SIAH2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SIAH2_HUMAN
• UniProt AC: O43255
• Protein Name: E3 ubiquitin-protein ligase SIAH2
• Gene Name: SIAH2
• Organism: Homo sapiens (Human).
• Sequence Length: 324
• 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 (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes. Has some overlapping function with SIAH1. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not. Promotes monoubiquitination of SNCA..
• Protein Sequence: MSRPSSTGPSANKPCSKQPPPQPQHTPSPAAPPAAATISAAGPGSSAVPAAAAVISGPGGGGGAGPVSPQHHELTSLFECPVCFDYVLPPILQCQAGHLVCNQCRQKLSCCPTCRGALTPSIRNLAMEKVASAVLFPCKYATTGCSLTLHHTEKPEHEDICEYRPYSCPCPGASCKWQGSLEAVMSHLMHAHKSITTLQGEDIVFLATDINLPGAVDWVMMQSCFGHHFMLVLEKQEKYEGHQQFFAIVLLIGTRKQAENFAYRLELNGNRRRLTWEATPRSIHDGVAAAIMNSDCLVFDTAIAHLFADNGNLGINVTISTCCP

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSRPSSTGP ------CCCCCCCCC	53.55	28450419
5	Phosphorylation	---MSRPSSTGPSAN ---CCCCCCCCCCCC	39.15	28450419
6	Phosphorylation	--MSRPSSTGPSANK --CCCCCCCCCCCCC	39.81	25159151
7	Phosphorylation	-MSRPSSTGPSANKP -CCCCCCCCCCCCCC	58.40	28450419
10	Phosphorylation	RPSSTGPSANKPCSK CCCCCCCCCCCCCCC	45.90	28450419
13	Ubiquitination	STGPSANKPCSKQPP CCCCCCCCCCCCCCC	47.30	-
16	Phosphorylation	PSANKPCSKQPPPQP CCCCCCCCCCCCCCC	42.74	22878263
26	Phosphorylation	PPPQPQHTPSPAAPP CCCCCCCCCCCCCCC	21.88	22878263
28	Phosphorylation	PQPQHTPSPAAPPAA CCCCCCCCCCCCCCE	28.46	22878263
68	Phosphorylation	GGGAGPVSPQHHELT CCCCCCCCHHHHCCC	23.21	22878263
107	Ubiquitination	VCNQCRQKLSCCPTC HHHHHHHHHCCCCCC	24.02	-
109	Phosphorylation	NQCRQKLSCCPTCRG HHHHHHHCCCCCCCC	22.25	28348404
119	Phosphorylation	PTCRGALTPSIRNLA CCCCCCCCHHHHHHH	17.92	22878263
121	Phosphorylation	CRGALTPSIRNLAME CCCCCCHHHHHHHHH	29.01	24719451
132	Phosphorylation	LAMEKVASAVLFPCK HHHHHHHHHHEECCC	23.15	28348404
167	Phosphorylation	ICEYRPYSCPCPGAS CCCCCCCCCCCCCCC	17.79	21409570
254	Phosphorylation	AIVLLIGTRKQAENF HEEHHHCCHHHHHHH	27.92	-
256	Ubiquitination	VLLIGTRKQAENFAY EHHHCCHHHHHHHEE	54.41	32142685

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
16	S	Phosphorylation	Kinase	DYRK2	Q92630	Uniprot
26	T	Phosphorylation	Kinase	CHEK2	O96017	GPS
26	T	Phosphorylation	Kinase	DYRK2	Q92630	Uniprot
26	T	Phosphorylation	Kinase	HIPK2	Q9H2X6	PSP
28	S	Phosphorylation	Kinase	CHEK2	O96017	GPS
28	S	Phosphorylation	Kinase	DYRK2	Q92630	Uniprot
28	S	Phosphorylation	Kinase	HIPK2	Q9H2X6	PSP
28	S	Phosphorylation	Kinase	MAPK14	Q16539	Uniprot
68	S	Phosphorylation	Kinase	CHEK2	O96017	GPS
68	S	Phosphorylation	Kinase	DYRK2	Q92630	Uniprot
68	S	Phosphorylation	Kinase	HIPK2	Q9H2X6	PSP
119	T	Phosphorylation	Kinase	CHEK2	O96017	GPS
119	T	Phosphorylation	Kinase	DYRK2	Q92630	Uniprot
119	T	Phosphorylation	Kinase	HIPK2	Q9H2X6	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
28	S	Phosphorylation	Phosphorylated at Ser-28 by DYRK2; this increases the ubiquitin ligase activity and promotes degradation of EGLN3.	22878263
28	S	Phosphorylation	Phosphorylated at Ser-28 by MAPK14, which mediates the degradation by the proteasome of EGLN3 (By similarity).	22878263
28	S	ubiquitylation	Phosphorylated at Ser-28 by DYRK2; this increases the ubiquitin ligase activity and promotes degradation of EGLN3.	22878263

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of SIAH2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CTIP_HUMAN	RBBP8	physical	14654780
VAV_HUMAN	VAV1	physical	10207103
AKAP1_MOUSE	Akap1	physical	18323779
AKAP1_HUMAN	AKAP1	physical	18323779
PIAS1_HUMAN	PIAS1	physical	17533377
PIAS2_HUMAN	PIAS2	physical	17533377
UBC9_HUMAN	UBE2I	physical	17533377
PIAS3_HUMAN	PIAS3	physical	17533377
SNCAP_HUMAN	SNCAIP	physical	16174773
ODO2_HUMAN	DLST	physical	15466852
SYUA_HUMAN	SNCA	physical	15064394
PLCE1_HUMAN	PLCE1	physical	17998205
UBP13_HUMAN	USP13	physical	21659512
HIPK2_HUMAN	HIPK2	physical	19043406
HDAC3_HUMAN	HDAC3	physical	20691163
SYUA_HUMAN	SNCA	physical	18070888
SYUA_HUMAN	SNCA	physical	19224863
PSMD4_HUMAN	PSMD4	physical	19240029
TINF2_HUMAN	TINF2	physical	22064479
SYUA_HUMAN	SNCA	physical	22065755
UBP19_HUMAN	USP19	physical	22128162
CEBPD_HUMAN	CEBPD	physical	22037769
UBC9_HUMAN	UBE2I	physical	9334332
SH3R1_HUMAN	SH3RF1	physical	21586138
MYPT1_HUMAN	PPP1R12A	physical	19744480
EGLN3_HUMAN	EGLN3	physical	15210114
PSMD4_HUMAN	PSMD4	physical	22350919
DYRK2_HUMAN	DYRK2	physical	22878263
PML_HUMAN	PML	physical	14645235
TPX2_HUMAN	TPX2	physical	17716627
UB2D2_HUMAN	UBE2D2	physical	19224863
UB2D2_HUMAN	UBE2D2	physical	16174773
UB2D1_HUMAN	UBE2D1	physical	18070888
UB2D2_HUMAN	UBE2D2	physical	22065755
KAT5_HUMAN	KAT5	physical	23044042
KAT2B_HUMAN	KAT2B	physical	23044042
ACK1_HUMAN	TNK2	physical	23208506
UBP19_HUMAN	USP19	physical	23500468
ASPP1_HUMAN	PPP1R13B	physical	23644657
ASPP2_HUMAN	TP53BP2	physical	23644657
NF2L2_HUMAN	NFE2L2	physical	23645672
SIAH2_HUMAN	SIAH2	physical	23891150
UB2D3_HUMAN	UBE2D3	physical	23891150
STAT3_HUMAN	STAT3	physical	21988832
UBC9_HUMAN	UBE2I	physical	21988832
UB2L6_HUMAN	UBE2L6	physical	11786535
EGLN3_HUMAN	EGLN3	physical	25202994
HIPK2_HUMAN	HIPK2	physical	25313037
XAF1_HUMAN	XAF1	physical	25313037
XAF1_HUMAN	XAF1	genetic	25313037
UB2D1_HUMAN	UBE2D1	physical	19240029
AK1C3_HUMAN	AKR1C3	physical	26160177
SIAH2_HUMAN	SIAH2	physical	26160177
UB2D1_HUMAN	UBE2D1	physical	26160177
CHK2_HUMAN	CHEK2	physical	26751770
EAF2_HUMAN	EAF2	physical	27058417
SIAH1_HUMAN	SIAH1	physical	16899216
SIAH2_HUMAN	SIAH2	physical	16899216
ZYX_HUMAN	ZYX	physical	27030211
LATS2_HUMAN	LATS2	physical	27030211

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.