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Q14190 (SIM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Single-minded homolog 2
Alternative name(s):
Class E basic helix-loop-helix protein 15
Short name=bHLHe15
Gene names
Name:SIM2
Synonyms:BHLHE15
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length667 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Nucleus Ref.11.

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 2 PAS (PER-ARNT-SIM) domains.

Contains 1 Single-minded C-terminal domain.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 667667Single-minded homolog 2
PRO_0000127441

Regions

Domain1 – 5353bHLH
Domain77 – 14973PAS 1
Domain218 – 28871PAS 2
Domain292 – 33544PAC
Domain336 – 667332Single-minded C-terminal
Motif367 – 38620Nuclear localization signal Ref.11

Natural variations

Alternative sequence526 – 57045APAAA…RDGAR → GGSGLLVGKVGGLRTAGSRS SHGGGWQMETEPSRFGQTCP LSASK in isoform SIM2S.
VSP_002148
Alternative sequence571 – 66797Missing in isoform SIM2S.
VSP_012767
Natural variant4831L → M. Ref.8
Corresponds to variant rs2073601 [ dbSNP | Ensembl ].
VAR_024281

Experimental info

Mutagenesis3671R → A or G: Reduced nuclear translocation. Ref.11
Mutagenesis3681K → A: No effect on nuclear translocation. Ref.11
Mutagenesis3691L → A: No effect on nuclear translocation. Ref.11
Mutagenesis3701V → A: No effect on nuclear translocation. Ref.11
Mutagenesis3711K → A: No effect on nuclear translocation. Ref.11
Mutagenesis3721P → A: No effect on nuclear translocation. Ref.11
Mutagenesis3731K → A or G: Reduced nuclear translocation. Ref.11
Mutagenesis3751T → A: No effect on nuclear translocation. Ref.11
Mutagenesis3761K → A: No effect on nuclear translocation. Ref.11
Mutagenesis3771M → A: No effect on nuclear translocation. Ref.11
Mutagenesis3781K → G: No effect on nuclear translocation. Ref.11
Mutagenesis3791T → A: No effect on nuclear translocation. Ref.11
Mutagenesis3801K → A: No effect on nuclear translocation. Ref.11
Mutagenesis3811L → A: No effect on nuclear translocation. Ref.11
Mutagenesis3821R → A: No effect on nuclear translocation. Ref.11
Mutagenesis3831T → A: No effect on nuclear translocation. Ref.11
Mutagenesis3851P → A: Reduced nuclear translocation. Ref.11
Mutagenesis3861Y → A: Reduced nuclear translocation. Ref.11
Sequence conflict183 – 1842IH → RI in BAA07909. Ref.7
Sequence conflict4531V → F in AAB62397. Ref.8
Sequence conflict4531V → F in CAA05055. Ref.8
Sequence conflict5261A → G in AAB62397. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform SIM2 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: A100880541A74E6B

FASTA66773,219
        10         20         30         40         50         60 
MKEKSKNAAK TRREKENGEF YELAKLLPLP SAITSQLDKA SIIRLTTSYL KMRAVFPEGL 

        70         80         90        100        110        120 
GDAWGQPSRA GPLDGVAKEL GSHLLQTLDG FVFVVASDGK IMYISETASV HLGLSQVELT 

       130        140        150        160        170        180 
GNSIYEYIHP SDHDEMTAVL TAHQPLHHHL LQEYEIERSF FLRMKCVLAK RNAGLTCSGY 

       190        200        210        220        230        240 
KVIHCSGYLK IRQYMLDMSL YDSCYQIVGL VAVGQSLPPS AITEIKLYSN MFMFRASLDL 

       250        260        270        280        290        300 
KLIFLDSRVT EVTGYEPQDL IEKTLYHHVH GCDVFHLRYA HHLLLVKGQV TTKYYRLLSK 

       310        320        330        340        350        360 
RGGWVWVQSY ATVVHNSRSS RPHCIVSVNY VLTEIEYKEL QLSLEQVSTA KSQDSWRTAL 

       370        380        390        400        410        420 
STSQETRKLV KPKNTKMKTK LRTNPYPPQQ YSSFQMDKLE CGQLGNWRAS PPASAAAPPE 

       430        440        450        460        470        480 
LQPHSESSDL LYTPSYSLPF SYHYGHFPLD SHVFSSKKPM LPAKFGQPQG SPCEVARFFL 

       490        500        510        520        530        540 
STLPASGECQ WHYANPLVPS SSSPAKNPPE PPANTARHSL VPSYEAPAAA VRRFGEDTAP 

       550        560        570        580        590        600 
PSFPSCGHYR EEPALGPAKA ARQAARDGAR LALARAAPEC CAPPTPEAPG APAQLPFVLL 

       610        620        630        640        650        660 
NYHRVLARRG PLGGAAPAAS GLACAPGGPE AATGALRLRH PSPAATSPPG APLPHYLGAS 


VIITNGR 

« Hide

Isoform SIM2S [UniParc].

Checksum: 8C68F4B8FD2823B0
Show »

FASTA57063,523

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] [Europe PMC] [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. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SIM2S).
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-247.
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58; 87-152; 183-247 AND 249-283.
[8]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 64-526, VARIANT MET-483.
Tissue: Fetal brain and Muscle.
[9]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 87-116.
[10]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 154-181.
[11]"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] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, MUTAGENESIS OF NUCLEAR LOCALIZATION SIGNAL.
[12]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CH471079 Genomic DNA. Translation: EAX09737.1.
BC110444 mRNA. Translation: AAI10445.1.
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.
CCDSCCDS13646.1. [Q14190-1]
CCDS46647.1. [Q14190-2]
PIRA58520.
I78525.
I78526.
RefSeqNP_005060.1. NM_005069.3. [Q14190-1]
NP_033664.2. NM_009586.2. [Q14190-2]
UniGeneHs.146186.

3D structure databases

ProteinModelPortalQ14190.
SMRQ14190. Positions 2-333.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112384. 7 interactions.
IntActQ14190. 2 interactions.
MINTMINT-7006105.
STRING9606.ENSP00000290399.

PTM databases

PhosphoSiteQ14190.

Polymorphism databases

DMDM2851630.

Proteomic databases

PaxDbQ14190.
PRIDEQ14190.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000290399; ENSP00000290399; ENSG00000159263. [Q14190-1]
ENST00000430056; ENSP00000404176; ENSG00000159263. [Q14190-2]
GeneID6493.
KEGGhsa:6493.
UCSCuc002yvq.3. human. [Q14190-2]
uc002yvr.2. human. [Q14190-1]

Organism-specific databases

CTD6493.
GeneCardsGC21P038071.
HGNCHGNC:10883. SIM2.
HPAHPA029295.
MIM600892. gene.
neXtProtNX_Q14190.
PharmGKBPA35783.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG310284.
HOVERGENHBG003936.
InParanoidQ14190.
KOK09100.
OMASDLLYAP.
OrthoDBEOG790G0R.
PhylomeDBQ14190.
TreeFamTF317772.

Gene expression databases

BgeeQ14190.
CleanExHS_SIM2.
GenevestigatorQ14190.

Family and domain databases

InterProIPR011598. bHLH_dom.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR013655. PAS_fold_3.
IPR010578. SIM_C.
[Graphical view]
PfamPF00989. PAS. 1 hit.
PF08447. PAS_3. 1 hit.
PF06621. SIM_C. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
PROSITEPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
PS51302. SIM_C. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSIM2.
GenomeRNAi6493.
NextBio25235.
PROQ14190.
SOURCESearch...

Entry information

Entry nameSIM2_HUMAN
AccessionPrimary (citable) accession number: Q14190
Secondary accession number(s): O60766 expand/collapse secondary AC list , Q15470, Q15471, Q15472, Q15473, Q16532, Q2TBD8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 15, 1998
Last modified: July 9, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM