dbPTM

RFFL_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	RFFL_HUMAN
UniProt AC	Q8WZ73
Protein Name	E3 ubiquitin-protein ligase rififylin {ECO:0000305}
Gene Name	RFFL {ECO:0000312\|HGNC:HGNC:24821}
Organism	Homo sapiens (Human).
Sequence Length	363
Subcellular Localization	Cytoplasm, cytosol. Cell membrane Peripheral membrane protein. Recycling endosome membrane Peripheral membrane protein. The FYVE-type zinc finger may mediate phosphatidylinositol phosphate-binding and control subcellular localization.
Protein Description	E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling..
Protein Sequence	MWATCCNWFCLDGQPEEVPPPQGARMQAYSNPGYSSFPSPTGLEPSCKSCGAHFANTARKQTCLDCKKNFCMTCSSQVGNGPRLCLLCQRFRATAFQREELMKMKVKDLRDYLSLHDISTEMCREKEELVLLVLGQQPVISQEDRTRASTLSPDFPEQQAFLTQPHSSMVPPTSPNLPSSSAQATSVPPAQVQENQQANGHVSQDQEEPVYLESVARVPAEDETQSIDSEDSFVPGRRASLSDLTDLEDIEGLTVRQLKEILARNFVNYKGCCEKWELMERVTRLYKDQKGLQHLVSGAEDQNGGAVPSGLEENLCKICMDSPIDCVLLECGHMVTCTKCGKRMNECPICRQYVIRAVHVFRS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
29	Phosphorylation	QGARMQAYSNPGYSS CCCCEECCCCCCCCC	7.65	21945579
30	Phosphorylation	GARMQAYSNPGYSSF CCCEECCCCCCCCCC	39.29	21945579
34	Phosphorylation	QAYSNPGYSSFPSPT ECCCCCCCCCCCCCC	11.46	21945579
35	Phosphorylation	AYSNPGYSSFPSPTG CCCCCCCCCCCCCCC	31.27	21945579
36	Phosphorylation	YSNPGYSSFPSPTGL CCCCCCCCCCCCCCC	32.47	21945579
39	Phosphorylation	PGYSSFPSPTGLEPS CCCCCCCCCCCCCCC	32.84	26657352
41	Phosphorylation	YSSFPSPTGLEPSCK CCCCCCCCCCCCCHH	59.75	21945579
46	Phosphorylation	SPTGLEPSCKSCGAH CCCCCCCCHHHCCCH	25.46	21945579
48	Ubiquitination	TGLEPSCKSCGAHFA CCCCCCHHHCCCHHC	53.79	21963094
57	Phosphorylation	CGAHFANTARKQTCL CCCHHCCCCCCCCCC	25.14	-
60	Ubiquitination	HFANTARKQTCLDCK HHCCCCCCCCCCCCC	47.71	33845483
105	Acetylation	REELMKMKVKDLRDY HHHHHCCCHHHHHHH	40.38	90777
114	Phosphorylation	KDLRDYLSLHDISTE HHHHHHHCHHHHCHH	19.89	27080861
126	Ubiquitination	STEMCREKEELVLLV CHHHHHCCHHEEEEE	36.82	29967540
149	Phosphorylation	QEDRTRASTLSPDFP HHHHHCHHCCCCCCH	26.96	22817900
150	Phosphorylation	EDRTRASTLSPDFPE HHHHCHHCCCCCCHH	30.21	22817900
152	Phosphorylation	RTRASTLSPDFPEQQ HHCHHCCCCCCHHHH	23.63	-
211	Phosphorylation	QDQEEPVYLESVARV CCCCCCEEEEEEEEC	18.57	25884760
224	Phosphorylation	RVPAEDETQSIDSED ECCCCCCCCCCCCCC	39.68	30266825
226	Phosphorylation	PAEDETQSIDSEDSF CCCCCCCCCCCCCCC	35.46	29255136
229	Phosphorylation	DETQSIDSEDSFVPG CCCCCCCCCCCCCCC	41.45	29255136
232	Phosphorylation	QSIDSEDSFVPGRRA CCCCCCCCCCCCCCC	24.88	30266825
240	Phosphorylation	FVPGRRASLSDLTDL CCCCCCCCHHHCCCH	26.96	25159151
242	Phosphorylation	PGRRASLSDLTDLED CCCCCCHHHCCCHHH	28.25	23927012
245	Phosphorylation	RASLSDLTDLEDIEG CCCHHHCCCHHHCCC	43.45	30278072
254	Phosphorylation	LEDIEGLTVRQLKEI HHHCCCCCHHHHHHH	25.21	20068231
259	Ubiquitination	GLTVRQLKEILARNF CCCHHHHHHHHHHCC	34.08	-
270	Ubiquitination	ARNFVNYKGCCEKWE HHCCCCCCCHHHHHH	40.02	33845483
283	Phosphorylation	WELMERVTRLYKDQK HHHHHHHHHHHHCHH	22.60	26074081
286	Phosphorylation	MERVTRLYKDQKGLQ HHHHHHHHHCHHHHH	14.82	26074081
297	Phosphorylation	KGLQHLVSGAEDQNG HHHHHHHHCCCCCCC	38.35	26074081
309	Phosphorylation	QNGGAVPSGLEENLC CCCCCCCCCHHHHHH	49.78	26074081

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
-	K	Ubiquitination	E3 ubiquitin ligase	RFFL	Q8WZ73	PMID:12859687

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of RFFL_HUMAN !!

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 RFFL_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
P53_HUMAN	TP53	physical	17121812
MDM2_HUMAN	MDM2	physical	18382127
P53_HUMAN	TP53	physical	18382127
UBP5_HUMAN	USP5	physical	22626734
ATX3_HUMAN	ATXN3	physical	22626734
UBP7_HUMAN	USP7	physical	22626734
OTUB1_HUMAN	OTUB1	physical	22626734
UCHL5_HUMAN	UCHL5	physical	22626734
OTUB2_HUMAN	OTUB2	physical	22626734
ATX3L_HUMAN	ATXN3L	physical	22626734
UBP28_HUMAN	USP28	physical	22626734
ESPL1_HUMAN	ESPL1	physical	22626734
STAM1_HUMAN	STAM	physical	22626734
UB2D3_HUMAN	UBE2D3	physical	22626734
UB2D2_HUMAN	UBE2D2	physical	23871895
RFFL_HUMAN	RFFL	physical	23871895
RIPK1_HUMAN	RIPK1	physical	18450452
UB2D1_HUMAN	UBE2D1	physical	18450452
NFH_HUMAN	NEFH	physical	26186194
IQCE_HUMAN	IQCE	physical	26186194
KPCD2_HUMAN	PRKD2	physical	26186194
RNF34_HUMAN	RNF34	physical	26186194
SHC1_HUMAN	SHC1	physical	26186194
EFCB7_HUMAN	EFCAB7	physical	26186194
SHC1_HUMAN	SHC1	physical	28514442
IQCE_HUMAN	IQCE	physical	28514442
KPCD2_HUMAN	PRKD2	physical	28514442
EFCB7_HUMAN	EFCAB7	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
There are no disease associations of PTM sites.

Regulatory Network of RFFL_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-226; SER-229; SER-240AND SER-242, AND MASS SPECTROMETRY.	19690332 [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-240, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Large-scale characterization of HeLa cell nuclear phosphoproteins."; Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,Li J., Cohn M.A., Cantley L.C., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, AND MASSSPECTROMETRY.	15302935 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-34, AND MASSSPECTROMETRY.	18083107 [Abstract]