dbPTM

WWOX_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	WWOX_HUMAN
UniProt AC	Q9NZC7
Protein Name	WW domain-containing oxidoreductase
Gene Name	WWOX
Organism	Homo sapiens (Human).
Sequence Length	414
Subcellular Localization	Cytoplasm . Nucleus . Mitochondrion . Golgi apparatus . Partially localizes to the mitochondria (PubMed:14695174). Translocates to the nucleus upon genotoxic stress or TNF stimulation (By similarity). Translocates to the nucleus in response to TGFB1
Protein Description	Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm..
Protein Sequence	MAALRYAGLDDTDSEDELPPGWEERTTKDGWVYYANHTEEKTQWEHPKTGKRKRVAGDLPYGWEQETDENGQVFFVDHINKRTTYLDPRLAFTVDDNPTKPTTRQRYDGSTTAMEILQGRDFTGKVVVVTGANSGIGFETAKSFALHGAHVILACRNMARASEAVSRILEEWHKAKVEAMTLDLALLRSVQHFAEAFKAKNVPLHVLVCNAATFALPWSLTKDGLETTFQVNHLGHFYLVQLLQDVLCRSAPARVIVVSSESHRFTDINDSLGKLDFSRLSPTKNDYWAMLAYNRSKLCNILFSNELHRRLSPRGVTSNAVHPGNMMYSNIHRSWWVYTLLFTLARPFTKSMQQGAATTVYCAAVPELEGLGGMYFNNCCRCMPSPEAQSEETARTLWALSERLIQERLGSQSG

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
6	Phosphorylation	--MAALRYAGLDDTD --CCCCCCCCCCCCC	13.08	30266825
12	Phosphorylation	RYAGLDDTDSEDELP CCCCCCCCCCCCCCC	40.88	26503892
14	Phosphorylation	AGLDDTDSEDELPPG CCCCCCCCCCCCCCC	49.38	26503892
28	Ubiquitination	GWEERTTKDGWVYYA CCCEEECCCEEEEEE	54.34	-
33	Phosphorylation	TTKDGWVYYANHTEE ECCCEEEEEEECCCC	7.14	21082442
33 (in isoform 4)	Phosphorylation	-	7.14	12514174
48	Ubiquitination	KTQWEHPKTGKRKRV CCCCCCCCCCCCEEE	72.34	-
61	Phosphorylation	RVAGDLPYGWEQETD EEECCCCCCCEEEEC	42.01	12514174
100 (in isoform 7)	Ubiquitination	-	41.44	21906983
100 (in isoform 6)	Ubiquitination	-	41.44	21906983
100 (in isoform 5)	Ubiquitination	-	41.44	21906983
100 (in isoform 3)	Ubiquitination	-	41.44	21906983
100 (in isoform 2)	Ubiquitination	-	41.44	21906983
100 (in isoform 1)	Ubiquitination	-	41.44	21906983
100	Ubiquitination	TVDDNPTKPTTRQRY ECCCCCCCCCCCCCC	41.44	21906983
111	Phosphorylation	RQRYDGSTTAMEILQ CCCCCCCCCHHHHHC	24.89	-
134	Phosphorylation	VVVTGANSGIGFETA EEEECCCCCCCHHHH	31.11	-
162	Phosphorylation	CRNMARASEAVSRIL CCHHHHHHHHHHHHH	22.12	-
176	Ubiquitination	LEEWHKAKVEAMTLD HHHHHHHHHHHHHHH	45.47	-
274 (in isoform 1)	Ubiquitination	-	50.61	21906983
274 (in isoform 2)	Ubiquitination	-	50.61	21906983
274	Ubiquitination	DINDSLGKLDFSRLS CCCCCCCCCCHHHCC	50.61	2190698
281	Phosphorylation	KLDFSRLSPTKNDYW CCCHHHCCCCCCHHH	29.43	24719451
284	Ubiquitination	FSRLSPTKNDYWAML HHHCCCCCCHHHHHH	51.73	-
287	Phosphorylation	LSPTKNDYWAMLAYN CCCCCCHHHHHHHHC	12.40	11956080
293	Phosphorylation	DYWAMLAYNRSKLCN HHHHHHHHCHHHHHH	13.72	18083107
312	Phosphorylation	NELHRRLSPRGVTSN CHHHHHCCCCCCCCC	15.67	-

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
33	Y	Phosphorylation	Kinase	SRC	P12931	PSP
287	Y	Phosphorylation	Kinase	ACK	Q07912	PSP

Functions of PTM Sites

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CPSF6_HUMAN	CPSF6	physical	16055720
ACK1_HUMAN	TNK2	physical	19144635
ACK1_HUMAN	TNK2	physical	16288044
ERBB4_HUMAN	ERBB4	physical	19047365
P53_HUMAN	TP53	physical	16219768
MDM2_HUMAN	MDM2	physical	16219768
P63_HUMAN	TP63	physical	23370280
RPB1_HUMAN	POLR2A	physical	16055720
RPB2_HUMAN	POLR2B	physical	16055720
SMRC1_HUMAN	SMARCC1	physical	16055720
TCRG1_HUMAN	TCERG1	physical	16055720
CPSF1_HUMAN	CPSF1	physical	16055720
CPSF2_HUMAN	CPSF2	physical	16055720
CPSF3_HUMAN	CPSF3	physical	16055720
CPSF5_HUMAN	NUDT21	physical	16055720
FIP1_HUMAN	FIP1L1	physical	16055720
CPSF7_HUMAN	CPSF7	physical	16055720
HNRPK_HUMAN	HNRNPK	physical	16055720
RPRD2_HUMAN	RPRD2	physical	16055720
PABP1_HUMAN	PABPC1	physical	16055720
SF3A1_HUMAN	SF3A1	physical	16055720
SF3B1_HUMAN	SF3B1	physical	16055720
SF3B3_HUMAN	SF3B3	physical	16055720
SFPQ_HUMAN	SFPQ	physical	16055720
SYMPK_HUMAN	SYMPK	physical	16055720
WIPF2_HUMAN	WIPF2	physical	16055720
WDR33_HUMAN	WDR33	physical	16055720
WBP2_HUMAN	WBP2	physical	16055720
ERBB4_HUMAN	ERBB4	physical	24550385
CPSF1_HUMAN	CPSF1	physical	24550385
RPRD2_HUMAN	RPRD2	physical	24550385
SF3B2_HUMAN	SF3B2	physical	24550385
FUBP2_HUMAN	KHSRP	physical	24550385
CSTF3_HUMAN	CSTF3	physical	24550385
HSP74_HUMAN	HSPA4	physical	24550385
WDR33_HUMAN	WDR33	physical	24550385
CPSF7_HUMAN	CPSF7	physical	24550385
DHX15_HUMAN	DHX15	physical	24550385
TGO1_HUMAN	MIA3	physical	24550385
OTU7B_HUMAN	OTUD7B	physical	24550385
PRP8_HUMAN	PRPF8	physical	24550385
CPSF6_HUMAN	CPSF6	physical	24550385
PABP1_HUMAN	PABPC1	physical	24550385
SYMPK_HUMAN	SYMPK	physical	24550385
ACINU_HUMAN	ACIN1	physical	24550385
PATL1_HUMAN	PATL1	physical	24550385
P4HA1_HUMAN	P4HA1	physical	24550385
DESP_HUMAN	DSP	physical	24550385
ANXA1_HUMAN	ANXA1	physical	24550385
PRC2A_HUMAN	PRRC2A	physical	24550385
SPB3_HUMAN	SERPINB3	physical	24550385
COIL_HUMAN	COIL	physical	24550385
6PGD_HUMAN	PGD	physical	24550385
CPSF2_HUMAN	CPSF2	physical	24550385
DIAP3_HUMAN	DIAPH3	physical	24550385
CSK21_HUMAN	CSNK2A1	physical	24550385
U520_HUMAN	SNRNP200	physical	24550385
DAZP1_HUMAN	DAZAP1	physical	24550385
RPR1B_HUMAN	RPRD1B	physical	24550385
HSP7C_HUMAN	HSPA8	physical	24550385
ENAH_HUMAN	ENAH	physical	24550385
PABP4_HUMAN	PABPC4	physical	24550385
IF2B1_HUMAN	IGF2BP1	physical	24550385
HCD2_HUMAN	HSD17B10	physical	24550385
VIGLN_HUMAN	HDLBP	physical	24550385
DVL2_HUMAN	DVL2	physical	24550385
SF3A3_HUMAN	SF3A3	physical	24550385
TCPB_HUMAN	CCT2	physical	24550385
SMD2_HUMAN	SNRPD2	physical	24550385
WBP2_HUMAN	WBP2	physical	24550385
SMCA4_HUMAN	SMARCA4	physical	24550385
CDC5L_HUMAN	CDC5L	physical	24550385
1433Z_HUMAN	YWHAZ	physical	24550385
SF3A1_HUMAN	SF3A1	physical	24550385
UBAP2_HUMAN	UBAP2	physical	24550385
CALX_HUMAN	CANX	physical	24550385
SMD1_HUMAN	SNRPD1	physical	24550385
PLAK_HUMAN	JUP	physical	24550385
RARA_HUMAN	RARA	physical	24550385
ANM5_HUMAN	PRMT5	physical	24550385
SR140_HUMAN	U2SURP	physical	24550385
TGM3_HUMAN	TGM3	physical	24550385
TDRD3_HUMAN	TDRD3	physical	24550385
KPYR_HUMAN	PKLR	physical	24550385
NOLC1_HUMAN	NOLC1	physical	24550385
YLPM1_HUMAN	YLPM1	physical	24550385
WASL_HUMAN	WASL	physical	24550385
CPSF3_HUMAN	CPSF3	physical	24550385
CSTF2_HUMAN	CSTF2	physical	24550385
MATR3_HUMAN	MATR3	physical	24550385
SFPQ_HUMAN	SFPQ	physical	24550385
TOE1_HUMAN	TOE1	physical	24550385
BCL9_HUMAN	BCL9	physical	24550385
CRNN_HUMAN	CRNN	physical	24550385
H2A2A_HUMAN	HIST2H2AA3	physical	24550385
DVL3_HUMAN	DVL3	physical	24550385
P3H1_HUMAN	P3H1	physical	24550385
FIP1_HUMAN	FIP1L1	physical	24550385
PRPF3_HUMAN	PRPF3	physical	24550385
CSK22_HUMAN	CSNK2A2	physical	24550385
SFR15_HUMAN	SCAF4	physical	24550385
DSG3_HUMAN	DSG3	physical	24550385
RBMX_HUMAN	RBMX	physical	24550385
CYFP1_HUMAN	CYFIP1	physical	24550385
US6NL_HUMAN	USP6NL	physical	24550385
DDX6_HUMAN	DDX6	physical	24550385
RPB1_HUMAN	POLR2A	physical	24550385
XRN2_HUMAN	XRN2	physical	24550385
INVO_HUMAN	IVL	physical	24550385
SYF1_HUMAN	XAB2	physical	24550385
AMOL1_HUMAN	AMOTL1	physical	24550385
MPDZ_HUMAN	MPDZ	physical	24550385
DDX3Y_HUMAN	DDX3Y	physical	24550385
WIPF2_HUMAN	WIPF2	physical	24550385
HNRL1_HUMAN	HNRNPUL1	physical	24550385
DHX9_HUMAN	DHX9	physical	24550385
RPAB1_HUMAN	POLR2E	physical	24550385
FBRS_HUMAN	FBRS	physical	24550385
MEP50_HUMAN	WDR77	physical	24550385
SC23A_HUMAN	SEC23A	physical	24550385
ZMAT5_HUMAN	ZMAT5	physical	24550385
DGC14_HUMAN	DGCR14	physical	24550385
LZTS2_HUMAN	LZTS2	physical	24550385
NOSIP_HUMAN	NOSIP	physical	24550385
DCAF7_HUMAN	DCAF7	physical	24550385
GEMI5_HUMAN	GEMIN5	physical	24550385
PR40A_HUMAN	PRPF40A	physical	24550385
IF4A3_HUMAN	EIF4A3	physical	24550385
SMRC1_HUMAN	SMARCC1	physical	24550385
SHIP2_HUMAN	INPPL1	physical	24550385
LSM4_HUMAN	LSM4	physical	24550385
DDX17_HUMAN	DDX17	physical	24550385
IF2B3_HUMAN	IGF2BP3	physical	24550385
RC3H1_HUMAN	RC3H1	physical	24550385
MPP5_HUMAN	MPP5	physical	24550385
RPB3_HUMAN	POLR2C	physical	24550385
SYFA_HUMAN	FARSA	physical	24550385
HNRH3_HUMAN	HNRNPH3	physical	24550385
DHX30_HUMAN	DHX30	physical	24550385
RPR1A_HUMAN	RPRD1A	physical	24550385
ZG16B_HUMAN	ZG16B	physical	24550385
NONO_HUMAN	NONO	physical	24550385
PREB_HUMAN	PREB	physical	24550385
PABP3_HUMAN	PABPC3	physical	24550385
LONP2_HUMAN	LONP2	physical	24550385
ATN1_HUMAN	ATN1	physical	24550385
GBRL2_HUMAN	GABARAPL2	physical	24550385
HNRPR_HUMAN	HNRNPR	physical	24550385
HNRC1_HUMAN	HNRNPCL1	physical	24550385
CYFP2_HUMAN	CYFIP2	physical	24550385
ELAV1_HUMAN	ELAVL1	physical	24550385
SF3B1_HUMAN	SF3B1	physical	24550385
ITCH_HUMAN	ITCH	physical	24550385
DRG1_HUMAN	DRG1	physical	24550385
SMD3_HUMAN	SNRPD3	physical	24550385
RPAP3_HUMAN	RPAP3	physical	24550385
RPB2_HUMAN	POLR2B	physical	24550385
RNC_HUMAN	DROSHA	physical	24550385
HNRPU_HUMAN	HNRNPU	physical	24550385
PYR1_HUMAN	CAD	physical	24550385
TCPH_HUMAN	CCT7	physical	24550385
PTN14_HUMAN	PTPN14	physical	24550385
PP1A_HUMAN	PPP1CA	physical	24550385
ROA3_HUMAN	HNRNPA3	physical	24550385
DX39B_HUMAN	DDX39B	physical	24550385
SG2A1_HUMAN	SCGB2A1	physical	24550385
K2C75_HUMAN	KRT75	physical	24550385
DDX21_HUMAN	DDX21	physical	24550385
SPART_HUMAN	SPG20	physical	24550385
CSDE1_HUMAN	CSDE1	physical	24550385
HNRPF_HUMAN	HNRNPF	physical	24550385
SRS10_HUMAN	SRSF10	physical	24550385
S23IP_HUMAN	SEC23IP	physical	24550385
AT2A1_HUMAN	ATP2A1	physical	24550385
DIAP1_HUMAN	DIAPH1	physical	24550385
LCN1_HUMAN	LCN1	physical	24550385
DOCK7_HUMAN	DOCK7	physical	24550385
CX057_HUMAN	CXorf57	physical	24550385
SF3A2_HUMAN	SF3A2	physical	24550385
HSPB1_HUMAN	HSPB1	physical	24550385
TADBP_HUMAN	TARDBP	physical	24550385
SF3B6_HUMAN	SF3B6	physical	24550385
AMOT_HUMAN	AMOT	physical	24550385
THOC6_HUMAN	THOC6	physical	24550385
KIF2A_HUMAN	KIF2A	physical	24550385
LC7L3_HUMAN	LUC7L3	physical	24550385
MYH7_HUMAN	MYH7	physical	24550385
MYH1_HUMAN	MYH1	physical	24550385
MYH4_HUMAN	MYH4	physical	24550385
DDX1_HUMAN	DDX1	physical	24550385
ENOA_HUMAN	ENO1	physical	24550385
P73_HUMAN	TP73	physical	24550385
TCPZ_HUMAN	CCT6A	physical	24550385
SMCE1_HUMAN	SMARCE1	physical	24550385
ANXA2_HUMAN	ANXA2	physical	24550385
ACLY_HUMAN	ACLY	physical	24550385
SCAF8_HUMAN	SCAF8	physical	24550385
AL3A1_HUMAN	ALDH3A1	physical	24550385
PPIB_HUMAN	PPIB	physical	24550385
EDC4_HUMAN	EDC4	physical	24550385
RL6_HUMAN	RPL6	physical	24550385
SNUT2_HUMAN	USP39	physical	24550385
EIF3A_HUMAN	EIF3A	physical	24550385
H2AZ_HUMAN	H2AFZ	physical	24550385
RL30_HUMAN	RPL30	physical	24550385
KDM3B_HUMAN	KDM3B	physical	24550385
FUS_HUMAN	FUS	physical	24550385
SPB5_HUMAN	SERPINB5	physical	24550385
DVL1_HUMAN	DVL1	physical	24550385
RPGF2_HUMAN	RAPGEF2	physical	24550385
DHX36_HUMAN	DHX36	physical	24550385
JUPI2_HUMAN	HN1L	physical	24550385
RPB7_HUMAN	POLR2G	physical	24550385
BAIP2_HUMAN	BAIAP2	physical	24550385
WDR91_HUMAN	WDR91	physical	24550385
DCTP1_HUMAN	DCTPP1	physical	24550385
IQEC1_HUMAN	IQSEC1	physical	24550385
PRDX5_HUMAN	PRDX5	physical	24550385
LZTS3_HUMAN	LZTS3	physical	24550385
SRSF3_HUMAN	SRSF3	physical	24550385
ZN598_HUMAN	ZNF598	physical	24550385
LACRT_HUMAN	LACRT	physical	24550385
IF2B2_HUMAN	IGF2BP2	physical	24550385
PUR6_HUMAN	PAICS	physical	24550385
K1522_HUMAN	KIAA1522	physical	24550385
NADAP_HUMAN	SLC4A1AP	physical	24550385
ATX2_HUMAN	ATXN2	physical	24550385
TR150_HUMAN	THRAP3	physical	24550385
RBM39_HUMAN	RBM39	physical	24550385
CAZA1_HUMAN	CAPZA1	physical	24550385
SC24C_HUMAN	SEC24C	physical	24550385
NOP56_HUMAN	NOP56	physical	24550385
SRPK1_HUMAN	SRPK1	physical	24550385
DKC1_HUMAN	DKC1	physical	24550385
RED_HUMAN	IK	physical	24550385
ECHA_HUMAN	HADHA	physical	24550385
OGT1_HUMAN	OGT	physical	24550385
PRP31_HUMAN	PRPF31	physical	24550385
DIDO1_HUMAN	DIDO1	physical	24550385
ATD3A_HUMAN	ATAD3A	physical	24550385
PDCD7_HUMAN	PDCD7	physical	24550385
ATM_HUMAN	ATM	physical	25331887
TIF1B_HUMAN	TRIM28	physical	25331887
ITCH_HUMAN	ITCH	physical	25331887
ATM_HUMAN	ATM	physical	26675548
FKB15_HUMAN	FKBP15	physical	28514442
NDKB_HUMAN	NME2	physical	28514442
DVL2_HUMAN	DVL2	physical	28514442
KAISO_HUMAN	ZBTB33	physical	28514442
LYSC_HUMAN	LYZ	physical	28514442
BRCA1_HUMAN	BRCA1	physical	27869163
SMAD3_HUMAN	SMAD3	physical	24330518

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
	Note=Defects in WWOX may be involved in several cancer types. The gene spans the second most common chromosomal fragile site (FRA16D) which is frequently altered in cancers. Alteration of the expression and expression of some isoforms is associated with cancers. However, it is still unclear if alteration of WWOX is directly implicated in cancerogenesis or if it corresponds to a secondary effect.
133239
614322	Spinocerebellar ataxia, autosomal recessive, 12 (SCAR12)
616211	Epileptic encephalopathy, early infantile, 28 (EIEE28)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of WWOX_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 THR-12 AND SER-14, AND MASSSPECTROMETRY.	19690332 [Abstract]
"Transforming growth factor beta1 signaling via interaction with cellsurface Hyal-2 and recruitment of WWOX/WOX1."; Hsu L.-J., Schultz L., Hong Q., Van Moer K., Heath J., Li M.-Y.,Lai F.-J., Lin S.-R., Lee M.-H., Lo C.-P., Lin Y.-S., Chen S.-T.,Chang N.-S.; J. Biol. Chem. 284:16049-16059(2009). Cited for: FUNCTION, PHOSPHORYLATION AT TYR-33, SUBCELLULAR LOCATION, ANDINTERACTION WITH HYAL2.	19366691 [Abstract]
"Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: roleof Ack1 in polyubiquitination of tumor suppressor Wwox."; Mahajan N.P., Whang Y.E., Mohler J.L., Earp H.S.; Cancer Res. 65:10514-10523(2005). Cited for: PHOSPHORYLATION AT TYR-287 BY TNK2, UBIQUITINATION, MUTAGENESIS OFTYR-287, AND INTERACTION WITH TNK2.	16288044 [Abstract]
"Functional association between Wwox tumor suppressor protein and p73,a p53 homolog."; Aqeilan R.I., Pekarsky Y., Herrero J.J., Palamarchuk A., Letofsky J.,Druck T., Trapasso F., Han S.-Y., Melino G., Huebner K., Croce C.M.; Proc. Natl. Acad. Sci. U.S.A. 101:4401-4406(2004). Cited for: FUNCTION, INTERACTION WITH TP73, DOMAIN, MUTAGENESIS OF TYR-33 ANDTYR-61, PHOSPHORYLATION AT TYR-33, AND SUBCELLULAR LOCATION.	15070730 [Abstract]