dbPTM

H2A2A_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	H2A2A_HUMAN
UniProt AC	Q6FI13
Protein Name	Histone H2A type 2-A
Gene Name	HIST2H2AA3
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	MSGRGKQGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGNYAERVGAGAPVYMAAVLEYLTAEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGKVTIAQGGVLPNIQAVLLPKKTESHHKAKGK

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSGRGKQGG ------CCCCCCCCH	36.88	16319397
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	19608861
6	Acetylation	--MSGRGKQGGKARA --CCCCCCCCHHHHH	44.39	16457589
6	Other	--MSGRGKQGGKARA --CCCCCCCCHHHHH	44.39	24681537
10	Acetylation	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	19608861
10	Lactoylation	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	-
10	Other	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	27105115
10	Succinylation	GRGKQGGKARAKAKS CCCCCCHHHHHHHHH	41.34	19608861
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	RVHRLLRKGNYAERV HHHHHHHCCCHHHHC	52.02	-
37	Crotonylation	RVHRLLRKGNYAERV HHHHHHHCCCHHHHC	52.02	21925322
37	Other	RVHRLLRKGNYAERV HHHHHHHCCCHHHHC	52.02	27105115
37	Ubiquitination	RVHRLLRKGNYAERV HHHHHHHCCCHHHHC	52.02	27667366
40	Phosphorylation	RLLRKGNYAERVGAG HHHHCCCHHHHCCCC	20.64	28152594
51	Phosphorylation	VGAGAPVYMAAVLEY CCCCHHHHHHHHHHH	4.68	-
58	Phosphorylation	YMAAVLEYLTAEILE HHHHHHHHHHHHHHH	12.75	-
72	Dimethylation	ELAGNAARDNKKTRI HHCCHHHHCCCCCCE	45.70	-
72	Methylation	ELAGNAARDNKKTRI HHCCHHHHCCCCCCE	45.70	-
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	Other	RNDEELNKLLGKVTI CCHHHHHHHHCCEEE	58.68	27105115
96	Glutarylation	RNDEELNKLLGKVTI CCHHHHHHHHCCEEE	58.68	31542297
96	Acetylation	RNDEELNKLLGKVTI CCHHHHHHHHCCEEE	58.68	19608861
96	Ubiquitination	RNDEELNKLLGKVTI CCHHHHHHHHCCEEE	58.68	27667366
96	Neddylation	RNDEELNKLLGKVTI CCHHHHHHHHCCEEE	58.68	32015554
96	Succinylation	RNDEELNKLLGKVTI CCHHHHHHHHCCEEE	58.68	19608861
100	Acetylation	ELNKLLGKVTIAQGG HHHHHHCCEEECCCC	35.85	158613
100	Ubiquitination	ELNKLLGKVTIAQGG HHHHHHCCEEECCCC	35.85	23000965
100	Glutarylation	ELNKLLGKVTIAQGG HHHHHHCCEEECCCC	35.85	31542297
102	Phosphorylation	NKLLGKVTIAQGGVL HHHHCCEEECCCCCC	17.68	24732914
105	Methylation	LGKVTIAQGGVLPNI HCCEEECCCCCCCCE	45.37	24352239
119	Neddylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	32015554
119	Acetylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	158653
119	N6-crotonyl-L-lysine	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	-
119	Ubiquitination	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	25015289
119	Glutarylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	31542297
119	Crotonylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	21925322
119	Other	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	27105115
119	Sumoylation	IQAVLLPKKTESHHK EEEEECCCCCHHHHH	72.76	19608861
120	Glutarylation	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	31542297
120	Ubiquitination	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	16457589
120	Crotonylation	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	21925322
120	N6-crotonyl-L-lysine	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	-
120	Acetylation	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	164053
120	Sumoylation	QAVLLPKKTESHHKA EEEECCCCCHHHHHC	56.43	-
121	Phosphorylation	AVLLPKKTESHHKAK EEECCCCCHHHHHCC	49.17	25159151
123	Phosphorylation	LLPKKTESHHKAKGK ECCCCCHHHHHCCCC	35.80	25159151
126	N6-crotonyl-L-lysine	KKTESHHKAKGK--- CCCHHHHHCCCC---	46.50	-
126	Ubiquitination	KKTESHHKAKGK--- CCCHHHHHCCCC---	46.50	23000965
126	Crotonylation	KKTESHHKAKGK--- CCCHHHHHCCCC---	46.50	21925322
126	Glutarylation	KKTESHHKAKGK--- CCCHHHHHCCCC---	46.50	31542297
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:21772249
-	K	Ubiquitination	E3 ubiquitin ligase	RNF2	Q99496	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	PRC1	O43663	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	BMI1#RNF2	P35226#Q99496	PMID:22199232

Functions of PTM Sites

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

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of H2A2A_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PARP1_HUMAN	PARP1	physical	20525793
DNJC2_HUMAN	DNAJC2	physical	21179169
RING2_HUMAN	RNF2	physical	21179169
BMI1_HUMAN	BMI1	physical	21179169
HDAC1_HUMAN	HDAC1	physical	21179169
A4_HUMAN	APP	physical	21832049

Drug and Disease Associations

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

Regulatory Network of H2A2A_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Precise characterization of human histones in the H2A gene family bytop down mass spectrometry."; Boyne M.T. II, Pesavento J.J., Mizzen C.A., Kelleher N.L.; J. Proteome Res. 5:248-253(2006). Cited for: MASS SPECTROMETRY, ACETYLATION AT SER-2 AND LYS-6, AND UBIQUITINATIONAT LYS-120.	16457589 [Abstract]
"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.	15823041 [Abstract]
"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). Cited for: IDENTIFICATION BY MASS SPECTROMETRY, ACETYLATION AT LYS-6, ANDPHOSPHORYLATION AT SER-2.	16319397 [Abstract]
Phosphorylation
Reference	PubMed
"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). Cited for: IDENTIFICATION BY MASS SPECTROMETRY, ACETYLATION AT LYS-6, ANDPHOSPHORYLATION AT SER-2.	16319397 [Abstract]
"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.	15010469 [Abstract]
Ubiquitylation
Reference	PubMed
"Precise characterization of human histones in the H2A gene family bytop down mass spectrometry."; Boyne M.T. II, Pesavento J.J., Mizzen C.A., Kelleher N.L.; J. Proteome Res. 5:248-253(2006). Cited for: MASS SPECTROMETRY, ACETYLATION AT SER-2 AND LYS-6, AND UBIQUITINATIONAT LYS-120.	16457589 [Abstract]
"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.	16702407 [Abstract]
"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.	16359901 [Abstract]
"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.	15386022 [Abstract]

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