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Protein

Core histone macro-H2A.1

Gene

H2AFY

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 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. Involved in stable X chromosome inactivation (PubMed:15897469). Inhibits the binding of transcription factors, including NF-kappa-B, and interferes with the activity of remodeling SWI/SNF complexes (PubMed:12718888, PubMed:16428466). Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin (PubMed:16428466, PubMed:16107708).5 Publications
Isoform 1: Binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation (PubMed:15902274). Increases the expression of genes involved in redox metabolism, including SOD3 (PubMed:23022728).2 Publications
Isoform 2: Represses SOD3 gene expression.1 Publication

GO - Molecular functioni

  • chromatin DNA binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • double-stranded methylated DNA binding Source: UniProtKB
  • enzyme binding Source: BHF-UCL
  • nucleosomal DNA binding Source: UniProtKB
  • promoter-specific chromatin binding Source: UniProtKB
  • protein heterodimerization activity Source: InterPro
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase inhibitor activity Source: UniProtKB
  • rDNA binding Source: UniProtKB
  • RNA polymerase II core promoter sequence-specific DNA binding Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • chromatin silencing Source: GO_Central
  • dosage compensation Source: MGI
  • establishment of protein localization to chromatin Source: UniProtKB
  • negative regulation of cell cycle G2/M phase transition Source: UniProtKB
  • negative regulation of gene expression, epigenetic Source: UniProtKB
  • negative regulation of histone H3-K27 methylation Source: UniProtKB
  • negative regulation of histone H3-K4 methylation Source: UniProtKB
  • negative regulation of histone phosphorylation Source: UniProtKB
  • negative regulation of protein localization to chromosome, telomeric region Source: BHF-UCL
  • negative regulation of protein serine/threonine kinase activity Source: UniProtKB
  • negative regulation of response to oxidative stress Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • negative regulation of transcription of nucleolar large rRNA by RNA polymerase I Source: UniProtKB
  • nucleosome assembly Source: UniProtKB
  • positive regulation of gene expression, epigenetic Source: UniProtKB
  • positive regulation of keratinocyte differentiation Source: UniProtKB
  • positive regulation of maintenance of mitotic sister chromatid cohesion Source: BHF-UCL
  • positive regulation of response to oxidative stress Source: UniProtKB
  • regulation of gene expression, epigenetic Source: UniProtKB
  • regulation of lipid metabolic process Source: UniProtKB
  • regulation of response to oxidative stress Source: UniProtKB

Keywordsi

Molecular functionChromatin regulator, DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Core histone macro-H2A.1
Short name:
Histone macroH2A1
Short name:
mH2A1
Alternative name(s):
Histone H2A.y
Short name:
H2A/y
Medulloblastoma antigen MU-MB-50.205
Gene namesi
Name:H2AFY
Synonyms:MACROH2A1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113648.16
HGNCiHGNC:4740 H2AFY
MIMi610054 gene
neXtProtiNX_O75367

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleosome core, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi9555
OpenTargetsiENSG00000113648
PharmGKBiPA29117

Polymorphism and mutation databases

BioMutaiH2AFY

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000553181 – 372Core histone macro-H2A.1Add BLAST372

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei18N6-methyllysine1 Publication1
Modified residuei116N6-acetyllysine; alternateBy similarity1
Cross-linki116Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Cross-linki117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei123N6,N6-dimethyllysine; alternate1 Publication1
Modified residuei123N6-acetyllysine; alternateBy similarity1
Cross-linki123Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei129PhosphothreonineCombined sources1 Publication1
Cross-linki167Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei170PhosphoserineCombined sources1
Modified residuei173PhosphoserineCombined sources1
Modified residuei178PhosphothreonineCombined sources1
Cross-linki189Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki323Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Monoubiquitinated at either Lys-116 or Lys-117. May also be polyubiquitinated. Ubiquitination is mediated by the CUL3/SPOP E3 complex and does not promote proteasomal degradation. Instead, it is required for enrichment in inactive X chromosome chromatin.3 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO75367
MaxQBiO75367
PaxDbiO75367
PeptideAtlasiO75367
PRIDEiO75367
ProteomicsDBi49934
49935 [O75367-2]
49936 [O75367-3]
TopDownProteomicsiO75367-1 [O75367-1]
O75367-2 [O75367-2]

2D gel databases

SWISS-2DPAGEiO75367

PTM databases

iPTMnetiO75367
PhosphoSitePlusiO75367
SwissPalmiO75367

Miscellaneous databases

PMAP-CutDBiO75367

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000113648
CleanExiHS_H2AFY
ExpressionAtlasiO75367 baseline and differential
GenevisibleiO75367 HS

Organism-specific databases

HPAiHPA041189
HPA050962

Interactioni

Subunit structurei

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. Interacts with HDAC1 and HDAC2 (By similarity). Interacts with SPOP. Part of a complex consisting of H2AFY, CUL3 and SPOP.By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • protein heterodimerization activity Source: InterPro
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114927, 95 interactors
CORUMiO75367
DIPiDIP-44283N
ELMiO75367
IntActiO75367, 36 interactors
MINTiO75367
STRINGi9606.ENSP00000423563

Structurei

Secondary structure

1372
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi15 – 19Combined sources5
Helixi25 – 35Combined sources11
Beta strandi36 – 38Combined sources3
Beta strandi39 – 41Combined sources3
Helixi44 – 70Combined sources27
Beta strandi74 – 76Combined sources3
Helixi78 – 86Combined sources9
Helixi89 – 94Combined sources6
Turni95 – 97Combined sources3
Beta strandi98 – 100Combined sources3
Helixi111 – 113Combined sources3
Beta strandi174 – 177Combined sources4
Beta strandi185 – 190Combined sources6
Beta strandi196 – 202Combined sources7
Helixi204 – 209Combined sources6
Beta strandi213 – 219Combined sources7
Helixi227 – 252Combined sources26
Beta strandi260 – 264Combined sources5
Beta strandi268 – 277Combined sources10
Helixi286 – 303Combined sources18
Beta strandi307 – 311Combined sources5
Beta strandi315 – 319Combined sources5
Helixi323 – 340Combined sources18
Beta strandi341 – 343Combined sources3
Beta strandi348 – 355Combined sources8
Helixi356 – 367Combined sources12

3D structure databases

ProteinModelPortaliO75367
SMRiO75367
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75367

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 117Histone H2AAdd BLAST116
Domaini184 – 370MacroPROSITE-ProRule annotationAdd BLAST187

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi118 – 162Lys-richAdd BLAST45

Phylogenomic databases

eggNOGiENOG410IV3A Eukaryota
KOG1756 Eukaryota
KOG2633 Eukaryota
COG2110 LUCA
COG5262 LUCA
GeneTreeiENSGT00910000143981
HOVERGENiHBG009342
InParanoidiO75367
KOiK11251
OMAiHCNSPIW
OrthoDBiEOG091G0XGD
PhylomeDBiO75367
TreeFamiTF332276

Family and domain databases

CDDicd00074 H2A, 1 hit
cd02904 Macro_H2A_like, 1 hit
Gene3Di1.10.20.10, 1 hit
InterProiView protein in InterPro
IPR021171 Core_histone_macro-H2A
IPR009072 Histone-fold
IPR002119 Histone_H2A
IPR007125 Histone_H2A/H2B/H3
IPR032454 Histone_H2A_C
IPR002589 Macro_dom
IPR035796 Macro_H2A
PfamiView protein in Pfam
PF00125 Histone, 1 hit
PF16211 Histone_H2A_C, 1 hit
PF01661 Macro, 1 hit
PIRSFiPIRSF037942 Core_histone_macro-H2A, 1 hit
PRINTSiPR00620 HISTONEH2A
SMARTiView protein in SMART
SM00506 A1pp, 1 hit
SM00414 H2A, 1 hit
SUPFAMiSSF47113 SSF47113, 1 hit
PROSITEiView protein in PROSITE
PS51154 MACRO, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: O75367-1) [UniParc]FASTAAdd to basket
Also known as: mH2A1.21 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSSRGGKKKS TKTSRSAKAG VIFPVGRMLR YIKKGHPKYR IGVGAPVYMA
60 70 80 90 100
AVLEYLTAEI LELAGNAARD NKKGRVTPRH ILLAVANDEE LNQLLKGVTI
110 120 130 140 150
ASGGVLPNIH PELLAKKRGS KGKLEAIITP PPAKKAKSPS QKKPVSKKAG
160 170 180 190 200
GKKGARKSKK KQGEVSKAAS ADSTTEGTPA DGFTVLSTKS LFLGQKLNLI
210 220 230 240 250
HSEISNLAGF EVEAIINPTN ADIDLKDDLG NTLEKKGGKE FVEAVLELRK
260 270 280 290 300
KNGPLEVAGA AVSAGHGLPA KFVIHCNSPV WGADKCEELL EKTVKNCLAL
310 320 330 340 350
ADDKKLKSIA FPSIGSGRNG FPKQTAAQLI LKAISSYFVS TMSSSIKTVY
360 370
FVLFDSESIG IYVQEMAKLD AN
Note: The preferential expression of isoform 2 over that of isoform 1 requires the presence of DDX5/DDX17.1 Publication
Length:372
Mass (Da):39,617
Last modified:January 23, 2007 - v4
Checksum:i37DED989EF7E69DC
GO
Isoform 1 (identifier: O75367-2) [UniParc]FASTAAdd to basket
Also known as: mH2A1.11 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     198-229: NLIHSEISNLAGFEVEAIINPTNADIDLKDDL → QVVQADIASIDSDAVVHPTNTDFYIGGEV

Note: Specifically binds ADP-ribose and O-acetyl-ADP-ribose. Important residues for binding are Asp-203, Gly-224, Gly-314 and Phe-348. Preferentially expressed over isoform 2 in the absence of DDX5/DDX17.2 Publications
Show »
Length:369
Mass (Da):39,184
Checksum:iD21A4CE6C7AA3BB1
GO
Isoform 3 (identifier: O75367-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     159-159: Missing.

Show »
Length:371
Mass (Da):39,489
Checksum:i54320BFD118454D1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti186L → F in BAB14565 (PubMed:14702039).Curated1
Sequence conflicti210F → S in BAB14565 (PubMed:14702039).Curated1
Sequence conflicti225L → P in AAC33433 (PubMed:9714746).Curated1
Sequence conflicti291E → G in AAH95406 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038379159Missing in isoform 3. 2 Publications1
Alternative sequenceiVSP_002056198 – 229NLIHS…LKDDL → QVVQADIASIDSDAVVHPTN TDFYIGGEV in isoform 1. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041483 mRNA Translation: AAC33433.1
AF044286 mRNA Translation: AAC33434.1
AF054174 mRNA Translation: AAC39908.1
AK023409 mRNA Translation: BAB14565.1
AC026691 Genomic DNA No translation available.
BC013331 mRNA Translation: AAH13331.1
BC095406 mRNA Translation: AAH95406.1
AY134746 mRNA Translation: AAN08620.1
CCDSiCCDS4183.1 [O75367-3]
CCDS4184.1 [O75367-2]
CCDS4185.1 [O75367-1]
RefSeqiNP_001035248.1, NM_001040158.1 [O75367-3]
NP_004884.1, NM_004893.2 [O75367-3]
NP_613075.1, NM_138609.2 [O75367-2]
NP_613258.2, NM_138610.2 [O75367-1]
XP_011542031.1, XM_011543729.2 [O75367-1]
XP_011542032.1, XM_011543730.2 [O75367-3]
UniGeneiHs.420272
Hs.599225

Genome annotation databases

EnsembliENST00000304332; ENSP00000302572; ENSG00000113648 [O75367-3]
ENST00000312469; ENSP00000310169; ENSG00000113648 [O75367-2]
ENST00000510038; ENSP00000424971; ENSG00000113648 [O75367-1]
ENST00000511689; ENSP00000423563; ENSG00000113648 [O75367-1]
GeneIDi9555
KEGGihsa:9555
UCSCiuc003lam.2 human [O75367-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiH2AY_HUMAN
AccessioniPrimary (citable) accession number: O75367
Secondary accession number(s): O75377
, Q503A8, Q7Z5E3, Q96D41, Q9H8P3, Q9UP96
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 189 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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