H3Y1

Summary

H3Y1 (H3.Y histone 1, HGNC:43735) is a protein-coding gene on chromosome 5p15.1, encoding Histone H3.Y (P0DPK2). Primate-specific variant histone H3, which constitutes a core component of nucleosomes.

Enables nucleosomal DNA binding activity. Located in nucleoplasm. Part of nucleosome.

Source: NCBI Gene 391769 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001355258

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:43735
Approved symbol	H3Y1
Name	H3.Y histone 1
Location	5p15.1
Locus type	gene with protein product
Status	Approved
Aliases	H3.Y, H3.Y.1
Ensembl gene	ENSG00000269466
Ensembl biotype	protein_coding
Entrez	391769

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000598383

RefSeq mRNA: 1 — MANE Select: NM_001355258 NM_001355258

CCDS: CCDS87290

Canonical transcript exons

ENST00000598383 — 1 exons

Exon	Start	End
ENSE00003218967	17654868	17655849

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 82.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0257 / max 16.3786, expressed in 10 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61069	0.0257	10

Top tissues by expression

123 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.19	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skeletal muscle tissue	UBERON:0001134	36.53	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
thoracic aorta	UBERON:0001515	34.77	gold quality
ascending aorta	UBERON:0001496	34.69	gold quality
muscle tissue	UBERON:0002385	33.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
descending thoracic aorta	UBERON:0002345	30.88	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
left coronary artery	UBERON:0001626	28.76	silver quality
liver	UBERON:0002107	28.28	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
popliteal artery	UBERON:0002250	27.55	silver quality
tibial artery	UBERON:0007610	27.44	silver quality
tonsil	UBERON:0002372	27.05	gold quality
leukocyte	CL:0000738	27.01	gold quality
monocyte	CL:0000576	26.95	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.26	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	509.93
E-MTAB-6142	no	13.25
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• ken together, H3.Y-containing nucleosomes around transcription start sites may form relaxed chromatin that allows transcription factor access, to regulate the transcription status of specific genes. (PMID:27016736)
• H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements. (PMID:28334823)
• DUX4-Induced Histone Variants H3.X and H3.Y Mark DUX4 Target Genes for Expression. (PMID:31722199)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	h3f3a	ENSDARG00000020504
danio_rerio	si:ch1073-429i10.3	ENSDARG00000068436
mus_musculus	H3f3b	ENSMUSG00000016559
rattus_norvegicus	H3f3b	ENSRNOG00000006532
rattus_norvegicus	H3f3bl1	ENSRNOG00000071166
rattus_norvegicus		ENSRNOG00000083953
drosophila_melanogaster	His3.3B	FBGN0004828
drosophila_melanogaster	His3.3A	FBGN0014857
caenorhabditis_elegans		WBGENE00001943
caenorhabditis_elegans		WBGENE00001944
caenorhabditis_elegans		WBGENE00012276

Paralogs (20): CENPA (ENSG00000115163), H3-3B (ENSG00000132475), H3-3A (ENSG00000163041), H3-4 (ENSG00000168148), H3C13 (ENSG00000183598), H3-5 (ENSG00000188375), H3C12 (ENSG00000197153), H3C4 (ENSG00000197409), H3C14 (ENSG00000203811), H3C15 (ENSG00000203852), H3Y2 (ENSG00000268799), H3-7 (ENSG00000273213), H3C8 (ENSG00000273983), H3C6 (ENSG00000274750), H3C11 (ENSG00000275379), H3C1 (ENSG00000275714), H3C7 (ENSG00000277775), H3C10 (ENSG00000278828), H3C2 (ENSG00000286522), H3C3 (ENSG00000287080)

Protein

Protein identifiers

Histone H3.Y — P0DPK2 (reviewed: P0DPK2)

Alternative names: Histone H3.Y1

All UniProt accessions (1): P0DPK2

UniProt curated annotations — full annotation on UniProt →

Function. Primate-specific variant histone H3, which constitutes a core component of nucleosomes. Histone H3.Y-containing nucleosomes accumulate around transcription start sites and have flexible DNA ends, suggesting that they form relaxed chromatin that allows transcription factor access. Histone H1 binds less efficiently to histone H3.Y-containing nucleosomes. 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 / interactions. 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 HIRA, a chaperone required for its incorporation into nucleosomes. Does not interact with DAXX chaperone.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed at low level in some tissues, such as testis and brain.

Post-translational modifications. 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). Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) impairs methylation and represses transcription. Asymmetric dimethylation at Arg-18 (H3R17me2a) is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) 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. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me), which are linked to gene repression, are underrepresented. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent acetylation of H3 and H4. Phosphorylation at Thr-7 (H3T6ph) 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. Phosphorylation at Thr-12 (H3T11ph) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me). Phosphorylation at Tyr-42 (H3Y41ph) promotes exclusion of CBX5 (HP1 alpha) from chromatin. Lysine deamination at Lys-5 (H3K4all) to form allysine. Allysine formation only takes place on H3K4me3 and results in gene repression. 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. Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.

Similarity. Belongs to the histone H3 family.

RefSeq proteins (1): NP_001342187* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000164	Histone_H3/CENP-A	Family
IPR007125	H2A/H2B/H3	Domain
IPR009072	Histone-fold	Homologous_superfamily

Pfam: PF00125

UniProt features (107 total): modified residue 86, mutagenesis site 9, helix 4, cross-link 2, initiator methionine 1, chain 1, strand 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5AY8	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DPK2-F1	85.64	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (88): 5, 5, 5, 5, 5, 5, 5, 6, 6, 7, 9, 9, 10, 10, 10, 10, 10, 10, 10, 10 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
135	impaired association between h3.y and h4.
43–47	triggers interaction with daxx.
43	enhanced binding of histone h1 to histone h3.y-containing nucleosomes. does not greatly affect the stability of the nucl
47	triggers interaction with daxx; when associated with i-63.
60	does not establish interaction with daxx.
63	does not affect stability of the nucleosome. triggers interaction with daxx; when associated with v-47.
125	impaired association between h3.y and h4 and stability of the nucleosome.
131	does not affect association between h3.y and h4.
133	does not affect association between h3.y and h4.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 46 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_ORGANELLE_FISSION, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_ORGANELLE_LOCALIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOBP_KINETOCHORE_ORGANIZATION, GOBP_NUCLEAR_CHROMOSOME_SEGREGATION, GOBP_METAPHASE_CHROMOSOME_ALIGNMENT, GOMF_CHROMATIN_BINDING

GO Biological Process (0):

GO Molecular Function (4): structural constituent of chromatin (GO:0030527), nucleosomal DNA binding (GO:0031492), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677)

GO Cellular Component (4): nucleosome (GO:0000786), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	2
structural molecule activity	1
chromatin DNA binding	1
nucleosome binding	1
protein dimerization activity	1
nucleic acid binding	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2083 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H3Y1	H2AB1	P0C5Y9	606
H3Y1	H2AB3	P0C5Z0	584
H3Y1	H2AZ1	P0C0S5	522
H3Y1	MACROH2A2	Q9P0M6	506
H3Y1	SUPT16H	Q9Y5B9	504
H3Y1	MBD3L3	A6NE82	496
H3Y1	H2AC20	Q16777	486
H3Y1	HIRA	P54198	476
H3Y1	DAXX	Q9UER7	474
H3Y1	H2AC19	P20670	469
H3Y1	DUX4L2	P0CJ85	450
H3Y1	H2BC21	Q16778	442
H3Y1	UBN1	Q9NPG3	440
H3Y1	LEUTX	A8MZ59	431
H3Y1	TRIM43	Q96BQ3	424

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2XHJ3, P02299, P02301, P02302, P08437, P08898, P09988, P0DPK2, P0DPK5, P10651, P22843, P59169, P68431, P68432, P68433, P69149, P69150, P69244, P69245, P80553, P84227, P84228, P84229, P84230, P84231, P84232, P84233, P84234, P84235, P84236, P84237, P84238, P84239, Q0JCT1, Q28D37, Q3C2E5, Q402E2, Q4QRF4, Q6LBE8, Q6LBF0

Diamond homologs: A1CP80, A1D240, A2QRR5, A2XHJ3, A2Y533, A5PK61, C0HL66, C0HL67, P02299, P02301, P02302, P06352, P08903, P09988, P0DPK2, P0DPK5, P10651, P22843, P23753, P59169, P59226, P61832, P61834, P68427, P68428, P68429, P68430, P68431, P68432, P68433, P69071, P69072, P69073, P69074, P69075, P69076, P69077, P69078, P69079, P69244

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SLBP	“up-regulates quantity by expression”	H3Y1	“translation regulation”
Sin3B_complex	“down-regulates activity”	H3Y1	binding
KAT2A	“down-regulates activity”	H3Y1	acetylation
KAT2B	“down-regulates activity”	H3Y1	acetylation
“SAGA complex”	“down-regulates activity”	H3Y1	acetylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

0 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

862 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:17655335:G:C	F68L	0.986
5:17655335:G:T	F68L	0.986
5:17655337:A:G	F68L	0.986
5:17655284:G:C	F85L	0.976
5:17655284:G:T	F85L	0.976
5:17655286:A:G	F85L	0.976
5:17655248:G:C	S97R	0.972
5:17655248:G:T	S97R	0.972
5:17655250:T:G	S97R	0.972
5:17655371:C:A	Q56H	0.971
5:17655371:C:G	Q56H	0.971
5:17655285:A:G	F85S	0.970
5:17655384:A:G	I52T	0.967
5:17655168:T:G	D124A	0.965
5:17655168:T:A	D124V	0.964
5:17655169:C:G	D124H	0.956
5:17655204:G:T	A112D	0.954
5:17655167:G:C	D124E	0.951
5:17655167:G:T	D124E	0.951
5:17655273:G:T	A89D	0.948
5:17655180:A:T	I120N	0.945
5:17655312:G:T	A76D	0.945
5:17655336:A:G	F68S	0.945
5:17655206:A:C	C111W	0.944
5:17655190:G:T	R117S	0.940
5:17655245:C:A	E98D	0.934
5:17655245:C:G	E98D	0.934
5:17655168:T:C	D124G	0.933
5:17655253:C:G	A96P	0.933
5:17655189:C:G	R117P	0.932

dbSNP variants (sampled 300 via entrez): RS1000009875 (5:17654377 AAAAATAAAAT>A,AAAAAT,AAAAATAAAATAAAAT), RS1000556394 (5:17656807 T>G), RS1002636228 (5:17655556 T>C), RS1002650037 (5:17656511 C>T), RS1002924602 (5:17656258 G>A), RS1003515078 (5:17654854 C>A), RS1004690354 (5:17657347 C>T), RS1004886920 (5:17656905 T>C), RS1004978427 (5:17655417 C>T), RS1005131073 (5:17655579 C>G,T), RS1005786488 (5:17654878 G>A), RS1006331663 (5:17656161 A>C,T), RS1006363048 (5:17655894 G>A,C), RS10074729 (5:17655230 C>A,G,T), RS1007687325 (5:17657555 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.