SIR2_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SIR2_RAT
• UniProt AC: Q5RJQ4
• Protein Name: NAD-dependent protein deacetylase sirtuin-2
• Gene Name: Sirt2
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 350
• Subcellular Localization: Nucleus . Cytoplasm, perinuclear region . Cytoplasm . Cytoplasm, cytoskeleton . Cytoplasm, cytoskeleton, microtubule organizing center, centrosome . Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole . Cytoplasm, cytoskeleton, s
• Protein Description: NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. [PubMed: 17344398 Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (By similarity Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (By similarity Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Deacetylates also EIF5A. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor (By similarity]
• Protein Sequence: MDFLRNLFTQTLGLGSQKERLLDELTLEGVTRYMQSERCRRVICLVGAGISTSAGIPDFRSPSTGLYANLEKYHLPYPEAIFEISYFKKHPEPFFALAKELYPGQFKPTICHYFIRLLKEKGLLLRCYTQNIDTLERVAGLEPQDLVEAHGTFYTSHCVNTSCGKEYTMSWMKEKIFSEATPKCEKCQNVVKPDIVFFGENLPPRFFSCMQSDFSKVDLLIIMGTSLQVQPFASLISKAPLATPRLLINKEKTGQTDPFLGMMMGLGGGMDFDSKKAYRDVAWLGDCDQGCLALADLLGWKELEDLVRREHANIDAQSGSQASNPSATVSPRKSPPPAKEAARTKEKEEH

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
16	Phosphorylation	TQTLGLGSQKERLLD HHHHCCCCHHHHHHH	43.02	27097102
18	Acetylation	TLGLGSQKERLLDEL HHCCCCHHHHHHHHH	46.64	22902405
18	Ubiquitination	TLGLGSQKERLLDEL HHCCCCHHHHHHHHH	46.64	-
61	Phosphorylation	AGIPDFRSPSTGLYA CCCCCCCCCCCCCCC	24.16	22673903
63	Phosphorylation	IPDFRSPSTGLYANL CCCCCCCCCCCCCCH	36.03	22673903
64	Phosphorylation	PDFRSPSTGLYANLE CCCCCCCCCCCCCHH	34.29	22673903
77	Phosphorylation	LEKYHLPYPEAIFEI HHHCCCCCCHHHHHC	21.77	25532521
89	Ubiquitination	FEISYFKKHPEPFFA HHCCHHHHCCCCCHH	55.27	-
121	Acetylation	FIRLLKEKGLLLRCY HHHHHHHCCCEEEEE	53.95	22902405
170	Phosphorylation	CGKEYTMSWMKEKIF CCCEEEHHHHHHHHH	19.07	28551015
173	Acetylation	EYTMSWMKEKIFSEA EEEHHHHHHHHHHCC	49.99	22902405
175	Acetylation	TMSWMKEKIFSEATP EHHHHHHHHHHCCCC	43.46	22902405
183	Acetylation	IFSEATPKCEKCQNV HHHCCCCCCHHCCCC	51.15	22902405
250	Ubiquitination	TPRLLINKEKTGQTD CCEEEECHHHCCCCC	54.30	-
250	Acetylation	TPRLLINKEKTGQTD CCEEEECHHHCCCCC	54.30	22902405
301	Acetylation	LADLLGWKELEDLVR HHHHHCHHHHHHHHH	51.10	22902405
318	Phosphorylation	HANIDAQSGSQASNP HCCCCCCCCCCCCCC	41.98	25403869
320	Phosphorylation	NIDAQSGSQASNPSA CCCCCCCCCCCCCCC	28.02	27097102
323	Phosphorylation	AQSGSQASNPSATVS CCCCCCCCCCCCCCC	41.45	27097102
326	Phosphorylation	GSQASNPSATVSPRK CCCCCCCCCCCCCCC	40.60	27097102
328	Phosphorylation	QASNPSATVSPRKSP CCCCCCCCCCCCCCC	26.34	27097102
330	Phosphorylation	SNPSATVSPRKSPPP CCCCCCCCCCCCCCC	18.03	23712012
334	Phosphorylation	ATVSPRKSPPPAKEA CCCCCCCCCCCHHHH	43.87	29779826

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

Oops, there are no upstream regulatory protein records of SIR2_RAT !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
330	S	Acetylation	Phosphorylated at Ser-330 by a mitotic kinase G1/S-specific cyclin E/Cdk2 complex; phosphorylation inactivates SIRT2-mediated alpha-tubulin deacetylation and thereby negatively regulates cell adhesion, cell migration and neurite outgrowth during neuronal differentiation.	22673903
330	S	Phosphorylation	Dephosphorylated at Ser-330 by CDC14A and CDC14B around early anaphase (By similarity).	22673903
330	S	Phosphorylation	Phosphorylated at Ser-330 by a mitotic kinase CDK1/cyclin B at the G2/M transition; phosphorylation regulates the delay in cell-cycle progression.	22673903
330	S	Phosphorylation	Phosphorylated at Ser-330 by a mitotic kinase G1/S-specific cyclin E/Cdk2 complex; phosphorylation inactivates SIRT2-mediated alpha-tubulin deacetylation and thereby negatively regulates cell adhesion, cell migration and neurite outgrowth during neuronal differentiation.	22673903

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of SIR2_RAT !!

Protein-Protein Interaction

Oops, there are no PPI records of SIR2_RAT !!

Drug and Disease Associations

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