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 24-JUL-2013, entry version 137. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS SIM2 AND SIM2S). RX PubMed=9199934; 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 RT SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome RT chromosomal 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., RA Shintani A., 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., RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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 RT syndrome chromosomal region."; RL DNA Res. 3:175-179(1996). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58; 87-152; 183-247 AND RP 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., RA Dufresne-Zacharia M.-C., Lopes C., Rabatel N., Gassanova-Maugenre S., RA Chettouh Z., Abramowski V., Fayet E., Yaspo M.-L., Korn B., RA Blouin J.-L., Lehrach H., Poustka A., Antonarakis S.E., Sinet P.-M., RA Creau N., Delabar J.-M.; RT "Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 RT involved 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., RA Decorte L., Sinet P.-M., Bloch B., Delabar J.-M.; RT "Down syndrome-critical region contains a gene homologous to RT Drosophila sim expressed during rat and human central nervous system RT 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 RT proteins SIM1 and SIM2."; RL Biochem. Biophys. Res. Commun. 313:482-488(2004). CC -!- FUNCTION: Transcription factor that may be a master gene of CNS CC development in cooperation with Arnt. It may have pleiotropic CC effects in the tissues expressed during development. CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another CC bHLH protein. Heterodimer of SIM2 and ARNT. CC -!- SUBCELLULAR LOCATION: Nucleus. 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 -!- SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. CC -!- SIMILARITY: Contains 1 PAC (PAS-associated C-terminal) domain. CC -!- SIMILARITY: Contains 2 PAS (PER-ARNT-SIM) domains. CC -!- SIMILARITY: Contains 1 Single-minded C-terminal domain. 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 IPI; IPI00029105; -. DR IPI; IPI00220895; -. DR PIR; A58520; A58520. DR PIR; I78525; I78525. DR PIR; I78526; I78526. DR RefSeq; NP_005060.1; NM_005069.3. DR RefSeq; NP_033664.2; NM_009586.2. DR UniGene; Hs.146186; -. DR ProteinModelPortal; Q14190; -. DR SMR; Q14190; 2-333. DR IntAct; Q14190; 1. DR MINT; MINT-7006105; -. DR STRING; 9606.ENSP00000290399; -. DR PhosphoSite; Q14190; -. DR DMDM; 2851630; -. DR PaxDb; Q14190; -. DR PRIDE; Q14190; -. DR Ensembl; ENST00000290399; ENSP00000290399; ENSG00000159263. DR Ensembl; ENST00000430056; ENSP00000404176; ENSG00000159263. DR GeneID; 6493; -. DR KEGG; hsa:6493; -. DR UCSC; uc002yvq.3; human. DR CTD; 6493; -. DR GeneCards; GC21P038071; -. DR HGNC; HGNC:10883; SIM2. DR HPA; HPA029295; -. DR MIM; 600892; gene. DR neXtProt; NX_Q14190; -. DR PharmGKB; PA35783; -. DR eggNOG; NOG310284; -. DR HOVERGEN; HBG003936; -. DR InParanoid; Q14190; -. DR KO; K09100; -. DR OMA; KKPMLPA; -. DR OrthoDB; EOG43N7CB; -. DR PhylomeDB; Q14190; -. DR GeneWiki; SIM2; -. DR GenomeRNAi; 6493; -. DR NextBio; 25235; -. DR Bgee; Q14190; -. DR CleanEx; HS_SIM2; -. DR Genevestigator; Q14190; -. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc. DR GO; GO:0004871; F:signal transducer activity; IEA:InterPro. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0009880; P:embryonic pattern specification; IEA:Compara. DR GO; GO:0030324; P:lung development; IEA:Compara. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR001610; PAC. DR InterPro; IPR000014; PAS. 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; SSF55785; SSF55785; 2. DR PROSITE; PS50888; BHLH; 1. DR PROSITE; PS50113; PAC; FALSE_NEG. DR PROSITE; PS50112; PAS; 2. DR PROSITE; PS51302; SIM_C; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Developmental protein; KW Differentiation; DNA-binding; Neurogenesis; Nucleus; Polymorphism; KW Reference proteome; Repeat; Transcription; Transcription regulation. FT CHAIN 1 667 Single-minded homolog 2. FT /FTId=PRO_0000127441. FT DOMAIN 1 53 bHLH. FT DOMAIN 77 149 PAS 1. FT DOMAIN 218 288 PAS 2. FT DOMAIN 292 335 PAC. FT DOMAIN 336 667 Single-minded C-terminal. FT MOTIF 367 386 Nuclear localization signal. FT VAR_SEQ 526 570 APAAAVRRFGEDTAPPSFPSCGHYREEPALGPAKAARQAAR FT DGAR -> GGSGLLVGKVGGLRTAGSRSSHGGGWQMETEPS FT RFGQTCPLSASK (in isoform SIM2S). FT /FTId=VSP_002148. FT VAR_SEQ 571 667 Missing (in isoform SIM2S). FT /FTId=VSP_012767. FT VARIANT 483 483 L -> M (in dbSNP:rs2073601). FT /FTId=VAR_024281. FT MUTAGEN 367 367 R->A,G: Reduced nuclear translocation. FT MUTAGEN 368 368 K->A: No effect on nuclear translocation. FT MUTAGEN 369 369 L->A: No effect on nuclear translocation. FT MUTAGEN 370 370 V->A: No effect on nuclear translocation. FT MUTAGEN 371 371 K->A: No effect on nuclear translocation. FT MUTAGEN 372 372 P->A: No effect on nuclear translocation. FT MUTAGEN 373 373 K->A,G: Reduced nuclear translocation. FT MUTAGEN 375 375 T->A: No effect on nuclear translocation. FT MUTAGEN 376 376 K->A: No effect on nuclear translocation. FT MUTAGEN 377 377 M->A: No effect on nuclear translocation. FT MUTAGEN 378 378 K->G: No effect on nuclear translocation. FT MUTAGEN 379 379 T->A: No effect on nuclear translocation. FT MUTAGEN 380 380 K->A: No effect on nuclear translocation. FT MUTAGEN 381 381 L->A: No effect on nuclear translocation. FT MUTAGEN 382 382 R->A: No effect on nuclear translocation. FT MUTAGEN 383 383 T->A: No effect on nuclear translocation. FT MUTAGEN 385 385 P->A: Reduced nuclear translocation. FT MUTAGEN 386 386 Y->A: Reduced nuclear translocation. FT CONFLICT 183 184 IH -> RI (in Ref. 7; BAA07909). FT CONFLICT 453 453 V -> F (in Ref. 8; AAB62397/CAA05055). FT CONFLICT 526 526 A -> G (in Ref. 8; AAB62397). 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 //