MACROH2A1 (macroH2A.1 histone)

Gene

• Entrez ID: 9555
• Gene name: MacroH2A.1 histone
• Gene symbol: MACROH2A1
• Synonyms (NCBI Gene): H2A.y, H2A/y, H2AF12M, H2AFY, MACROH2A1.1, mH2A1, macroH2A1.2
• Chromosome: 5
• Chromosome location: 5q31.1
• Summary: 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 hi

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IBA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IMP	19734898
GO:0000182	Function	RDNA binding	IDA	24071584
GO:0000228	Component	Nuclear chromosome	IDA	18936163
GO:0000781	Component	Chromosome, telomeric region	HDA	19135898
GO:0000785	Component	Chromatin	IDA	19734898, 22194607, 24071584
GO:0000785	Component	Chromatin	IEA
GO:0000786	Component	Nucleosome	IBA
GO:0000786	Component	Nucleosome	IEA
GO:0000786	Component	Nucleosome	NAS	9714746
GO:0000793	Component	Condensed chromosome	IEA
GO:0000976	Function	Transcription cis-regulatory region binding	IDA	19734898, 20008927
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	23595991
GO:0001739	Component	Sex chromatin	TAS	19486527
GO:0001740	Component	Barr body	IDA	11331621, 18936163
GO:0001740	Component	Barr body	IEA
GO:0002082	Process	Regulation of oxidative phosphorylation	IEA
GO:0002082	Process	Regulation of oxidative phosphorylation	ISS
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	NAS	9714746
GO:0003682	Function	Chromatin binding	IEA
GO:0005515	Function	Protein binding	IPI	22391447, 22589551, 25416956, 25609649, 26373281, 32296183
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	ISS
GO:0005654	Component	Nucleoplasm	IDA
GO:0005694	Component	Chromosome	IEA
GO:0005721	Component	Pericentric heterochromatin	IDA	19486527
GO:0005730	Component	Nucleolus	IDA	24071584
GO:0006281	Process	DNA repair	IDA	21211722
GO:0006325	Process	Chromatin organization	IEA
GO:0006334	Process	Nucleosome assembly	IEA
GO:0006334	Process	Nucleosome assembly	NAS	9714746
GO:0009048	Process	Dosage compensation by inactivation of X chromosome	IDA	11331621
GO:0010385	Function	Double-stranded methylated DNA binding	IDA	24071584
GO:0019216	Process	Regulation of lipid metabolic process	IMP	25526730
GO:0019899	Function	Enzyme binding	IPI	26373281
GO:0019901	Function	Protein kinase binding	IPI	22194607
GO:0030291	Function	Protein serine/threonine kinase inhibitor activity	IMP	22194607
GO:0030527	Function	Structural constituent of chromatin	IBA
GO:0030527	Function	Structural constituent of chromatin	IDA	21211722
GO:0030527	Function	Structural constituent of chromatin	IEA
GO:0031490	Function	Chromatin DNA binding	IDA	19734898, 24071584
GO:0031490	Function	Chromatin DNA binding	IEA
GO:0031492	Function	Nucleosomal DNA binding	IDA	20008927
GO:0031492	Function	Nucleosomal DNA binding	IEA
GO:0031492	Function	Nucleosomal DNA binding	ISS
GO:0031507	Process	Heterochromatin formation	IBA
GO:0034184	Process	Positive regulation of maintenance of mitotic sister chromatid cohesion	IDA	26373281
GO:0040029	Process	Epigenetic regulation of gene expression	IMP	20008927
GO:0045618	Process	Positive regulation of keratinocyte differentiation	IEA
GO:0045618	Process	Positive regulation of keratinocyte differentiation	IMP	23595991
GO:0045814	Process	Negative regulation of gene expression, epigenetic	IEA
GO:0045814	Process	Negative regulation of gene expression, epigenetic	IMP	19734898, 23595991, 24071584
GO:0045815	Process	Transcription initiation-coupled chromatin remodeling	IMP	25526730
GO:0046982	Function	Protein heterodimerization activity	IEA
GO:0061187	Process	Regulation of rDNA heterochromatin formation	IMP	24071584
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0070212	Process	Protein poly-ADP-ribosylation	IDA	15674325
GO:0071169	Process	Establishment of protein localization to chromatin	IEA
GO:0071169	Process	Establishment of protein localization to chromatin	IMP	19734898
GO:0072570	Function	ADP-D-ribose binding	IDA	15902274
GO:0090734	Component	Site of DNA damage	IDA	21211722
GO:0160002	Function	ADP-D-ribose modification-dependent protein binding	IEA
GO:0160002	Function	ADP-D-ribose modification-dependent protein binding	ISS
GO:0160004	Function	Poly-ADP-D-ribose modification-dependent protein binding	ISS
GO:1901837	Process	Negative regulation of transcription of nucleolar large rRNA by RNA polymerase I	IBA
GO:1901837	Process	Negative regulation of transcription of nucleolar large rRNA by RNA polymerase I	IEA
GO:1901837	Process	Negative regulation of transcription of nucleolar large rRNA by RNA polymerase I	IGI	24071584
GO:1901837	Process	Negative regulation of transcription of nucleolar large rRNA by RNA polymerase I	IMP	24071584
GO:1902688	Process	Regulation of NAD metabolic process	IEA
GO:1902688	Process	Regulation of NAD metabolic process	ISS
GO:1902750	Process	Negative regulation of cell cycle G2/M phase transition	IMP	22194607
GO:1902882	Process	Regulation of response to oxidative stress	IEA
GO:1902882	Process	Regulation of response to oxidative stress	IMP	23022728
GO:1902883	Process	Negative regulation of response to oxidative stress	IMP	23022728
GO:1902884	Process	Positive regulation of response to oxidative stress	IMP	23022728
GO:1903226	Process	Positive regulation of endodermal cell differentiation	IMP	23595991
GO:1904815	Process	Negative regulation of protein localization to chromosome, telomeric region	IDA	26373281
GO:1990841	Function	Promoter-specific chromatin binding	IEA
GO:1990841	Function	Promoter-specific chromatin binding	ISS

Other IDs

• MIM: 610054
• HGNC: 4740
• e!Ensembl: ENSG00000113648

Protein

• UniProt ID: O75367
• Protein name: Core histone macro-H2A.1 (Histone macroH2A1) (mH2A1) (Histone H2A.y) (H2A/y) (Medulloblastoma antigen MU-MB-50.205)
• Protein function: Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription (PubMed:12718888, PubMed:15621527, PubMed:16428466). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to t
• PDB: 1U35, 1ZR3, 1ZR5, 2F8N, 2FXK, 3HQH, 3HSV, 3IID, 3IIF, 3IVB, 5IIT, 5LNC, 7D3Y
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00125	Histone	2 → 88	Core histone H2A/H2B/H3/H4	Domain
  PF16211	Histone_H2A_C	89 → 123	C-terminus of histone H2A	Family
  PF01661	Macro	216 → 330	Macro domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9714746}.
• Sequence:

  MSSRGGKKKSTKTSRSAKAGVIFPVGRMLRYIKKGHPKYRIGVGAPVYMAAVLEYLTAEI
  LELAGNAARDNKKGRVTPRHILLAVANDEELNQLLKGVTIASGGVLPNIHPELLAKKRGS
  KGKLEAIITPPPAKKAKSPSQKKPVSKKAGGKKGARKSKKKQGEVSKAASADSTTEGTPA
  DGFTVLSTKSLFLGQKLNLIHSEISNLAGFEVEAIINPTNADIDLKDDLGNTLEKKGGKE
  FVEAVLELRKKNGPLEVAGAAVSAGHGLPAKFVIHCNSPVWGADKCEELLEKTVKNCLAL
  ADDKKLKSIAFPSIGSGRNGFPKQTAAQLILKAISSYFVSTMSSSIKTVYFVLFDSESIG
  IYVQEMAKLDAN

• Sequence length: 372

Pathways

KEGG:

ATP-dependent chromatin remodeling
Necroptosis
Neutrophil extracellular trap formation
Alcoholism
Systemic lupus erythematosus

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BRACHYDACTYLY-ELBOW WRIST DYSPLASIA SYNDROME	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Autistic Disorder	Autism	BEFREE	18053270		★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	26028027		★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly-elbow wrist dysplasia syndrome	Brachydactyly-Elbow Wrist Dysplasia Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	24911873		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	21844227, 24911873	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	Pubtator	25188299	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	33858382, 34899687, 35472308	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	26028027		★☆☆☆☆ Found in Text Mining only
Cirrhosis	Cirrhosis	BEFREE	26772755		★☆☆☆☆ Found in Text Mining only
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	22542848		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	22542848	Inhibit	★☆☆☆☆ Found in Text Mining only
Huntington Disease	Huntington Disease	BEFREE	21969577		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	29666008	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	29666008		★☆☆☆☆ Found in Text Mining only
Lipoidosis	Lipoidosis	BEFREE	25526730		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	23372727, 25526730, 26772755, 28913935, 30165787		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	BEFREE	26772755		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	25526730		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus	Lupus Erythematosus	BEFREE	20833509		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Discoid	Lupus Erythematosus	BEFREE	20833509		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	20833509		★☆☆☆☆ Found in Text Mining only
Lupus Vulgaris	Lupus Vulgaris	BEFREE	20833509		★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	24911873		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	31164793		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	27092877		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	26028027		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	21030442, 21844227, 30165787		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	22542848		★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndromes	Myelodysplastic syndrome	Pubtator	28436936, 37852977	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	21030442, 24911873, 26028027, 28913935, 30165787, 31488827		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	31164793		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	28131897	Associate	★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	23372727		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	27092877		★☆☆☆☆ Found in Text Mining only
Synostosis, Carpal, with Dysplastic Elbow Joints and Brachydactyly	BRACHYDACTYLY WITH JOINT DYSPLASIA	ORPHANET_DG	30711920		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	24911873	Associate	★☆☆☆☆ Found in Text Mining only