ID SIM2_HUMAN STANDARD; PRT; 667 AA. AC Q14190; O60766; Q15470; Q15471; Q15472; Q15473; Q16532; DT 01-NOV-1997 (Rel. 35, Created) DT 15-JUL-1998 (Rel. 36, Last sequence update) DT 13-SEP-2005 (Rel. 48, Last annotation update) DE Single-minded homolog 2. GN Name=SIM2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS SIM2 AND SIM2S). RX MEDLINE=97343329; 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. 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 MEDLINE=20289799; 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 [GENOMIC DNA] OF 1-247. RX PubMed=8905236; 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 [5] RP NUCLEOTIDE SEQUENCE OF 1-58; 87-152; 183-247 AND 249-283. RX MEDLINE=95375794; PubMed=7647800; 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 64-526. RC TISSUE=Fetal brain, and Muscle; RX MEDLINE=98163741; 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 [7] RP NUCLEOTIDE SEQUENCE OF 87-116. RX MEDLINE=96016135; PubMed=7568099; 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 [8] RP NUCLEOTIDE SEQUENCE OF 154-181. RX MEDLINE=96299750; 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 [9] RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF RP NLS. 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: Nuclear. 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 basic helix-loop-helix (bHLH) 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; 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 PIR; A58520; A58520. DR PIR; I78525; I78525. DR PIR; I78526; I78526. DR TRANSFAC; T04910; -. DR Ensembl; ENSG00000159263; Homo sapiens. DR HGNC; HGNC:10883; SIM2. DR MIM; 600892; -. DR GO; GO:0003700; F:transcription factor activity; TAS. DR GO; GO:0007399; P:neurogenesis; TAS. DR InterPro; IPR001092; HLH_basic. DR InterPro; IPR001067; Nuc_translocat. DR InterPro; IPR001610; PAC. DR InterPro; IPR000014; PAS. DR InterPro; IPR000700; PAS-assoc_C. DR InterPro; IPR010578; SIM_C. DR Pfam; PF00010; HLH; 1. DR Pfam; PF00989; PAS; 1. DR Pfam; PF06621; SIM_C; 1. DR PRINTS; PR00785; NCTRNSLOCATR. DR SMART; SM00353; HLH; 1. DR SMART; SM00086; PAC; 1. DR SMART; SM00091; PAS; 2. DR PROSITE; PS50888; HLH; 1. DR PROSITE; PS50113; PAC; FALSE_NEG. DR PROSITE; PS50112; PAS; 2. KW Alternative splicing; Developmental protein; Differentiation; KW DNA-binding; Neurogenesis; Nuclear protein; Repeat; Transcription; KW Transcription regulation. FT DOMAIN 14 54 Helix-loop-helix motif. FT DOMAIN 77 149 PAS 1. FT DOMAIN 218 288 PAS 2. FT DOMAIN 292 335 PAC. FT DOMAIN 358 661 Single-minded C-terminal. FT DNA_BIND 1 13 Basic motif. FT MOTIF 367 386 Nuclear localization signal. FT VARSPLIC 526 570 APAAAVRRFGEDTAPPSFPSCGHYREEPALGPAKAARQAAR FT DGAR -> GGSGLLVGKVGGLRTAGSRSSHGGGWQMETEPS FT RFGQTCPLSASK (in isoform SIM2S). FT /FTId=VSP_002148. FT VARSPLIC 571 667 Missing (in isoform SIM2S). FT /FTId=VSP_012767. 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. 5; BAA07909). FT CONFLICT 453 453 V -> F (in Ref. 6). FT CONFLICT 483 483 L -> M (in Ref. 6). FT CONFLICT 526 526 A -> G (in Ref. 6). 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 //