HMGB1_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HMGB1_RAT
• UniProt AC: P63159
• Protein Name: High mobility group protein B1
• Gene Name: Hmgb1
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 215
• Subcellular Localization: Nucleus . Cytoplasm . Secreted . Chromosome . 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. 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. [PubMed: 23519706]
• Protein Sequence: MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKKCSERWKTMSAKEKGKFEDMAKADKARYEREMKTYIPPKGETKKKFKDPNAPKRPPSAFFLFCSEYRPKIKGEHPGLSIGDVAKKLGEMWNNTAADDKQPYEKKAAKLKEKYEKDIAAYRAKGKPDAAKKGVVKAEKSKKKKEEEDDEEDEEDEEEEEEEEDEDEEEDDDDE

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
3	Acetylation	-----MGKGDPKKPR -----CCCCCCCCCC	59.86	17269659
7	Acetylation	-MGKGDPKKPRGKMS -CCCCCCCCCCCCCH	78.96	-
8	Acetylation	MGKGDPKKPRGKMSS CCCCCCCCCCCCCHH	45.39	-
12	Acetylation	DPKKPRGKMSSYAFF CCCCCCCCCHHHHHH	36.57	-
23	Sulfation	YAFFVQTCREEHKKK HHHHHHHHHHHHHHH	2.63	22869893
23	Oxidation	YAFFVQTCREEHKKK HHHHHHHHHHHHHHH	2.63	22869893
23	Cysteine derivative	YAFFVQTCREEHKKK HHHHHHHHHHHHHHH	2.63	-
28	Acetylation	QTCREEHKKKHPDAS HHHHHHHHHHCCCCC	67.79	-
29	Acetylation	TCREEHKKKHPDASV HHHHHHHHHCCCCCC	59.21	-
30	Acetylation	CREEHKKKHPDASVN HHHHHHHHCCCCCCC	66.24	-
30	Succinylation	CREEHKKKHPDASVN HHHHHHHHCCCCCCC	66.24	26843850
35	Phosphorylation	KKKHPDASVNFSEFS HHHCCCCCCCHHHHH	25.60	27097102
39	Phosphorylation	PDASVNFSEFSKKCS CCCCCCHHHHHHHHH	32.31	25575281
42	Phosphorylation	SVNFSEFSKKCSERW CCCHHHHHHHHHHHH	27.44	25575281
43	Acetylation	VNFSEFSKKCSERWK CCHHHHHHHHHHHHH	64.22	22902405
45	Cysteine derivative	FSEFSKKCSERWKTM HHHHHHHHHHHHHCC	6.16	-
45	Oxidation	FSEFSKKCSERWKTM HHHHHHHHHHHHHCC	6.16	22869893
45	Sulfation	FSEFSKKCSERWKTM HHHHHHHHHHHHHCC	6.16	22869893
55	Acetylation	RWKTMSAKEKGKFED HHHCCCHHHCCCHHH	53.29	22902405
57	Acetylation	KTMSAKEKGKFEDMA HCCCHHHCCCHHHHH	67.69	22902405
59	Succinylation	MSAKEKGKFEDMAKA CCHHHCCCHHHHHHH	57.56	26843850
59	Acetylation	MSAKEKGKFEDMAKA CCHHHCCCHHHHHHH	57.56	22902405
65	Acetylation	GKFEDMAKADKARYE CCHHHHHHHHHHHHH	50.94	22902405
82	Succinylation	MKTYIPPKGETKKKF HHHCCCCCCCCCCCC	65.11	26843850
82	Acetylation	MKTYIPPKGETKKKF HHHCCCCCCCCCCCC	65.11	22902405
90	Succinylation	GETKKKFKDPNAPKR CCCCCCCCCCCCCCC	79.67	26843850
90	Acetylation	GETKKKFKDPNAPKR CCCCCCCCCCCCCCC	79.67	22902405
100	Phosphorylation	NAPKRPPSAFFLFCS CCCCCCCCCEEHHCC	40.15	23984901
106	Sulfation	PSAFFLFCSEYRPKI CCCEEHHCCCCCCCC	3.08	22869893
106	Cysteine derivative	PSAFFLFCSEYRPKI CCCEEHHCCCCCCCC	3.08	-
106	Oxidation	PSAFFLFCSEYRPKI CCCEEHHCCCCCCCC	3.08	22869893
114	Succinylation	SEYRPKIKGEHPGLS CCCCCCCCCCCCCCC	65.46	26843850
114	Ubiquitination	SEYRPKIKGEHPGLS CCCCCCCCCCCCCCC	65.46	-
114	Acetylation	SEYRPKIKGEHPGLS CCCCCCCCCCCCCCC	65.46	22902405
127	Acetylation	LSIGDVAKKLGEMWN CCHHHHHHHHHHHHH	48.67	22902405
128	Acetylation	SIGDVAKKLGEMWNN CHHHHHHHHHHHHHC	52.57	22902405
141	Acetylation	NNTAADDKQPYEKKA HCCCCCCCCHHHHHH	54.44	22902405
172	Acetylation	KGKPDAAKKGVVKAE CCCCCHHHHCCCHHH	52.35	-
173	Acetylation	GKPDAAKKGVVKAEK CCCCHHHHCCCHHHH	52.81	-
177	Acetylation	AAKKGVVKAEKSKKK HHHHCCCHHHHHHCC	48.71	22902405
180	Acetylation	KGVVKAEKSKKKKEE HCCCHHHHHHCCCCC	72.87	-
181	ADP-ribosylation	GVVKAEKSKKKKEEE CCCHHHHHHCCCCCC	41.01	-
181	Phosphorylation	GVVKAEKSKKKKEEE CCCHHHHHHCCCCCC	41.01	21257610
182	Acetylation	VVKAEKSKKKKEEED CCHHHHHHCCCCCCC	78.62	-
183	Acetylation	VKAEKSKKKKEEEDD CHHHHHHCCCCCCCC	75.95	-
184	Acetylation	KAEKSKKKKEEEDDE HHHHHHCCCCCCCCC	69.98	-
185	Acetylation	AEKSKKKKEEEDDEE HHHHHCCCCCCCCCC	78.29	-

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

Oops, there are no upstream regulatory protein records of HMGB1_RAT !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
3	K	Acetylation	Acetylation on Lys-3 results in preferential binding to DNA ends and impairs DNA bending activity.	14532127
23	C	Oxidation	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).	16962095
45	C	Oxidation	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).	16962095
106	C	Oxidation	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).	16962095

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of HMGB1_RAT !!

Protein-Protein Interaction

Oops, there are no PPI records of HMGB1_RAT !!

Drug and Disease Associations

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