SIM1_HUMAN
ID SIM1_HUMAN Reviewed; 766 AA.
AC P81133; Q5TDP7;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Single-minded homolog 1;
DE AltName: Full=Class E basic helix-loop-helix protein 14;
DE Short=bHLHe14;
GN Name=SIM1; Synonyms=BHLHE14;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9199934; DOI=10.1101/gr.7.6.615;
RA Chrast R., Scott H.S., Chen H., Kudoh J., Rossier C., Minoshima S.,
RA Wang Y., Shimizu N., Antonarakis S.E.;
RT "Cloning of two human homologs of the Drosophila single-minded gene SIM1 on
RT chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal
RT region.";
RL Genome Res. 7:615-624(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=14697214; DOI=10.1016/j.bbrc.2003.11.168;
RA Yamaki A., Kudoh J., Shimizu N., Shimizu Y.;
RT "A novel nuclear localization signal in the human single-minded proteins
RT SIM1 and SIM2.";
RL Biochem. Biophys. Res. Commun. 313:482-488(2004).
CC -!- FUNCTION: Transcriptional factor that may have pleiotropic effects
CC during embryogenesis and in the adult.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Heterodimer; forms a heterodimer with ARNT, ARNT2 (By
CC similarity). {ECO:0000250|UniProtKB:Q61045}.
CC -!- INTERACTION:
CC P81133; A0A087WVE9: ARNT2; NbExp=3; IntAct=EBI-12808088, EBI-12808086;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00632,
CC ECO:0000255|PROSITE-ProRule:PRU00981}.
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DR EMBL; U70212; AAB62395.1; -; mRNA.
DR EMBL; AL121948; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z86062; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS5045.1; -.
DR RefSeq; NP_005059.2; NM_005068.2.
DR RefSeq; XP_005267157.1; XM_005267100.2.
DR RefSeq; XP_016866686.1; XM_017011197.1.
DR AlphaFoldDB; P81133; -.
DR SMR; P81133; -.
DR BioGRID; 112383; 4.
DR IntAct; P81133; 1.
DR STRING; 9606.ENSP00000358210; -.
DR iPTMnet; P81133; -.
DR PhosphoSitePlus; P81133; -.
DR BioMuta; SIM1; -.
DR DMDM; 109940166; -.
DR MassIVE; P81133; -.
DR PaxDb; P81133; -.
DR PeptideAtlas; P81133; -.
DR PRIDE; P81133; -.
DR ProteomicsDB; 57691; -.
DR Antibodypedia; 899; 162 antibodies from 25 providers.
DR DNASU; 6492; -.
DR Ensembl; ENST00000262901.4; ENSP00000262901.4; ENSG00000112246.10.
DR Ensembl; ENST00000369208.8; ENSP00000358210.4; ENSG00000112246.10.
DR GeneID; 6492; -.
DR KEGG; hsa:6492; -.
DR MANE-Select; ENST00000369208.8; ENSP00000358210.4; NM_005068.3; NP_005059.2.
DR UCSC; uc063qgu.1; human.
DR CTD; 6492; -.
DR DisGeNET; 6492; -.
DR GeneCards; SIM1; -.
DR HGNC; HGNC:10882; SIM1.
DR HPA; ENSG00000112246; Tissue enhanced (brain, kidney, skeletal muscle).
DR MalaCards; SIM1; -.
DR MIM; 603128; gene.
DR neXtProt; NX_P81133; -.
DR OpenTargets; ENSG00000112246; -.
DR Orphanet; 171829; 6q16 microdeletion syndrome.
DR Orphanet; 369873; Obesity due to SIM1 deficiency.
DR Orphanet; 398079; SIM1-related Prader-Willi-like syndrome.
DR PharmGKB; PA35782; -.
DR VEuPathDB; HostDB:ENSG00000112246; -.
DR eggNOG; KOG3559; Eukaryota.
DR GeneTree; ENSGT00940000156143; -.
DR HOGENOM; CLU_010044_4_0_1; -.
DR InParanoid; P81133; -.
DR OMA; ANTSPCE; -.
DR OrthoDB; 231698at2759; -.
DR PhylomeDB; P81133; -.
DR TreeFam; TF317772; -.
DR PathwayCommons; P81133; -.
DR SignaLink; P81133; -.
DR SIGNOR; P81133; -.
DR BioGRID-ORCS; 6492; 8 hits in 1094 CRISPR screens.
DR ChiTaRS; SIM1; human.
DR GeneWiki; SIM1; -.
DR GenomeRNAi; 6492; -.
DR Pharos; P81133; Tbio.
DR PRO; PR:P81133; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P81133; protein.
DR Bgee; ENSG00000112246; Expressed in renal medulla and 51 other tissues.
DR Genevisible; P81133; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR InterPro; IPR013655; PAS_fold_3.
DR InterPro; IPR010578; SIM_C.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF08447; PAS_3; 1.
DR Pfam; PF06621; SIM_C; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
DR PROSITE; PS51302; SIM_C; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Neurogenesis; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation.
FT CHAIN 1..766
FT /note="Single-minded homolog 1"
FT /id="PRO_0000127439"
FT DOMAIN 1..53
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 77..147
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 218..288
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 292..335
FT /note="PAC"
FT DOMAIN 336..766
FT /note="Single-minded C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00632"
FT REGION 353..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 528..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 368..387
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 353..394
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 536..563
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 175
FT /note="L -> F (in dbSNP:rs438766)"
FT /id="VAR_049549"
FT VARIANT 352
FT /note="P -> T (in dbSNP:rs3734354)"
FT /id="VAR_034496"
FT VARIANT 371
FT /note="A -> V (in dbSNP:rs3734355)"
FT /id="VAR_034497"
FT CONFLICT 30
FT /note="P -> A (in Ref. 1; AAB62395)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="L -> V (in Ref. 1; AAB62395)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 766 AA; 85515 MW; 05988D428A84431F CRC64;
MKEKSKNAAR TRREKENSEF YELAKLLPLP SAITSQLDKA SIIRLTTSYL KMRVVFPEGL
GEAWGHSSRT SPLDNVGREL GSHLLQTLDG FIFVVAPDGK IMYISETASV HLGLSQVELT
GNSIYEYIHP ADHDEMTAVL TAHQPYHSHF VQEYEIERSF FLRMKCVLAK RNAGLTCGGY
KVIHCSGYLK IRQYSLDMSP FDGCYQNVGL VAVGHSLPPS AVTEIKLHSN MFMFRASLDM
KLIFLDSRVA ELTGYEPQDL IEKTLYHHVH GCDTFHLRCA HHLLLVKGQV TTKYYRFLAK
HGGWVWVQSY ATIVHNSRSS RPHCIVSVNY VLTDTEYKGL QLSLDQISAS KPAFSYTSSS
TPTMTDNRKG AKSRLSSSKS KSRTSPYPQY SGFHTERSES DHDSQWGGSP LTDTASPQLL
DPADRPGSQH DASCAYRQFS DRSSLCYGFA LDHSRLVEER HFHTQACEGG RCEAGRYFLG
TPQAGREPWW GSRAALPLTK ASPESREAYE NSMPHIASVH RIHGRGHWDE DSVVSSPDPG
SASESGDRYR TEQYQSSPHE PSKIETLIRA TQQMIKEEEN RLQLRKAPSD QLASINGAGK
KHSLCFANYQ QPPPTGEVCH GSALANTSPC DHIQQREGKM LSPHENDYDN SPTALSRISS
PNSDRISKSS LILAKDYLHS DISPHQTAGD HPTVSPNCFG SHRQYFDKHA YTLTGYALEH
LYDSETIRNY SLGCNGSHFD VTSHLRMQPD PAQGHKGTSV IITNGS
