INSM1_MOUSE
ID INSM1_MOUSE Reviewed; 521 AA.
AC Q63ZV0; Q9Z113;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Insulinoma-associated protein 1;
DE AltName: Full=Zinc finger protein IA-1;
GN Name=Insm1; Synonyms=Ia1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SORBS1, DEVELOPMENTAL STAGE,
RP AND SUBCELLULAR LOCATION.
RX PubMed=12079283; DOI=10.1006/geno.2002.6800;
RA Xie J., Cai T., Zhang H., Lan M.S., Notkins A.L.;
RT "The zinc-finger transcription factor INSM1 is expressed during embryo
RT development and interacts with the Cbl-associated protein.";
RL Genomics 80:54-61(2002).
RN [2]
RP DEVELOPMENTAL STAGE.
RX PubMed=12890672; DOI=10.1074/jbc.m306795200;
RA Breslin M.B., Zhu M., Lan M.S.;
RT "NeuroD1/E47 regulates the E-box element of a novel zinc finger
RT transcription factor, IA-1, in developing nervous system.";
RL J. Biol. Chem. 278:38991-38997(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=16511571; DOI=10.1038/sj.emboj.7601011;
RA Mellitzer G., Bonne S., Luco R.F., Van De Casteele M., Lenne-Samuel N.,
RA Collombat P., Mansouri A., Lee J., Lan M., Pipeleers D., Nielsen F.C.,
RA Ferrer J., Gradwohl G., Heimberg H.;
RT "IA1 is NGN3-dependent and essential for differentiation of the endocrine
RT pancreas.";
RL EMBO J. 25:1344-1352(2006).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=16951258; DOI=10.1101/gad.381806;
RA Gierl M.S., Karoulias N., Wende H., Strehle M., Birchmeier C.;
RT "The zinc-finger factor Insm1 (IA-1) is essential for the development of
RT pancreatic beta cells and intestinal endocrine cells.";
RL Genes Dev. 20:2465-2478(2006).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=18094025; DOI=10.1242/dev.011783;
RA Wildner H., Gierl M.S., Strehle M., Pla P., Birchmeier C.;
RT "Insm1 (IA-1) is a crucial component of the transcriptional network that
RT controls differentiation of the sympatho-adrenal lineage.";
RL Development 135:473-481(2008).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=18940587; DOI=10.1016/j.neuron.2008.09.020;
RA Farkas L.M., Haffner C., Giger T., Khaitovich P., Nowick K., Birchmeier C.,
RA Paabo S., Huttner W.B.;
RT "Insulinoma-associated 1 has a panneurogenic role and promotes the
RT generation and expansion of basal progenitors in the developing mouse
RT neocortex.";
RL Neuron 60:40-55(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INTERACTION WITH
RP HDAC1; HDAC2; KDM1A AND RCOR1, AND DOMAIN.
RX PubMed=24227653; DOI=10.1242/dev.097642;
RA Welcker J.E., Hernandez-Miranda L.R., Paul F.E., Jia S., Ivanov A.,
RA Selbach M., Birchmeier C.;
RT "Insm1 controls development of pituitary endocrine cells and requires a
RT SNAG domain for function and for recruitment of histone-modifying
RT factors.";
RL Development 140:4947-4958(2013).
CC -!- FUNCTION: Sequence-specific DNA-binding transcriptional regulator that
CC plays a key role in neurogenesis and neuroendocrine cell
CC differentiation during embryonic and/or fetal development. Binds to the
CC consensus sequence 5'-[TG][TC][TC][TT][GA]GGG[CG]A-3' in target
CC promoters. Acts as a transcriptional repressor of NEUROD1 and INS
CC expression via its interaction with cyclin CCND1 in a cell cycle-
CC independent manner. Negatively regulates skeletal muscle-specific gene
CC expression in endocrine cells of the pituitary by inhibiting the Notch
CC signaling pathway. Represses target gene transcription by recruiting
CC chromatin-modifying factors, such as HDAC1, HDAC2, HDAC3, KDM1A and
CC RCOR1 histone deacetylases. Binds to its own promoter, suggesting
CC autoregulation as a self-control feedback mechanism. Competes with
CC histone H3 for the same binding site on the histone demethylase complex
CC formed by KDM1A and RCOR1, and thereby inhibits demethylation of
CC histone H3 at 'Lys-4' (By similarity). Promotes the generation and
CC expansion of neuronal basal progenitor cells in the developing
CC neocortex. Involved in the differentiation of endocrine cells of the
CC developing anterior pituitary gland, of the pancreas and intestine, and
CC of sympatho-adrenal cells in the peripheral nervous system. Promotes
CC cell cycle signaling arrest and inhibition of cellular proliferation.
CC {ECO:0000250|UniProtKB:Q01101, ECO:0000269|PubMed:16511571,
CC ECO:0000269|PubMed:16951258, ECO:0000269|PubMed:18094025,
CC ECO:0000269|PubMed:18940587, ECO:0000269|PubMed:24227653}.
CC -!- SUBUNIT: Interacts (via the N-terminal region) with CCND1 (via cyclin
CC N-terminal domain); the interaction competes with the binding of CCND1
CC to CDK4 during cell cycle progression and increases its transcriptional
CC repressor activity. Interacts with HDAC3; the interaction increases its
CC transcriptional repressor activity (By similarity). Interacts (via the
CC SNAG domain) with HDAC1. Interacts (via the SNAG domain) with HDAC2.
CC Interacts (via the SNAG domain) with KDM1A. Interacts (via the SNAG
CC domain) with RCOR1. Interacts with SORBS1.
CC {ECO:0000250|UniProtKB:Q01101, ECO:0000269|PubMed:12079283,
CC ECO:0000269|PubMed:24227653}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12079283,
CC ECO:0000269|PubMed:24227653}.
CC -!- TISSUE SPECIFICITY: Expressed in adrenal gland. Expressed in the
CC dentate gyrus of the hippocampus and the wall of the lateral ventricle.
CC Expressed in pancreatic and intestinal endocrine cells.
CC {ECO:0000269|PubMed:16951258, ECO:0000269|PubMed:18094025,
CC ECO:0000269|PubMed:18940587}.
CC -!- DEVELOPMENTAL STAGE: Expressed in differentiating endocrine cells of
CC the anterior pituitary gland between 11.5 and 17.5 dpc. Expressed in
CC all hormone-secreting cell types of the pituitary gland. Expressed in
CC primary sympathetic ganglion chain, spinal cord and in neurons of the
CC dorsal root ganglia at 9.5 dpc. Expressed in chromaffin cells of the
CC adrenal medulla at 13.5 dpc (at protein level). Expressed in the
CC developing central nervous system (CNS). Expressed in midbrain-
CC hindbrain region at 9.5 dpc, in the spinal cord and telencephalon at 11
CC dpc. Expressed in the forebrain, midbrain, hind brain, spinal cord,
CC cerebellum, olfactory bulb and retina between 11.5 and 14.5 dpc.
CC Expressed in neural stem and progenitor cells of the developing
CC neocortex in both the ventricular zone (VZ) and in the adjacent
CC subventricular zone (SVZ), and in the external granule cell layer of
CC the developing cerebellum between 11 and 16.5 dpc. Expressed in neural
CC progenitor cells at the apical side of the VZ, collectively referred to
CC as apical basal cells (APs; neuroepithelial cells, radial glial cells
CC and short neural precursors) between 10.5 and 16.5 dpc. Expressed in
CC neural progenitor cells in the basal region of the VZ between 10.5 and
CC 16.5 dpc and at later stages in basal progenitor cells (BPs) of the
CC SVZ. Expressed in the cerebellum and pineal gland at 18.5 dpc.
CC Expressed in islet progenitor cells at 10.5 dpc. Expressed in endocrine
CC pancreatic cells, enteric nervous system, duodenum, stomach, thymus,
CC thyroid, adrenal glands at 15.5 dpc. {ECO:0000269|PubMed:12079283,
CC ECO:0000269|PubMed:12890672, ECO:0000269|PubMed:16511571,
CC ECO:0000269|PubMed:16951258, ECO:0000269|PubMed:18094025,
CC ECO:0000269|PubMed:18940587, ECO:0000269|PubMed:24227653}.
CC -!- DOMAIN: The C-terminal region is necessary for NEUROD1 promoter DNA-
CC binding and transcriptional repressor activity. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice die during the second half of gestation;
CC lethality is caused by heart failure due to insufficient catecholamine
CC synthesis. Display pancreatic, intestinal and sympatho-adrenal
CC endocrine cell development impairment. Exhibits fewer terminally
CC dividing neuronogenic basal progenitor cells (BPs) in the neocortex.
CC {ECO:0000269|PubMed:16951258, ECO:0000269|PubMed:18094025,
CC ECO:0000269|PubMed:18940587}.
CC -!- SIMILARITY: Belongs to the INSM1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD15718.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF044669; AAD15718.1; ALT_FRAME; mRNA.
DR EMBL; BC082809; AAH82809.1; -; mRNA.
DR CCDS; CCDS16830.1; -.
DR RefSeq; NP_058585.2; NM_016889.3.
DR AlphaFoldDB; Q63ZV0; -.
DR BioGRID; 207343; 2.
DR STRING; 10090.ENSMUSP00000092048; -.
DR iPTMnet; Q63ZV0; -.
DR PhosphoSitePlus; Q63ZV0; -.
DR MaxQB; Q63ZV0; -.
DR PaxDb; Q63ZV0; -.
DR PRIDE; Q63ZV0; -.
DR ProteomicsDB; 269066; -.
DR Antibodypedia; 9637; 85 antibodies from 24 providers.
DR DNASU; 53626; -.
DR Ensembl; ENSMUST00000089257; ENSMUSP00000092048; ENSMUSG00000068154.
DR GeneID; 53626; -.
DR KEGG; mmu:53626; -.
DR UCSC; uc008msh.2; mouse.
DR CTD; 3642; -.
DR MGI; MGI:1859980; Insm1.
DR VEuPathDB; HostDB:ENSMUSG00000068154; -.
DR eggNOG; KOG3993; Eukaryota.
DR GeneTree; ENSGT00940000162552; -.
DR HOGENOM; CLU_033476_1_0_1; -.
DR InParanoid; Q63ZV0; -.
DR OMA; REHEKHK; -.
DR OrthoDB; 1306883at2759; -.
DR PhylomeDB; Q63ZV0; -.
DR TreeFam; TF320538; -.
DR BioGRID-ORCS; 53626; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Insm1; mouse.
DR PRO; PR:Q63ZV0; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q63ZV0; protein.
DR Bgee; ENSMUSG00000068154; Expressed in medial ganglionic eminence and 143 other tissues.
DR ExpressionAtlas; Q63ZV0; baseline and differential.
DR Genevisible; Q63ZV0; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0061104; P:adrenal chromaffin cell differentiation; IMP:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0031018; P:endocrine pancreas development; IMP:MGI.
DR GO; GO:0035270; P:endocrine system development; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0003358; P:noradrenergic neuron development; IMP:UniProtKB.
DR GO; GO:0042421; P:norepinephrine biosynthetic process; IMP:UniProtKB.
DR GO; GO:0003310; P:pancreatic A cell differentiation; IDA:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IMP:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0010564; P:regulation of cell cycle process; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0061549; P:sympathetic ganglion development; IMP:UniProtKB.
DR GO; GO:0060290; P:transdifferentiation; ISS:UniProtKB.
DR GO; GO:0003323; P:type B pancreatic cell development; IMP:MGI.
DR GO; GO:0003309; P:type B pancreatic cell differentiation; IDA:UniProtKB.
DR InterPro; IPR042972; INSM1/2.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR15065; PTHR15065; 1.
DR Pfam; PF00096; zf-C2H2; 4.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Cell cycle; Developmental protein; Differentiation; DNA-binding;
KW Metal-binding; Neurogenesis; Nucleus; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..521
FT /note="Insulinoma-associated protein 1"
FT /id="PRO_0000047269"
FT ZN_FING 272..292
FT /note="C2H2-type 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 300..322
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 373..395
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 452..475
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 480..503
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..20
FT /note="SNAG domain"
FT /evidence="ECO:0000305|PubMed:24227653"
FT REGION 2..7
FT /note="Required and sufficient for interaction with KDM1A"
FT /evidence="ECO:0000250|UniProtKB:Q01101"
FT REGION 43..56
FT /note="Necessary for interaction with CCND1"
FT /evidence="ECO:0000250"
FT REGION 76..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 180..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 320..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..59
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..212
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..418
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 59
FT /note="L -> R (in Ref. 1; AAD15718)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="V -> L (in Ref. 1; AAD15718)"
FT /evidence="ECO:0000305"
FT CONFLICT 266
FT /note="T -> A (in Ref. 1; AAD15718)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="R -> G (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="S -> T (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="G -> R (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 431
FT /note="Q -> H (in Ref. 1; AAD15718)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="G -> S (in Ref. 1; AAD15718)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="S -> N (in Ref. 1; AAD15718)"
FT /evidence="ECO:0000305"
FT CONFLICT 454..456
FT /note="CPV -> FPL (in Ref. 1; AAD15718)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="S -> T (in Ref. 1; AAD15718)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 521 AA; 54050 MW; 84D0D8E64504D351 CRC64;
MPRGFLVKRS KKSTPVSYRV RGGEDSDRAL LLSPGCGGAR AEPPVPSPGP LPPPPPPALA
ERAHAALAAA LACAPGPPPP PPPGPRAAHF GNPEAAHPAP LYSPTRPVSR EHEKHKYFER
SFNLGSPVSA ESFPTPAALL AGGGSGANGA GGGGGGTCGG DALLFAPAEL KMGTAFSAGA
EAARGPGTGP PLSPAAALRP PGKRPAPPAA VATEPPAKAA KAPSAKKPKA IRKLHFEDEV
TTSPVLGLKI KEGPVEAPRG RAGGATRPLG EFICQLCKEE YADPFALAQH KCSRIVRVEY
RCPECAKVFS CPANLASHRR WHKPRPVPAA ARAPEPEAAT RAEAREAAGG GSSDRDTPSP
GGVSESGSED GLYECHHCAK KFRRQAYLRK HLLAHHQALQ AKGAPPPPPP PPPPAEDILA
FYAGPDEKAP QEASGDGEAA GVLGLSATAQ CHLCPVCGET FPSKGAQERH LRLLHAAQVF
PCKYCPATFY SSPGLTRHIN KCHPSENRQV ILLQVPVRPA C
