H2A2B_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: H2A2B_HUMAN
• UniProt AC: Q8IUE6
• Protein Name: Histone H2A type 2-B
• Gene Name: HIST2H2AB
• 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: MSGRGKQGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGNYAERVGAGAPVYLAAVLEYLTAEILELAGNAARDNKKTRIIPRHLQLAVRNDEELNKLLGGVTIAQGGVLPNIQAVLLPKKTESHKPGKNK

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	Citrullination	----MSGRGKQGGKA ----CCCCCCCCHHH	41.66	15823041
4	Methylation	----MSGRGKQGGKA ----CCCCCCCCHHH	41.66	-
6	Methylation	--MSGRGKQGGKARA --CCCCCCCCHHHHH	44.39	20612053
6	Acetylation	--MSGRGKQGGKARA --CCCCCCCCHHHHH	44.39	20612053
6	Other	--MSGRGKQGGKARA --CCCCCCCCHHHHH	44.39	24681537
10	Succinylation	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	22389435
10	Other	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	27105115
10	Lactoylation	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	-
10	Acetylation	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	20612049
14	Other	QGGKARAKAKSRSSR CCHHHHHHHHHHHHC	51.28	27105115
14	Ubiquitination	QGGKARAKAKSRSSR CCHHHHHHHHHHHHC	51.28	22980979
14	Acetylation	QGGKARAKAKSRSSR CCHHHHHHHHHHHHC	51.28	-
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	RVHRLLRKGNYAERV HHHHHHHCCCHHHHC	52.02	-
37	Ubiquitination	RVHRLLRKGNYAERV HHHHHHHCCCHHHHC	52.02	27667366
37	Crotonylation	RVHRLLRKGNYAERV HHHHHHHCCCHHHHC	52.02	21925322
37	Other	RVHRLLRKGNYAERV HHHHHHHCCCHHHHC	52.02	27105115
40	Phosphorylation	RLLRKGNYAERVGAG HHHHCCCHHHHCCCC	20.64	28152594
58	Phosphorylation	YLAAVLEYLTAEILE HHHHHHHHHHHHHHH	12.75	-
75	Other	GNAARDNKKTRIIPR CHHHHCCCCCCEEHH	60.87	24681537
76	Other	NAARDNKKTRIIPRH HHHHCCCCCCEEHHH	49.65	24681537
89	Methylation	RHLQLAVRNDEELNK HHHHHHHCCHHHHHH	39.00	24391501
96	Glutarylation	RNDEELNKLLGGVTI CCHHHHHHHHCCEEE	58.68	31542297
96	Ubiquitination	RNDEELNKLLGGVTI CCHHHHHHHHCCEEE	58.68	22817900
96	Succinylation	RNDEELNKLLGGVTI CCHHHHHHHHCCEEE	58.68	22389435
96	Other	RNDEELNKLLGGVTI CCHHHHHHHHCCEEE	58.68	27105115
102	Phosphorylation	NKLLGGVTIAQGGVL HHHHCCEEEECCCCC	17.55	20703100
105	Methylation	LGGVTIAQGGVLPNI HCCEEEECCCCCCCE	45.37	24352239
119	Glutarylation	IQAVLLPKKTESHKP EEEEECCCCCCCCCC	72.76	31542297
119	Acetylation	IQAVLLPKKTESHKP EEEEECCCCCCCCCC	72.76	22650731
119	Crotonylation	IQAVLLPKKTESHKP EEEEECCCCCCCCCC	72.76	21925322
119	Other	IQAVLLPKKTESHKP EEEEECCCCCCCCCC	72.76	27105115
119	N6-crotonyl-L-lysine	IQAVLLPKKTESHKP EEEEECCCCCCCCCC	72.76	-
119	Neddylation	IQAVLLPKKTESHKP EEEEECCCCCCCCCC	72.76	32015554
119	Sumoylation	IQAVLLPKKTESHKP EEEEECCCCCCCCCC	72.76	-
119	Ubiquitination	IQAVLLPKKTESHKP EEEEECCCCCCCCCC	72.76	25015289
120	Crotonylation	QAVLLPKKTESHKPG EEEECCCCCCCCCCC	56.43	21925322
120	Ubiquitination	QAVLLPKKTESHKPG EEEECCCCCCCCCCC	56.43	23000965
120	Methylation	QAVLLPKKTESHKPG EEEECCCCCCCCCCC	56.43	-
120	Glutarylation	QAVLLPKKTESHKPG EEEECCCCCCCCCCC	56.43	31542297
120	"N6,N6-dimethyllysine"	QAVLLPKKTESHKPG EEEECCCCCCCCCCC	56.43	-
120	Acetylation	QAVLLPKKTESHKPG EEEECCCCCCCCCCC	56.43	30589205
121	Phosphorylation	AVLLPKKTESHKPGK EEECCCCCCCCCCCC	49.17	25470042
123	Phosphorylation	LLPKKTESHKPGKNK ECCCCCCCCCCCCCC	41.88	30576142
125	Ubiquitination	PKKTESHKPGKNK-- CCCCCCCCCCCCC--	65.82	23000965
128	Ubiquitination	TESHKPGKNK----- CCCCCCCCCC-----	70.82	21906983
128	"N6,N6-dimethyllysine"	TESHKPGKNK----- CCCCCCCCCC-----	70.82	-
128	Methylation	TESHKPGKNK----- CCCCCCCCCC-----	70.82	-
130	Ubiquitination	SHKPGKNK------- CCCCCCCC-------	66.26	-

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	RNF8	O76064	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	HUWE1	Q7Z6Z7	PMID:22199232
-	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 H2A2B_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
A4_HUMAN	APP	physical	21832049

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

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

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