Reviewed, UniProtKB/Swiss-Prot Q93077 (H2A1C_HUMAN)

Names and origin

Protein names

Recommended name:
    Histone H2A type 1-C
Alternative name(s):
    H2A/l

Gene names

Name:	HIST1H2AC
Synonyms:	H2AFL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	130 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.
Post-translational modification	The chromatin-associated form is phosphorylated on Thr-121 during mitosis Probable. Deiminated on Arg-4 in granulocytes upon calcium entry. Monoubiquitination of Lys-120 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. Monoubiquitination of Lys-120 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. Monoubiquitination and ionizing radiation-induced 'Lys-63'-linked ubiquitination are distinct events. Ref.7 Ref.9 Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 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.
Sequence similarities	Belongs to the histone H2A family.
Mass spectrometry	Molecular mass is 14007.8 Da from positions 2 - 130. Determined by ESI. Monoisotopic with N-acetylserine. Ref.12

Ontologies

Keywords
Cellular component	Chromosomal protein Nucleosome core Nucleus
Ligand	DNA-binding
PTM	Acetylation Citrullination Isopeptide bond Methylation Phosphoprotein Ubl conjugation
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 By similarity
	Chain	2 – 130	129	Histone H2A type 1-C		PRO_0000055236
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.8 Ref.12
	Modified residue	2	1	Phosphoserine Ref.11 Ref.6
	Modified residue	4	1	Citrulline; alternate
	Modified residue	4	1	Symmetric dimethylarginine; alternate By similarity
	Modified residue	6	1	N6-acetyllysine Ref.11
	Modified residue	121	1	Phosphothreonine Probable
	Cross-link	120		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.7 Ref.9 Ref.10
Experimental info
	Mutagenesis	2	1	S → A: Blocks the inhibition of transcription by RPS6KA5/MSK1. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q93077-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: ECEF06C793FE9AC2	FASTA	130	14,105
	10 20 30 40 50 60 MSGRGKQGGK ARAKAKSRSS RAGLQFPVGR VHRLLRKGNY AERVGAGAPV YLAAVLEYLT 70 80 90 100 110 120 AEILELAGNA ARDNKKTRII PRHLQLAIRN DEELNKLLGR VTIAQGGVLP NIQAVLLPKK 130 TESHHKAKGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human histone gene organization: nonregular arrangement within a large cluster." Albig W., Kioschis P., Poustka A., Meergans K., Doenecke D. Genomics 40:314-322(1997) [PubMed: 9119399] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"A 1.1-Mb transcript map of the hereditary hemochromatosis locus." Ruddy D.A., Kronmal G.S., Lee V.K., Mintier G.A., Quintana L., Domingo R. Jr., Meyer N.C., Irrinki A., McClelland E.E., Fullan A., Mapa F.A., Moore T., Thomas W., Loeb D.B., Harmon C., Tsuchihashi Z., Wolff R.K., Schatzman R.C., Feder J.N. Genome Res. 7:441-456(1997) [PubMed: 9149941] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 12408966] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Blood, Skin and Uterus.
[5]	"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: 15078818] [Abstract] Cited for: PHOSPHORYLATION AT THR-121.
[6]	"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: 15010469] [Abstract] Cited for: PHOSPHORYLATION AT SER-2, MUTAGENESIS OF SER-2.
[7]	"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: 15386022] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[8]	"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: 15823041] [Abstract] Cited for: ACETYLATION AT SER-2, CITRULLINATION AT ARG-4, MASS SPECTROMETRY.
[9]	"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: 16359901] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[10]	"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: 16702407] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[11]	"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: 16319397] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, ACETYLATION AT LYS-6, PHOSPHORYLATION AT SER-2.
[12]	"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: 16457589] [Abstract] Cited for: MASS SPECTROMETRY, ACETYLATION AT SER-2.
[13]	"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: 18001824] [Abstract] Cited for: UBIQUITINATION.
[14]	"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: 18001825] [Abstract] Cited for: UBIQUITINATION.
[15]	"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: 19203578] [Abstract] Cited for: UBIQUITINATION.
[16]	"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: 19203579] [Abstract] Cited for: UBIQUITINATION.

Cross-references

Sequence databases
EMBLGenBankDDBJ	Z80778 Genomic DNA. Translation: CAB02540.1. U91328 Genomic DNA. Translation: AAB82086.1. U90551 mRNA. Translation: AAB53429.1. AY131984 Genomic DNA. Translation: AAN59965.1. BC017379 mRNA. Translation: AAH17379.1. BC050602 mRNA. Translation: AAH50602.1. BC085010 mRNA. Translation: AAH85010.1.
IPI	IPI00216456.
RefSeq	NP_003503.1.
UniGene	Hs.484950
3D structure databases
HSSP	HSSP built from PDB template 1AOI based on UniProtKB P06897.
SMR	Q93077. Positions 2-124.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q93077. 1 interaction.
PTM databases
PhosphoSite	Q93077.
Proteomic databases
PRIDE	Q93077.
Genome annotation databases
Ensembl	ENSG00000180573. Homo sapiens. [Contig view]
GeneID	8334.
KEGG	hsa:8334.
Organism-specific databases
GeneCards	GC06P026232.
H-InvDB	HIX0005639.
HGNC	HGNC:4733. HIST1H2AC.
MIM	602794. gene.
PharmGKB	PA29110.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q93077.
HOVERGEN	Q93077.
OMA	Q93077. EYLAVEI.
Enzyme and pathway databases
Reactome	REACT_7970. Telomere Maintenance.
Gene expression databases
ArrayExpress	Q93077.
Bgee	Q93077.
CleanEx	HS_HIST1H2AC.
GermOnline	ENSG00000180573. Homo sapiens.
Family and domain databases
InterPro	IPR007125. Histone_core_D. IPR002119. Histone_H2A. [Graphical view]
PANTHER	PTHR23430. Histone_H2A. 1 hit.
Pfam	PF00125. Histone. 1 hit. [Graphical view]
PRINTS	PR00620. HISTONEH2A.
ProDom	PD000522. Histone_H2A. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00414. H2A. 1 hit. [Graphical view]
PROSITE	PS00046. HISTONE_H2A. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	31208.
SOURCE	Search...

Entry information

Entry name

H2A1C_HUMAN

Accession

Primary (citable) accession number: Q93077
Secondary accession number(s): O00775 , O00776, O00777, O00778, Q540R1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)