PCNA_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PCNA_MOUSE
• UniProt AC: P17918
• Protein Name: Proliferating cell nuclear antigen
• Gene Name: Pcna
• Organism: Mus musculus (Mouse).
• Sequence Length: 261
• Subcellular Localization: Nucleus . Colocalizes with CREBBP, EP300 and POLD1 to sites of DNA damage (By similarity). Forms nuclear foci representing sites of ongoing DNA replication and vary in morphology and number during S phase. Together with APEX2, is redistributed in dis
• Protein Description: Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion (By similarity)..
• Protein Sequence: MFEARLIQGSILKKVLEALKDLINEACWDVSSGGVNLQSMDSSHVSLVQLTLRSEGFDTYRCDRNLAMGVNLTSMSKILKCAGNEDIITLRAEDNADTLALVFEAPNQEKVSDYEMKLMDLDVEQLGIPEQEYSCVIKMPSGEFARICRDLSHIGDAVVISCAKNGVKFSASGELGNGNIKLSQTSNVDKEEEAVTIEMNEPVHLTFALRYLNFFTKATPLSPTVTLSMSADVPLVVEYKIADMGHLKYYLAPKIEDEEAS

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
13	Acetylation	LIQGSILKKVLEALK HHCHHHHHHHHHHHH	38.88	22826441
14	Acetylation	IQGSILKKVLEALKD HCHHHHHHHHHHHHH	48.91	-
54	Phosphorylation	LVQLTLRSEGFDTYR EEEEEECCCCCCEEE	45.22	25777480
59	Phosphorylation	LRSEGFDTYRCDRNL ECCCCCCEEECCCCC	15.59	25777480
60	Phosphorylation	RSEGFDTYRCDRNLA CCCCCCEEECCCCCC	15.87	25777480
73	Phosphorylation	LAMGVNLTSMSKILK CCCCCCHHHHHHHHH	19.72	25777480
74	Phosphorylation	AMGVNLTSMSKILKC CCCCCHHHHHHHHHH	24.99	25777480
76	Phosphorylation	GVNLTSMSKILKCAG CCCHHHHHHHHHHHC	19.13	25777480
77	Acetylation	VNLTSMSKILKCAGN CCHHHHHHHHHHHCC	43.34	22826441
80	Ubiquitination	TSMSKILKCAGNEDI HHHHHHHHHHCCCCE	26.05	-
80	Acetylation	TSMSKILKCAGNEDI HHHHHHHHHHCCCCE	26.05	23806337
80	Malonylation	TSMSKILKCAGNEDI HHHHHHHHHHCCCCE	26.05	26320211
81	S-nitrosylation	SMSKILKCAGNEDII HHHHHHHHHCCCCEE	5.41	20925432
81	Glutathionylation	SMSKILKCAGNEDII HHHHHHHHHCCCCEE	5.41	24333276
81	S-nitrosocysteine	SMSKILKCAGNEDII HHHHHHHHHCCCCEE	5.41	-
114	Phosphorylation	NQEKVSDYEMKLMDL CCCCCCCHHEEECCC	15.49	-
117	Ubiquitination	KVSDYEMKLMDLDVE CCCCHHEEECCCCHH	28.81	-
135	S-nitrosylation	IPEQEYSCVIKMPSG CCCCEEEEEEECCCC	3.43	19483679
135	Glutathionylation	IPEQEYSCVIKMPSG CCCCEEEEEEECCCC	3.43	24333276
135	S-nitrosocysteine	IPEQEYSCVIKMPSG CCCCEEEEEEECCCC	3.43	-
162	S-nitrosylation	GDAVVISCAKNGVKF CCEEEEEEECCCCEE	4.25	19483679
162	Glutathionylation	GDAVVISCAKNGVKF CCEEEEEEECCCCEE	4.25	24333276
162	S-nitrosocysteine	GDAVVISCAKNGVKF CCEEEEEEECCCCEE	4.25	-
164	Ubiquitination	AVVISCAKNGVKFSA EEEEEEECCCCEEEE	59.57	22790023
168	Ubiquitination	SCAKNGVKFSASGEL EEECCCCEEEECCCC	34.69	-
211	Phosphorylation	HLTFALRYLNFFTKA HHHHHHHHHHCCCCC	13.57	17115032
216	Phosphorylation	LRYLNFFTKATPLSP HHHHHCCCCCCCCCC	18.68	22006019
217	Ubiquitination	RYLNFFTKATPLSPT HHHHCCCCCCCCCCE	45.14	-
248	Ubiquitination	IADMGHLKYYLAPKI ECCCCCCEEEECCCC	26.61	-
248	Acetylation	IADMGHLKYYLAPKI ECCCCCCEEEECCCC	26.61	23806337
248	Succinylation	IADMGHLKYYLAPKI ECCCCCCEEEECCCC	26.61	23806337
254	Ubiquitination	LKYYLAPKIEDEEAS CEEEECCCCCCCCCC	53.79	-
254	Acetylation	LKYYLAPKIEDEEAS CEEEECCCCCCCCCC	53.79	22826441
261	Phosphorylation	KIEDEEAS------- CCCCCCCC-------	43.99	23984901

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
211	Y	Phosphorylation	Kinase	EGFR	Q01279	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Paxip1	Q6NZQ4	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Rad18	Q9QXK2	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
13	K	Acetylation	Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation.	-
14	K	Acetylation	Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation.	-
63	K	ubiquitylation	An error-free pathway also exists and requires non-canonical polyubiquitination on Lys-164 through 'Lys-63' linkage of ubiquitin moieties by the E2 complex UBE2N-UBE2V2 and the E3 ligases, HLTF, RNF8 and SHPRH.	-
77	K	Acetylation	Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation.	-
80	K	Acetylation	Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation.	-
164	K	ubiquitylation	An error-free pathway also exists and requires non-canonical polyubiquitination on Lys-164 through 'Lys-63' linkage of ubiquitin moieties by the E2 complex UBE2N-UBE2V2 and the E3 ligases, HLTF, RNF8 and SHPRH.	-
164	K	ubiquitylation	Following induction of replication stress, monoubiquitinated by the UBE2B-RAD18 complex on Lys-164, leading to recruit translesion (TLS) polymerases, which are able to synthesize across DNA lesions in a potentially error-prone manner.	-
164	K	ubiquitylation	Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, leading to enhance PCNA-dependent translesion DNA synthesis.	-

Disease-associated PTM Sites based on SAP

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

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
REV1_MOUSE	Rev1	physical	16857592
DPOLB_MOUSE	Polb	physical	12063248
POLK_MOUSE	Polk	physical	18162470
PK3CB_MOUSE	Pik3cb	physical	19416922
PCNA_HUMAN	PCNA	physical	20360068
NBN_MOUSE	Nbn	physical	12792649
BACD2_RAT	Tnfaip1	physical	15726626
GA45A_MOUSE	Gadd45a	physical	17599061
APEX1_MOUSE	Apex1	physical	17599061
APOB_HUMAN	APOB	physical	26496610
CDN1A_HUMAN	CDKN1A	physical	26496610
DNMT1_HUMAN	DNMT1	physical	26496610
MSH2_HUMAN	MSH2	physical	26496610
DPOD1_HUMAN	POLD1	physical	26496610
DPOD2_HUMAN	POLD2	physical	26496610
RBBP5_HUMAN	RBBP5	physical	26496610
RFC1_HUMAN	RFC1	physical	26496610
RFC2_HUMAN	RFC2	physical	26496610
ELOB_HUMAN	TCEB2	physical	26496610
PAF15_HUMAN	KIAA0101	physical	26496610
SIVA_HUMAN	SIVA1	physical	26496610
DPOD3_HUMAN	POLD3	physical	26496610
APEX2_HUMAN	APEX2	physical	26496610
PKN3_HUMAN	PKN3	physical	26496610
ANKH1_HUMAN	ANKHD1	physical	26496610
CENPJ_HUMAN	CENPJ	physical	26496610
UBFD1_HUMAN	UBFD1	physical	26496610
XPO5_HUMAN	XPO5	physical	26496610
RN219_HUMAN	RNF219	physical	26496610
TEFM_HUMAN	TEFM	physical	26496610
EPIPL_HUMAN	EPPK1	physical	26496610
UBP32_HUMAN	USP32	physical	26496610
RM53_HUMAN	MRPL53	physical	26496610
RM54_HUMAN	MRPL54	physical	26496610

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Tyrosine phosphorylation controls PCNA function through proteinstability.";
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C.,McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.;
Nat. Cell Biol. 8:1359-1368(2006).
Cited for: PHOSPHORYLATION AT TYR-211.
PubMed: 17115032