SIM2_HUMAN
ID SIM2_HUMAN Reviewed; 667 AA.
AC Q14190; O60766; Q15470; Q15471; Q15472; Q15473; Q16532; Q2TBD8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Single-minded homolog 2;
DE AltName: Full=Class E basic helix-loop-helix protein 15;
DE Short=bHLHe15;
GN Name=SIM2; Synonyms=BHLHE15;
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 [GENOMIC DNA / MRNA] (ISOFORMS SIM2 AND SIM2S).
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 [GENOMIC DNA].
RA Shibuya K., Kudoh J., Minoshima S., Kawasaki K., Nakatoh E., Shintani A.,
RA Asakawa S., Shimizu N.;
RT "Genomic sequencing of 1.2-Mb region on human chromosome 21q22.2.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SIM2S).
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-247.
RX PubMed=8905236; DOI=10.1093/dnares/3.3.175;
RA Osoegawa K., Okano S., Kato Y., Nishimura Y., Soeda E.;
RT "A 19-kb CpG island associated with single-minded gene 2 in Down syndrome
RT chromosomal region.";
RL DNA Res. 3:175-179(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58; 87-152; 183-247 AND 249-283.
RX PubMed=7647800; DOI=10.1038/ng0595-9;
RA Chen H., Chrast R., Rossier C., Gos A., Antonarakis S.E., Kudoh J.,
RA Yamaki A., Shindoh N., Maeda H., Minoshima S., Shimizu N.;
RT "Single-minded and Down syndrome?";
RL Nat. Genet. 10:9-10(1995).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 64-526, AND VARIANT MET-483.
RC TISSUE=Fetal brain, and Muscle;
RX PubMed=9503011; DOI=10.1006/geno.1997.5146;
RA Dahmane N., Ait-Ghezala G., Gosset P., Chamoun Z., Dufresne-Zacharia M.-C.,
RA Lopes C., Rabatel N., Gassanova-Maugenre S., Chettouh Z., Abramowski V.,
RA Fayet E., Yaspo M.-L., Korn B., Blouin J.-L., Lehrach H., Poustka A.,
RA Antonarakis S.E., Sinet P.-M., Creau N., Delabar J.-M.;
RT "Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved
RT in Down syndrome.";
RL Genomics 48:12-23(1998).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 87-116.
RX PubMed=7568099; DOI=10.1073/pnas.92.20.9191;
RA Dahmane N., Charron G., Lopes C., Yaspo M.-L., Maunoury C., Decorte L.,
RA Sinet P.-M., Bloch B., Delabar J.-M.;
RT "Down syndrome-critical region contains a gene homologous to Drosophila sim
RT expressed during rat and human central nervous system development.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:9191-9195(1995).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 154-181.
RX PubMed=8661114; DOI=10.1006/geno.1996.0332;
RA Yamaki A., Noda S., Kudoh J., Shindoh N., Maeda H., Minoshima S.,
RA Kawasaki K., Shimizu Y., Shimizu N.;
RT "The mammalian single-minded (SIM) gene: mouse cDNA structure and
RT diencephalic expression indicate a candidate gene for Down syndrome.";
RL Genomics 35:136-143(1996).
RN [11]
RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF
RP 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).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Transcription factor that may be a master gene of CNS
CC development in cooperation with Arnt. It may have pleiotropic effects
CC in the tissues expressed during development.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Heterodimer of SIM2 and ARNT.
CC -!- INTERACTION:
CC Q14190-2; O60260-5: PRKN; NbExp=3; IntAct=EBI-21623725, EBI-21251460;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00632,
CC ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:14697214}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=SIM2;
CC IsoId=Q14190-1; Sequence=Displayed;
CC Name=SIM2S;
CC IsoId=Q14190-2; Sequence=VSP_002148, VSP_012767;
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DR EMBL; U80456; AAB62396.1; -; mRNA.
DR EMBL; U80457; AAB62397.1; -; mRNA.
DR EMBL; AB003185; BAA21489.1; -; Genomic_DNA.
DR EMBL; AB003185; BAA21490.1; -; Genomic_DNA.
DR EMBL; AP000697; BAA89433.1; -; Genomic_DNA.
DR EMBL; AP001726; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471079; EAX09737.1; -; Genomic_DNA.
DR EMBL; BC110444; AAI10445.1; -; mRNA.
DR EMBL; D85922; BAA12919.1; -; Genomic_DNA.
DR EMBL; D44444; BAA07906.1; -; Genomic_DNA.
DR EMBL; D44445; BAA07907.1; -; Genomic_DNA.
DR EMBL; D44446; BAA07908.1; -; Genomic_DNA.
DR EMBL; D44447; BAA07909.1; -; Genomic_DNA.
DR EMBL; D44448; BAA07910.1; -; Genomic_DNA.
DR EMBL; AJ001858; CAA05055.1; -; mRNA.
DR EMBL; X84790; CAA59261.1; -; mRNA.
DR EMBL; D70838; BAA11108.1; -; Genomic_DNA.
DR CCDS; CCDS13646.1; -. [Q14190-1]
DR PIR; A58520; A58520.
DR PIR; I78525; I78525.
DR PIR; I78526; I78526.
DR RefSeq; NP_005060.1; NM_005069.5. [Q14190-1]
DR RefSeq; NP_033664.2; NM_009586.4. [Q14190-2]
DR AlphaFoldDB; Q14190; -.
DR SMR; Q14190; -.
DR BioGRID; 112384; 15.
DR IntAct; Q14190; 31.
DR MINT; Q14190; -.
DR STRING; 9606.ENSP00000290399; -.
DR iPTMnet; Q14190; -.
DR PhosphoSitePlus; Q14190; -.
DR BioMuta; SIM2; -.
DR DMDM; 2851630; -.
DR MassIVE; Q14190; -.
DR MaxQB; Q14190; -.
DR PaxDb; Q14190; -.
DR PeptideAtlas; Q14190; -.
DR PRIDE; Q14190; -.
DR ProteomicsDB; 59911; -. [Q14190-1]
DR ProteomicsDB; 59912; -. [Q14190-2]
DR Antibodypedia; 23108; 176 antibodies from 30 providers.
DR DNASU; 6493; -.
DR Ensembl; ENST00000290399.11; ENSP00000290399.6; ENSG00000159263.16. [Q14190-1]
DR GeneID; 6493; -.
DR KEGG; hsa:6493; -.
DR MANE-Select; ENST00000290399.11; ENSP00000290399.6; NM_005069.6; NP_005060.1.
DR UCSC; uc002yvr.3; human. [Q14190-1]
DR CTD; 6493; -.
DR DisGeNET; 6493; -.
DR GeneCards; SIM2; -.
DR HGNC; HGNC:10883; SIM2.
DR HPA; ENSG00000159263; Tissue enhanced (esophagus, kidney, skeletal muscle).
DR MIM; 600892; gene.
DR neXtProt; NX_Q14190; -.
DR OpenTargets; ENSG00000159263; -.
DR PharmGKB; PA35783; -.
DR VEuPathDB; HostDB:ENSG00000159263; -.
DR eggNOG; KOG3559; Eukaryota.
DR GeneTree; ENSGT00940000159985; -.
DR HOGENOM; CLU_010044_4_1_1; -.
DR InParanoid; Q14190; -.
DR OMA; SECQWHY; -.
DR OrthoDB; 231698at2759; -.
DR PhylomeDB; Q14190; -.
DR TreeFam; TF317772; -.
DR PathwayCommons; Q14190; -.
DR SignaLink; Q14190; -.
DR SIGNOR; Q14190; -.
DR BioGRID-ORCS; 6493; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; SIM2; human.
DR GeneWiki; SIM2; -.
DR GenomeRNAi; 6493; -.
DR Pharos; Q14190; Tbio.
DR PRO; PR:Q14190; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q14190; protein.
DR Bgee; ENSG00000159263; Expressed in renal medulla and 100 other tissues.
DR ExpressionAtlas; Q14190; baseline and differential.
DR Genevisible; Q14190; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; IEA:Ensembl.
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:0009880; P:embryonic pattern specification; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
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 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; 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 Alternative splicing; Developmental protein; Differentiation; DNA-binding;
KW Neurogenesis; Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation.
FT CHAIN 1..667
FT /note="Single-minded homolog 2"
FT /id="PRO_0000127441"
FT DOMAIN 1..53
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 77..149
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..667
FT /note="Single-minded C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00632"
FT REGION 356..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 409..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 367..386
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:14697214"
FT VAR_SEQ 526..570
FT /note="APAAAVRRFGEDTAPPSFPSCGHYREEPALGPAKAARQAARDGAR -> GGS
FT GLLVGKVGGLRTAGSRSSHGGGWQMETEPSRFGQTCPLSASK (in isoform
FT SIM2S)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9199934"
FT /id="VSP_002148"
FT VAR_SEQ 571..667
FT /note="Missing (in isoform SIM2S)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9199934"
FT /id="VSP_012767"
FT VARIANT 483
FT /note="L -> M (in dbSNP:rs2073601)"
FT /evidence="ECO:0000269|PubMed:9503011"
FT /id="VAR_024281"
FT MUTAGEN 367
FT /note="R->A,G: Reduced nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 368
FT /note="K->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 369
FT /note="L->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 370
FT /note="V->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 371
FT /note="K->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 372
FT /note="P->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 373
FT /note="K->A,G: Reduced nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 375
FT /note="T->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 376
FT /note="K->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 377
FT /note="M->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 378
FT /note="K->G: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 379
FT /note="T->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 380
FT /note="K->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 381
FT /note="L->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 382
FT /note="R->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 383
FT /note="T->A: No effect on nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 385
FT /note="P->A: Reduced nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT MUTAGEN 386
FT /note="Y->A: Reduced nuclear translocation."
FT /evidence="ECO:0000269|PubMed:14697214"
FT CONFLICT 183..184
FT /note="IH -> RI (in Ref. 7; BAA07909)"
FT /evidence="ECO:0000305"
FT CONFLICT 453
FT /note="V -> F (in Ref. 8; AAB62397/CAA05055)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="A -> G (in Ref. 8; AAB62397)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 667 AA; 73219 MW; A100880541A74E6B CRC64;
MKEKSKNAAK TRREKENGEF YELAKLLPLP SAITSQLDKA SIIRLTTSYL KMRAVFPEGL
GDAWGQPSRA GPLDGVAKEL GSHLLQTLDG FVFVVASDGK IMYISETASV HLGLSQVELT
GNSIYEYIHP SDHDEMTAVL TAHQPLHHHL LQEYEIERSF FLRMKCVLAK RNAGLTCSGY
KVIHCSGYLK IRQYMLDMSL YDSCYQIVGL VAVGQSLPPS AITEIKLYSN MFMFRASLDL
KLIFLDSRVT EVTGYEPQDL IEKTLYHHVH GCDVFHLRYA HHLLLVKGQV TTKYYRLLSK
RGGWVWVQSY ATVVHNSRSS RPHCIVSVNY VLTEIEYKEL QLSLEQVSTA KSQDSWRTAL
STSQETRKLV KPKNTKMKTK LRTNPYPPQQ YSSFQMDKLE CGQLGNWRAS PPASAAAPPE
LQPHSESSDL LYTPSYSLPF SYHYGHFPLD SHVFSSKKPM LPAKFGQPQG SPCEVARFFL
STLPASGECQ WHYANPLVPS SSSPAKNPPE PPANTARHSL VPSYEAPAAA VRRFGEDTAP
PSFPSCGHYR EEPALGPAKA ARQAARDGAR LALARAAPEC CAPPTPEAPG APAQLPFVLL
NYHRVLARRG PLGGAAPAAS GLACAPGGPE AATGALRLRH PSPAATSPPG APLPHYLGAS
VIITNGR
