INSM1_BOVIN
ID INSM1_BOVIN Reviewed; 522 AA.
AC A6H7J1;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 1.
DT 25-MAY-2022, entry version 83.
DE RecName: Full=Insulinoma-associated protein 1;
DE AltName: Full=Zinc finger protein IA-1;
GN Name=INSM1; Synonyms=IA1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal pons;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
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'. Promotes the generation and expansion of
CC neuronal basal progenitor cells in the developing neocortex. Involved
CC in the differentiation of endocrine cells of the developing anterior
CC pituitary gland, of the pancreas and intestine, and of sympatho-adrenal
CC cells in the peripheral nervous system. Promotes cell cycle signaling
CC arrest and inhibition of cellular proliferation.
CC {ECO:0000250|UniProtKB:Q01101}.
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. Interacts (via the SNAG domain)
CC with HDAC1. Interacts (via the SNAG domain) with HDAC2. Interacts (via
CC the SNAG domain) with KDM1A. Interacts (via the SNAG domain) with
CC RCOR1. Interacts with SORBS1. {ECO:0000250|UniProtKB:Q01101,
CC ECO:0000250|UniProtKB:Q63ZV0}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q63ZV0}.
CC -!- DOMAIN: The C-terminal region is necessary for NEUROD1 promoter DNA-
CC binding and transcriptional repressor activity. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the INSM1 family. {ECO:0000305}.
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DR EMBL; BC146266; AAI46267.1; -; mRNA.
DR RefSeq; NP_001094700.1; NM_001101230.1.
DR AlphaFoldDB; A6H7J1; -.
DR PaxDb; A6H7J1; -.
DR GeneID; 100137721; -.
DR KEGG; bta:100137721; -.
DR CTD; 3642; -.
DR eggNOG; KOG3993; Eukaryota.
DR InParanoid; A6H7J1; -.
DR OrthoDB; 1306883at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
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; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0061104; P:adrenal chromaffin cell differentiation; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0042421; P:norepinephrine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0003310; P:pancreatic A cell differentiation; ISS:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISS:UniProtKB.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; ISS: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; ISS:UniProtKB.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0061549; P:sympathetic ganglion development; ISS:UniProtKB.
DR GO; GO:0060290; P:transdifferentiation; ISS:UniProtKB.
DR GO; GO:0003309; P:type B pancreatic cell differentiation; ISS: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 2: Evidence at transcript 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..522
FT /note="Insulinoma-associated protein 1"
FT /id="PRO_0000331575"
FT ZN_FING 277..297
FT /note="C2H2-type 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 305..327
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 378..400
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 453..476
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 481..504
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..20
FT /note="SNAG domain"
FT /evidence="ECO:0000250|UniProtKB:Q63ZV0"
FT REGION 2..7
FT /note="Required and sufficient for interaction with KDM1A"
FT /evidence="ECO:0000250|UniProtKB:Q01101"
FT REGION 43..57
FT /note="Necessary for interaction with CCND1"
FT /evidence="ECO:0000250"
FT REGION 182..235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 325..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..61
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..210
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 522 AA; 53935 MW; C095C23457AB9963 CRC64;
MPRGFLVKRS KKSTPVSYRI RGGEDGDRAL LLLPGCGGAR ASPPAPGPGP VPGPLQPPPP
TERAHAALAA ALACAPGPPP PPPGLRAAHF GNPEAAHPAP LYSPTRPVSR EHEKHKYFER
SFNLGSPVSA ESFPTPAALL VGGGGGGGGG GANGAGGGGT CSGDPLLFAP AELKMGTAFS
AAAEAARGPG PGPPLPPAAA LRPPGKRPSP PASAAAAAEP PAKVAKAPGS KKPKAIRKLH
FEDEVTTSPV LGLKIKEGPV EAPRGRAGGA ARPLGEFICQ LCKEEYADPF ALAQHKCSRI
VRVEYRCPEC AKVFSCPANL ASHRRWHKPR PAPAAARACE PETPARAEAR EATGGGGSDR
DTPSPGGVSE SGSEDGLYEC HHCAKKFRRQ AYLRKHLLAH HQALQAKGAP PPAPPAEDLL
ALYPGPDEKV PQEAAGDGEA AGVLGLSASA ECHLCPVCGE TFPSKGAQER HLRLLHAAQV
FPCKYCPATF YSSPGLTRHI NKCHPSENRQ VILLQVPVRP AC
