Reviewed,
UniProtKB/Swiss-Prot Q14190 (SIM2_HUMAN)
Last modified
November 25, 2008.
Version 89.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Single-minded homolog 2 | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 667 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Transcription factor that may be a master gene of CNS development in cooperation with Arnt. It may have pleiotropic effects in the tissues expressed during development. |
| Subunit structure | Efficient DNA binding requires dimerization with another bHLH protein. Heterodimer of SIM2 and ARNT. |
| Subcellular location | |
| Sequence similarities | Contains 1 basic helix-loop-helix (bHLH) domain. Contains 1 PAC (PAS-associated C-terminal) domain. Contains 2 PAS (PER-ARNT-SIM) domains. Contains 1 Single-minded C-terminal domain. |
Ontologies
Keywords | |
|---|---|
| Biological process | Differentiation Neurogenesis Transcription Transcription regulation |
| Cellular component | Nucleus |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Repeat |
| Ligand | DNA-binding |
| Molecular function | Developmental protein |
Gene Ontology (GO) | |
| Biological process | cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW nervous system development Ref.1Traceable author statement. Source: ProtInc signal transductionInferred from electronic annotation. Source: InterPro |
| Cellular component | nucleus Inferred from electronic annotation. Source: InterPro |
| Molecular function | signal transducer activity Inferred from electronic annotation. Source: InterPro transcription factor activity Ref.1 Ref.8Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform SIM2 (identifier: Q14190-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform SIM2S (identifier: Q14190-2) The sequence of this isoform differs from the canonical sequence as follows: 526-570: APAAAVRRFG...ARQAARDGAR → GGSGLLVGKV...GQTCPLSASK 571-667: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 667 | 667 | Single-minded homolog 2 | PRO_0000127441 | |||||
Regions | |||||||||
| Domain | 14 – 54 | 41 | Helix-loop-helix motif | ||||||
| Domain | 77 – 149 | 73 | PAS 1 | ||||||
| Domain | 218 – 288 | 71 | PAS 2 | ||||||
| Domain | 292 – 335 | 44 | PAC | ||||||
| Domain | 336 – 667 | 332 | Single-minded C-terminal | ||||||
| DNA binding | 1 – 13 | 13 | Basic motif | ||||||
| Motif | 367 – 386 | 20 | Nuclear localization signal | ||||||
Natural variations | |||||||||
| Alternative sequence | 526 – 570 | 45 | APAAA…RDGAR → GGSGLLVGKVGGLRTAGSRS SHGGGWQMETEPSRFGQTCP LSASK in isoform SIM2S. | VSP_002148 | |||||
| Alternative sequence | 571 – 667 | 97 | Missing in isoform SIM2S. | VSP_012767 | |||||
| Natural variant | 483 | 1 | L → M: dbSNP rs2073601. | VAR_024281 | |||||
Experimental info | |||||||||
| Mutagenesis | 367 | 1 | R → A or G: Reduced nuclear translocation | ||||||
| Mutagenesis | 368 | 1 | K → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 369 | 1 | L → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 370 | 1 | V → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 371 | 1 | K → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 372 | 1 | P → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 373 | 1 | K → A or G: Reduced nuclear translocation | ||||||
| Mutagenesis | 375 | 1 | T → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 376 | 1 | K → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 377 | 1 | M → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 378 | 1 | K → G: No effect on nuclear translocation | ||||||
| Mutagenesis | 379 | 1 | T → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 380 | 1 | K → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 381 | 1 | L → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 382 | 1 | R → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 383 | 1 | T → A: No effect on nuclear translocation | ||||||
| Mutagenesis | 385 | 1 | P → A: Reduced nuclear translocation | ||||||
| Mutagenesis | 386 | 1 | Y → A: Reduced nuclear translocation | ||||||
| Sequence conflict | 183 – 184 | 2 | IH → RI in BAA07909. Ref.5 | ||||||
| Sequence conflict | 453 | 1 | V → F in AAB62397 and CAA05055. Ref.6 | ||||||
| Sequence conflict | 526 | 1 | A → G in AAB62397. Ref.6 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region." Chrast R., Scott H.S., Chen H., Kudoh J., Rossier C., Minoshima S., Wang Y., Shimizu N., Antonarakis S.E. Genome Res. 7:615-624(1997) [PubMed: 9199934] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS SIM2 AND SIM2S). |
| [2] | "Genomic sequencing of 1.2-Mb region on human chromosome 21q22.2." Shibuya K., Kudoh J., Minoshima S., Kawasaki K., Nakatoh E., Shintani A., Asakawa S., Shimizu N. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. Yaspo M.-L.Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "A 19-kb CpG island associated with single-minded gene 2 in Down syndrome chromosomal region." Osoegawa K., Okano S., Kato Y., Nishimura Y., Soeda E. DNA Res. 3:175-179(1996) [PubMed: 8905236] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-247. |
| [5] | "Single-minded and Down syndrome?" Chen H., Chrast R., Rossier C., Gos A., Antonarakis S.E., Kudoh J., Yamaki A., Shindoh N., Maeda H., Minoshima S., Shimizu N. Nat. Genet. 10:9-10(1995) [PubMed: 7647800] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58; 87-152; 183-247 AND 249-283. |
| [6] | "Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome." Dahmane N., Ait Ghezala G., Gosset P., Chamoun Z., Dufresne-Zacharia M.-C., Lopes C., Rabatel N., Gassanova-Maugenre S., Chettouh Z., Abramowski V., Fayet E., Yaspo M.-L., Korn B., Blouin J.-L., Lehrach H., Poustka A., Antonarakis S.E., Sinet P.-M., Creau N., Delabar J.-M. Genomics 48:12-23(1998) [PubMed: 9503011] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 64-526, VARIANT MET-483. Tissue: Fetal brain and Muscle. |
| [7] | "Down syndrome-critical region contains a gene homologous to Drosophila sim expressed during rat and human central nervous system development." Dahmane N., Charron G., Lopes C., Yaspo M.-L., Maunoury C., Decorte L., Sinet P.-M., Bloch B., Delabar J.-M. Proc. Natl. Acad. Sci. U.S.A. 92:9191-9195(1995) [PubMed: 7568099] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 87-116. |
| [8] | "The mammalian single-minded (SIM) gene: mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome." Yamaki A., Noda S., Kudoh J., Shindoh N., Maeda H., Minoshima S., Kawasaki K., Shimizu Y., Shimizu N. Genomics 35:136-143(1996) [PubMed: 8661114] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 154-181. |
| [9] | "A novel nuclear localization signal in the human single-minded proteins SIM1 and SIM2." Yamaki A., Kudoh J., Shimizu N., Shimizu Y. Biochem. Biophys. Res. Commun. 313:482-488(2004) [PubMed: 14697214] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, MUTAGENESIS OF NLS. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U80456 mRNA. Translation: AAB62396.1. U80457 mRNA. Translation: AAB62397.1. AB003185 Genomic DNA. Translation: BAA21489.1. AB003185 Genomic DNA. Translation: BAA21490.1. AP000697 Genomic DNA. Translation: BAA89433.1. AP001726 Genomic DNA. No translation available. D85922 Genomic DNA. Translation: BAA12919.1. D44444 Genomic DNA. Translation: BAA07906.1. D44445 Genomic DNA. Translation: BAA07907.1. D44446 Genomic DNA. Translation: BAA07908.1. D44447 Genomic DNA. Translation: BAA07909.1. D44448 Genomic DNA. Translation: BAA07910.1. AJ001858 mRNA. Translation: CAA05055.1. X84790 mRNA. Translation: CAA59261.1. D70838 Genomic DNA. Translation: BAA11108.1. | |
| PIR | A58520. I78525. I78526. |
| RefSeq | NP_005060.1. NP_033664.2. |
| UniGene | Hs.146186 |
3D structure databases | |
| ModBase | Search... |
Genome annotation databases | |
| Ensembl | ENSG00000159263. Homo sapiens. [Contig view] |
| GeneID | 6493. |
| KEGG | hsa:6493. |
Organism-specific databases | |
| H-InvDB | HIX0040884. |
| HGNC | HGNC:10883. SIM2. |
| MIM | 600892. gene. |
| PharmGKB | PA35783. |
| GenAtlas | Search... |
| GeneCards | Search... |
Phylogenomic databases | |
| HOVERGEN | Q14190. |
Gene expression databases | |
| CleanEx | HS_SIM2. |
| GermOnline | ENSG00000159263. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR001092. HLH_basic. IPR001067. Nuc_translocat. IPR001610. PAC. IPR000014. PAS. IPR000700. PAS-assoc_C. IPR013655. PAS_3. IPR013767. PAS_fold. IPR010578. SIM_C. [Graphical view] |
| Pfam | PF00010. HLH. 1 hit. PF00989. PAS. 1 hit. PF08447. PAS_3. 1 hit. PF06621. SIM_C. 1 hit. [Graphical view] |
| PRINTS | PR00785. NCTRNSLOCATR. |
| SMART | SM00353. HLH. 1 hit. SM00086. PAC. 1 hit. SM00091. PAS. 2 hits. [Graphical view] |
| PROSITE | PS50888. HLH. 1 hit. PS50113. PAC. False negative. PS50112. PAS. 2 hits. PS51302. SIM_C. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 25235. |
| SOURCE | Search... |
Entry information
| Entry name | SIM2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q14190 Secondary accession number(s): O60766 Q16532 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 21 Human chromosome 21: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| UniProtKB secondary accession numbers Index of UniProtKB secondary accession numbers |
| SIMILARITY comments Index of protein domains and families |

Clusters with


