LOCUS       NM_005542               2908 bp    mRNA    linear   PRI 06-JUN-2024
DEFINITION  Homo sapiens insulin induced gene 1 (INSIG1), transcript variant 1,
            mRNA.
ACCESSION   NM_005542
VERSION     NM_005542.6
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2908)
  AUTHORS   Xiong,L., Liu,H.S., Zhou,C., Yang,X., Huang,L., Jie,H.Q.,
            Zeng,Z.W., Zheng,X.B., Li,W.X., Liu,Z.Z., Kang,L. and Liang,Z.X.
  TITLE     A novel protein encoded by circINSIG1 reprograms cholesterol
            metabolism by promoting the ubiquitin-dependent degradation of
            INSIG1 in colorectal cancer
  JOURNAL   Mol Cancer 22 (1), 72 (2023)
   PUBMED   37087475
  REMARK    GeneRIF: A novel protein encoded by circINSIG1 reprograms
            cholesterol metabolism by promoting the ubiquitin-dependent
            degradation of INSIG1 in colorectal cancer.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2908)
  AUTHORS   Watanabe,Y., Sasaki,T., Miyoshi,S., Shimizu,M., Yamauchi,Y. and
            Sato,R.
  TITLE     Insulin-induced genes INSIG1 and INSIG2 mediate oxysterol-dependent
            activation of the PERK-eIF2alpha-ATF4 axis
  JOURNAL   J Biol Chem 297 (2), 100989 (2021)
   PUBMED   34298014
  REMARK    GeneRIF: Insulin-induced genes INSIG1 and INSIG2 mediate
            oxysterol-dependent activation of the PERK-eIF2alpha-ATF4 axis.
REFERENCE   3  (bases 1 to 2908)
  AUTHORS   Ferri,F., Carotti,S., Carpino,G., Mischitelli,M., Cantafora,A.,
            Molinaro,A., Argenziano,M.E., Parisse,S., Corsi,A., Riminucci,M.,
            Lai,Q., Mennini,G., Spadetta,G., Pugliese,F., Rossi,M., Morini,S.,
            Gaudio,E. and Ginanni Corradini,S.
  TITLE     The Propensity of the Human Liver to Form Large Lipid Droplets Is
            Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1
            Expression and Increased Fibrogenetic Capacity
  JOURNAL   Int J Mol Sci 22 (11), 6100 (2021)
   PUBMED   34198853
  REMARK    GeneRIF: The Propensity of the Human Liver to Form Large Lipid
            Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and
            NPC1L1 Expression and Increased Fibrogenetic Capacity.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2908)
  AUTHORS   Azzu,V., Vacca,M., Kamzolas,I., Hall,Z., Leslie,J., Carobbio,S.,
            Virtue,S., Davies,S.E., Lukasik,A., Dale,M., Bohlooly-Y,M.,
            Acharjee,A., Linden,D., Bidault,G., Petsalaki,E., Griffin,J.L.,
            Oakley,F., Allison,M.E.D. and Vidal-Puig,A.
  TITLE     Suppression of insulin-induced gene 1 (INSIG1) function promotes
            hepatic lipid remodelling and restrains NASH progression
  JOURNAL   Mol Metab 48, 101210 (2021)
   PUBMED   33722690
  REMARK    GeneRIF: Suppression of insulin-induced gene 1 (INSIG1) function
            promotes hepatic lipid remodelling and restrains NASH progression.
REFERENCE   5  (bases 1 to 2908)
  AUTHORS   Dong,X.Y. and Tang,S.Q.
  TITLE     Insulin-induced gene: a new regulator in lipid metabolism
  JOURNAL   Peptides 31 (11), 2145-2150 (2010)
   PUBMED   20817058
  REMARK    Review article
REFERENCE   6  (bases 1 to 2908)
  AUTHORS   Janowski,B.A.
  TITLE     The hypocholesterolemic agent LY295427 up-regulates INSIG-1,
            identifying the INSIG-1 protein as a mediator of cholesterol
            homeostasis through SREBP
  JOURNAL   Proc Natl Acad Sci U S A 99 (20), 12675-12680 (2002)
   PUBMED   12242342
  REMARK    GeneRIF: INSIG-1 plays a role in regulating cholesterol
            concentration in human cells
REFERENCE   7  (bases 1 to 2908)
  AUTHORS   Yabe,D., Brown,M.S. and Goldstein,J.L.
  TITLE     Insig-2, a second endoplasmic reticulum protein that binds SCAP and
            blocks export of sterol regulatory element-binding proteins
  JOURNAL   Proc Natl Acad Sci U S A 99 (20), 12753-12758 (2002)
   PUBMED   12242332
REFERENCE   8  (bases 1 to 2908)
  AUTHORS   Yang,T., Espenshade,P.J., Wright,M.E., Yabe,D., Gong,Y.,
            Aebersold,R., Goldstein,J.L. and Brown,M.S.
  TITLE     Crucial step in cholesterol homeostasis: sterols promote binding of
            SCAP to INSIG-1, a membrane protein that facilitates retention of
            SREBPs in ER
  JOURNAL   Cell 110 (4), 489-500 (2002)
   PUBMED   12202038
REFERENCE   9  (bases 1 to 2908)
  AUTHORS   Kaneda,A., Kaminishi,M., Nakanishi,Y., Sugimura,T. and Ushijima,T.
  TITLE     Reduced expression of the insulin-induced protein 1 and p41 Arp2/3
            complex genes in human gastric cancers
  JOURNAL   Int J Cancer 100 (1), 57-62 (2002)
   PUBMED   12115587
  REMARK    GeneRIF: INSIG1 and p41 Arp2/3 complex (p41-Arc)reduced expression
            might be involved in gastric cancer development or progression
REFERENCE   10 (bases 1 to 2908)
  AUTHORS   Peng,Y., Schwarz,E.J., Lazar,M.A., Genin,A., Spinner,N.B. and
            Taub,R.
  TITLE     Cloning, human chromosomal assignment, and adipose and hepatic
            expression of the CL-6/INSIG1 gene
  JOURNAL   Genomics 43 (3), 278-284 (1997)
   PUBMED   9268630
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC001880.1, AK095977.1,
            AC231970.2 and BM995866.1.
            
            On Nov 23, 2018 this sequence version replaced NM_005542.5.
            
            Summary: This gene encodes an endoplasmic reticulum membrane
            protein that regulates cholesterol metabolism, lipogenesis, and
            glucose homeostasis. The encoded protein has six transmembrane
            helices which contain an effector protein binding site. It binds
            the sterol-sensing domains of sterol regulatory element-binding
            protein (SREBP) cleavage-activating protein (SCAP) and
            3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA
            reductase), and is essential for the sterol-mediated trafficking of
            these two proteins. It promotes the endoplasmic reticulum retention
            of SCAP and the ubiquitin-mediated degradation of HMG-CoA
            reductase. Alternative splicing results in multiple transcript
            variants. [provided by RefSeq, Oct 2016].
            
            Transcript Variant: This variant (1) encodes isoform 1. Variants 1
            and 6 encode the same protein.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660809.88902.1,
                                           SRR1803615.170569.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1966682, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000340368.9/ ENSP00000344741.4
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1422              BC001880.1         41-1462
            1423-1743           AK095977.1         803-1123
            1744-1744           AC231970.2         8546-8546           c
            1745-2881           AK095977.1         1125-2261
            2882-2908           BM995866.1         11-37               c
FEATURES             Location/Qualifiers
     source          1..2908
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q36.3"
     gene            1..2908
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /note="insulin induced gene 1"
                     /db_xref="GeneID:3638"
                     /db_xref="HGNC:HGNC:6083"
                     /db_xref="MIM:602055"
     exon            1..82
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /inference="alignment:Splign:2.1.0"
     exon            83..521
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /inference="alignment:Splign:2.1.0"
     CDS             110..943
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /note="isoform 1 is encoded by transcript variant 1;
                     INSIG-1 membrane protein; insulin-induced gene 1 protein"
                     /codon_start=1
                     /product="insulin-induced gene 1 protein isoform 1"
                     /protein_id="NP_005533.2"
                     /db_xref="CCDS:CCDS5938.1"
                     /db_xref="GeneID:3638"
                     /db_xref="HGNC:HGNC:6083"
                     /db_xref="MIM:602055"
                     /translation="MPRLHDHFWSCSCAHSARRRGPPRASAAGLAAKVGEMINVSVSG
                     PSLLAAHGAPDADPAPRGRSAAMSGPEPGSPYPNTWHHRLLQRSLVLFSVGVVLALVL
                     NLLQIQRNVTLFPEEVIATIFSSAWWVPPCCGTAAAVVGLLYPCIDSHLGEPHKFKRE
                     WASVMRCIAVFVGINHASAKLDFANNVQLSLTLAALSLGLWWTFDRSRSGLGLGITIA
                     FLATLITQFLVYNGVYQYTSPDFLYIRSWLPCIFFSGGVTVGNIGRQLAMGVPEKPHS
                     D"
     exon            522..646
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /inference="alignment:Splign:2.1.0"
     exon            647..813
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /inference="alignment:Splign:2.1.0"
     exon            814..913
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /inference="alignment:Splign:2.1.0"
     exon            914..2908
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2890..2895
                     /regulatory_class="polyA_signal_sequence"
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /note="hexamer: ATTAAA"
     polyA_site      2908
                     /gene="INSIG1"
                     /gene_synonym="CL6"
                     /note="major polyA site"
ORIGIN      
        1 gcggccgtcc cgggccgtga ctcctccttt cccccgcccc gcctccgttc ggagagccgg
       61 cgggcgggcg cctctcggcc aggaagcgcc tcttggacgc gtgtgaccga tgcccagatt
      121 gcacgaccac ttctggagct gctcctgtgc gcacagcgcg aggcgccgag gccccccgcg
      181 agccagcgcc gcggggctgg cggccaaggt tggggagatg atcaacgttt ccgtgtccgg
      241 gccctccctg ctggcggccc acggtgcccc ggacgctgac cccgcgccca ggggccgcag
      301 tgctgcgatg agcggccccg agcccggcag cccctacccc aacacctggc atcatcgcct
      361 gttgcagagg agcctcgtgc tcttctcggt tggggtggtc ctagccctgg tgctcaacct
      421 gctgcagatc cagaggaatg tcactctctt ccccgaggag gtgatcgcca ccatcttttc
      481 ctccgcctgg tgggtccctc cctgctgcgg gacagcagct gctgttgttg gcctactgta
      541 cccctgtatc gacagtcacc tcggagaacc ccacaaattt aagagagaat gggccagtgt
      601 catgcgctgc atagcagttt ttgttggcat taaccacgcc agtgctaaat tggattttgc
      661 caataatgtc cagctgtcct tgactttagc agccctatct ttgggccttt ggtggacatt
      721 tgatcgttcc agaagtggcc ttgggctggg gatcaccata gcttttctag ctacgctgat
      781 cacgcagttt ctcgtgtata atggtgtcta tcagtataca tccccagatt tcctctatat
      841 tcgttcttgg ctcccttgta tatttttctc aggaggcgtc acggtgggga acataggacg
      901 acagttagct atgggtgttc ctgaaaagcc ccatagtgat tgagtcttca aaaccaccga
      961 ttctgagagc aaggaagatt ttggaagaaa atctgactgt ggattatgac aaagattatc
     1021 ttttttctta agtaatctat ttagatcggg ctgactgtac aaatgactcc tggaaaaaac
     1081 tcttcaccta gtctagaata gggaggtgga gaatgatgac ttaccctgaa gtcttccctt
     1141 gactgcccgc actggcgcct gtctgtgccc tggagcattc tgcccaggct acgtgggttc
     1201 aggcaggtgg cagcttccca agtattcgat ttcattcatg tgattaaaac aagttgccat
     1261 atttcaaagc cttgaactaa gactcaatta ccaacccgca gttttgtgtc agtgcccaaa
     1321 ggaggtaggt tgatggtgct taacaaacat gaagtatggt gtaataggaa taatatttat
     1381 ccaaaagatt tttaaaaata gggctgtgtt taaaaaaaaa aacaaaacaa gaaaagcagc
     1441 agtgattata gagaggtcac actctaagtg gggtcgcggc gtggccacgc ttcacggtca
     1501 cgctcgtccg tcctgcagtg gcgtgtttac atggtcacac gtgtgtgtat caccagtggg
     1561 tcaactgctt gtcattcctc ccgtggcagt ttgtgtagac aatcttactg agcaaaaggc
     1621 aatgaaaagt cttggttccc acactgcgat atattggaat tttcacctca gtttatgaag
     1681 tttatttcga aatccatagt catctaagaa tgaatacctg tctgccatgt atttcaatct
     1741 tagtgagcca aaattgtttg tttgttacta cagaatagag atgactgttt tttgccacag
     1801 ccctatggaa tttgcaatct gtgattgcct tgtaaaaagg agagtgcata tggcactgca
     1861 ttaaacgtgt ggtgtttcta gtcaatgata ttggtgagca caatgtattc atttaatggc
     1921 atagaccata ccagacctaa tttgcaagta ttgggtctta aacttcaagt gcaatgtata
     1981 tgaaaaccaa tctgagcctt gtatctctta aatatttatt ttttttaacg tgtgagatgt
     2041 tcgagagaag gttctccatt catttcagtg ctgcctggag gaaactcggc aatgatttct
     2101 ttcagttgtg aagttccttt cgtgttacac cctccactga accctcaacc ttcgaaatac
     2161 tccagttttg tgggtttggt catttttact tataaattta cctttttgta ttttgcaatt
     2221 tacatgtgtt tggtttgttt taaattctgt gaaagtggct tgattaaaag actcctttta
     2281 aatggaagcc accagtcagc agaatggaag cttagaggaa cttgcctgtg agcgctggtc
     2341 tttgtgtttg gttttgtgat gtaacgatct ttgctggggt tttttgcttt gttttgaggg
     2401 aaatgtcttg gagtaaattt taagttcctg gagttaattt gttttacagg aattttgttt
     2461 tttaaaaaaa taggatcatt ctgaactttg gaatgacccc cttatatatt ttctgaaaat
     2521 gaaaacagtt acatgaaaaa aatttccaat gaagatgtca gcattttatg aaaaaccaga
     2581 agttattaga tgaaagcagc gagtgaatct ttaaaacaga cttgatcacg cacacacaat
     2641 aagtctttct ctccgaaacc ggaagtaaat ctatatctgt tagaaataat gtagccaaaa
     2701 gaatgtaaat ttgaggattt ttttgccaat agtttataga aaatatatga accaaagtga
     2761 tttgagtttg taaaaatgta aaatagtatg aacaaaattt gcactctacc agatttgaac
     2821 atctagtgag gttcacattc atactaagtt ttcaacattg tgttcttttt gcattcattt
     2881 tttactttta ttaaaggttc aaaaccaa
//
