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Q9Y5U4

- INSI2_HUMAN

UniProt

Q9Y5U4 - INSI2_HUMAN

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Protein

Insulin-induced gene 2 protein

Gene
INSIG2
Organism
Homo sapiens (Human)
Status
Reviewed - 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 - Molecular functioni

  1. protein binding Source: UniProtKB

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; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei32 – 5221Helical; Reviewed predictionAdd
BLAST
Transmembranei71 – 9121Helical; Reviewed predictionAdd
BLAST
Transmembranei131 – 14818Helical; Reviewed predictionAdd
BLAST
Transmembranei154 – 17421Helical; Reviewed predictionAdd
BLAST
Transmembranei186 – 20621Helical; Reviewed predictionAdd
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

ArrayExpressiQ9Y5U4.
BgeeiQ9Y5U4.
CleanExiHS_INSIG2.
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.
IntActiQ9Y5U4. 3 interactions.
STRINGi9606.ENSP00000245787.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4J82X-ray1.46C/D221-225[»]
ProteinModelPortaliQ9Y5U4.

Family & Domainsi

Sequence similaritiesi

Belongs to the INSIG family.

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG263628.
HOGENOMiHOG000253021.
HOVERGENiHBG058958.
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

MAEGETESPG PKKCGPYISS VTSQSVNLMI RGVVLFFIGV FLALVLNLLQ    50
IQRNVTLFPP DVIASIFSSA WWVPPCCGTA SAVIGLLYPC IDRHLGEPHK 100
FKREWSSVMR CVAVFVGINH ASAKVDFDNN IQLSLTLAAL SIGLWWTFDR 150
SRSGFGLGVG IAFLATVVTQ LLVYNGVYQY TSPDFLYVRS WLPCIFFAGG 200
ITMGNIGRQL AMYECKVIAE KSHQE 225
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.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS2122.1.
RefSeqi NP_057217.2. NM_016133.2.
UniGenei Hs.7089.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4J82 X-ray 1.46 C/D 221-225 [» ]
ProteinModelPortali Q9Y5U4.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 119325. 36 interactions.
IntActi Q9Y5U4. 3 interactions.
STRINGi 9606.ENSP00000245787.

PTM databases

PhosphoSitei Q9Y5U4.

Polymorphism databases

DMDMi 147646722.

Proteomic databases

MaxQBi Q9Y5U4.
PaxDbi Q9Y5U4.
PRIDEi Q9Y5U4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000245787 ; ENSP00000245787 ; ENSG00000125629 .
GeneIDi 51141.
KEGGi hsa:51141.
UCSCi uc002tlk.3. human.

Organism-specific databases

CTDi 51141.
GeneCardsi GC02P118846.
HGNCi HGNC:20452. INSIG2.
HPAi CAB033861.
MIMi 608660. gene.
neXtProti NX_Q9Y5U4.
PharmGKBi PA134890284.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG263628.
HOGENOMi HOG000253021.
HOVERGENi HBG058958.
OMAi HRFKREW.
PhylomeDBi Q9Y5U4.
TreeFami TF331013.

Enzyme and pathway databases

Reactomei REACT_147797. Regulation of cholesterol biosynthesis by SREBP (SREBF).

Miscellaneous databases

GeneWikii INSIG2.
GenomeRNAii 51141.
NextBioi 53994.
PROi Q9Y5U4.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9Y5U4.
Bgeei Q9Y5U4.
CleanExi HS_INSIG2.
Genevestigatori Q9Y5U4.

Family and domain databases

InterProi IPR025929. INSIG_fam.
[Graphical view ]
Pfami PF07281. INSIG. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 81 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

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