 protein. The secondary structure of the ZNF821 protein is composed of several alpha helical structures along with two small regions of beta sheets. The tertiary structure of the ZNF821 protein provides exposure of the Zinc Fingers for presumed DNA-binding.
Cellular Localization The ZNF821 protein binds to DNA making it highly likely to be localized to the nucleus, there is also a bipartite nuclear localization sequence from Lys280 to Arg297, Lys304 to Leu320, and Lys338 to Arg354. An analysis of the subcellular localization in both close and distant orthologs resulted in a >99% chance of being localized to the nucleus for all orthologs.
Regulation The ZNF821 protein is predicted to be modified post-translationally at several different positions. When compared with both close and distant orthologous sequences two phosphorylation sites are conserved, the Serine at position 2 and the Threonine at position 7. It is also predicted by several sources to have further phosphorylation sites of the Serine at position 254 and the Tyrosine at position 279.
Interactions Several proteins have been shown to interact with the ZNF821 protein, many of them relating to transcriptional regulation. AbbreviationProtein NameIdentification MethodFunctionATMATM Serine/Threonine kinaseTwo Hybrid ArrayActivates checkpoint signaling upon sensing DNA damageCCDC85BCoiled-coil domain-containing protein 85BTwo Hybrid PoolingTranscriptional RepressorSMARCA2Probable global transcription activator SNF2L2Two Hybrid PoolingTranscriptional activation and repression by chromatin remodelingCDCA7LCell division cycle-associated 7-like proteinTwo Hybrid ArrayTranscriptional RepressorPIM2Serine/threonine-protein kinase Pim-2Two Hybrid ArrayProto-oncogeneDVL3Segment polarity protein dishevelled homolog DVL-3Two Hybrid ArrayCell signal transductionRUNDC3ARUN domain-containing protein 3ATwo Hybrid ArrayEffector of RAPA2AFXR1Fragile X mental retardation syndrome-related protein 1Two Hybrid PoolingRNA-binding protein
Homology
Paralogs ZNF821 has no paralogs in humans.
Orthologs There are orthologs for ZNF821 across vertebrates, but none for the protein in invertebrates. The Zinc Finger motifs are conserved into invertebrates. The STPR domain is only present in mammals. GenusSpeciesCommon nameTaxonomyDate of Divergence (MYA)Sequence length (AA)Sequence identity (%)HomosapiensHumanPrimates0.00412100.00PongoabeliiSumatran OrangutanPrimates15.2041299.76LacertaagilisSand lizardSquamata318.0042976.33Chrysemyspicta belliiWestern Painted turtleTestudines318.0041187.65GopherusevgoodeiSinaloan desert tortoiseTestudines318.0041386.44AntrostomuscarolinensisChuck-will's-widowCaprimulgiformes318.0041186.20ApteryxrowiOkarito kiwiApterygiformes318.0048287.41LeptosomusdiscolorCuckoo rollerLeptosomiformes318.0041085.68XenopuslaevisTwo-lined caecilianGymnophiona351.7040976.76GeotrypetesseraphiniGaboon caecilianGymnophiona351.7037875.26BufobufoCommon toadAnura351.7039566.75RhinatremabivittatumAfrican clawed frogAnura351.7039869.64PygocentrusnattereriRed-bellied piranhaCharaciformes433.0045648.58CyprinuscarpioCommon CarpCypriniformes433.0044149.56PolypterussenegalusSenegal bichirPolypteriformes433.0053954.59ErpetoichthyscalabaricusReedfishPolypteriformes433.0047149.58ParamormyropskingsleyaeOld Calabar mormyridOsteoglossiformes433.0044353.63CarcharodoncarchariasGreat white sharkLamniformes465.0036042.07
The relative rate of divergence is slow when compared to the rates of two reference proteins, Cytochrome c and Fibrinogen alpha, but increases to slightly faster than Cytochrome c as the date of divergence gets closer to the present.
Clinical Significance ZNF821 has been associated in some capacity with several different diseases and conditions. It has been implicated in causing craniosynostosis through interactions with the transcription factor BCL11B by affecting the charges on the arginine-3, arginine-5, and lysine-3 residues, thereby increasing their conformational flexibility. It has also been found to be a possible biomarker for methamphetamine-associated psychosis (MAP) via the process of RNA-degradation. Another disease association is that with breast cancer as part of a DNA-repair sub network. ZNF821 was found to be dysregulated among breast cancer patients. Finally, there is a study showing an increase in methylation over time on ZNF821 in Parkinson's disease patients who did not receive L-dopa/entacapone. This provides a clearer view of changes due only to Parkinson's pathophysiology.
References