RNF8_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: RNF8_MOUSE
• UniProt AC: Q8VC56
• Protein Name: E3 ubiquitin-protein ligase RNF8 {ECO:0000255|HAMAP-Rule:MF_03067}
• Gene Name: Rnf8 {ECO:0000255|HAMAP-Rule:MF_03067}
• Organism: Mus musculus (Mouse).
• Sequence Length: 488
• Subcellular Localization: Nucleus . Cytoplasm . Midbody . Chromosome, telomere . Recruited at uncapped telomeres (PubMed:21857671, PubMed:22101936). Following DNA double-strand breaks, recruited to the sites of damage. During prophase, concomitant with nuclear envelope breakd
• Protein Description: E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Following DNA damage, mediates the ubiquitination and degradation of POLD4/p12, a subunit of DNA polymerase delta. In the absence of POLD4, DNA polymerase delta complex exhibits higher proofreading activity. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. [PubMed: 20153262]
• Protein Sequence: MGEPDPLVSGQLAARRSWCLRRLGMDCEWLQLEAGTEVTIGRGLSVTYQLISKVCPLMISRSHCVLKQNPEGQWTIMDNKSLNGVWLNRERLAPLQGYCIRKGDHIQLGVPLESRETAEYEYEVIEEDWESLAPCLAPKNDQRMEKHKGSRTKRKFSSPGLENLPAEGSSDLRCPLANVASKPIEPEKLHGKGDASSQSLGCLCPGLTSLKASERAAGPHACSALPKVLELSCPKKQKACRPSASQNSLELFKVTMSRMLKLKTQMQEKQIAVLNVKRQTRKGSSKKIVRMEKELRNLQSQLYAEQAQQQARVEQLEKTFQEEAHYLQGLEKEQGECDLKQQLVQALQEHQALMEELNCSKKDFEKIIQAKNKELEQTKEEKDKVQAQKEEVLSHMNDLLENELQCIICSEYFIEAVTLNCAHSFCSFCINEWMKRKVECPICRKDIESRTNSLVLDNCISKMVDNLSSDVKERRSVLIRERRAKRLS

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
157	Phosphorylation	SRTKRKFSSPGLENL CCCCCCCCCCCHHCC	38.36	21082442
158	Phosphorylation	RTKRKFSSPGLENLP CCCCCCCCCCHHCCC	26.56	28833060
264	Phosphorylation	SRMLKLKTQMQEKQI HHHHHHHHHHCHHHH	39.44	24759943
373	Acetylation	KIIQAKNKELEQTKE HHHHHHHHHHHHHHH	64.07	7625415
449	Phosphorylation	ICRKDIESRTNSLVL CCCCHHHHHCCHHHH	44.75	29899451
451	Phosphorylation	RKDIESRTNSLVLDN CCHHHHHCCHHHHHH	38.14	29899451

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

Oops, there are no upstream regulatory protein records of RNF8_MOUSE !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
29	K	ubiquitylation	'Lys-29'-type polyubiquitination is also observed, but it doesn't require its own functional RING-type zinc finger.	-
48	K	ubiquitylation	Autoubiquitinated through 'Lys-48' and 'Lys-63' of ubiquitin.	-
63	K	ubiquitylation	'Lys-63' polyubiquitination is mediated by UBE2N.	-
63	K	ubiquitylation	Autoubiquitinated through 'Lys-48' and 'Lys-63' of ubiquitin.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of RNF8_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TPP1_MOUSE	Tpp1	physical	22101936
H2A2C_MOUSE	Hist2h2ac	physical	21706008
H2B2E_MOUSE	Hist2h2be	physical	21706008
UBE2N_MOUSE	Ube2n	physical	21706008
UB2V1_MOUSE	Ube2v1	physical	21706008

Drug and Disease Associations

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