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Q9Y5U4 (INSI2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 77. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Insulin-induced gene 2 protein

Short name=INSIG-2
Gene names
Name:INSIG2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length225 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 225225Insulin-induced gene 2 protein
PRO_0000286797

Regions

Transmembrane32 – 5221Helical; Potential
Transmembrane71 – 9121Helical; Potential
Transmembrane131 – 14818Helical; Potential
Transmembrane154 – 17421Helical; Potential
Transmembrane186 – 20621Helical; Potential

Experimental info

Mutagenesis1491D → A: Loss of ability to suppress the cleavage of SREBP2 and to accelerate the degradation of HMGCR. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Q9Y5U4 [UniParc].

Last modified May 15, 2007. Version 2.
Checksum: 13E0392F1B30F08C

FASTA22524,778
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
RefSeqNP_057217.2. NM_016133.2.
UniGeneHs.7089.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4J82X-ray1.46C/D221-225[»]
ProteinModelPortalQ9Y5U4.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119325. 35 interactions.
IntActQ9Y5U4. 3 interactions.
STRING9606.ENSP00000245787.

PTM databases

PhosphoSiteQ9Y5U4.

Polymorphism databases

DMDM147646722.

Proteomic databases

PaxDbQ9Y5U4.
PRIDEQ9Y5U4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000245787; ENSP00000245787; ENSG00000125629.
GeneID51141.
KEGGhsa:51141.
UCSCuc002tlk.3. human.

Organism-specific databases

CTD51141.
GeneCardsGC02P118846.
HGNCHGNC:20452. INSIG2.
HPACAB033861.
MIM608660. gene.
neXtProtNX_Q9Y5U4.
PharmGKBPA134890284.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG263628.
HOGENOMHOG000253021.
HOVERGENHBG058958.
OMAHRFKREW.
PhylomeDBQ9Y5U4.
TreeFamTF331013.

Enzyme and pathway databases

ReactomeREACT_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

ArrayExpressQ9Y5U4.
BgeeQ9Y5U4.
CleanExHS_INSIG2.
GenevestigatorQ9Y5U4.

Family and domain databases

InterProIPR009904. INSIG.
IPR025929. INSIG_fam.
[Graphical view]
PANTHERPTHR15301:SF4. PTHR15301:SF4. 1 hit.
PfamPF07281. INSIG. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiINSIG2.
GenomeRNAi51141.
NextBio53994.
PROQ9Y5U4.
SOURCESearch...

Entry information

Entry nameINSI2_HUMAN
AccessionPrimary (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 16, 2014
This is version 77 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM