H2A1A_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: H2A1A_HUMAN
• UniProt AC: Q96QV6
• Protein Name: Histone H2A type 1-A
• Gene Name: HIST1H2AA
• Organism: Homo sapiens (Human).
• Sequence Length: 131
• 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: MSGRGKQGGKARAKSKSRSSRAGLQFPVGRIHRLLRKGNYAERIGAGAPVYLAAVLEYLTAEILELAGNASRDNKKTRIIPRHLQLAIRNDEELNKLLGGVTIAQGGVLPNIQAVLLPKKTESHHHKAQSK

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 ------CCCCCCCCC	36.88	15823041
2	Acetylation	------MSGRGKQGG ------CCCCCCCCC	36.88	15823041
4	Methylation	----MSGRGKQGGKA ----CCCCCCCCCCC	41.66	-
4	Citrullination	----MSGRGKQGGKA ----CCCCCCCCCCC	41.66	-
4	Citrullination	----MSGRGKQGGKA ----CCCCCCCCCCC	41.66	15823041
6	Acetylation	--MSGRGKQGGKARA --CCCCCCCCCCCCC	44.39	-
6	Other	--MSGRGKQGGKARA --CCCCCCCCCCCCC	44.39	24681537
6	Lactylation	--MSGRGKQGGKARA --CCCCCCCCCCCCC	44.39	31645732
10	Acetylation	GRGKQGGKARAKSKS CCCCCCCCCCCCCCC	41.34	22389435
10	Other	GRGKQGGKARAKSKS CCCCCCCCCCCCCCC	41.34	27105115
10	Lactylation	GRGKQGGKARAKSKS CCCCCCCCCCCCCCC	41.34	31645732
10	Succinylation	GRGKQGGKARAKSKS CCCCCCCCCCCCCCC	41.34	22389435
10	Lactoylation	GRGKQGGKARAKSKS CCCCCCCCCCCCCCC	41.34	-
14	Ubiquitination	QGGKARAKSKSRSSR CCCCCCCCCCCHHHC	53.51	22980979
14	Other	QGGKARAKSKSRSSR CCCCCCCCCCCHHHC	53.51	27105115
16	Ubiquitination	GKARAKSKSRSSRAG CCCCCCCCCHHHCCC	49.54	22980979
17	Phosphorylation	KARAKSKSRSSRAGL CCCCCCCCHHHCCCC	44.48	30622161
19	Phosphorylation	RAKSKSRSSRAGLQF CCCCCCHHHCCCCCC	31.13	30622161
20	Phosphorylation	AKSKSRSSRAGLQFP CCCCCHHHCCCCCCC	25.66	27966365
21	Methylation	KSKSRSSRAGLQFPV CCCCHHHCCCCCCCH	33.64	-
30	Methylation	GLQFPVGRIHRLLRK CCCCCHHHHHHHHHC	23.05	-
37	N6-crotonyl-L-lysine	RIHRLLRKGNYAERI HHHHHHHCCCHHHHH	52.02	-
37	Other	RIHRLLRKGNYAERI HHHHHHHCCCHHHHH	52.02	27105115
37	Ubiquitination	RIHRLLRKGNYAERI HHHHHHHCCCHHHHH	52.02	25015289
37	Crotonylation	RIHRLLRKGNYAERI HHHHHHHCCCHHHHH	52.02	21925322
37	Lactylation	RIHRLLRKGNYAERI HHHHHHHCCCHHHHH	52.02	31645732
40	Phosphorylation	RLLRKGNYAERIGAG HHHHCCCHHHHHCCC	20.64	20860994
58	Phosphorylation	YLAAVLEYLTAEILE HHHHHHHHHHHHHHH	12.75	-
71	Phosphorylation	LELAGNASRDNKKTR HHHCCCCCCCCCCCC	44.13	24532841
75	Other	GNASRDNKKTRIIPR CCCCCCCCCCCEEHH	60.87	24681537
76	Other	NASRDNKKTRIIPRH CCCCCCCCCCEEHHH	49.65	24681537
77	Phosphorylation	ASRDNKKTRIIPRHL CCCCCCCCCEEHHHH	28.80	23882029
82	Methylation	KKTRIIPRHLQLAIR CCCCEEHHHHHHHHC	32.51	-
89	Methylation	RHLQLAIRNDEELNK HHHHHHHCCHHHHHH	38.65	-
96	Succinylation	RNDEELNKLLGGVTI CCHHHHHHHHCCEEE	58.68	22389435
96	Glutarylation	RNDEELNKLLGGVTI CCHHHHHHHHCCEEE	58.68	31542297
96	Ubiquitination	RNDEELNKLLGGVTI CCHHHHHHHHCCEEE	58.68	22817900
96	Other	RNDEELNKLLGGVTI CCHHHHHHHHCCEEE	58.68	27105115
102	Phosphorylation	NKLLGGVTIAQGGVL HHHHCCEEEECCCCC	17.55	20703100
105	Methylation	LGGVTIAQGGVLPNI HCCEEEECCCCCCCE	45.37	24352239
119	Ubiquitination	IQAVLLPKKTESHHH EEEEECCCCCCCCCC	72.76	25015289
119	Neddylation	IQAVLLPKKTESHHH EEEEECCCCCCCCCC	72.76	32015554
119	Sumoylation	IQAVLLPKKTESHHH EEEEECCCCCCCCCC	72.76	-
119	Other	IQAVLLPKKTESHHH EEEEECCCCCCCCCC	72.76	27105115
119	Glutarylation	IQAVLLPKKTESHHH EEEEECCCCCCCCCC	72.76	31542297
119	Crotonylation	IQAVLLPKKTESHHH EEEEECCCCCCCCCC	72.76	21925322
119	Acetylation	IQAVLLPKKTESHHH EEEEECCCCCCCCCC	72.76	28641651
119	N6-crotonyl-L-lysine	IQAVLLPKKTESHHH EEEEECCCCCCCCCC	72.76	-
120	Glutarylation	QAVLLPKKTESHHHK EEEECCCCCCCCCCH	56.43	31542297
120	Crotonylation	QAVLLPKKTESHHHK EEEECCCCCCCCCCH	56.43	21925322
120	Acetylation	QAVLLPKKTESHHHK EEEECCCCCCCCCCH	56.43	20167786
120	Ubiquitination	QAVLLPKKTESHHHK EEEECCCCCCCCCCH	56.43	23000965
120	N6-crotonyl-L-lysine	QAVLLPKKTESHHHK EEEECCCCCCCCCCH	56.43	-
121	Phosphorylation	AVLLPKKTESHHHKA EEECCCCCCCCCCHH	49.17	24140421
123	Phosphorylation	LLPKKTESHHHKAQS ECCCCCCCCCCHHCC	33.09	29759185
127	Crotonylation	KTESHHHKAQSK--- CCCCCCCHHCCC---	43.71	21925322
127	Acetylation	KTESHHHKAQSK--- CCCCCCCHHCCC---	43.71	20167786
127	N6-crotonyl-L-lysine	KTESHHHKAQSK--- CCCCCCCHHCCC---	43.71	-

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	PRC1	O43663	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	DDB2	Q92466	PMID:18593899
-	K	Ubiquitination	E3 ubiquitin ligase	RNF8	O76064	PMID:18001824
-	K	Ubiquitination	E3 ubiquitin ligase	BMI1	P35226	PMID:16751658
-	K	Ubiquitination	E3 ubiquitin ligase	BRCA1	P38398	PMID:11927591
-	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 H2A1A_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
H2B1A_HUMAN	HIST1H2BA	physical	22939629
RSSA_HUMAN	RPSA	physical	22939629
H2B1B_HUMAN	HIST1H2BB	physical	22939629
RS14_HUMAN	RPS14	physical	22939629
RS4X_HUMAN	RPS4X	physical	22939629
HDAC1_HUMAN	HDAC1	physical	24722339
HDAC2_HUMAN	HDAC2	physical	24722339
HDAC3_HUMAN	HDAC3	physical	24722339

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

"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