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   24-JAN-2024, entry version 201.
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; Q9HBZ2: ARNT2; NbExp=3; IntAct=EBI-12808088, EBI-765971;
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; 5.
DR   IntAct; P81133; 1.
DR   STRING; 9606.ENSP00000358210; -.
DR   GlyGen; P81133; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P81133; -.
DR   PhosphoSitePlus; P81133; -.
DR   BioMuta; SIM1; -.
DR   DMDM; 109940166; -.
DR   MassIVE; P81133; -.
DR   PaxDb; 9606-ENSP00000358210; -.
DR   PeptideAtlas; P81133; -.
DR   ProteomicsDB; 57691; -.
DR   Antibodypedia; 899; 194 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   AGR; HGNC:10882; -.
DR   CTD; 6492; -.
DR   DisGeNET; 6492; -.
DR   GeneCards; SIM1; -.
DR   HGNC; HGNC:10882; SIM1.
DR   HPA; ENSG00000112246; Tissue enhanced (epididymis, 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; HQTVGDH; -.
DR   OrthoDB; 5396877at2759; -.
DR   PhylomeDB; P81133; -.
DR   TreeFam; TF317772; -.
DR   PathwayCommons; P81133; -.
DR   SignaLink; P81133; -.
DR   SIGNOR; P81133; -.
DR   BioGRID-ORCS; 6492; 9 hits in 1172 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 53 other cell types or tissues.
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; cd19738; bHLH-PAS_SIM1; 1.
DR   CDD; cd00130; PAS; 2.
DR   Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR   Gene3D; 3.30.450.20; PAS domain; 2.
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   PANTHER; PTHR23043; HYPOXIA-INDUCIBLE FACTOR 1 ALPHA; 1.
DR   PANTHER; PTHR23043:SF22; SINGLE-MINDED HOMOLOG 1; 1.
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; HLH, helix-loop-helix DNA-binding domain; 1.
DR   SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2.
DR   PROSITE; PS50888; BHLH; 1.
DR   PROSITE; PS50112; PAS; 2.
DR   PROSITE; PS51302; SIM_C; 1.
DR   Genevisible; P81133; HS.
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
//