dbPTM

RIR2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	RIR2_HUMAN
UniProt AC	P31350
Protein Name	Ribonucleoside-diphosphate reductase subunit M2
Gene Name	RRM2
Organism	Homo sapiens (Human).
Sequence Length	389
Subcellular Localization	Cytoplasm.
Protein Description	Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling..
Protein Sequence	MLSLRVPLAPITDPQQLQLSPLKGLSLVDKENTPPALSGTRVLASKTARRIFQEPTEPKTKAAAPGVEDEPLLRENPRRFVIFPIEYHDIWQMYKKAEASFWTAEEVDLSKDIQHWESLKPEERYFISHVLAFFAASDGIVNENLVERFSQEVQITEARCFYGFQIAMENIHSEMYSLLIDTYIKDPKEREFLFNAIETMPCVKKKADWALRWIGDKEATYGERVVAFAAVEGIFFSGSFASIFWLKKRGLMPGLTFSNELISRDEGLHCDFACLMFKHLVHKPSEERVREIIINAVRIEQEFLTEALPVKLIGMNCTLMKQYIEFVADRLMLELGFSKVFRVENPFDFMENISLEGKTNFFEKRVGEYQRMGVMSSPTENSFTLDADF

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
3	Phosphorylation	-----MLSLRVPLAP -----CCCCCCCCCC	16.90	24173317
12	Phosphorylation	RVPLAPITDPQQLQL CCCCCCCCCHHHCCC	40.34	23927012
20	Phosphorylation	DPQQLQLSPLKGLSL CHHHCCCCCCCCCCC	18.41	29255136
23	Ubiquitination	QLQLSPLKGLSLVDK HCCCCCCCCCCCCCC	62.28	21963094
26	Phosphorylation	LSPLKGLSLVDKENT CCCCCCCCCCCCCCC	34.71	22617229
30	Ubiquitination	KGLSLVDKENTPPAL CCCCCCCCCCCCCCC	45.44	21906983
33	Phosphorylation	SLVDKENTPPALSGT CCCCCCCCCCCCCCC	31.57	25159151
38	Phosphorylation	ENTPPALSGTRVLAS CCCCCCCCCCHHCCC	39.98	30266825
40	Phosphorylation	TPPALSGTRVLASKT CCCCCCCCHHCCCHH	17.77	25867546
45	Phosphorylation	SGTRVLASKTARRIF CCCHHCCCHHHHHHH	26.78	25954137
46	Acetylation	GTRVLASKTARRIFQ CCHHCCCHHHHHHHC	40.37	25953088
46	Ubiquitination	GTRVLASKTARRIFQ CCHHCCCHHHHHHHC	40.37	21906983
47	Phosphorylation	TRVLASKTARRIFQE CHHCCCHHHHHHHCC	23.93	-
56	Phosphorylation	RRIFQEPTEPKTKAA HHHHCCCCCCCCCCC	65.25	23186163
59	Ubiquitination	FQEPTEPKTKAAAPG HCCCCCCCCCCCCCC	57.32	27667366
61	Ubiquitination	EPTEPKTKAAAPGVE CCCCCCCCCCCCCCC	42.00	21906983
80	Phosphorylation	LRENPRRFVIFPIEY HCCCCCCEEEEEECH	5.36	32645325
83	Ubiquitination	NPRRFVIFPIEYHDI CCCCEEEEEECHHHH	4.13	21963094
86	Phosphorylation	RFVIFPIEYHDIWQM CEEEEEECHHHHHHH	36.73	27251275
90	Ubiquitination	FPIEYHDIWQMYKKA EEECHHHHHHHHHHH	1.43	27667366
93	Phosphorylation	EYHDIWQMYKKAEAS CHHHHHHHHHHHHHH	2.96	27251275
95	Ubiquitination	HDIWQMYKKAEASFW HHHHHHHHHHHHHCC	39.92	21890473
96	Ubiquitination	DIWQMYKKAEASFWT HHHHHHHHHHHHCCC	33.69	23503661
106	Ubiquitination	ASFWTAEEVDLSKDI HHCCCHHHCCCCCCH	38.58	27667366
111	Ubiquitination	AEEVDLSKDIQHWES HHHCCCCCCHHHHHH	67.17	21963094
119	Ubiquitination	DIQHWESLKPEERYF CHHHHHHCCHHHHHH	7.91	27667366
120	Ubiquitination	IQHWESLKPEERYFI HHHHHHCCHHHHHHH	60.71	21906983
121	Ubiquitination	QHWESLKPEERYFIS HHHHHCCHHHHHHHH	54.71	27667366
155	Ubiquitination	RFSQEVQITEARCFY HHHHHHHCCCHHHHH	4.55	21890473
156	Ubiquitination	FSQEVQITEARCFYG HHHHHHCCCHHHHHH	13.39	23503661
171	Ubiquitination	FQIAMENIHSEMYSL HHHHHHCHHHHHHHH	2.11	21963094
180	Ubiquitination	SEMYSLLIDTYIKDP HHHHHHHHHHHCCCH	4.51	22817900
200	Sulfoxidation	LFNAIETMPCVKKKA HHHHHHHCHHHHHHC	1.25	21406390
204	Ubiquitination	IETMPCVKKKADWAL HHHCHHHHHHCHHHH	56.10	22817900
204	Acetylation	IETMPCVKKKADWAL HHHCHHHHHHCHHHH	56.10	26051181
205	Ubiquitination	ETMPCVKKKADWALR HHCHHHHHHCHHHHH	32.56	22817900
206	Ubiquitination	TMPCVKKKADWALRW HCHHHHHHCHHHHHH	45.95	22817900
212	Methylation	KKADWALRWIGDKEA HHCHHHHHHHCCCCC	18.41	115492905
217	Ubiquitination	ALRWIGDKEATYGER HHHHHCCCCCCCCCH	43.99	21906983
220	Phosphorylation	WIGDKEATYGERVVA HHCCCCCCCCCHHHH	32.90	28064214
221	Phosphorylation	IGDKEATYGERVVAF HCCCCCCCCCHHHHH	24.84	25839225
256	Phosphorylation	RGLMPGLTFSNELIS CCCCCCCEECHHHHH	30.82	20068231
263	Phosphorylation	TFSNELISRDEGLHC EECHHHHHCCCCCCC	46.43	24719451
264	Ubiquitination	FSNELISRDEGLHCD ECHHHHHCCCCCCCH	38.72	22817900
265	Ubiquitination	SNELISRDEGLHCDF CHHHHHCCCCCCCHH	47.74	22817900
266	Ubiquitination	NELISRDEGLHCDFA HHHHHCCCCCCCHHH	63.65	22817900
277	Ubiquitination	CDFACLMFKHLVHKP CHHHHHHHHHHCCCC	2.66	22817900
278	Ubiquitination	DFACLMFKHLVHKPS HHHHHHHHHHCCCCC	23.28	21963094
283	Ubiquitination	MFKHLVHKPSEERVR HHHHHCCCCCHHHHH	42.64	21906983
311	Ubiquitination	LTEALPVKLIGMNCT HHHCCCHHHHCCCCH	32.23	21963094
318	Phosphorylation	KLIGMNCTLMKQYIE HHHCCCCHHHHHHHH	25.53	20068231
321	Ubiquitination	GMNCTLMKQYIEFVA CCCCHHHHHHHHHHH	42.96	21963094
338	Ubiquitination	LMLELGFSKVFRVEN HHHHHCCCEEEEECC	26.55	21963094
343	Ubiquitination	GFSKVFRVENPFDFM CCCEEEEECCCCCHH	5.91	21963094
358	Ubiquitination	ENISLEGKTNFFEKR HHCCCCCCCCHHHHH	30.81	21963094
364	Ubiquitination	GKTNFFEKRVGEYQR CCCCHHHHHHHHCCC	47.42	27667366
364	Acetylation	GKTNFFEKRVGEYQR CCCCHHHHHHHHCCC	47.42	7298869
369	Phosphorylation	FEKRVGEYQRMGVMS HHHHHHHCCCCCCCC	8.76	20007894
371	Ubiquitination	KRVGEYQRMGVMSSP HHHHHCCCCCCCCCC	23.95	21963094
376	Phosphorylation	YQRMGVMSSPTENSF CCCCCCCCCCCCCCE	30.66	30278072
377	Phosphorylation	QRMGVMSSPTENSFT CCCCCCCCCCCCCEE	20.11	30278072
379	Phosphorylation	MGVMSSPTENSFTLD CCCCCCCCCCCEECC	50.15	25159151
381	Ubiquitination	VMSSPTENSFTLDAD CCCCCCCCCEECCCC	44.92	21963094
382	Phosphorylation	MSSPTENSFTLDADF CCCCCCCCEECCCCC	17.24	20068231
384	Phosphorylation	SPTENSFTLDADF-- CCCCCCEECCCCC--	24.45	20068231
418	Ubiquitination	------------------------------------ ------------------------------------		21963094
424	Ubiquitination	------------------------------------------ ------------------------------------------		27667366
429	Phosphorylation	----------------------------------------------- -----------------------------------------------		27642862
439	Phosphorylation	--------------------------------------------------------- ---------------------------------------------------------		27251275

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
20	S	Phosphorylation	Kinase	CDK1	P06493	PSP
20	S	Phosphorylation	Kinase	CDK2	P24941	PSP
33	T	Phosphorylation	Kinase	CDK1	P06493	PSP
33	T	Phosphorylation	Kinase	CDK2	P24941	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	CCNF	P41002	PMID:24658274

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
20	S	Phosphorylation		-
Phosphorylation on Ser-20 relieves the inhibitory effect on Wnt signaling.

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 RIR2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
P53_HUMAN	TP53	physical	12615712
CCNF_HUMAN	CCNF	physical	22632967
RIR1_HUMAN	RRM1	physical	22632967
NR1H4_HUMAN	NR1H4	physical	22632967
SKP2_HUMAN	SKP2	physical	18820369
SHIP2_HUMAN	INPPL1	physical	26186194
FZR1_HUMAN	FZR1	physical	26186194
CDC27_HUMAN	CDC27	physical	26186194
APC4_HUMAN	ANAPC4	physical	26186194
CSTF1_HUMAN	CSTF1	physical	26344197
NPL4_HUMAN	NPLOC4	physical	26344197
WEE1_HUMAN	WEE1	genetic	28319113
VHL_HUMAN	VHL	genetic	28319113
FZR1_HUMAN	FZR1	physical	28514442
SHIP2_HUMAN	INPPL1	physical	28514442
APC4_HUMAN	ANAPC4	physical	28514442
CDC27_HUMAN	CDC27	physical	28514442
JIP4_HUMAN	SPAG9	physical	28514442

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
DB00242	Cladribine
DB05260	Gallium nitrate

Regulatory Network of RIR2_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20 AND THR-33, AND MASSSPECTROMETRY.	19690332 [Abstract]
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND MASSSPECTROMETRY.	19413330 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20; THR-33 AND SER-377,AND MASS SPECTROMETRY.	18691976 [Abstract]
"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-20, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."; Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.; Anal. Sci. 24:161-166(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND MASSSPECTROMETRY.	18187866 [Abstract]
"Quantitative phosphoproteome profiling of Wnt3a-mediated signalingnetwork: indicating the involvement of ribonucleoside-diphosphatereductase M2 subunit phosphorylation at residue serine 20 in canonicalWnt signal transduction."; Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S.,Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.; Mol. Cell. Proteomics 6:1952-1967(2007). Cited for: FUNCTION IN WNT SIGNALING INHIBITION, PHOSPHORYLATION AT SER-20,MUTAGENESIS OF SER-20, AND MASS SPECTROMETRY.	17693683 [Abstract]
"Improved titanium dioxide enrichment of phosphopeptides from HeLacells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."; Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; J. Proteome Res. 6:4150-4162(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND MASSSPECTROMETRY.	17924679 [Abstract]
"A probability-based approach for high-throughput proteinphosphorylation analysis and site localization."; Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; Nat. Biotechnol. 24:1285-1292(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND MASSSPECTROMETRY.	16964243 [Abstract]

show