dbPTM

FEN1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	FEN1_HUMAN
UniProt AC	P39748
Protein Name	Flap endonuclease 1 {ECO:0000255\|HAMAP-Rule:MF_03140}
Gene Name	FEN1 {ECO:0000255\|HAMAP-Rule:MF_03140}
Organism	Homo sapiens (Human).
Sequence Length	380
Subcellular Localization	Isoform 1: Nucleus, nucleolus. Nucleus, nucleoplasm. Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage. Isoform FENMIT: Mitochondrion .
Protein Description	Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA..
Protein Sequence	MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGGDVLQNEEGETTSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKRSERRAEAEKQLQQAQAAGAEQEVEKFTKRLVKVTKQHNDECKHLLSLMGIPYLDAPSEAEASCAALVKAGKVYAAATEDMDCLTFGSPVLMRHLTASEAKKLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRGIGPKRAVDLIQKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSEPNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTQGRLDDFFKVTGSLSSAKRKEPEPKGSTKKKAKTGAAGKFKRGK

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
8	Ubiquitination	MGIQGLAKLIADVAP CCHHHHHHHHHHHCC	45.53	21890473
16	Phosphorylation	LIADVAPSAIRENDI HHHHHCCHHHHHCCH	26.96	23186163
19	Symmetric dimethylarginine	DVAPSAIRENDIKSY HHCCHHHHHCCHHHH	36.06	-
19	Methylation	DVAPSAIRENDIKSY HHCCHHHHHCCHHHH	36.06	20729856
24	Sumoylation	AIRENDIKSYFGRKV HHHHCCHHHHHCCCH	41.80	-
24	2-Hydroxyisobutyrylation	AIRENDIKSYFGRKV HHHHCCHHHHHCCCH	41.80	-
24	Acetylation	AIRENDIKSYFGRKV HHHHCCHHHHHCCCH	41.80	26822725
24	Sumoylation	AIRENDIKSYFGRKV HHHHCCHHHHHCCCH	41.80	-
24	Ubiquitination	AIRENDIKSYFGRKV HHHHCCHHHHHCCCH	41.80	-
25	Phosphorylation	IRENDIKSYFGRKVA HHHCCHHHHHCCCHH	26.48	21601212
37	Sulfoxidation	KVAIDASMSIYQFLI CHHHHHHHHHHHHHH	2.79	28183972
60	Phosphorylation	LQNEEGETTSHLMGM ECCCCCCCHHHHHHH	44.44	22210691
61	Phosphorylation	QNEEGETTSHLMGMF CCCCCCCHHHHHHHH	15.17	22210691
62	Phosphorylation	NEEGETTSHLMGMFY CCCCCCHHHHHHHHH	23.26	22210691
69	Phosphorylation	SHLMGMFYRTIRMME HHHHHHHHHHHHHHH	9.65	22210691
71	Phosphorylation	LMGMFYRTIRMMENG HHHHHHHHHHHHHCC	11.10	22210691
80	Acetylation	RMMENGIKPVYVFDG HHHHCCCCCEEEECC	29.81	19608861
80	Ubiquitination	RMMENGIKPVYVFDG HHHHCCCCCEEEECC	29.81	19608861
83	Phosphorylation	ENGIKPVYVFDGKPP HCCCCCEEEECCCCC	12.15	26074081
88	Sumoylation	PVYVFDGKPPQLKSG CEEEECCCCCCCCCC	56.20	-
88	Sumoylation	PVYVFDGKPPQLKSG CEEEECCCCCCCCCC	56.20	-
88	Ubiquitination	PVYVFDGKPPQLKSG CEEEECCCCCCCCCC	56.20	-
93	Sumoylation	DGKPPQLKSGELAKR CCCCCCCCCCHHHHH	51.68	-
99	Acetylation	LKSGELAKRSERRAE CCCCHHHHHHHHHHH	69.91	25953088
99	Ubiquitination	LKSGELAKRSERRAE CCCCHHHHHHHHHHH	69.91	-
100	Symmetric dimethylarginine	KSGELAKRSERRAEA CCCHHHHHHHHHHHH	37.84	-
100	Methylation	KSGELAKRSERRAEA CCCHHHHHHHHHHHH	37.84	20729856
101	Phosphorylation	SGELAKRSERRAEAE CCHHHHHHHHHHHHH	34.45	-
104	Symmetric dimethylarginine	LAKRSERRAEAEKQL HHHHHHHHHHHHHHH	32.50	-
104	Methylation	LAKRSERRAEAEKQL HHHHHHHHHHHHHHH	32.50	20729856
109	Acetylation	ERRAEAEKQLQQAQA HHHHHHHHHHHHHHH	64.45	23954790
109	Ubiquitination	ERRAEAEKQLQQAQA HHHHHHHHHHHHHHH	64.45	21890473
125	Sumoylation	GAEQEVEKFTKRLVK CCHHHHHHHHHHHHH	64.61	-
125	Acetylation	GAEQEVEKFTKRLVK CCHHHHHHHHHHHHH	64.61	23954790
125	Sumoylation	GAEQEVEKFTKRLVK CCHHHHHHHHHHHHH	64.61	-
125	Ubiquitination	GAEQEVEKFTKRLVK CCHHHHHHHHHHHHH	64.61	21890473
128	Sumoylation	QEVEKFTKRLVKVTK HHHHHHHHHHHHHHH	47.03	-
128	Ubiquitination	QEVEKFTKRLVKVTK HHHHHHHHHHHHHHH	47.03	-
132	Ubiquitination	KFTKRLVKVTKQHND HHHHHHHHHHHHCCH	49.10	-
135	Ubiquitination	KRLVKVTKQHNDECK HHHHHHHHHCCHHHH	53.17	-
142	Ubiquitination	KQHNDECKHLLSLMG HHCCHHHHHHHHHCC	34.93	-
168	Sumoylation	ASCAALVKAGKVYAA HHHHHHHHCCCEEEE	52.88	-
168	Sumoylation	ASCAALVKAGKVYAA HHHHHHHHCCCEEEE	52.88	-
168	Ubiquitination	ASCAALVKAGKVYAA HHHHHHHHCCCEEEE	52.88	-
171	Ubiquitination	AALVKAGKVYAAATE HHHHHCCCEEEEECC	36.61	-
173	Phosphorylation	LVKAGKVYAAATEDM HHHCCCEEEEECCCC	8.26	29496907
177	Phosphorylation	GKVYAAATEDMDCLT CCEEEEECCCCCCCC	28.00	29496907
182	Glutathionylation	AATEDMDCLTFGSPV EECCCCCCCCCCCHH	2.86	22555962
187	Phosphorylation	MDCLTFGSPVLMRHL CCCCCCCCHHHHHHC	13.98	12853968
192	Symmetric dimethylarginine	FGSPVLMRHLTASEA CCCHHHHHHCCHHHH	19.94	-
192	Methylation	FGSPVLMRHLTASEA CCCHHHHHHCCHHHH	19.94	20729856
195	Phosphorylation	PVLMRHLTASEAKKL HHHHHHCCHHHHHCC	23.24	20068231
197	Phosphorylation	LMRHLTASEAKKLPI HHHHCCHHHHHCCCC	32.62	20068231
200	2-Hydroxyisobutyrylation	HLTASEAKKLPIQEF HCCHHHHHCCCCCHH	51.28	-
200	Acetylation	HLTASEAKKLPIQEF HCCHHHHHCCCCCHH	51.28	23954790
200	Succinylation	HLTASEAKKLPIQEF HCCHHHHHCCCCCHH	51.28	23954790
200	Ubiquitination	HLTASEAKKLPIQEF HCCHHHHHCCCCCHH	51.28	-
201	Sumoylation	LTASEAKKLPIQEFH CCHHHHHCCCCCHHH	67.55	-
201	Acetylation	LTASEAKKLPIQEFH CCHHHHHCCCCCHHH	67.55	7675223
201	Sumoylation	LTASEAKKLPIQEFH CCHHHHHCCCCCHHH	67.55	-
201	Ubiquitination	LTASEAKKLPIQEFH CCHHHHHCCCCCHHH	67.55	-
210	Phosphorylation	PIQEFHLSRILQELG CCCHHHHHHHHHHCC	14.54	29523821
234	Phosphorylation	CILLGSDYCESIRGI HHHHCCHHHHHHCCC	10.38	22817900
252	2-Hydroxyisobutyrylation	RAVDLIQKHKSIEEI HHHHHHHHCCCHHHH	46.11	-
252	Acetylation	RAVDLIQKHKSIEEI HHHHHHHHCCCHHHH	46.11	25953088
252	Ubiquitination	RAVDLIQKHKSIEEI HHHHHHHHCCCHHHH	46.11	-
254	Sumoylation	VDLIQKHKSIEEIVR HHHHHHCCCHHHHHH	61.23	-
254	Acetylation	VDLIQKHKSIEEIVR HHHHHHCCCHHHHHH	61.23	27452117
254	Sumoylation	VDLIQKHKSIEEIVR HHHHHHCCCHHHHHH	61.23	-
254	Ubiquitination	VDLIQKHKSIEEIVR HHHHHHCCCHHHHHH	61.23	-
255	Phosphorylation	DLIQKHKSIEEIVRR HHHHHCCCHHHHHHH	34.65	20873877
267	Sumoylation	VRRLDPNKYPVPENW HHHHCCCCCCCCCCC	57.21	-
267	Acetylation	VRRLDPNKYPVPENW HHHHCCCCCCCCCCC	57.21	19608861
267	Sumoylation	VRRLDPNKYPVPENW HHHHCCCCCCCCCCC	57.21	19608861
267	Ubiquitination	VRRLDPNKYPVPENW HHHHCCCCCCCCCCC	57.21	19608861
268	Phosphorylation	RRLDPNKYPVPENWL HHHCCCCCCCCCCCC	18.99	28152594
277	Ubiquitination	VPENWLHKEAHQLFL CCCCCCCHHHHHHHH	55.19	21906983
293	Phosphorylation	PEVLDPESVELKWSE CHHCCHHHCCCCCCC	26.70	28450419
297	Sumoylation	DPESVELKWSEPNEE CHHHCCCCCCCCCHH	34.86	-
297	Sumoylation	DPESVELKWSEPNEE CHHHCCCCCCCCCHH	34.86	-
297	Ubiquitination	DPESVELKWSEPNEE CHHHCCCCCCCCCHH	34.86	2190698
299	Phosphorylation	ESVELKWSEPNEEEL HHCCCCCCCCCHHHH	41.40	27067055
308	Acetylation	PNEEELIKFMCGEKQ CCHHHHHHHHHCCCC	39.40	26051181
308	Sumoylation	PNEEELIKFMCGEKQ CCHHHHHHHHHCCCC	39.40	-
308	Ubiquitination	PNEEELIKFMCGEKQ CCHHHHHHHHHCCCC	39.40	-
314	Sumoylation	IKFMCGEKQFSEERI HHHHHCCCCCCHHHH	41.76	-
314	2-Hydroxyisobutyrylation	IKFMCGEKQFSEERI HHHHHCCCCCCHHHH	41.76	-
314	Acetylation	IKFMCGEKQFSEERI HHHHHCCCCCCHHHH	41.76	25953088
314	Sumoylation	IKFMCGEKQFSEERI HHHHHCCCCCCHHHH	41.76	-
314	Ubiquitination	IKFMCGEKQFSEERI HHHHHCCCCCCHHHH	41.76	-
317	Phosphorylation	MCGEKQFSEERIRSG HHCCCCCCHHHHHHH	35.73	25159151
329	Phosphorylation	RSGVKRLSKSRQGST HHHHHHHHHHCCCCC	32.39	-
331	Phosphorylation	GVKRLSKSRQGSTQG HHHHHHHHCCCCCCC	26.85	23403867
335	Phosphorylation	LSKSRQGSTQGRLDD HHHHCCCCCCCCHHH	14.82	25159151
336	Phosphorylation	SKSRQGSTQGRLDDF HHHCCCCCCCCHHHH	41.70	25159151
345	Sumoylation	GRLDDFFKVTGSLSS CCHHHHHHHHCCCCC	38.59	-
345	Methylation	GRLDDFFKVTGSLSS CCHHHHHHHHCCCCC	38.59	-
345	Sumoylation	GRLDDFFKVTGSLSS CCHHHHHHHHCCCCC	38.59	-
345	Ubiquitination	GRLDDFFKVTGSLSS CCHHHHHHHHCCCCC	38.59	-
347	Phosphorylation	LDDFFKVTGSLSSAK HHHHHHHHCCCCCCC	22.95	20873877
349	Phosphorylation	DFFKVTGSLSSAKRK HHHHHHCCCCCCCCC	18.73	20873877
351	Phosphorylation	FKVTGSLSSAKRKEP HHHHCCCCCCCCCCC	29.91	25159151
352	Phosphorylation	KVTGSLSSAKRKEPE HHHCCCCCCCCCCCC	43.00	25159151
354	Sumoylation	TGSLSSAKRKEPEPK HCCCCCCCCCCCCCC	66.98	-
354	2-Hydroxyisobutyrylation	TGSLSSAKRKEPEPK HCCCCCCCCCCCCCC	66.98	-
354	Acetylation	TGSLSSAKRKEPEPK HCCCCCCCCCCCCCC	66.98	11430825
354	Succinylation	TGSLSSAKRKEPEPK HCCCCCCCCCCCCCC	66.98	23954790
354	Sumoylation	TGSLSSAKRKEPEPK HCCCCCCCCCCCCCC	66.98	11430825
354	Ubiquitination	TGSLSSAKRKEPEPK HCCCCCCCCCCCCCC	66.98	11430825
363	Phosphorylation	KEPEPKGSTKKKAKT CCCCCCCCCCHHCCC	43.08	30576142
364	Phosphorylation	EPEPKGSTKKKAKTG CCCCCCCCCHHCCCC	56.40	20068231
375	Sumoylation	AKTGAAGKFKRGK-- CCCCCCCCCCCCC--	42.88	-
375	Acetylation	AKTGAAGKFKRGK-- CCCCCCCCCCCCC--	42.88	19608861
375	Sumoylation	AKTGAAGKFKRGK-- CCCCCCCCCCCCC--	42.88	19608861
377	Acetylation	TGAAGKFKRGK---- CCCCCCCCCCC----	64.82	11430825
380	Acetylation	AGKFKRGK------- CCCCCCCC-------	62.29	11430825

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
187	S	Phosphorylation	Kinase	CDK1	P06493	PSP
187	S	Phosphorylation	Kinase	CDK2	P24941	Uniprot
195	T	Phosphorylation	Kinase	CHEK1	O14757	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
187	S	Methylation	18443037
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.
187	S	Phosphorylation	18443037
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.
187	S	Phosphorylation	18443037
Phosphorylation at Ser-187 by CDK2 occurs during late S-phase and results in dissociation from PCNA.
192	R	Methylation	20729856
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.
192	R	Phosphorylation	20729856
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.

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 FEN1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ROA1_HUMAN	HNRNPA1	physical	14690413
EP300_HUMAN	EP300	physical	11430825
PCNA_HUMAN	PCNA	physical	11430825
EF1G_HUMAN	EEF1G	physical	16169070
PCNA_HUMAN	PCNA	physical	8876181
PCNA_HUMAN	PCNA	physical	11601988
APEX1_HUMAN	APEX1	physical	11601988
WRN_HUMAN	WRN	physical	11598021
HUS1_HUMAN	HUS1	physical	16216273
RAD9A_HUMAN	RAD9A	physical	16216273
RAD1_HUMAN	RAD1	physical	16216273
PCNA_HUMAN	PCNA	physical	16216273
WRN_HUMAN	WRN	physical	16326861
BLM_HUMAN	BLM	physical	16326861
DDX11_HUMAN	DDX11	physical	18499658
PCNA_HUMAN	PCNA	physical	9178907
PCNA_HUMAN	PCNA	physical	22606318
A4_HUMAN	APP	physical	21832049
RAP1A_HUMAN	RAP1A	physical	22939629
VRK1_HUMAN	VRK1	physical	22939629
PCNA_HUMAN	PCNA	physical	15616578
PCNA_HUMAN	PCNA	physical	14657243
WRN_HUMAN	WRN	physical	14657243
LPP_HUMAN	LPP	physical	22863883
2A5D_HUMAN	PPP2R5D	physical	22863883
PCNA_HUMAN	PCNA	physical	26186194
DRG1_HUMAN	DRG1	physical	26344197
TFG_HUMAN	TFG	physical	26344197
PCNA_HUMAN	PCNA	physical	26496610
TRA2A_HUMAN	TRA2A	physical	26496610
CHPF2_HUMAN	CHPF2	physical	26496610
WDR4_HUMAN	WDR4	physical	26751069
PCNA_HUMAN	PCNA	physical	28514442
PARP1_HUMAN	PARP1	genetic	28628639
PARP2_HUMAN	PARP2	genetic	28628639

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
There are no disease associations of PTM sites.

Regulatory Network of FEN1_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-80; LYS-267 AND LYS-375, ANDMASS SPECTROMETRY.	19608861 [Abstract]
"Regulation of human flap endonuclease-1 activity by acetylationthrough the transcriptional coactivator p300."; Hasan S., Stucki M., Hassa P.O., Imhof R., Gehrig P., Hunziker P.,Hubscher U., Hottiger M.O.; Mol. Cell 7:1221-1231(2001). Cited for: INTERACTION WITH P300, AND ACETYLATION AT LYS-354; LYS-375; LYS-377AND LYS-380.	11430825 [Abstract]
Methylation
Reference	PubMed
"Methylation of FEN1 suppresses nearby phosphorylation and facilitatesPCNA binding."; Guo Z., Zheng L., Xu H., Dai H., Zhou M., Pascua M.R., Chen Q.M.,Shen B.; Nat. Chem. Biol. 6:766-773(2010). Cited for: FUNCTION, MUTAGENESIS OF ARG-192, METHYLATION AT ARG-192, ANDPHOSPHORYLATION AT SER-187.	20729856 [Abstract]
Phosphorylation
Reference	PubMed
"Methylation of FEN1 suppresses nearby phosphorylation and facilitatesPCNA binding."; Guo Z., Zheng L., Xu H., Dai H., Zhou M., Pascua M.R., Chen Q.M.,Shen B.; Nat. Chem. Biol. 6:766-773(2010). Cited for: FUNCTION, MUTAGENESIS OF ARG-192, METHYLATION AT ARG-192, ANDPHOSPHORYLATION AT SER-187.	20729856 [Abstract]

show

show

show

show

show