INSI2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: INSI2_HUMAN
• UniProt AC: Q9Y5U4
• Protein Name: Insulin-induced gene 2 protein
• Gene Name: INSIG2
• Organism: Homo sapiens (Human).
• Sequence Length: 225
• Subcellular Localization: Endoplasmic reticulum membrane ; Multi-pass membrane protein .
• Protein Description: Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Seems to regulate the ubiquitin-mediated proteasomal degradation of HMGCR..
• Protein Sequence: MAEGETESPGPKKCGPYISSVTSQSVNLMIRGVVLFFIGVFLALVLNLLQIQRNVTLFPPDVIASIFSSAWWVPPCCGTASAVIGLLYPCIDRHLGEPHKFKREWSSVMRCVAVFVGINHASAKVDFDNNIQLSLTLAALSIGLWWTFDRSRSGFGLGVGIAFLATVVTQLLVYNGVYQYTSPDFLYVRSWLPCIFFAGGITMGNIGRQLAMYECKVIAEKSHQE

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
6	Phosphorylation	--MAEGETESPGPKK --CCCCCCCCCCCCC	53.25	29255136
8	Phosphorylation	MAEGETESPGPKKCG CCCCCCCCCCCCCCC	42.44	29255136
100	Ubiquitination	RHLGEPHKFKREWSS HHCCCCCHHHHHHHH	64.39	16549805
102	Ubiquitination	LGEPHKFKREWSSVM CCCCCHHHHHHHHHH	54.96	1654980
151	Phosphorylation	LWWTFDRSRSGFGLG HHHCCCCCCCCCCCC	32.42	32322062
215	Oxidation	RQLAMYECKVIAEKS HHHHHHCCCHHHCHH	2.05	31953408
221	Ubiquitination	ECKVIAEKSHQE--- CCCHHHCHHCCC---	44.19	-

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
151	S	Phosphorylation	Kinase	PCK1	P35558	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
151	S	Phosphorylation	Phosphorylation at Ser-151 by PCK1 reduces binding to oxysterol, disrupting the interaction between INSIG2 and SCAP, thereby promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes.	32322062
215	C	Oxidation	In differentiated myotubes, Cys-215 oxidation prevents ubiquitination at the same site, resulting in protein stabilization.	31953408
215	C	ubiquitylation	In differentiated myotubes, Cys-215 oxidation prevents ubiquitination at the same site, resulting in protein stabilization.	31953408
215	C	ubiquitylation	Oxidized at Cys-215 in differentiated myotubes, preventing ubiquitination at the same site, and resulting in protein stabilization.	31953408
215	C	ubiquitylation	Polyubiquitinated by AMFR/gp78 at Cys-215 in some tissues such as adipose tissues, undifferentiated myoblasts and liver, leading to its degradation.	31953408

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of INSI2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SCAP_HUMAN	SCAP	physical	16549805
AMFR_HUMAN	AMFR	physical	19815544
UBQL2_HUMAN	UBQLN2	physical	19815544
UBQL1_HUMAN	UBQLN1	physical	19815544
TERA_HUMAN	VCP	physical	19815544
RPN1_HUMAN	RPN1	physical	19815544
PRS8_HUMAN	PSMC5	physical	19815544
BAG6_HUMAN	BAG6	physical	19815544
ADRM1_HUMAN	ADRM1	physical	19815544
PSDE_HUMAN	PSMD14	physical	19815544
PSD11_HUMAN	PSMD11	physical	19815544
HSP7C_HUMAN	HSPA8	physical	19815544
GRP78_HUMAN	HSPA5	physical	19815544
PSD13_HUMAN	PSMD13	physical	19815544
DESP_HUMAN	DSP	physical	19815544
PLAK_HUMAN	JUP	physical	19815544
ENOA_HUMAN	ENO1	physical	19815544
LEG7_HUMAN	LGALS7	physical	19815544
PSMD4_HUMAN	PSMD4	physical	19815544
PRS7_HUMAN	PSMC2	physical	19815544
PRS10_HUMAN	PSMC6	physical	19815544
PSB3_HUMAN	PSMB3	physical	19815544
PSA2_HUMAN	PSMA2	physical	19815544
PSD12_HUMAN	PSMD12	physical	19815544
FAF2_HUMAN	FAF2	physical	19815544
HSP76_HUMAN	HSPA6	physical	19815544
PRS6A_HUMAN	PSMC3	physical	19815544
PSA7_HUMAN	PSMA7	physical	19815544
PSB1_HUMAN	PSMB1	physical	19815544
SCAP_HUMAN	SCAP	physical	12242332
SRBP1_HUMAN	SREBF1	physical	12242332
HMDH_HUMAN	HMGCR	physical	24371122

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.