Reactome | UniProt:Q16695 H3-4

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UniProt:Q16695 H3-4 Show undefined attributes

chain	initiator methionine:1 chain:2-136
checksum	37375A2C3A377B2B
comment	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. Interacts with TONSL; CHAF1A and CHAF1B (PubMed:33857403).INTERACTION 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). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability (By similarity).PTM Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.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 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 MAP3K20 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 or isoform M2 of PKM (PKM2) 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.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).PTM Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.PTM Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.PTM Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).SIMILARITY Belongs to the histone H3 family.
crossReference	[DatabaseIdentifier:12291745] Pharos - Targets:Q16695 [DatabaseIdentifier:12387691] RefSeq:NP_003484.1 [DatabaseIdentifier:11481384] ENSEMBL:ENSG00000168148 [DatabaseIdentifier:11481385] ENSEMBL:ENSG00000285435 [DatabaseIdentifier:11582497] ENSEMBL:ENSP00000355657 [DatabaseIdentifier:11582498] ENSEMBL:ENSP00000494070 [DatabaseIdentifier:11705197] ENSEMBL:ENST00000644869 [DatabaseIdentifier:11705196] ENSEMBL:ENST00000366696 [DatabaseIdentifier:11793903] GeneCards:H3-4 [DatabaseIdentifier:11809858] GlyGen:Q16695 [DatabaseIdentifier:11846892] HPA:ENSG00000168148-H3-4 [DatabaseIdentifier:12131557] OpenTargets:ENSG00000168148 [DatabaseIdentifier:12213224] PDB:6WAU [DatabaseIdentifier:12163667] PDB:3T6R [DatabaseIdentifier:12182451] PDB:4V2V [DatabaseIdentifier:12159231] PDB:3A6N [DatabaseIdentifier:12165192] PDB:8VMI [DatabaseIdentifier:12178953] PDB:8Z50 [DatabaseIdentifier:12182498] PDB:2YBS [DatabaseIdentifier:12182452] PDB:4V2W [DatabaseIdentifier:12139611] PDB:2V1D [DatabaseIdentifier:12166273] PDB:6OIE [DatabaseIdentifier:12144185] PDB:6WAT [DatabaseIdentifier:12182511] PDB:2YBP [DatabaseIdentifier:12274569] PRO:Q16695
databaseName	UniProt
dbId	56219
description	recommendedName: Histone H3.1t shortName: H3/t shortName: H3t alternativeName: H3/g alternativeName: fullName evidence="10"Histone H3.4
displayName	UniProt:Q16695 H3-4
geneName	H3-4 H3FT HIST3H3
identifier	Q16695
isSequenceChanged	false
keyword	3D-structure Acetylation ADP-ribosylation Chromosome Citrullination DNA-binding Hydroxylation Isopeptide bond Methylation Nucleosome core Nucleus Phosphoprotein Proteomics identification Reference proteome Ubl conjugation
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	H3-4
otherIdentifier	11734595_at 16700233 208572_PM_at 208572_at 2459606 2459607 7924884 8290 ADDON002893.hg A_23_P137909 GE568338 GO:0000228 GO:0000781 GO:0000786 GO:0000792 GO:0000794 GO:0003677 GO:0005198 GO:0005515 GO:0005634 GO:0005654 GO:0005694 GO:0006325 GO:0006334 GO:0006335 GO:0007284 GO:0030527 GO:0045595 GO:0046982 GO:0065003 GO:0070062 GO:0070828 HMNXSV003053825 ILMN_1707173 PH_hs_0029513 TC01003915.hg g4504298_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-181914] HIST3H3 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2245188] Me3K5-HIST3H3 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2245186] Me2K5-HIST3H3 [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000168148] ENSEMBL:ENSG00000168148 H3-4 [ReferenceDNASequence:12693372] UCSC:Q16695 H3-4 [ReferenceDNASequence:11346807] BioGPS Gene:8290 H3-4 [ReferenceDNASequence:11393190] COSMIC - genes:HIST3H3 H3-4 [ReferenceDNASequence:11422523] CTD Gene:8290 H3-4 [ReferenceDNASequence:11429129] dbSNP Gene:8290 H3-4 [ReferenceDNASequence:11825598] HGNC:4778 H3-4 [ReferenceDNASequence:11886903] KEGG:hsa:8290 H3-4 [ReferenceDNASequence:11976596] Monarch:8290 H3-4 [ReferenceDNASequence:12060689] NCBI Gene:8290 H3-4 [ReferenceDNASequence:12116007] OMIM:602820 H3-4
referenceTranscript	[ReferenceRNASequence:12569485] RefSeq:NM_003493.3 H3-4
schemaClass	ReferenceGeneProduct
secondaryIdentifier	H31T_HUMAN B2R5K3 Q6FGU4
sequenceLength	136
species	[Species:48887] Homo sapiens
stId	uniprot:Q16695
url	http://purl.uniprot.org/uniprot/Q16695

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-181914] HIST3H3 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-2245188] Me3K5-HIST3H3 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-2245186] Me2K5-HIST3H3 [nucleoplasm]
(referenceSequence)	[ModifiedResidue:2245192] N6,N6,N6-trimethyl-L-lysine at 5 [ModifiedResidue:2245185] N6,N6-dimethyl-L-lysine at 5
(interactor)	[UndirectedInteraction:11158825] UniProt:Q96GD4 <-> UniProt:Q16695 (IntAct) [UndirectedInteraction:11162719] UniProt:P62805 <-> UniProt:Q16695 (IntAct) [UndirectedInteraction:11192071] UniProt:Q16695 <-> UniProt:P16104 (IntAct) [UndirectedInteraction:11192073] UniProt:Q16695 <-> UniProt:O75164 (IntAct) [UndirectedInteraction:11192075] UniProt:Q16695 <-> UniProt:P04908 (IntAct) [UndirectedInteraction:11192077] UniProt:Q16695 <-> UniProt:P45973 (IntAct) [UndirectedInteraction:11192079] UniProt:Q16695 <-> UniProt:Q9UHJ3 (IntAct) [UndirectedInteraction:11192081] UniProt:Q16695 <-> UniProt:P49321-2 (IntAct) [UndirectedInteraction:11192083] UniProt:Q16695 <-> UniProt:Q0D2K3 (IntAct)

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