H2A3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: H2A3_HUMAN
• UniProt AC: Q7L7L0
• Protein Name: Histone H2A type 3
• Gene Name: HIST3H2A
• Organism: Homo sapiens (Human).
• Sequence Length: 130
• Subcellular Localization: Nucleus. Chromosome.
• Protein Description: 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..
• Protein Sequence: MSGRGKQGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGNYSERVGAGAPVYLAAVLEYLTAEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGRVTIAQGGVLPNIQAVLLPKKTESHHKAKGK

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSGRGKQGG ------CCCCCCCCH	36.88	15823041
2	Acetylation	------MSGRGKQGG ------CCCCCCCCH	36.88	15823041
4	Citrullination	----MSGRGKQGGKA ----CCCCCCCCHHH	41.66	-
4	Methylation	----MSGRGKQGGKA ----CCCCCCCCHHH	41.66	-
4	Citrullination	----MSGRGKQGGKA ----CCCCCCCCHHH	41.66	15823041
6	Methylation	--MSGRGKQGGKARA --CCCCCCCCHHHHH	44.39	24846259
6	Acetylation	--MSGRGKQGGKARA --CCCCCCCCHHHHH	44.39	24846259
6	Other	--MSGRGKQGGKARA --CCCCCCCCHHHHH	44.39	24681537
10	Acetylation	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	24846269
10	Lactoylation	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	-
10	Other	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	27105115
10	Succinylation	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	22389435
14	Acetylation	QGGKARAKAKSRSSR CCHHHHHHHHHHHHC	51.28	-
14	Ubiquitination	QGGKARAKAKSRSSR CCHHHHHHHHHHHHC	51.28	22980979
14	Other	QGGKARAKAKSRSSR CCHHHHHHHHHHHHC	51.28	27105115
16	Ubiquitination	GKARAKAKSRSSRAG HHHHHHHHHHHHCCC	45.77	22980979
17	Phosphorylation	KARAKAKSRSSRAGL HHHHHHHHHHHCCCC	42.10	23882029
19	Phosphorylation	RAKAKSRSSRAGLQF HHHHHHHHHCCCCCC	31.13	30622161
20	Phosphorylation	AKAKSRSSRAGLQFP HHHHHHHHCCCCCCC	25.66	27966365
21	Methylation	KAKSRSSRAGLQFPV HHHHHHHCCCCCCCH	33.64	-
30	Methylation	GLQFPVGRVHRLLRK CCCCCHHHHHHHHHC	22.69	-
37	N6-crotonyl-L-lysine	RVHRLLRKGNYSERV HHHHHHHCCCCHHCC	52.02	-
37	Ubiquitination	RVHRLLRKGNYSERV HHHHHHHCCCCHHCC	52.02	27667366
37	Crotonylation	RVHRLLRKGNYSERV HHHHHHHCCCCHHCC	52.02	21925322
37	Other	RVHRLLRKGNYSERV HHHHHHHCCCCHHCC	52.02	27105115
41	O-linked_Glycosylation	LLRKGNYSERVGAGA HHHCCCCHHCCCCCH	23.95	27615797
58	Phosphorylation	YLAAVLEYLTAEILE HHHHHHHHHHHHHHH	12.75	-
75	Other	GNAARDNKKTRIIPR CHHHHCCCCCCEEHH	60.87	24681537
76	Other	NAARDNKKTRIIPRH HHHHCCCCCCEEHHH	49.65	24681537
77	Phosphorylation	AARDNKKTRIIPRHL HHHCCCCCCEEHHHH	28.80	23882029
82	Methylation	KKTRIIPRHLQLAIR CCCCEEHHHHHHHHC	32.51	-
89	Methylation	RHLQLAIRNDEELNK HHHHHHHCCHHHHHH	38.65	-
96	Succinylation	RNDEELNKLLGRVTI CCHHHHHHHHCCEEE	58.68	22389435
96	Glutarylation	RNDEELNKLLGRVTI CCHHHHHHHHCCEEE	58.68	31542297
96	Other	RNDEELNKLLGRVTI CCHHHHHHHHCCEEE	58.68	27105115
96	Acetylation	RNDEELNKLLGRVTI CCHHHHHHHHCCEEE	58.68	22389435
96	Ubiquitination	RNDEELNKLLGRVTI CCHHHHHHHHCCEEE	58.68	23000965
100	Methylation	ELNKLLGRVTIAQGG HHHHHHCCEEECCCC	23.52	-
102	Phosphorylation	NKLLGRVTIAQGGVL HHHHCCEEECCCCCC	14.83	24732914
105	Methylation	LGRVTIAQGGVLPNI HCCEEECCCCCCCCE	45.37	24352239
119	Acetylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	24469589
119	N6-crotonyl-L-lysine	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	-
119	Ubiquitination	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	25015289
119	Crotonylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	21925322
119	Sumoylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	-
119	Glutarylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	31542297
119	Other	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	27105115
119	Neddylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	32015554
120	Sumoylation	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	-
120	Crotonylation	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	21925322
120	Glutarylation	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	31542297
120	Ubiquitination	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	27667366
120	N6-crotonyl-L-lysine	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	-
120	Acetylation	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	30589217
121	Phosphorylation	AVLLPKKTESHHKAK EEECCCCCHHHHHCC	49.17	25159151
123	Phosphorylation	LLPKKTESHHKAKGK ECCCCCHHHHHCCCC	35.80	25159151
126	Crotonylation	KKTESHHKAKGK--- CCCHHHHHCCCC---	46.50	21925322
126	Glutarylation	KKTESHHKAKGK--- CCCHHHHHCCCC---	46.50	31542297
126	Ubiquitination	KKTESHHKAKGK--- CCCHHHHHCCCC---	46.50	23000965
126	N6-crotonyl-L-lysine	KKTESHHKAKGK--- CCCHHHHHCCCC---	46.50	-
128	Ubiquitination	TESHHKAKGK----- CHHHHHCCCC-----	72.53	25015289
130	Ubiquitination	SHHKAKGK------- HHHHCCCC-------	57.36	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
2	S	Phosphorylation	Kinase	RPS6KA5	O75582	Uniprot
121	T	Phosphorylation	Kinase	DCAF1	Q9Y4B6	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	BMI1	P35226	PMID:16359901
-	K	Ubiquitination	E3 ubiquitin ligase	BMI1#RNF2	P35226#Q99496	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
2	S	Acetylation	Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1.	15010469
2	S	Phosphorylation	Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1.	15010469
2	S	Phosphorylation	Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis.	15010469
2	S	Phosphorylation	Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription.	15010469
4	R	Methylation	Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.	15823041
14	K	ubiquitylation	Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired.	22980979
14	K	ubiquitylation	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.	22980979
16	K	ubiquitylation	Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired.	22980979
16	K	ubiquitylation	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.	22980979
27	K	Methylation	Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me).	15386022
27	K	ubiquitylation	Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me).	15386022
63	K	ubiquitylation	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.	15386022
105	Q	Methylation	Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I.	24352239
120	K	ubiquitylation	Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals.	15386022
120	K	ubiquitylation	Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers.	15386022
121	T	Phosphorylation	Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.	15078818

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of H2A3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
H31T_HUMAN	HIST3H3	physical	22606318
KR103_HUMAN	KRTAP10-3	physical	25416956

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Acetylation

"Deimination of histone H2A and H4 at arginine 3 in HL-60granulocytes.";
Hagiwara T., Hidaka Y., Yamada M.;
Biochemistry 44:5827-5834(2005).
Cited for: ACETYLATION AT SER-2, CITRULLINATION AT ARG-4, AND MASS SPECTROMETRY.
PubMed: 15823041

"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-10 AND LYS-96, ANDMASS SPECTROMETRY.
PubMed: 19608861

Phosphorylation

"Phosphorylation of histone H2A inhibits transcription on chromatintemplates.";
Zhang Y., Griffin K., Mondal N., Parvin J.D.;
J. Biol. Chem. 279:21866-21872(2004).
Cited for: PHOSPHORYLATION AT SER-2, AND MUTAGENESIS OF SER-2.
PubMed: 15010469

"Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 duringmitosis 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).
Cited for: PHOSPHORYLATION AT THR-121.
PubMed: 15078818

Ubiquitylation

"DNA damage triggers nucleotide excision repair-dependentmonoubiquitylation 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).
Cited for: UBIQUITINATION AT LYS-120.
PubMed: 16702407

"Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox genesilencing.";
Cao R., Tsukada Y., Zhang Y.;
Mol. Cell 20:845-854(2005).
Cited for: UBIQUITINATION AT LYS-120.
PubMed: 16359901

"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).
Cited for: UBIQUITINATION AT LYS-120.
PubMed: 15386022