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Q9Y5U4

- INSI2_HUMAN

UniProt

Q9Y5U4 - INSI2_HUMAN

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
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    • History
      Entry version 82 (01 Oct 2014)
      Sequence version 2 (15 May 2007)
      Previous versions | rss
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    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

    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

    GO - Cellular componenti

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

    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.
    DIPiDIP-60913N.
    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    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

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the INSIG family.Curated

    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.
    DIPi DIP-60913N.
    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

    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: October 1, 2014
    This is version 82 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