dbPTM

INSI1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	INSI1_HUMAN
UniProt AC	O15503
Protein Name	Insulin-induced gene 1 protein
Gene Name	INSIG1 {ECO:0000312\|HGNC:HGNC:6083}
Organism	Homo sapiens (Human).
Sequence Length	277
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. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth..
Protein Sequence	MPRLHDHFWSCSCAHSARRRGPPRASAAGLAAKVGEMINVSVSGPSLLAAHGAPDADPAPRGRSAAMSGPEPGSPYPNTWHHRLLQRSLVLFSVGVVLALVLNLLQIQRNVTLFPEEVIATIFSSAWWVPPCCGTAAAVVGLLYPCIDSHLGEPHKFKREWASVMRCIAVFVGINHASAKLDFANNVQLSLTLAALSLGLWWTFDRSRSGLGLGITIAFLATLITQFLVYNGVYQYTSPDFLYIRSWLPCIFFSGGVTVGNIGRQLAMGVPEKPHSD

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
16	Phosphorylation	WSCSCAHSARRRGPP HHHHCHHHHHHHCCC	12.63	-
33	Ubiquitination	SAAGLAAKVGEMINV CHHHHHHHHCCCEEE	45.20	-
144	Ubiquitination	AAVVGLLYPCIDSHL HHHHHHHHHHHHHHC	10.91	-
153	Ubiquitination	CIDSHLGEPHKFKRE HHHHHCCCCCHHHHH	51.06	-
156	Ubiquitination	SHLGEPHKFKREWAS HHCCCCCHHHHHHHH	64.39	16399501
158	Ubiquitination	LGEPHKFKREWASVM CCCCCHHHHHHHHHH	54.96	16399501
161	Ubiquitination	PHKFKREWASVMRCI CCHHHHHHHHHHHHH	9.62	-
207	Phosphorylation	LWWTFDRSRSGLGLG HHHHCCCCCCCCCHH	32.42	32322062
222	Phosphorylation	ITIAFLATLITQFLV HHHHHHHHHHHHHHH	22.35	-
273	Ubiquitination	LAMGVPEKPHSD--- HHCCCCCCCCCC---	41.79	16399501

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
207	S	Phosphorylation	Kinase	PCK1	P35558	Uniprot
222	T	Phosphorylation	Kinase	AMPKA1	Q13131	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	AMFR	Q9UKV5	PMID:16168377
-	K	Ubiquitination	E3 ubiquitin ligase	RNF139	Q8WU17	PMID:20068067

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
207	S	Phosphorylation		32322062
Phosphorylation at Ser-207 by PCK1 reduces binding to oxysterol, disrupting the interaction between INSIG1 and SCAP, thereby promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes.

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 INSI1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SCAP_HUMAN	SCAP	physical	12842885
SRBP2_HUMAN	SREBF2	physical	12842885
SCAP_MOUSE	Scap	physical	12202038
SRBP2_HUMAN	SREBF2	physical	12202038
TERA_HUMAN	VCP	physical	18835813
FAF2_HUMAN	FAF2	physical	18835813
SCAP_HUMAN	SCAP	physical	18835813
AMFR_HUMAN	AMFR	physical	16168377
TERA_HUMAN	VCP	physical	16168377
HMDH_HUMAN	HMGCR	physical	16168377
HMDH_HUMAN	HMGCR	physical	19458199
AMFR_HUMAN	AMFR	physical	17043353
SCAP_HUMAN	SCAP	physical	17043353
AMFR_HUMAN	AMFR	physical	19815544
PRS6A_HUMAN	PSMC3	physical	19815544
PSA7_HUMAN	PSMA7	physical	19815544
TERA_HUMAN	VCP	physical	19815544
FAF2_HUMAN	FAF2	physical	19815544
INSI1_HUMAN	INSIG1	physical	19617589
INSI2_HUMAN	INSIG2	physical	19617589
ERLN2_HUMAN	ERLIN2	physical	21343306
AMFR_HUMAN	AMFR	physical	21343306
PGRC1_HUMAN	PGRMC1	physical	15782218
SCAP_HUMAN	SCAP	physical	12242332
SRBP1_HUMAN	SREBF1	physical	12242332
NCPR_HUMAN	POR	physical	21081644
HMDH_HUMAN	HMGCR	physical	24371122
SCAP_HUMAN	SCAP	physical	23564452

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 INSI1_HUMAN

Related Literatures of Post-Translational Modification

Ubiquitylation
Reference	PubMed
"Sterol-regulated ubiquitination and degradation of Insig-1 creates aconvergent mechanism for feedback control of cholesterol synthesis anduptake."; Gong Y., Lee J.N., Lee P.C., Goldstein J.L., Brown M.S., Ye J.; Cell Metab. 3:15-24(2006). Cited for: FUNCTION, INTERACTION WITH SCAP AND SREBP2 COMPLEX, UBIQUITINATION ATLYS-156 AND LYS-158, AND MUTAGENESIS OF LYS-156 AND LYS-158.	16399501 [Abstract]