Q99878 (H2A1J_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone H2A type 1-J

Alternative name(s):
Histone H2A/e

Gene names

Name:	HIST1H2AJ
Synonyms:	H2AFE

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	128 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 structure	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.
Subcellular location	Nucleus. Chromosome.
Post-translational modification	The chromatin-associated form is phosphorylated on Thr-121 during mitosis Probable. Ref.6 Ref.7 Deiminated on Arg-4 in granulocytes upon calcium entry. Monoubiquitination of Lys-120 (H2AK119Ub) by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events. Ref.8 Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20 Phosphorylation on Ser-2 is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage By similarity. 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. Ref.18
Sequence similarities	Belongs to the histone H2A family.
Mass spectrometry	Molecular mass is 13838.7 Da from positions 2 - 128. Determined by ESI. Monoisotopic with N-acetylserine. Ref.13

Ontologies

Keywords
Cellular component	Chromosome Nucleosome core Nucleus
Ligand	DNA-binding
PTM	Acetylation Citrullination Isopeptide bond Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nucleosome assembly Non-traceable author statement. Source: UniProtKB
Cellular_component	nucleosome Non-traceable author statement. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 128	127	Histone H2A type 1-J		PRO_0000055239
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.9 Ref.13
	Modified residue	2	1	Phosphoserine; by RPS6KA5 Ref.7
	Modified residue	4	1	Citrulline; alternate
	Modified residue	6	1	N6-acetyllysine
	Modified residue	37	1	N6-crotonyl-L-lysine Ref.18
	Modified residue	119	1	N6-crotonyl-L-lysine Ref.18
	Modified residue	120	1	N6-crotonyl-L-lysine; alternate Ref.18
	Modified residue	121	1	Phosphothreonine Probable
	Modified residue	126	1	N6-crotonyl-L-lysine Ref.18
	Cross-link	14		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.19 Ref.20
	Cross-link	16		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.19 Ref.20
	Cross-link	120		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate Ref.8 Ref.10 Ref.11
Experimental info
	Mutagenesis	2	1	S → A: Blocks the inhibition of transcription by RPS6KA5/MSK1. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q99878 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 638BE3FE8256343E	FASTA	128	13,936
	10 20 30 40 50 60 MSGRGKQGGK ARAKAKTRSS RAGLQFPVGR VHRLLRKGNY AERVGAGAPV YLAAVLEYLT 70 80 90 100 110 120 AEILELAGNA ARDNKKTRII PRHLQLAIRN DEELNKLLGK VTIAQGGVLP NIQAVLLPKK TESHHKTK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human histone gene cluster at the D6S105 locus." Albig W., Doenecke D. Hum. Genet. 101:284-294(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The human and mouse replication-dependent histone genes." Marzluff W.F., Gongidi P., Woods K.R., Jin J., Maltais L.J. Genomics 80:487-498(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo." Aihara H., Nakagawa T., Yasui K., Ohta T., Hirose S., Dhomae N., Takio K., Kaneko M., Takeshima Y., Muramatsu M., Ito T. Genes Dev. 18:877-888(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-121.
[7]	"Phosphorylation of histone H2A inhibits transcription on chromatin templates." Zhang Y., Griffin K., Mondal N., Parvin J.D. J. Biol. Chem. 279:21866-21872(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-2, MUTAGENESIS OF SER-2.
[8]	"Role of histone H2A ubiquitination in Polycomb silencing." Wang H., Wang L., Erdjument-Bromage H., Vidal M., Tempst P., Jones R.S., Zhang Y. Nature 431:873-878(2004) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[9]	"Deimination of histone H2A and H4 at arginine 3 in HL-60 granulocytes." Hagiwara T., Hidaka Y., Yamada M. Biochemistry 44:5827-5834(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT SER-2, CITRULLINATION AT ARG-4, MASS SPECTROMETRY.
[10]	"Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing." Cao R., Tsukada Y., Zhang Y. Mol. Cell 20:845-854(2005) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[11]	"DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A." Bergink S., Salomons F.A., Hoogstraten D., Groothuis T.A.M., de Waard H., Wu J., Yuan L., Citterio E., Houtsmuller A.B., Neefjes J., Hoeijmakers J.H.J., Vermeulen W., Dantuma N.P. Genes Dev. 20:1343-1352(2006) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[12]	"Characterization of histones H2A and H2B variants and their post-translational modifications by mass spectrometry." Bonenfant D., Coulot M., Towbin H., Schindler P., van Oostrum J. Mol. Cell. Proteomics 5:541-552(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Precise characterization of human histones in the H2A gene family by top down mass spectrometry." Boyne M.T. II, Pesavento J.J., Mizzen C.A., Kelleher N.L. J. Proteome Res. 5:248-253(2006) [PubMed] [Europe PMC] [Abstract] Cited for: MASS SPECTROMETRY, ACETYLATION AT SER-2.
[14]	"RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins." Mailand N., Bekker-Jensen S., Faustrup H., Melander F., Bartek J., Lukas C., Lukas J. Cell 131:887-900(2007) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[15]	"RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly." Huen M.S.Y., Grant R., Manke I., Minn K., Yu X., Yaffe M.B., Chen J. Cell 131:901-914(2007) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[16]	"The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage." Stewart G.S., Panier S., Townsend K., Al-Hakim A.K., Kolas N.K., Miller E.S., Nakada S., Ylanko J., Olivarius S., Mendez M., Oldreive C., Wildenhain J., Tagliaferro A., Pelletier L., Taubenheim N., Durandy A., Byrd P.J., Stankovic T., Taylor A.M.R., Durocher D. Cell 136:420-434(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[17]	"RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins." Doil C., Mailand N., Bekker-Jensen S., Menard P., Larsen D.H., Pepperkok R., Ellenberg J., Panier S., Durocher D., Bartek J., Lukas J., Lukas C. Cell 136:435-446(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[18]	"Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification." Tan M., Luo H., Lee S., Jin F., Yang J.S., Montellier E., Buchou T., Cheng Z., Rousseaux S., Rajagopal N., Lu Z., Ye Z., Zhu Q., Wysocka J., Ye Y., Khochbin S., Ren B., Zhao Y. Cell 146:1016-1028(2011) [PubMed] [Europe PMC] [Abstract] Cited for: CROTONYLATION AT LYS-37; LYS-119; LYS-120 AND LYS-126.
[19]	"RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA Damage signaling." Mattiroli F., Vissers J.H., van Dijk W.J., Ikpa P., Citterio E., Vermeulen W., Marteijn J.A., Sixma T.K. Cell 150:1182-1195(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-14 AND LYS-16 BY RNF168.
[20]	"A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase." Gatti M., Pinato S., Maspero E., Soffientini P., Polo S., Penengo L. Cell Cycle 11:2538-2544(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-14 AND LYS-16 BY RNF168.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z83736 Genomic DNA. Translation: CAB06031.1. AY131990 Genomic DNA. Translation: AAN59971.1. AL049822 Genomic DNA. Translation: CAB81656.1. CH471081 Genomic DNA. Translation: EAX03109.1. BC066232 mRNA. Translation: AAH66232.1. BC066233 mRNA. Translation: AAH66233.1. BC066234 mRNA. Translation: AAH66234.1. BC066235 mRNA. Translation: AAH66235.1. BC066236 mRNA. Translation: AAH66236.1. BC066237 mRNA. Translation: AAH66237.1. BC133048 mRNA. Translation: AAI33049.1. BC133050 mRNA. Translation: AAI33051.1.
IPI	IPI00552873.
RefSeq	NP_066544.1. NM_021066.2.
UniGene	Hs.406691. Hs.734717.
3D structure databases
ProteinModelPortal	Q99878.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99878. 14 interactions.
STRING	9606.ENSP00000328484.
PTM databases
PhosphoSite	Q99878.
2D gel databases
SWISS-2DPAGE	P99059.
Proteomic databases
PaxDb	Q99878.
PRIDE	Q99878.
Protocols and materials databases
DNASU	8331.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000333151; ENSP00000328484; ENSG00000182611.
GeneID	8331.
KEGG	hsa:8331.
UCSC	uc003njn.1. human.
Organism-specific databases
CTD	8331.
GeneCards	GC06M027782.
HGNC	HGNC:4727. HIST1H2AJ.
MIM	602791. gene.
neXtProt	NX_Q99878.
PharmGKB	PA29104.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5262.
HOGENOM	HOG000234652.
HOVERGEN	HBG009342.
InParanoid	Q99878.
KO	K11251.
OMA	KASHADD.
OrthoDB	EOG4CC42V.
PhylomeDB	Q99878.
Enzyme and pathway databases
Reactome	REACT_111183. Meiosis. REACT_115566. Cell Cycle. REACT_116125. Disease.
Gene expression databases
CleanEx	HS_HIST1H2AJ.
Genevestigator	Q99878.
GermOnline	ENSG00000182611. Homo sapiens.
Family and domain databases
Gene3D	1.10.20.10. 1 hit.
InterPro	IPR009072. Histone-fold. IPR007125. Histone_core_D. IPR002119. Histone_H2A. [Graphical view]
Pfam	PF00125. Histone. 1 hit. [Graphical view]
PRINTS	PR00620. HISTONEH2A.
SMART	SM00414. H2A. 1 hit. [Graphical view]
SUPFAM	SSF47113. Histone-fold. 1 hit.
PROSITE	PS00046. HISTONE_H2A. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8331.
NextBio	31198.
SOURCE	Search...

Entry information

Entry name

H2A1J_HUMAN

Accession

Primary (citable) accession number: Q99878
Secondary accession number(s): A2RUU6, Q5JXQ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 129 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.