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Protein

Core histone macro-H2A.1

Gene

H2AFY

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. 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. Inhibits the binding of transcription factors and interferes with the activity of remodeling SWI/SNF complexes. Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin. In addition, isoform 1, but not isoform 2, binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation.5 Publications

GO - Molecular functioni

  • chromatin DNA binding Source: UniProtKB
  • core promoter sequence-specific 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
  • 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 modification Source: UniProtKB-KW
  • 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 transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of transcription of nuclear large rRNA transcript from RNA polymerase I promoter 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
  • regulation of gene expression, epigenetic Source: UniProtKB
  • regulation of lipid metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113648-MONOMER.

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

HGNCiHGNC:4740. H2AFY.

Subcellular locationi

GO - Cellular componenti

  • Barr body Source: UniProtKB
  • condensed chromosome Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • nuclear chromatin Source: UniProtKB
  • nuclear chromosome Source: UniProtKB
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nucleolus Source: UniProtKB
  • nucleosome Source: UniProtKB
  • nucleus Source: UniProtKB
  • pericentric heterochromatin Source: BHF-UCL
  • sex chromatin Source: BHF-UCL
Complete GO annotation...

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
Modified residuei129PhosphothreonineCombined sources1 Publication1
Modified residuei170PhosphoserineCombined sources1
Modified residuei173PhosphoserineCombined sources1
Modified residuei178PhosphothreonineCombined sources1

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.
TopDownProteomicsiO75367-1. [O75367-1]
O75367-2. [O75367-2]

2D gel databases

SWISS-2DPAGEO75367.

PTM databases

iPTMnetiO75367.
PhosphoSitePlusiO75367.
SwissPalmiO75367.

Miscellaneous databases

PMAP-CutDBO75367.

Expressioni

Tissue specificityi

Ubiquitous.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

WithEntry#Exp.IntActNotes
ATRXP461002EBI-6249599,EBI-396461
ERBB2P046266EBI-2868511,EBI-641062
ERICH2A1L1625EBI-2868511,EBI-2682520
MAXP612442EBI-2868511,EBI-751711
TNKSO952716EBI-6249599,EBI-1105254

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114927. 76 interactors.
DIPiDIP-44283N.
IntActiO75367. 26 interactors.
MINTiMINT-2866965.
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 – 206Combined sources3
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1U35X-ray3.00C/G1-120[»]
1ZR3X-ray1.66A/B/C/D162-372[»]
1ZR5X-ray2.92A/B161-372[»]
2F8NX-ray2.90G1-120[»]
2FXKX-ray2.54A/B162-372[»]
3HQHX-ray2.30M167-181[»]
3HSVX-ray1.43M172-186[»]
3IIDX-ray1.90A162-372[»]
3IIFX-ray2.10A/B/C162-372[»]
3IVBX-ray1.75M167-181[»]
5IITX-ray2.13A/B/C/D181-369[»]
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

Sequence similaritiesi

Contains 1 histone H2A domain.Curated
Contains 1 Macro domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IV3A. Eukaryota.
KOG1756. Eukaryota.
KOG2633. Eukaryota.
COG2110. LUCA.
COG5262. LUCA.
GeneTreeiENSGT00860000133717.
HOVERGENiHBG009342.
InParanoidiO75367.
KOiK11251.
OMAiKGGKEFT.
OrthoDBiEOG091G0XGD.
PhylomeDBiO75367.
TreeFamiTF332276.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR021171. Core_histone_macro-H2A.
IPR009072. Histone-fold.
IPR002119. Histone_H2A.
IPR007125. Histone_H2A/H2B/H3.
IPR032454. Histone_H2A_C.
IPR002589. Macro_dom.
[Graphical view]
PfamiPF00125. Histone. 1 hit.
PF16211. Histone_H2A_C. 1 hit.
PF01661. Macro. 1 hit.
[Graphical view]
PIRSFiPIRSF037942. Core_histone_macro-H2A. 1 hit.
PRINTSiPR00620. HISTONEH2A.
SMARTiSM00506. A1pp. 1 hit.
SM00414. H2A. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS51154. MACRO. 1 hit.
[Graphical view]

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

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
Length:372
Mass (Da):39,617
Last modified:January 23, 2007 - v4
Checksum:i37DED989EF7E69DC
GO
Isoform 1 (identifier: O75367-2) [UniParc]FASTAAdd to basket

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.
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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1U35X-ray3.00C/G1-120[»]
1ZR3X-ray1.66A/B/C/D162-372[»]
1ZR5X-ray2.92A/B161-372[»]
2F8NX-ray2.90G1-120[»]
2FXKX-ray2.54A/B162-372[»]
3HQHX-ray2.30M167-181[»]
3HSVX-ray1.43M172-186[»]
3IIDX-ray1.90A162-372[»]
3IIFX-ray2.10A/B/C162-372[»]
3IVBX-ray1.75M167-181[»]
5IITX-ray2.13A/B/C/D181-369[»]
ProteinModelPortaliO75367.
SMRiO75367.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114927. 76 interactors.
DIPiDIP-44283N.
IntActiO75367. 26 interactors.
MINTiMINT-2866965.
STRINGi9606.ENSP00000423563.

PTM databases

iPTMnetiO75367.
PhosphoSitePlusiO75367.
SwissPalmiO75367.

Polymorphism and mutation databases

BioMutaiH2AFY.

2D gel databases

SWISS-2DPAGEO75367.

Proteomic databases

EPDiO75367.
MaxQBiO75367.
PaxDbiO75367.
PeptideAtlasiO75367.
PRIDEiO75367.
TopDownProteomicsiO75367-1. [O75367-1]
O75367-2. [O75367-2]

Protocols and materials databases

DNASUi9555.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi9555.
DisGeNETi9555.
GeneCardsiH2AFY.
HGNCiHGNC:4740. H2AFY.
HPAiHPA041189.
HPA050962.
MIMi610054. gene.
neXtProtiNX_O75367.
OpenTargetsiENSG00000113648.
PharmGKBiPA29117.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IV3A. Eukaryota.
KOG1756. Eukaryota.
KOG2633. Eukaryota.
COG2110. LUCA.
COG5262. LUCA.
GeneTreeiENSGT00860000133717.
HOVERGENiHBG009342.
InParanoidiO75367.
KOiK11251.
OMAiKGGKEFT.
OrthoDBiEOG091G0XGD.
PhylomeDBiO75367.
TreeFamiTF332276.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113648-MONOMER.

Miscellaneous databases

ChiTaRSiH2AFY. human.
EvolutionaryTraceiO75367.
GeneWikiiH2AFY.
GenomeRNAii9555.
PMAP-CutDBO75367.
PROiO75367.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113648.
CleanExiHS_H2AFY.
ExpressionAtlasiO75367. baseline and differential.
GenevisibleiO75367. HS.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR021171. Core_histone_macro-H2A.
IPR009072. Histone-fold.
IPR002119. Histone_H2A.
IPR007125. Histone_H2A/H2B/H3.
IPR032454. Histone_H2A_C.
IPR002589. Macro_dom.
[Graphical view]
PfamiPF00125. Histone. 1 hit.
PF16211. Histone_H2A_C. 1 hit.
PF01661. Macro. 1 hit.
[Graphical view]
PIRSFiPIRSF037942. Core_histone_macro-H2A. 1 hit.
PRINTSiPR00620. HISTONEH2A.
SMARTiSM00506. A1pp. 1 hit.
SM00414. H2A. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS51154. MACRO. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiH2AY_HUMAN
AccessioniPrimary (citable) accession number: O75367
Secondary accession number(s): O75377
, Q503A8, Q7Z5E3, Q96D41, Q9H8P3, Q9UP96
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 174 of the entry and version 4 of the sequence. [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

Miscellaneous

The number of individuals with antibodies against this antigen is 2-fold higher in pediatric patients with cancer compared to healthy controls.

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
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.