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 27-MAR-2024, entry version 216. 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; Q15185: PTGES3; NbExp=2; IntAct=EBI-6427100, EBI-1049387; 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; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 16. DR IntAct; Q14190; 35. 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; 9606-ENSP00000290399; -. DR PeptideAtlas; Q14190; -. DR ProteomicsDB; 59911; -. [Q14190-1] DR ProteomicsDB; 59912; -. [Q14190-2] DR Antibodypedia; 23108; 195 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 AGR; HGNC:10883; -. DR DisGeNET; 6493; -. DR GeneCards; SIM2; -. DR HGNC; HGNC:10883; SIM2. DR HPA; ENSG00000159263; Group enriched (esophagus, kidney). 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; 5396877at2759; -. DR PhylomeDB; Q14190; -. DR TreeFam; TF317772; -. DR PathwayCommons; Q14190; -. DR SignaLink; Q14190; -. DR SIGNOR; Q14190; -. DR BioGRID-ORCS; 6493; 12 hits in 1149 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 cell types or tissues. DR ExpressionAtlas; Q14190; baseline and differential. 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; 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:SF19; SINGLE-MINDED HOMOLOG 2; 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; Q14190; HS. 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 //