dbPTM

HMGB1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	HMGB1_HUMAN
UniProt AC	P09429
Protein Name	High mobility group protein B1
Gene Name	HMGB1
Organism	Homo sapiens (Human).
Sequence Length	215
Subcellular Localization	Nucleus . Chromosome . Cytoplasm . Secreted . Cell membrane Peripheral membrane protein Extracellular side . Endosome . Endoplasmic reticulum-Golgi intermediate compartment . In basal state predominantly nuclear. Shuttles between the cytoplasm an
Protein Description	Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability. Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functions as sensor and/or chaperone for immunogenic nucleic acids implicating the activation of TLR9-mediated immune responses, and mediates autophagy. Acts as danger associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury. [PubMed: 27362237 Released to the extracellular environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates cells through engagement of multiple surface receptors. In the extracellular compartment fully reduced HMGB1 (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine, and sulfonyl HMGB1 (released from apoptotic cells) promotes immunological tolerance]
Protein Sequence	MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKKCSERWKTMSAKEKGKFEDMAKADKARYEREMKTYIPPKGETKKKFKDPNAPKRPPSAFFLFCSEYRPKIKGEHPGLSIGDVAKKLGEMWNNTAADDKQPYEKKAAKLKEKYEKDIAAYRAKGKPDAAKKGVVKAEKSKKKKEEEEDEEDEEDEEEEEDEEDEDEEEDDDDE

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
3	Acetylation	-----MGKGDPKKPR -----CCCCCCCCCC	59.86	15005629
3	Methylation	-----MGKGDPKKPR -----CCCCCCCCCC	59.86	66045
7	2-Hydroxyisobutyrylation	-MGKGDPKKPRGKMS -CCCCCCCCCCCCCH	78.96	-
7	Acetylation	-MGKGDPKKPRGKMS -CCCCCCCCCCCCCH	78.96	-
8	Acetylation	MGKGDPKKPRGKMSS CCCCCCCCCCCCCHH	45.39	-
12	Acetylation	DPKKPRGKMSSYAFF CCCCCCCCCHHHHHH	36.57	23954790
12	Malonylation	DPKKPRGKMSSYAFF CCCCCCCCCHHHHHH	36.57	26320211
12	Ubiquitination	DPKKPRGKMSSYAFF CCCCCCCCCHHHHHH	36.57	19608861
14	Phosphorylation	KKPRGKMSSYAFFVQ CCCCCCCHHHHHHHH	24.55	28152594
15	Phosphorylation	KPRGKMSSYAFFVQT CCCCCCHHHHHHHHH	19.58	28152594
16	Phosphorylation	PRGKMSSYAFFVQTC CCCCCHHHHHHHHHH	10.50	28152594
23	Cysteine derivative	YAFFVQTCREEHKKK HHHHHHHHHHHHHHH	2.63	-
23	Glutathionylation	YAFFVQTCREEHKKK HHHHHHHHHHHHHHH	2.63	22555962
23	Oxidation	YAFFVQTCREEHKKK HHHHHHHHHHHHHHH	2.63	-
24	Methylation	AFFVQTCREEHKKKH HHHHHHHHHHHHHHC	56.58	-
28	Acetylation	QTCREEHKKKHPDAS HHHHHHHHHHCCCCC	67.79	19666589
29	Acetylation	TCREEHKKKHPDASV HHHHHHHHHCCCCCC	59.21	-
30	Acetylation	CREEHKKKHPDASVN HHHHHHHHCCCCCCC	66.24	19608861
30	Malonylation	CREEHKKKHPDASVN HHHHHHHHCCCCCCC	66.24	26320211
30	Ubiquitination	CREEHKKKHPDASVN HHHHHHHHCCCCCCC	66.24	19608861
35	Phosphorylation	KKKHPDASVNFSEFS HHHCCCCCCCHHHHH	25.60	23927012
39	Phosphorylation	PDASVNFSEFSKKCS CCCCCCHHHHHHHHH	32.31	23927012
42	Phosphorylation	SVNFSEFSKKCSERW CCCHHHHHHHHHHHH	27.44	23927012
43	2-Hydroxyisobutyrylation	VNFSEFSKKCSERWK CCHHHHHHHHHHHHH	64.22	-
43	Acetylation	VNFSEFSKKCSERWK CCHHHHHHHHHHHHH	64.22	23954790
43	Methylation	VNFSEFSKKCSERWK CCHHHHHHHHHHHHH	64.22	18513496
43	Ubiquitination	VNFSEFSKKCSERWK CCHHHHHHHHHHHHH	64.22	21906983
44	Acetylation	NFSEFSKKCSERWKT CHHHHHHHHHHHHHC	41.62	129707
44	Ubiquitination	NFSEFSKKCSERWKT CHHHHHHHHHHHHHC	41.62	-
45	Cysteine derivative	FSEFSKKCSERWKTM HHHHHHHHHHHHHCC	6.16	-
45	Oxidation	FSEFSKKCSERWKTM HHHHHHHHHHHHHCC	6.16	-
46	Phosphorylation	SEFSKKCSERWKTMS HHHHHHHHHHHHCCC	38.79	-
50	Acetylation	KKCSERWKTMSAKEK HHHHHHHHCCCHHHC	40.34	25953088
50	Ubiquitination	KKCSERWKTMSAKEK HHHHHHHHCCCHHHC	40.34	-
51	Phosphorylation	KCSERWKTMSAKEKG HHHHHHHCCCHHHCC	14.92	22673903
53	Phosphorylation	SERWKTMSAKEKGKF HHHHHCCCHHHCCCH	41.23	30624053
55	2-Hydroxyisobutyrylation	RWKTMSAKEKGKFED HHHCCCHHHCCCHHH	53.29	-
55	Acetylation	RWKTMSAKEKGKFED HHHCCCHHHCCCHHH	53.29	129711
55	Ubiquitination	RWKTMSAKEKGKFED HHHCCCHHHCCCHHH	53.29	21906983
57	Acetylation	KTMSAKEKGKFEDMA HCCCHHHCCCHHHHH	67.69	23749302
59	2-Hydroxyisobutyrylation	MSAKEKGKFEDMAKA CCHHHCCCHHHHHHH	57.56	-
59	Acetylation	MSAKEKGKFEDMAKA CCHHHCCCHHHHHHH	57.56	23749302
59	Malonylation	MSAKEKGKFEDMAKA CCHHHCCCHHHHHHH	57.56	26320211
59	Methylation	MSAKEKGKFEDMAKA CCHHHCCCHHHHHHH	57.56	22641245
59	Ubiquitination	MSAKEKGKFEDMAKA CCHHHCCCHHHHHHH	57.56	19608861
65	2-Hydroxyisobutyrylation	GKFEDMAKADKARYE CCHHHHHHHHHHHHH	50.94	-
65	Acetylation	GKFEDMAKADKARYE CCHHHHHHHHHHHHH	50.94	25953088
65	Ubiquitination	GKFEDMAKADKARYE CCHHHHHHHHHHHHH	50.94	21906983
71	Phosphorylation	AKADKARYEREMKTY HHHHHHHHHHHHHHC	24.97	26074081
76	Acetylation	ARYEREMKTYIPPKG HHHHHHHHHCCCCCC	33.16	20167786
76	Ubiquitination	ARYEREMKTYIPPKG HHHHHHHHHCCCCCC	33.16	-
77	Phosphorylation	RYEREMKTYIPPKGE HHHHHHHHCCCCCCC	25.93	28152594
78	Nitration	YEREMKTYIPPKGET HHHHHHHCCCCCCCC	13.10	-
78	Phosphorylation	YEREMKTYIPPKGET HHHHHHHCCCCCCCC	13.10	28152594
82	Acetylation	MKTYIPPKGETKKKF HHHCCCCCCCCCCCC	65.11	19166815
82	Ubiquitination	MKTYIPPKGETKKKF HHHCCCCCCCCCCCC	65.11	19608861
88	Acetylation	PKGETKKKFKDPNAP CCCCCCCCCCCCCCC	60.24	25953088
90	Acetylation	GETKKKFKDPNAPKR CCCCCCCCCCCCCCC	79.67	23749302
90	Ubiquitination	GETKKKFKDPNAPKR CCCCCCCCCCCCCCC	79.67	-
100	O-linked_Glycosylation	NAPKRPPSAFFLFCS CCCCCCCCCEEHHCC	40.15	23301498
100	Phosphorylation	NAPKRPPSAFFLFCS CCCCCCCCCEEHHCC	40.15	20058876
106	Cysteine derivative	PSAFFLFCSEYRPKI CCCEEHHCCCCCCCC	3.08	-
106	Oxidation	PSAFFLFCSEYRPKI CCCEEHHCCCCCCCC	3.08	-
107	O-linked_Glycosylation	SAFFLFCSEYRPKIK CCEEHHCCCCCCCCC	30.26	23301498
107	Phosphorylation	SAFFLFCSEYRPKIK CCEEHHCCCCCCCCC	30.26	28152594
109	Phosphorylation	FFLFCSEYRPKIKGE EEHHCCCCCCCCCCC	18.87	27273156
112	Acetylation	FCSEYRPKIKGEHPG HCCCCCCCCCCCCCC	48.31	26051181
112	Methylation	FCSEYRPKIKGEHPG HCCCCCCCCCCCCCC	48.31	-
112	Ubiquitination	FCSEYRPKIKGEHPG HCCCCCCCCCCCCCC	48.31	21906983
114	Sumoylation	SEYRPKIKGEHPGLS CCCCCCCCCCCCCCC	65.46	-
114	Acetylation	SEYRPKIKGEHPGLS CCCCCCCCCCCCCCC	65.46	26051181
114	Malonylation	SEYRPKIKGEHPGLS CCCCCCCCCCCCCCC	65.46	26320211
114	Methylation	SEYRPKIKGEHPGLS CCCCCCCCCCCCCCC	65.46	72610353
114	Sumoylation	SEYRPKIKGEHPGLS CCCCCCCCCCCCCCC	65.46	-
114	Ubiquitination	SEYRPKIKGEHPGLS CCCCCCCCCCCCCCC	65.46	21890473
121	Phosphorylation	KGEHPGLSIGDVAKK CCCCCCCCHHHHHHH	30.36	25159151
127	2-Hydroxyisobutyrylation	LSIGDVAKKLGEMWN CCHHHHHHHHHHHHH	48.67	-
127	Acetylation	LSIGDVAKKLGEMWN CCHHHHHHHHHHHHH	48.67	25953088
127	Malonylation	LSIGDVAKKLGEMWN CCHHHHHHHHHHHHH	48.67	26320211
127	Ubiquitination	LSIGDVAKKLGEMWN CCHHHHHHHHHHHHH	48.67	-
128	Acetylation	SIGDVAKKLGEMWNN CHHHHHHHHHHHHHC	52.57	25953088
128	Malonylation	SIGDVAKKLGEMWNN CHHHHHHHHHHHHHC	52.57	26320211
128	Ubiquitination	SIGDVAKKLGEMWNN CHHHHHHHHHHHHHC	52.57	21890473
132	Sulfoxidation	VAKKLGEMWNNTAAD HHHHHHHHHHCCCCC	4.38	30846556
136	Phosphorylation	LGEMWNNTAADDKQP HHHHHHCCCCCCCCH	21.73	20860994
141	Acetylation	NNTAADDKQPYEKKA HCCCCCCCCHHHHHH	54.44	25953088
141	Ubiquitination	NNTAADDKQPYEKKA HCCCCCCCCHHHHHH	54.44	-
144	Phosphorylation	AADDKQPYEKKAAKL CCCCCCHHHHHHHHH	37.58	28450419
146	Acetylation	DDKQPYEKKAAKLKE CCCCHHHHHHHHHHH	41.70	23236377
146	Malonylation	DDKQPYEKKAAKLKE CCCCHHHHHHHHHHH	41.70	26320211
146	Ubiquitination	DDKQPYEKKAAKLKE CCCCHHHHHHHHHHH	41.70	21906983
147	Ubiquitination	DKQPYEKKAAKLKEK CCCHHHHHHHHHHHH	41.45	-
154	Acetylation	KAAKLKEKYEKDIAA HHHHHHHHHHHHHHH	58.06	23749302
154	Ubiquitination	KAAKLKEKYEKDIAA HHHHHHHHHHHHHHH	58.06	21890473
155	Phosphorylation	AAKLKEKYEKDIAAY HHHHHHHHHHHHHHH	29.33	28152594
157	2-Hydroxyisobutyrylation	KLKEKYEKDIAAYRA HHHHHHHHHHHHHHH	51.88	-
157	Acetylation	KLKEKYEKDIAAYRA HHHHHHHHHHHHHHH	51.88	23954790
157	Malonylation	KLKEKYEKDIAAYRA HHHHHHHHHHHHHHH	51.88	26320211
157	Ubiquitination	KLKEKYEKDIAAYRA HHHHHHHHHHHHHHH	51.88	21890473
162	Phosphorylation	YEKDIAAYRAKGKPD HHHHHHHHHHCCCCC	11.33	25839225
172	2-Hydroxyisobutyrylation	KGKPDAAKKGVVKAE CCCCCHHHHCCHHHH	52.35	-
172	Acetylation	KGKPDAAKKGVVKAE CCCCCHHHHCCHHHH	52.35	-
173	Acetylation	GKPDAAKKGVVKAEK CCCCHHHHCCHHHHH	52.81	26051181
177	Sumoylation	AAKKGVVKAEKSKKK HHHHCCHHHHHHHHH	48.71	-
177	Acetylation	AAKKGVVKAEKSKKK HHHHCCHHHHHHHHH	48.71	25953088
177	Sumoylation	AAKKGVVKAEKSKKK HHHHCCHHHHHHHHH	48.71	-
180	Acetylation	KGVVKAEKSKKKKEE HCCHHHHHHHHHHHH	72.87	-
181	ADP-ribosylation	GVVKAEKSKKKKEEE CCHHHHHHHHHHHHH	41.01	28190768
181	Phosphorylation	GVVKAEKSKKKKEEE CCHHHHHHHHHHHHH	41.01	22750245
182	Acetylation	VVKAEKSKKKKEEEE CHHHHHHHHHHHHHC	78.62	-
183	Acetylation	VKAEKSKKKKEEEED HHHHHHHHHHHHHCC	75.95	-
184	Acetylation	KAEKSKKKKEEEEDE HHHHHHHHHHHHCCC	69.98	-
185	Acetylation	AEKSKKKKEEEEDEE HHHHHHHHHHHCCCC	78.29	-

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
39	S	Phosphorylation	Kinase	PKCZ	Q05513	PSP
46	S	Phosphorylation	Kinase	PKCA	P05696	PSP
53	S	Phosphorylation	Kinase	PKCZ	Q05513	PSP
181	S	Phosphorylation	Kinase	PKCZ	Q05513	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
3	K	Acetylation	19608861
Acetylation on Lys-3 results in preferential binding to DNA ends and impairs DNA bending activity (By similarity).
23	C	Oxidation	22869893
Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-106 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- fully reduced HMGB1 (HMGB1C23hC45hC106h), 2- disulfide HMGB1 (HMGB1C23-C45C106h) and 3- sulfonyl HMGB1 (HMGB1C23soC45soC106so).
45	C	Oxidation	22869893
Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-106 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- fully reduced HMGB1 (HMGB1C23hC45hC106h), 2- disulfide HMGB1 (HMGB1C23-C45C106h) and 3- sulfonyl HMGB1 (HMGB1C23soC45soC106so).
106	C	Oxidation	18631454
Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-106 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- fully reduced HMGB1 (HMGB1C23hC45hC106h), 2- disulfide HMGB1 (HMGB1C23-C45C106h) and 3- sulfonyl HMGB1 (HMGB1C23soC45soC106so).

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 HMGB1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ERG28_HUMAN	C14orf1	physical	16169070
DPYL1_HUMAN	CRMP1	physical	16169070
LRIF1_HUMAN	LRIF1	physical	16169070
U119A_HUMAN	UNC119	physical	16169070
P53_HUMAN	TP53	physical	11106654
HXB1_HUMAN	HOXB1	physical	8890171
HXB3_HUMAN	HOXB3	physical	8890171
HXC6_HUMAN	HOXC6	physical	8890171
HXD3_HUMAN	HOXD3	physical	8890171
HXD8_HUMAN	HOXD8	physical	8890171
HXD9_HUMAN	HOXD9	physical	8890171
HXD10_HUMAN	HOXD10	physical	8890171
HXD11_HUMAN	HOXD11	physical	8890171
NCAN_HUMAN	NCAN	physical	9507007
PTPRZ_HUMAN	PTPRZ1	physical	9507007
TPA_HUMAN	PLAT	physical	8366113
RAG1_HUMAN	RAG1	physical	10490593
P73_HUMAN	TP73	physical	11748232
HMGB2_HUMAN	HMGB2	physical	12517784
PDIA3_HUMAN	PDIA3	physical	12517784
HSP7C_HUMAN	HSPA8	physical	12517784
ORF73_HHV8P	HHV8GK18_gp81	physical	22379092
XPC_HUMAN	XPC	physical	19446504
RD23B_HUMAN	RAD23B	physical	19446504
SSRP1_HUMAN	SSRP1	physical	22939629
SMCE1_HUMAN	SMARCE1	physical	22939629
HNF1A_HUMAN	HNF1A	physical	18160415
HMGA1_HUMAN	HMGA1	physical	18850631
ATRAP_HUMAN	AGTRAP	physical	25416956
IMA7_HUMAN	KPNA6	physical	26344197
SP100_HUMAN	SP100	physical	28514442
POTEE_HUMAN	POTEE	physical	28514442
AT2A1_HUMAN	ATP2A1	physical	28514442
GFAP_HUMAN	GFAP	physical	28514442
TBA3C_HUMAN	TUBA3C	physical	28514442
UBE2N_HUMAN	UBE2N	physical	27173435

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.

Regulatory Network of HMGB1_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"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-12 AND LYS-30, AND MASSSPECTROMETRY.	19608861 [Abstract]
"Substrate and functional diversity of lysine acetylation revealed bya proteomics survey."; Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T.,Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.; Mol. Cell 23:607-618(2006). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-30, AND MASS SPECTROMETRY.	16916647 [Abstract]
Phosphorylation
Reference	PubMed
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 AND SER-100, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Global proteomic profiling of phosphopeptides using electron transferdissociation tandem mass spectrometry."; Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.; Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND MASSSPECTROMETRY.	17287340 [Abstract]
Ubiquitylation
Reference	PubMed
"Proteomic analysis of ubiquitinated proteins in normal hepatocytecell line Chang liver cells."; Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E.,Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X.; Proteomics 8:2885-2896(2008). Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-112, AND MASSSPECTROMETRY.	18655026 [Abstract]

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