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Details on Person UniProt:P68431 H3C1

Class:IdReferenceGeneProduct:355446
_chainChangeLoginitiator methionine:1 added on Fri February 6 2015;chain:2-136 added on Fri February 6 2015;initiator methionine:1 for 355446 removed on Fri Nov 03 2023;initiator methionine: for 355446 added on Fri Nov 03 2023;initiator methionine: for 355446 removed on Fri Aug 15 2025;initiator methionine:1 for 355446 added on Fri Aug 15 2025
_displayNameUniProt:P68431 H3C1
_timestamp2026-02-20 22:22:10
chaininitiator methionine:1
chain:2-136
checksum9B89008EA50A0EF6
commentFUNCTION 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 (PubMed:36435862). The octamer wraps approximately 147 bp of DNA. Interacts with TONSL; CHAF1A; CHAF1B; MCM2 and DNAJC9 (PubMed:33857403). Interacts with NASP; NASP is a histone chaperone that stabilizes and maintains a soluble pool of Histone H3-H4 dimers (PubMed:22195965).INTERACTION 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.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.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.PTM Phosphorylated at Thr-4 (H3T3ph) by VRK1 (PubMed:31527692). Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase (PubMed:15681610, PubMed:16185088). 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 Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.PTM Monoubiquitinated at Lys-15 (H3K14ub), Lys-19 (H3K18ub) and Lys-24 (H3K23ub) by UHRF1 and HLTF at hemimethylated DNA sites following DNA replication, promoting recruitment of DNMT1 DNA methyltransferase and replication-coupled DNA methylation maintenance (PubMed:27595565, PubMed:29053958). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity). Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation (PubMed:16678110). This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (PubMed:16678110).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.PTM Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.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 (PubMed:29211711). It gives a specific tag for epigenetic transcription activation (PubMed:29211711). Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair (PubMed:27436229).PTM Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:30257210, PubMed:34874266). Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L (PubMed:34874266). H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac) (PubMed:30257210).PTM Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).PTM Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (PubMed:32273471). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).PTM Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.DISEASE The gene represented in this entry is involved in disease pathogenesis. HIST1H3B mutations affecting residue Lys-28 involved in post-translational modifications of histone H3.1 are recurrent in malignant, aggressive gliomas including pediatric non-brain stem glioblastoma and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histone methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23603901).DISEASE HIST1H3B or HIST1H3C mutations affecting residue Lys-37 of histone H3.1 are involved in the pathogenesis of pediatric undifferentiated soft tissue sarcomas. The mechanism through which mutations lead to tumorigenesis involves altered histones methylation with gain of global H3K27 methylation, altered Polycomb repressive complex 1 (PRC1) activity, aberrant epigenetic regulation of gene expression and impaired differentiation of mesenchimal progenitor cells.MISCELLANEOUS This histone is only present in mammals and is enriched in acetylation of Lys-15 and dimethylation of Lys-10 (H3K9me2).SIMILARITY Belongs to the histone H3 family.CAUTION The original paper reporting lysine deamination at Lys-5 by LOXL2 has been retracted due to inappropriate manipulation of figure data (PubMed:22483618, PubMed:27392148). However, this modification was confirmed in a subsequent publication (PubMed:27735137).
created[InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12
descriptionrecommendedName: Histone H3.1 alternativeName: Histone H3/a alternativeName: Histone H3/b alternativeName: Histone H3/c alternativeName: Histone H3/d alternativeName: Histone H3/f alternativeName: Histone H3/h alternativeName: Histone H3/i alternativeName: Histone H3/j alternativeName: Histone H3/k alternativeName: Histone H3/l
geneNameH3C1
H3FA
HIST1H3A
H3C2
H3FL
HIST1H3B
H3C3
H3FC HIST1H3C
H3C4
H3FB
HIST1H3D
H3C6
H3FD
HIST1H3E
H3C7
H3FI
HIST1H3F
H3C8
H3FH
HIST1H3G
H3C10
H3FK
HIST1H3H
H3C11
H3FF
HIST1H3I
H3C12
H3FJ
HIST1H3J
identifierP68431
isSequenceChangedFALSE
keyword3D-structure
Acetylation
ADP-ribosylation
Chromosome
Citrullination
Direct protein sequencing
Disease variant
DNA-binding
Hydroxylation
Isopeptide bond
Lipoprotein
Methylation
Nucleosome core
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Ubl conjugation
modified[InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39
[InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18
[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
[InstanceEdit:423310] Kanapin, AA
[InstanceEdit:435478] Kanapin, AA
[InstanceEdit:435871] Kanapin, AA
[InstanceEdit:447347] Kanapin, AA
[InstanceEdit:525883] Kanapin, AA
[InstanceEdit:613449] Kanapin, AA
[InstanceEdit:797602] Kanapin, AA
[InstanceEdit:937368] Yung, CK
[InstanceEdit:1042053] Yung, CK
[InstanceEdit:1220657] Yung, CK
[InstanceEdit:1300696] Yung, CK
[InstanceEdit:1301627] Yung, CK
[InstanceEdit:1551960] Weiser, JD
[InstanceEdit:1995863] Weiser, JD
[InstanceEdit:2132304] Weiser, JD
[InstanceEdit:2265580] Weiser, JD
[InstanceEdit:2455454] Weiser, JD
[InstanceEdit:3132113] Weiser, JD
[InstanceEdit:5083144] Weiser, JD
[InstanceEdit:5433710] Weiser, JD
[InstanceEdit:5618415] Weiser, JD
[InstanceEdit:5634237] Weiser, JD
[InstanceEdit:5673015] Weiser, JD
[InstanceEdit:6807888] Weiser, JD
[InstanceEdit:8987656] Weiser, JD
[InstanceEdit:9027688] Weiser, JD
[InstanceEdit:9037114] Weiser, JD
[InstanceEdit:9607352] Weiser, JD
[InstanceEdit:9637257] Weiser, JD
[InstanceEdit:9666080] Weiser, JD
[InstanceEdit:9676415] Weiser, JD
[InstanceEdit:9715482] Weiser, JD
[InstanceEdit:9730071] Weiser, JD
[InstanceEdit:9767224] Weiser, Joel
[InstanceEdit:9796772] Weiser, Joel
[InstanceEdit:9819394] Weiser, Joel
[InstanceEdit:9834092] Weiser, Joel
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameH3C1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8957971] ENSEMBL:ENSG00000275379 H3C1 [Homo sapiens]
[ReferenceDNASequence:8957487] ENSEMBL:ENSG00000274750 H3C1 [Homo sapiens]
[ReferenceDNASequence:8958093] ENSEMBL:ENSG00000197409 H3C1 [Homo sapiens]
[ReferenceDNASequence:8958439] ENSEMBL:ENSG00000197153 H3C1 [Homo sapiens]
[ReferenceDNASequence:8957689] ENSEMBL:ENSG00000275714 H3C1 [Homo sapiens]
[ReferenceDNASequence:8958496] ENSEMBL:ENSG00000278828 H3C1 [Homo sapiens]
[ReferenceDNASequence:9666118] ENSEMBL:ENSG00000287080 H3C1 [Homo sapiens]
[ReferenceDNASequence:9666117] ENSEMBL:ENSG00000286522 H3C1 [Homo sapiens]
[ReferenceDNASequence:8957848] ENSEMBL:ENSG00000273983 H3C1 [Homo sapiens]
[ReferenceDNASequence:8991303] ENSEMBL:ENSG00000277775 H3C1 [Homo sapiens]
secondaryIdentifierH31_HUMAN
A0PJT7
A5PLR1
P02295
P02296
P16106
Q6ISV8
Q6NWP8
Q6NWP9
Q6NXU4
Q71DJ3
Q93081
sequenceLength136
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:212070] HIST1H3A [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:212105] MeK10-HIST1H3A [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:212220] Me3K28-HIST1H3A [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:427378] Me2K10-HIST1H3A [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:427507] 2xAcK-HIST1H3A [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:427734] Me3K10-HIST1H3A [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:977570] HIST1H3A [extracellular region] [Homo sapiens]
[EntityWithAccessionedSequence:1214170] Me2K5-HIST1H3A [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:1214186] Me3K5-HIST1H3A [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:4549217] Ack15-HIST1H3A [nucleoplasm] [Homo sapiens]
List all 65 refering instances
(referenceSequence)[ModifiedResidue:212044] N6-methyl-L-lysine at 10
[ModifiedResidue:417279] N6-methyl-L-lysine at 27
[ModifiedResidue:427506] N6-acetyl-L-lysine at 10
[ModifiedResidue:448755] N6,N6-dimethyl-L-lysine at 10
[ModifiedResidue:448758] N6,N6,N6-trimethyl-L-lysine at 10
[ModifiedResidue:448785] N6,N6,N6-trimethyl-L-lysine at 28
[ModifiedResidue:1214174] N6,N6-dimethyl-L-lysine at 5
[ModifiedResidue:1214179] N6,N6,N6-trimethyl-L-lysine at 5
[ModifiedResidue:4551289] N6-acetyl-L-lysine at unknown position
[ModifiedResidue:4568759] N6-acetyl-L-lysine at 5
List all 43 refering instances
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No pathways have been reviewed or authored by UniProt:P68431 H3C1 (355446)