Q9Y5U4 (INSI2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-induced gene 2 protein
Short name=INSIG-2

Gene names

Name:

INSIG2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	225 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.7
Subunit structure	Binds to the SCAP-SREBF2 complex only in the presence of sterols. Interacts with RNF139. Ref.1 Ref.8
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.1.
Miscellaneous	Does not require nuclear SREBPs for its expression. When nuclear SREBP activity is low, is the only form of INSIG present in the cell.
Sequence similarities	Belongs to the INSIG family.
Sequence caution	The sequence AAD43048.1 differs from that shown. Reason: Frameshift at position 221.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism Sterol metabolism
Cellular component	Endoplasmic reticulum Membrane
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	SREBP signaling pathway Inferred from direct assay Ref.1. Source: UniProtKB cholesterol biosynthetic process Inferred from electronic annotation. Source: Compara cranial suture morphogenesis Inferred from electronic annotation. Source: Compara inner ear morphogenesis Inferred from electronic annotation. Source: Compara middle ear morphogenesis Inferred from electronic annotation. Source: Compara negative regulation of fatty acid biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of steroid biosynthetic process Inferred from electronic annotation. Source: Compara palate development Inferred from electronic annotation. Source: Compara response to fatty acid Inferred from electronic annotation. Source: Compara response to insulin stimulus Inferred from electronic annotation. Source: Compara triglyceride metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	SREBP-SCAP-Insig complex Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 225	225	Insulin-induced gene 2 protein		PRO_0000286797
Regions
	Transmembrane	32 – 52	21	Helical; Potential
	Transmembrane	71 – 91	21	Helical; Potential
	Transmembrane	131 – 148	18	Helical; Potential
	Transmembrane	154 – 174	21	Helical; Potential
	Transmembrane	186 – 206	21	Helical; Potential
Experimental info
	Mutagenesis	149	1	D → A: Loss of ability to suppress the cleavage of SREBP2 and to accelerate the degradation of HMGCR. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5U4 [UniParc]. Last modified May 15, 2007. Version 2. Checksum: 13E0392F1B30F08C	FASTA	225	24,778
	10 20 30 40 50 60 MAEGETESPG PKKCGPYISS VTSQSVNLMI RGVVLFFIGV FLALVLNLLQ IQRNVTLFPP 70 80 90 100 110 120 DVIASIFSSA WWVPPCCGTA SAVIGLLYPC IDRHLGEPHK FKREWSSVMR CVAVFVGINH 130 140 150 160 170 180 ASAKVDFDNN IQLSLTLAAL SIGLWWTFDR SRSGFGLGVG IAFLATVVTQ LLVYNGVYQY 190 200 210 220 TSPDFLYVRS WLPCIFFAGG ITMGNIGRQL AMYECKVIAE KSHQE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins." Yabe D., Brown M.S., Goldstein J.L. Proc. Natl. Acad. Sci. U.S.A. 99:12753-12758(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH THE SCAP-SREBF2 COMPLEX, SUBCELLULAR LOCATION. Tissue: Hypothalamus.
[2]	"Homo sapiens insulin induced protein 2 mRNA." Bao Q., Song H., Huang Q., Dai M., Mao Y., Zhang Q., Guan Z., Luo M., Chen J., Hu R. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pituitary.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for cholesterol homeostasis." Gong Y., Lee J.N., Brown M.S., Goldstein J.L., Ye J. Proc. Natl. Acad. Sci. U.S.A. 103:6154-6159(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-149.
[8]	"The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways." Lee J.P., Brauweiler A., Rudolph M., Hooper J.E., Drabkin H.A., Gemmill R.M. Mol. Cancer Res. 8:93-106(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RNF139.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF527632 mRNA. Translation: AAN28333.1. AF125392 mRNA. Translation: AAD43048.1. Frameshift. AK291433 mRNA. Translation: BAF84122.1. AC009303 Genomic DNA. Translation: AAX93280.1. CH471103 Genomic DNA. Translation: EAW95199.1. BC022475 mRNA. Translation: AAH22475.1.
IPI	IPI00413159.
RefSeq	NP_057217.2. NM_016133.2.
UniGene	Hs.7089.
3D structure databases
ProteinModelPortal	Q9Y5U4.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000245787.
PTM databases
PhosphoSite	Q9Y5U4.
Polymorphism databases
DMDM	147646722.
Proteomic databases
PaxDb	Q9Y5U4.
PRIDE	Q9Y5U4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000245787; ENSP00000245787; ENSG00000125629.
GeneID	51141.
KEGG	hsa:51141.
UCSC	uc002tlk.3. human.
Organism-specific databases
CTD	51141.
GeneCards	GC02P118846.
HGNC	HGNC:20452. INSIG2.
HPA	CAB033861.
MIM	608660. gene.
neXtProt	NX_Q9Y5U4.
PharmGKB	PA134890284.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG263628.
HOGENOM	HOG000253021.
HOVERGEN	HBG058958.
OMA	QLALYEY.
OrthoDB	EOG4JDH7K.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_147768. SREBP2 (SREBF2) is retained in the endoplasmic reticulum by SCAP:INSIG2:oxysterol. REACT_147840. SREBP1A/1C/2 is retained in the endoplasmic reticulum by SCAP:cholesterol:INSIG.
Gene expression databases
ArrayExpress	Q9Y5U4.
Bgee	Q9Y5U4.
CleanEx	HS_INSIG2.
Genevestigator	Q9Y5U4.
Family and domain databases
InterPro	IPR009904. INSIG. IPR025929. INSIG_fam. [Graphical view]
PANTHER	PTHR15301. PTHR15301. 1 hit.
Pfam	PF07281. INSIG. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	51141.
NextBio	53994.
SOURCE	Search...

Entry information

Entry name

INSI2_HUMAN

Accession

Primary (citable) accession number: Q9Y5U4
Secondary accession number(s): A8K5W8, Q8TBI8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	May 15, 2007
Last modified:	April 3, 2013
This is version 70 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.