dbPTM

SIAH1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	SIAH1_HUMAN
UniProt AC	Q8IUQ4
Protein Name	E3 ubiquitin-protein ligase SIAH1
Gene Name	SIAH1
Organism	Homo sapiens (Human).
Sequence Length	282
Subcellular Localization	Cytoplasm. Nucleus. Predominantly cytoplasmic. Partially nuclear.
Protein Description	E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins..
Protein Sequence	MSRQTATALPTGTSKCPPSQRVPALTGTTASNNDLASLFECPVCFDYVLPPILQCQSGHLVCSNCRPKLTCCPTCRGPLGSIRNLAMEKVANSVLFPCKYASSGCEITLPHTEKADHEELCEFRPYSCPCPGASCKWQGSLDAVMPHLMHQHKSITTLQGEDIVFLATDINLPGAVDWVMMQSCFGFHFMLVLEKQEKYDGHQQFFAIVQLIGTRKQAENFAYRLELNGHRRRLTWEATPRSIHEGIATAIMNSDCLVFDTSIAQLFAENGNLGINVTISMC

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSRQTATAL ------CCCCCCCCC	32.85	18669648
7	Phosphorylation	-MSRQTATALPTGTS -CCCCCCCCCCCCCC	31.92	22985185
11	Phosphorylation	QTATALPTGTSKCPP CCCCCCCCCCCCCCH	54.67	22985185
13	Phosphorylation	ATALPTGTSKCPPSQ CCCCCCCCCCCCHHH	27.73	18669648
14	Phosphorylation	TALPTGTSKCPPSQR CCCCCCCCCCCHHHC	33.34	22985185
15	Ubiquitination	ALPTGTSKCPPSQRV CCCCCCCCCCHHHCC	51.07	-
19	Phosphorylation	GTSKCPPSQRVPALT CCCCCCHHHCCCCCC	18.76	9858595
19 (in isoform 2)	Phosphorylation	-	18.76	-
33 (in isoform 2)	Phosphorylation	-	43.08	18669648
46 (in isoform 2)	Ubiquitination	-	27.75	-
70	Phosphorylation	SNCRPKLTCCPTCRG CCCCCCCEECCCCCC	20.42	26714015
74	Phosphorylation	PKLTCCPTCRGPLGS CCCEECCCCCCCCHH	10.83	-
89	Acetylation	IRNLAMEKVANSVLF HHHHHHHHHHHHCCC	33.30	19825753
100	Phosphorylation	SVLFPCKYASSGCEI HCCCEEECCCCCCEE	20.59	16230351
126	Phosphorylation	ELCEFRPYSCPCPGA HHCCCCCCCCCCCCC	20.74	16230351
216	Ubiquitination	VQLIGTRKQAENFAY HHHHCCHHHHHHHHH	54.41	33845483
235	Phosphorylation	NGHRRRLTWEATPRS CCCCCCCCEECCCCC	21.32	-
239	Phosphorylation	RRLTWEATPRSIHEG CCCCEECCCCCHHHH	14.02	-
247	Ubiquitination	PRSIHEGIATAIMNS CCCHHHHHHHHHHCC	2.54	22053931

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
19	S	Phosphorylation	Kinase	ATM	Q13315	Uniprot
19	S	Phosphorylation	Kinase	ATR	Q13535	Uniprot
70	T	Phosphorylation	Kinase	ASK1	Q99683	PSP
74	T	Phosphorylation	Kinase	ASK1	Q99683	PSP
235	T	Phosphorylation	Kinase	ASK1	Q99683	PSP
239	T	Phosphorylation	Kinase	ASK1	Q99683	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
19	S	Phosphorylation		18536714
Phosphorylated on Ser-19 by ATM and ATR.

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 SIAH1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KIF22_HUMAN	KIF22	physical	11146551
CYBP_HUMAN	CACYBP	physical	11389839
AFF4_HUMAN	AFF4	physical	16189514
KHDR3_HUMAN	KHDRBS3	physical	16189514
CTIP_HUMAN	RBBP8	physical	14654780
PEG10_HUMAN	PEG10	physical	12810624
DAB1_HUMAN	DAB1	physical	12646221
UB2E3_HUMAN	UBE2E3	physical	11389839
UB2D1_HUMAN	UBE2D1	physical	11389839
VAV_HUMAN	VAV1	physical	10207103
BAG1_HUMAN	BAG1	physical	9582267
SIAH1_HUMAN	SIAH1	physical	9582267
NUMB_HUMAN	NUMB	physical	11752454
SIAH1_HUMAN	SIAH1	physical	11752454
HIF1N_HUMAN	HIF1AN	physical	18280659
TRIB3_HUMAN	TRIB3	physical	18276110
PIAS1_HUMAN	PIAS1	physical	17533377
PIAS2_HUMAN	PIAS2	physical	17533377
UBC9_HUMAN	UBE2I	physical	17533377
PIAS3_HUMAN	PIAS3	physical	17533377
SIAH1_HUMAN	SIAH1	physical	17420721
SNCAP_HUMAN	SNCAIP	physical	15064394
SNCAP_HUMAN	SNCAIP	physical	14506261
RUNX1_HUMAN	RUNX1	physical	18073335
RNF12_HUMAN	RLIM	physical	18073335
PHC2_HUMAN	PHC2	physical	20471960
PLCE1_HUMAN	PLCE1	physical	17998205
EF1D_HUMAN	EEF1D	physical	21633900
HIPK2_HUMAN	HIPK2	physical	19043406
HERP1_HUMAN	HERPUD1	physical	20604806
CTNB1_HUMAN	CTNNB1	physical	20181957
CYBP_HUMAN	CACYBP	physical	20181957
XIAP_HUMAN	XIAP	physical	21185211
SYUA_HUMAN	SNCA	physical	18065497
UB2E2_HUMAN	UBE2E2	physical	18065497
SYUA_HUMAN	SNCA	physical	18070888
SYUA_HUMAN	SNCA	physical	19224863
SIAH1_HUMAN	SIAH1	physical	19224863
PRS8_HUMAN	PSMC5	physical	20479273
PRS10_HUMAN	PSMC6	physical	20479273
TERF2_HUMAN	TERF2	physical	21057505
FLT3_HUMAN	FLT3	physical	20508617
PARD3_HUMAN	PARD3	physical	21109632
ELL2_HUMAN	ELL2	physical	22483617
CYBP_HUMAN	CACYBP	physical	16085652
HIPK2_HUMAN	HIPK2	physical	18536714
AFF1_HUMAN	AFF1	physical	15221006
SH3R1_HUMAN	SH3RF1	physical	16230351
SIAH1_HUMAN	SIAH1	physical	12421809
CYBP_HUMAN	CACYBP	physical	12421809
BAG1_HUMAN	BAG1	physical	12421809
UBC9_HUMAN	UBE2I	physical	9334332
G3P_HUMAN	GAPDH	physical	22534308
HIPK2_HUMAN	HIPK2	physical	19250734
HIPK1_HUMAN	HIPK1	physical	19250734
MYB_MOUSE	Myb	physical	10747903
UB2D2_HUMAN	UBE2D2	physical	19224863
UB2D3_HUMAN	UBE2D3	physical	22483617
UB2D3_HUMAN	UBE2D3	physical	17420721
UB2D2_HUMAN	UBE2D2	physical	18536714
UB2D1_HUMAN	UBE2D1	physical	20181957
UB2D3_HUMAN	UBE2D3	physical	19250734
UB2D1_HUMAN	UBE2D1	physical	18070888
NPM_HUMAN	NPM1	physical	23027902
G3P_HUMAN	GAPDH	physical	23027902
SIAH1_HUMAN	SIAH1	physical	23027902
PUF60_HUMAN	PUF60	physical	23208506
CYBP_HUMAN	CACYBP	physical	23208506
KHDR3_HUMAN	KHDRBS3	physical	23208506
ACK1_HUMAN	TNK2	physical	23208506
UBP19_HUMAN	USP19	physical	23500468
HIPK2_HUMAN	HIPK2	physical	23503458
SIAH1_HUMAN	SIAH1	physical	22493164
TRIM8_HUMAN	TRIM8	physical	22493164
THIO_HUMAN	TXN	physical	21988832
TFDP1_HUMAN	TFDP1	physical	21988832
SIAH1_HUMAN	SIAH1	physical	21988832
STAT3_HUMAN	STAT3	physical	21988832
ASPP2_HUMAN	TP53BP2	physical	21988832
ACK1_HUMAN	TNK2	physical	21988832
MARE3_HUMAN	MAPRE3	physical	19696028
SIAH1_HUMAN	SIAH1	physical	24316825
SIAH1_HUMAN	SIAH1	physical	20940148
UB2D1_HUMAN	UBE2D1	physical	18298843
SIAH1_HUMAN	SIAH1	physical	25416956
ASPP2_HUMAN	TP53BP2	physical	25416956
NELFA_HUMAN	NELFA	physical	25416956
ZN148_HUMAN	ZNF148	physical	25416956
IDLC_HUMAN	DNALI1	physical	25416956
FZD9_HUMAN	FZD9	physical	25416956
UXT_HUMAN	UXT	physical	25416956
CDC23_HUMAN	CDC23	physical	25416956
CD5R1_HUMAN	CDK5R1	physical	25416956
SYT7_HUMAN	SYT7	physical	25416956
RB33A_HUMAN	RAB33A	physical	25416956
R51A1_HUMAN	RAD51AP1	physical	25416956
PUF60_HUMAN	PUF60	physical	25416956
MABP1_HUMAN	MAPKBP1	physical	25416956
PEG10_HUMAN	PEG10	physical	25416956
KIF1B_HUMAN	KIF1B	physical	25416956
ARIP4_HUMAN	RAD54L2	physical	25416956
PRP31_HUMAN	PRPF31	physical	25416956
AFF4_HUMAN	AFF4	physical	25416956
DJC15_HUMAN	DNAJC15	physical	25416956
LACB2_HUMAN	LACTB2	physical	25416956
DDX41_HUMAN	DDX41	physical	25416956
TOLIP_HUMAN	TOLLIP	physical	25416956
ZCH10_HUMAN	ZCCHC10	physical	25416956
QRIC1_HUMAN	QRICH1	physical	25416956
NTAQ1_HUMAN	WDYHV1	physical	25416956
F90A1_HUMAN	FAM90A1	physical	25416956
CN105_HUMAN	C14orf105	physical	25416956
TB22B_HUMAN	TBC1D22B	physical	25416956
SKT_HUMAN	KIAA1217	physical	25416956
Z512B_HUMAN	ZNF512B	physical	25416956
ADPPT_HUMAN	AASDHPPT	physical	25416956
ZMAT3_HUMAN	ZMAT3	physical	25416956
NOL6_HUMAN	NOL6	physical	25416956
OTUB2_HUMAN	OTUB2	physical	25416956
ZFY21_HUMAN	ZFYVE21	physical	25416956
TMM43_HUMAN	TMEM43	physical	25416956
ZN671_HUMAN	ZNF671	physical	25416956
K319L_HUMAN	KIAA0319L	physical	25416956
ARMC9_HUMAN	ARMC9	physical	25416956
K1683_HUMAN	KIAA1683	physical	25416956
ZBP1_HUMAN	ZBP1	physical	25416956
GDPD5_HUMAN	GDPD5	physical	25416956
TRIM7_HUMAN	TRIM7	physical	25416956
KATL1_HUMAN	KATNAL1	physical	25416956
SPC1L_HUMAN	SPATC1L	physical	25416956
AROS_HUMAN	RPS19BP1	physical	25416956
PTPM1_HUMAN	PTPMT1	physical	25416956
EXAS1_HUMAN	EXOC3-AS1	physical	25416956
PR20E_HUMAN	PRR20A	physical	25416956
PR20C_HUMAN	PRR20A	physical	25416956
PR20D_HUMAN	PRR20A	physical	25416956
PR20B_HUMAN	PRR20A	physical	25416956
PR20A_HUMAN	PRR20A	physical	25416956
SPAT4_HUMAN	SPATA4	physical	25416956
MOB3C_HUMAN	MOB3C	physical	25416956
UPP2_HUMAN	UPP2	physical	25416956
IF3M_HUMAN	MTIF3	physical	25416956
ZCH13_HUMAN	ZCCHC13	physical	25416956
SYPH_HUMAN	SYP	physical	25755825
M3K5_HUMAN	MAP3K5	physical	25391652
DLDH_HUMAN	DLD	physical	26186194
SIAH2_HUMAN	SIAH2	physical	26186194
G3P_HUMAN	GAPDH	physical	26438826
LATS2_HUMAN	LATS2	physical	25587023
SIAH2_HUMAN	SIAH2	physical	16899216
UBP19_HUMAN	USP19	physical	27776223
SIAH2_HUMAN	SIAH2	physical	28514442
DLDH_HUMAN	DLD	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 SIAH1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpointkinases ATM and ATR."; Winter M., Sombroek D., Dauth I., Moehlenbrink J., Scheuermann K.,Crone J., Hofmann T.G.; Nat. Cell Biol. 10:812-824(2008). Cited for: FUNCTION, MUTAGENESIS OF SER-19 AND CYS-44, INTERACTION WITH HIPK2,AND PHOSPHORYLATION AT SER-19 BY ATM AND ATR.	18536714 [Abstract]

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