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Protein

Insulin-induced gene 2 protein

Gene

INSIG2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Biological processi

  1. cholesterol biosynthetic process Source: Ensembl
  2. cranial suture morphogenesis Source: Ensembl
  3. inner ear morphogenesis Source: Ensembl
  4. middle ear morphogenesis Source: Ensembl
  5. negative regulation of fatty acid biosynthetic process Source: Ensembl
  6. negative regulation of steroid biosynthetic process Source: Ensembl
  7. palate development Source: Ensembl
  8. response to fatty acid Source: Ensembl
  9. response to insulin Source: Ensembl
  10. small molecule metabolic process Source: Reactome
  11. SREBP signaling pathway Source: UniProtKB
  12. triglyceride metabolic process Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

ReactomeiREACT_147797. Regulation of cholesterol biosynthesis by SREBP (SREBF).

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-induced gene 2 protein
Short name:
INSIG-2
Gene namesi
Name:INSIG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:20452. INSIG2.

Subcellular locationi

Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei32 – 5221HelicalSequence AnalysisAdd
BLAST
Transmembranei71 – 9121HelicalSequence AnalysisAdd
BLAST
Transmembranei131 – 14818HelicalSequence AnalysisAdd
BLAST
Transmembranei154 – 17421HelicalSequence AnalysisAdd
BLAST
Transmembranei186 – 20621HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: Reactome
  2. SREBP-SCAP-Insig complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi149 – 1491D → A: Loss of ability to suppress the cleavage of SREBP2 and to accelerate the degradation of HMGCR. 1 Publication

Organism-specific databases

PharmGKBiPA134890284.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 225225Insulin-induced gene 2 proteinPRO_0000286797Add
BLAST

Proteomic databases

MaxQBiQ9Y5U4.
PaxDbiQ9Y5U4.
PRIDEiQ9Y5U4.

PTM databases

PhosphoSiteiQ9Y5U4.

Expressioni

Gene expression databases

BgeeiQ9Y5U4.
CleanExiHS_INSIG2.
ExpressionAtlasiQ9Y5U4. baseline and differential.
GenevestigatoriQ9Y5U4.

Organism-specific databases

HPAiCAB033861.

Interactioni

Subunit structurei

Binds to the SCAP-SREBF2 complex only in the presence of sterols. Interacts with RNF139.2 Publications

Protein-protein interaction databases

BioGridi119325. 36 interactions.
DIPiDIP-60913N.
IntActiQ9Y5U4. 3 interactions.
STRINGi9606.ENSP00000245787.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4J82X-ray1.46C/D221-225[»]
ProteinModelPortaliQ9Y5U4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the INSIG family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG263628.
GeneTreeiENSGT00580000081600.
HOGENOMiHOG000253021.
HOVERGENiHBG058958.
InParanoidiQ9Y5U4.
OMAiHRFKREW.
PhylomeDBiQ9Y5U4.
TreeFamiTF331013.

Family and domain databases

InterProiIPR025929. INSIG_fam.
[Graphical view]
PfamiPF07281. INSIG. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Y5U4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEGETESPG PKKCGPYISS VTSQSVNLMI RGVVLFFIGV FLALVLNLLQ
60 70 80 90 100
IQRNVTLFPP DVIASIFSSA WWVPPCCGTA SAVIGLLYPC IDRHLGEPHK
110 120 130 140 150
FKREWSSVMR CVAVFVGINH ASAKVDFDNN IQLSLTLAAL SIGLWWTFDR
160 170 180 190 200
SRSGFGLGVG IAFLATVVTQ LLVYNGVYQY TSPDFLYVRS WLPCIFFAGG
210 220
ITMGNIGRQL AMYECKVIAE KSHQE
Length:225
Mass (Da):24,778
Last modified:May 15, 2007 - v2
Checksum:i13E0392F1B30F08C
GO

Sequence cautioni

The sequence AAD43048.1 differs from that shown. Reason: Frameshift at position 221. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2122.1.
RefSeqiNP_057217.2. NM_016133.2.
UniGeneiHs.7089.

Genome annotation databases

EnsembliENST00000245787; ENSP00000245787; ENSG00000125629.
GeneIDi51141.
KEGGihsa:51141.
UCSCiuc002tlk.3. human.

Polymorphism databases

DMDMi147646722.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2122.1.
RefSeqiNP_057217.2. NM_016133.2.
UniGeneiHs.7089.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4J82X-ray1.46C/D221-225[»]
ProteinModelPortaliQ9Y5U4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119325. 36 interactions.
DIPiDIP-60913N.
IntActiQ9Y5U4. 3 interactions.
STRINGi9606.ENSP00000245787.

PTM databases

PhosphoSiteiQ9Y5U4.

Polymorphism databases

DMDMi147646722.

Proteomic databases

MaxQBiQ9Y5U4.
PaxDbiQ9Y5U4.
PRIDEiQ9Y5U4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245787; ENSP00000245787; ENSG00000125629.
GeneIDi51141.
KEGGihsa:51141.
UCSCiuc002tlk.3. human.

Organism-specific databases

CTDi51141.
GeneCardsiGC02P118846.
HGNCiHGNC:20452. INSIG2.
HPAiCAB033861.
MIMi608660. gene.
neXtProtiNX_Q9Y5U4.
PharmGKBiPA134890284.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG263628.
GeneTreeiENSGT00580000081600.
HOGENOMiHOG000253021.
HOVERGENiHBG058958.
InParanoidiQ9Y5U4.
OMAiHRFKREW.
PhylomeDBiQ9Y5U4.
TreeFamiTF331013.

Enzyme and pathway databases

ReactomeiREACT_147797. Regulation of cholesterol biosynthesis by SREBP (SREBF).

Miscellaneous databases

ChiTaRSiINSIG2. human.
GeneWikiiINSIG2.
GenomeRNAii51141.
NextBioi53994.
PROiQ9Y5U4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y5U4.
CleanExiHS_INSIG2.
ExpressionAtlasiQ9Y5U4. baseline and differential.
GenevestigatoriQ9Y5U4.

Family and domain databases

InterProiIPR025929. INSIG_fam.
[Graphical view]
PfamiPF07281. INSIG. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiINSI2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5U4
Secondary accession number(s): A8K5W8, Q8TBI8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: May 15, 2007
Last modified: March 4, 2015
This is version 87 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.