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O15503

- INSI1_HUMAN

UniProt

O15503 - INSI1_HUMAN

Protein

Insulin-induced gene 1 protein

Gene

INSIG1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 3 (03 Oct 2006)
      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. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth.5 Publications

    GO - Molecular functioni

    1. protein binding Source: UniProtKB

    GO - Biological processi

    1. cell proliferation Source: ProtInc
    2. cholesterol biosynthetic process Source: Ensembl
    3. cranial suture morphogenesis Source: Ensembl
    4. inner ear morphogenesis Source: Ensembl
    5. metabolic process Source: ProtInc
    6. middle ear morphogenesis Source: Ensembl
    7. negative regulation of cargo loading into COPII-coated vesicle Source: UniProtKB
    8. negative regulation of fat cell differentiation Source: Ensembl
    9. negative regulation of fatty acid biosynthetic process Source: Ensembl
    10. negative regulation of steroid biosynthetic process Source: Ensembl
    11. palate development Source: Ensembl
    12. small molecule metabolic process Source: Reactome
    13. SREBP signaling pathway Source: UniProtKB
    14. 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 1 protein
    Short name:
    INSIG-1
    Gene namesi
    Name:INSIG1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:6083. INSIG1.

    Subcellular locationi

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

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi156 – 1561K → R: Loss of ubiquitination and degradation. 1 Publication
    Mutagenesisi158 – 1581K → R: Loss of ubiquitination and degradation. 1 Publication
    Mutagenesisi205 – 2051D → A: Loss of ability to suppress the cleavage of SREBP2 and to accelerate the degradation of HMGCR. 1 Publication

    Organism-specific databases

    PharmGKBiPA29890.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 277277Insulin-induced gene 1 proteinPRO_0000191675Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki156 – 156Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Cross-linki158 – 158Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications

    Post-translational modificationi

    Ubiquitinated. Subsequent to sterol deprivation, the SCAP-SREBF2 complex becomes dissociated from INSIG1, is then ubiquitinated and degraded in proteasomes. Although ubiquitination is required for rapid INSIG1 degradation, it is not required for release of the SCAP-SREBP complex. Ubiquitinated by RNF139.2 Publications

    Keywords - PTMi

    Isopeptide bond, Ubl conjugation

    Proteomic databases

    PaxDbiO15503.
    PRIDEiO15503.

    PTM databases

    PhosphoSiteiO15503.

    Expressioni

    Tissue specificityi

    Expressed in all tissues tested with highest expression in the liver.1 Publication

    Inductioni

    By insulin.

    Gene expression databases

    ArrayExpressiO15503.
    BgeeiO15503.
    CleanExiHS_INSIG1.
    GenevestigatoriO15503.

    Interactioni

    Subunit structurei

    Binds to the SCAP-SREBF2 complex only in the presence of sterols. Interacts with RNF139. Interacts with HMGCR (via its SSD); the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with AMFR/gp78 (via its membrane domain); the interaction recruits HMCR at the ER membrane for its ubiquitination and degradation by the sterol-mediated ERAD pathway.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CYP2C1P001802EBI-6252425,EBI-6251821From a different organism.
    CYP2C2P001813EBI-6252425,EBI-4320576From a different organism.

    Protein-protein interaction databases

    BioGridi109850. 20 interactions.
    IntActiO15503. 5 interactions.
    MINTiMINT-4723340.
    STRINGi9606.ENSP00000344741.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4J81X-ray1.74C/D273-277[»]
    ProteinModelPortaliO15503.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 8787Cytoplasmic1 PublicationAdd
    BLAST
    Topological domaini109 – 12618LumenalSequence AnalysisAdd
    BLAST
    Topological domaini148 – 16013Cytoplasmic1 PublicationAdd
    BLAST
    Topological domaini178 – 1825LumenalSequence Analysis
    Topological domaini204 – 2096Cytoplasmic1 Publication
    Topological domaini231 – 24111LumenalSequence AnalysisAdd
    BLAST
    Topological domaini263 – 27715Cytoplasmic1 PublicationAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei88 – 10821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei127 – 14721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei161 – 17717HelicalSequence AnalysisAdd
    BLAST
    Transmembranei183 – 20321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei210 – 23021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei242 – 26221HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the INSIG family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG263628.
    HOGENOMiHOG000253021.
    HOVERGENiHBG058958.
    OMAiAMSGPEP.
    OrthoDBiEOG7RNK13.
    PhylomeDBiO15503.
    TreeFamiTF331013.

    Family and domain databases

    InterProiIPR009904. INSIG-1.
    IPR025929. INSIG_fam.
    [Graphical view]
    PANTHERiPTHR15301:SF11. PTHR15301:SF11. 1 hit.
    PfamiPF07281. INSIG. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O15503-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MPRLHDHFWS CSCAHSARRR GPPRASAAGL AAKVGEMINV SVSGPSLLAA    50
    HGAPDADPAP RGRSAAMSGP EPGSPYPNTW HHRLLQRSLV LFSVGVVLAL 100
    VLNLLQIQRN VTLFPEEVIA TIFSSAWWVP PCCGTAAAVV GLLYPCIDSH 150
    LGEPHKFKRE WASVMRCIAV FVGINHASAK LDFANNVQLS LTLAALSLGL 200
    WWTFDRSRSG LGLGITIAFL ATLITQFLVY NGVYQYTSPD FLYIRSWLPC 250
    IFFSGGVTVG NIGRQLAMGV PEKPHSD 277
    Length:277
    Mass (Da):29,987
    Last modified:October 3, 2006 - v3
    Checksum:i198068D53C658A58
    GO
    Isoform 2 (identifier: O15503-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         138-164: AVVGLLYPCIDSHLGEPHKFKREWASV → GIHPQISSIFVLGSLVYFSQEASRWGT
         165-277: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:164
    Mass (Da):17,530
    Checksum:i06076ED6ACE57C04
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti31 – 322AA → PP in AAB69121. (PubMed:9268630)Curated
    Sequence conflicti99 – 991A → T in AAB69121. (PubMed:9268630)Curated
    Sequence conflicti170 – 1723VFV → GFG in AAB69121. (PubMed:9268630)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti27 – 271A → T.1 Publication
    Corresponds to variant rs1129825 [ dbSNP | Ensembl ].
    VAR_027683

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei138 – 16427AVVGL…EWASV → GIHPQISSIFVLGSLVYFSQ EASRWGT in isoform 2. 1 PublicationVSP_045084Add
    BLAST
    Alternative sequencei165 – 277113Missing in isoform 2. 1 PublicationVSP_045085Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U96876 Genomic DNA. Translation: AAB69121.1.
    AY112745 mRNA. Translation: AAM44086.1.
    BT007227 mRNA. Translation: AAP35891.1.
    AK291675 mRNA. Translation: BAF84364.1.
    DN996424 mRNA. No translation available.
    AC144652 Genomic DNA. No translation available.
    AC231970 Genomic DNA. No translation available.
    CH236962 Genomic DNA. Translation: EAL23729.1.
    CH236962 Genomic DNA. Translation: EAL23730.1.
    CH471149 Genomic DNA. Translation: EAX04529.1.
    CH471149 Genomic DNA. Translation: EAX04530.1.
    BC001880 mRNA. Translation: AAH01880.1.
    CCDSiCCDS5938.1. [O15503-1]
    CCDS5939.1. [O15503-2]
    RefSeqiNP_005533.2. NM_005542.4. [O15503-1]
    NP_938150.2. NM_198336.2.
    NP_938151.1. NM_198337.2. [O15503-2]
    UniGeneiHs.520819.

    Genome annotation databases

    EnsembliENST00000340368; ENSP00000344741; ENSG00000186480. [O15503-1]
    ENST00000342407; ENSP00000344035; ENSG00000186480. [O15503-2]
    GeneIDi3638.
    KEGGihsa:3638.
    UCSCiuc003wly.3. human. [O15503-1]
    uc003wlz.3. human.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Insig1 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U96876 Genomic DNA. Translation: AAB69121.1 .
    AY112745 mRNA. Translation: AAM44086.1 .
    BT007227 mRNA. Translation: AAP35891.1 .
    AK291675 mRNA. Translation: BAF84364.1 .
    DN996424 mRNA. No translation available.
    AC144652 Genomic DNA. No translation available.
    AC231970 Genomic DNA. No translation available.
    CH236962 Genomic DNA. Translation: EAL23729.1 .
    CH236962 Genomic DNA. Translation: EAL23730.1 .
    CH471149 Genomic DNA. Translation: EAX04529.1 .
    CH471149 Genomic DNA. Translation: EAX04530.1 .
    BC001880 mRNA. Translation: AAH01880.1 .
    CCDSi CCDS5938.1. [O15503-1 ]
    CCDS5939.1. [O15503-2 ]
    RefSeqi NP_005533.2. NM_005542.4. [O15503-1 ]
    NP_938150.2. NM_198336.2.
    NP_938151.1. NM_198337.2. [O15503-2 ]
    UniGenei Hs.520819.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4J81 X-ray 1.74 C/D 273-277 [» ]
    ProteinModelPortali O15503.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109850. 20 interactions.
    IntActi O15503. 5 interactions.
    MINTi MINT-4723340.
    STRINGi 9606.ENSP00000344741.

    PTM databases

    PhosphoSitei O15503.

    Proteomic databases

    PaxDbi O15503.
    PRIDEi O15503.

    Protocols and materials databases

    DNASUi 3638.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000340368 ; ENSP00000344741 ; ENSG00000186480 . [O15503-1 ]
    ENST00000342407 ; ENSP00000344035 ; ENSG00000186480 . [O15503-2 ]
    GeneIDi 3638.
    KEGGi hsa:3638.
    UCSCi uc003wly.3. human. [O15503-1 ]
    uc003wlz.3. human.

    Organism-specific databases

    CTDi 3638.
    GeneCardsi GC07P155089.
    HGNCi HGNC:6083. INSIG1.
    MIMi 602055. gene.
    neXtProti NX_O15503.
    PharmGKBi PA29890.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG263628.
    HOGENOMi HOG000253021.
    HOVERGENi HBG058958.
    OMAi AMSGPEP.
    OrthoDBi EOG7RNK13.
    PhylomeDBi O15503.
    TreeFami TF331013.

    Enzyme and pathway databases

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

    Miscellaneous databases

    ChiTaRSi INSIG1. human.
    GeneWikii INSIG1.
    GenomeRNAii 3638.
    NextBioi 14239.
    PROi O15503.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15503.
    Bgeei O15503.
    CleanExi HS_INSIG1.
    Genevestigatori O15503.

    Family and domain databases

    InterProi IPR009904. INSIG-1.
    IPR025929. INSIG_fam.
    [Graphical view ]
    PANTHERi PTHR15301:SF11. PTHR15301:SF11. 1 hit.
    Pfami PF07281. INSIG. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning, human chromosomal assignment, and adipose and hepatic expression of the CL-6/INSIG1 gene."
      Peng Y., Schwarz E.J., Lazar M.A., Genin A., Spinner N.B., Taub R.
      Genomics 43:278-284(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-27.
    2. "Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER."
      Yang T., Espenshade P.J., Wright M.E., Yabe D., Gong Y., Aebersold R., Goldstein J.L., Brown M.S.
      Cell 110:489-500(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 40-61 AND 64-83, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SCAP AND SREBP2 COMPLEX.
    3. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    4. "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] (ISOFORM 1).
      Tissue: Placenta.
    5. "High-throughput cloning of full-length human cDNAs directly from cDNA libraries optimized for large and rare transcripts."
      Birkett C., Cho J., Gau Y., Hamer R., Kelly S., Kovacs K., Liu L., Liu X., Porter J., Sachs A., Shu Y., Sun Z., Wong J., Wu M., Zhang X., Jay G., He W.
      Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Mammary tumor.
    6. "Human chromosome 7: DNA sequence and biology."
      Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
      , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
      Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "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] (ISOFORM 1).
      Tissue: Skin.
    9. "Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain."
      Sever N., Yang T., Brown M.S., Goldstein J.L., DeBose-Boyd R.A.
      Mol. Cell 11:25-33(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HMGCR, FUNCTION.
    10. "Membrane topology of human insig-1, a protein regulator of lipid synthesis."
      Feramisco J.D., Goldstein J.L., Brown M.S.
      J. Biol. Chem. 279:8487-8496(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY.
    11. "Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase."
      Song B.L., Sever N., DeBose-Boyd R.A.
      Mol. Cell 19:829-840(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AMFR, FUNCTION.
    12. "Sterol-regulated ubiquitination and degradation of Insig-1 creates a convergent mechanism for feedback control of cholesterol synthesis and uptake."
      Gong Y., Lee J.N., Lee P.C., Goldstein J.L., Brown M.S., Ye J.
      Cell Metab. 3:15-24(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH SCAP AND SREBP2 COMPLEX, UBIQUITINATION AT LYS-156 AND LYS-158, MUTAGENESIS OF LYS-156 AND LYS-158.
    13. "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-205.
    14. "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, UBIQUITINATION BY RNF139.

    Entry informationi

    Entry nameiINSI1_HUMAN
    AccessioniPrimary (citable) accession number: O15503
    Secondary accession number(s): A4D2N1
    , A8K6L0, Q53XW8, Q9BUV5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: October 3, 2006
    Last modified: October 1, 2014
    This is version 122 of the entry and version 3 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

    Expressed at high levels when nuclear SREBP levels are high as a result of sterol deprivation.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

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