Human Gene HIST3H3 (uc001hsx.1) Description and Page Index
  Description: Homo sapiens histone cluster 3, H3 (HIST3H3), mRNA.
RefSeq Summary (NM_003493): Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H3 family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is located separately from the other H3 genes that are in the histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript is intronless :: BC069079.1 [ECO:0000345] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on single protein-coding transcript replication-dependent histone :: PMID: 12408966 ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr1:228,612,546-228,613,026 Size: 481 Total Exon Count: 1 Strand: -
Coding Region
   Position: hg19 chr1:228,612,616-228,613,026 Size: 411 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:228,612,546-228,613,026)mRNA (may differ from genome)Protein (136 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
HGNCHPRDLynxMGIneXtProtOMIM
PubMedReactomeStanford SOURCETreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: H31T_HUMAN
DESCRIPTION: RecName: Full=Histone H3.1t; Short=H3/t; Short=H3t; AltName: Full=H3/g;
FUNCTION: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
SUBUNIT: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.
INTERACTION: O60341:KDM1A; NbExp=2; IntAct=EBI-358900, EBI-710124; O75164:KDM4A; NbExp=6; IntAct=EBI-358900, EBI-936709;
SUBCELLULAR LOCATION: Nucleus. Chromosome.
TISSUE SPECIFICITY: Expressed in testicular cells.
DEVELOPMENTAL STAGE: Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.
PTM: Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me) (By similarity).
PTM: Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription (By similarity).
PTM: Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).
PTM: Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double- strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication (By similarity).
PTM: Phosphorylated at Thr-4 (H3T3ph) by GSG2/haspin during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MLTK isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin (By similarity).
PTM: Ubiquitinated (By similarity).
PTM: Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).
SIMILARITY: Belongs to the histone H3 family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): HIST3H3
CDC HuGE Published Literature: HIST3H3
Positive Disease Associations: Body Mass Index , Body Weight , Waist Circumference
Related Studies:
  1. Body Mass Index
    , , . [PubMed 0]
  2. Body Weight
    , , . [PubMed 0]
  3. Waist Circumference
    , , . [PubMed 0]
           more ... click here to view the complete list

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 2.44 RPKM in Testis
Total median expression: 4.32 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -21.0070-0.300 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009072 - Histone-fold
IPR007125 - Histone_core_D
IPR000164 - Histone_H3

Pfam Domains:
PF00125 - Core histone H2A/H2B/H3/H4

SCOP Domains:
47113 - Histone-fold

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2V1D
- X-ray

2YBP
- X-ray MuPIT

2YBS
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3A6N - X-ray MuPIT 3T6R - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q16695
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
      
      
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0005515 protein binding
GO:0031492 nucleosomal DNA binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0006303 double-strand break repair via nonhomologous end joining
GO:0006334 nucleosome assembly
GO:0016233 telomere capping
GO:0032460 negative regulation of protein oligomerization
GO:0051290 protein heterotetramerization

Cellular Component:
GO:0000784 nuclear chromosome, telomeric region
GO:0000786 nucleosome
GO:0000788 nuclear nucleosome
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  LF213218 - JP 2014500723-A/20721: Polycomb-Associated Non-Coding RNAs.
BC101837 - Homo sapiens histone cluster 3, H3, mRNA (cDNA clone MGC:126886 IMAGE:8069343), complete cds.
BC101839 - Homo sapiens histone cluster 3, H3, mRNA (cDNA clone MGC:126888 IMAGE:8069345), complete cds.
BC069079 - Homo sapiens histone cluster 3, H3, mRNA (cDNA clone MGC:95354 IMAGE:7216893), complete cds.
JD139645 - Sequence 120669 from Patent EP1572962.
AK312217 - Homo sapiens cDNA, FLJ92506, Homo sapiens histone 3, H3 (HIST3H3), mRNA.
KJ897820 - Synthetic construct Homo sapiens clone ccsbBroadEn_07214 HIST3H3 gene, encodes complete protein.
CR542013 - Homo sapiens full open reading frame cDNA clone RZPDo834E0435D for gene HIST3H3, histone 3, H3; complete cds, without stopcodon.
DQ575776 - Homo sapiens piRNA piR-43888, complete sequence.
DQ574441 - Homo sapiens piRNA piR-42553, complete sequence.
DQ587912 - Homo sapiens piRNA piR-55024, complete sequence.
MA448795 - JP 2018138019-A/20721: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05322 - Systemic lupus erythematosus

Reactome (by CSHL, EBI, and GO)

Protein Q16695 (Reactome details) participates in the following event(s):

R-HSA-176700 Incorporation Of Extended And Processed Telomere End Into Higher Order T-Loop And Associated Protein Structure
R-HSA-181450 Incorporation Of Extended And Processed Telomere End Into Associated Protein Structure
R-HSA-5683930 WICH phosphorylates H2AFX on Y142
R-HSA-5684071 RNF4 ubiquitinates MDC1
R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break
R-HSA-5693602 ATM recognizes H2AFX-Nucleosomes
R-HSA-3451147 KAT5 HAT complex acetylates TCF4 gene at histone H4
R-HSA-912467 BRCA1 is recruited to unsynapsed regions
R-HSA-912470 ATR phosphorylates Histone H2A.X at unsynapsed regions
R-HSA-5693583 MDC1 associates with gamma-H2AFX at nuclear foci
R-HSA-5683967 EYA1-4 dephosphorylates tyrosine Y142 of H2AFX
R-HSA-5693549 ATM phosphorylates histone H2AFX on S139 at DNA DSBs
R-HSA-5683986 APBB1 and MAPK8 bind diphosphorylated H2AFX
R-HSA-912450 ATR Kinase is recruited to unsynapsed regions
R-HSA-5682967 WHSC1 binds DNA DSBs
R-HSA-5693536 ATM phosphorylates MDC1
R-HSA-5683964 ATM phosphorylates EYA1-4
R-HSA-3364026 SET1 complex trimethylates H3K4 at the MYC gene
R-HSA-2288097 Condensin II complex binds H4K20me1-containing nucleosomes
R-HSA-2245218 CDK1 phosphorylates PHF8
R-HSA-5682983 ATM phosphorylates WHSC1
R-HSA-5682965 WHSC1 dimethylates histone H4 on lysine K21 at DSBs
R-HSA-5682992 KDM4A,B bind H4K20Me2
R-HSA-2172678 PHF8 demethylates histone H4K20me1
R-HSA-2301205 SETD8 monomethylates histone H4
R-HSA-2294600 CDK1 phosphorylates condensin II subunit NCAPD3
R-HSA-2294580 PLK1 hyperphosphorylates Condensin II complex
R-HSA-2294590 PLK1 binds phosphorylated condensin II complex
R-HSA-5682588 RNF8 binds phosphorylated MDC1 at DNA DSBs
R-HSA-5693566 TP53BP1 associates with H4K20Me2 at DNA DSBs
R-HSA-5683077 RNF8 and RNF168 ubiquitinate KDM4A,B
R-HSA-5682586 HERC2 and PIAS4 are recruited to DNA DSBs
R-HSA-5682629 HERC2 facilitates UBE2N:UBE2V2 binding to RNF8
R-HSA-5682607 PIAS4 SUMOylates HERC2 with SUMO1 at DNA DSBs
R-HSA-5682863 RNF168 binds DNA DSBs
R-HSA-5682858 RNF8 and RNF168 ubiquitinate H2AFX
R-HSA-5683384 UIMC1 and FAM175A bind DNA DSBs
R-HSA-5683405 PPP5C dephosphorylates TP53BP1
R-HSA-5683425 ATM phosphorylates TP53BP1 at DNA DSBs
R-HSA-5682598 ATM phosphorylates HERC2
R-HSA-5693551 Phosphorylation of BRCA1-A complex at multiple sites by ATM
R-HSA-5683385 Formation of BRCA1-A complex at DNA DSBs
R-HSA-5683735 CHEK2 is recruited to DNA DSBs
R-HSA-5683801 CHEK2 phosphorylates BRCA1
R-HSA-69891 Phosphorylation and activation of CHEK2 by ATM
R-HSA-5684052 PIAS4 SUMOylates MDC1
R-HSA-5686685 RIF1 and PAX1IP bind TP53BP1 at DNA DSBs
R-HSA-5686900 TP53BP1 recruits DCLRE1C to ATM
R-HSA-5686704 Activated ATM phosphorylates DCLRE1C
R-HSA-171306 Packaging Of Telomere Ends
R-HSA-912446 Meiotic recombination
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-1221632 Meiotic synapsis
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence
R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex
R-HSA-157579 Telomere Maintenance
R-HSA-1500620 Meiosis
R-HSA-5693606 DNA Double Strand Break Response
R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-5693532 DNA Double-Strand Break Repair
R-HSA-2559583 Cellular Senescence
R-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-73886 Chromosome Maintenance
R-HSA-1474165 Reproduction
R-HSA-1640170 Cell Cycle
R-HSA-5693538 Homology Directed Repair
R-HSA-73894 DNA Repair
R-HSA-2299718 Condensation of Prophase Chromosomes
R-HSA-2262752 Cellular responses to stress
R-HSA-195721 Signaling by WNT
R-HSA-68875 Mitotic Prophase
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-162582 Signal Transduction
R-HSA-68886 M Phase
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-69473 G2/M DNA damage checkpoint
R-HSA-69481 G2/M Checkpoints
R-HSA-69620 Cell Cycle Checkpoints

-  Other Names for This Gene
  Alternate Gene Symbols: B2R5K3, H31T_HUMAN, H3FT, NM_003493, NP_003484, Q16695, Q6FGU4
UCSC ID: uc001hsx.1
RefSeq Accession: NM_003493
Protein: Q16695 (aka H31T_HUMAN)
CCDS: CCDS1572.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_003493.2
exon count: 1CDS single in 3' UTR: no RNA size: 481
ORF size: 411CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1022.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.