Q14190 (SIM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	667 AA.
Sequence status	Complete.
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	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.

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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW embryonic pattern specification Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara nervous system development Traceable author statement Ref.1. Source: ProtInc transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay. Source: HPA
Molecular_function	DNA binding Traceable author statement Ref.10. Source: ProtInc sequence-specific DNA binding transcription factor activity Traceable author statement Ref.10Ref.1. Source: ProtInc signal transducer activity Inferred from electronic annotation. Source: InterPro
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	1 – 53	53	bHLH
	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
	Motif	367 – 386	20	Nuclear localization signal Ref.11
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. Ref.8 Corresponds to variant rs2073601 [ dbSNP | Ensembl ].		VAR_024281
Experimental info
	Mutagenesis	367	1	R → A or G: Reduced nuclear translocation. Ref.11
	Mutagenesis	368	1	K → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	369	1	L → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	370	1	V → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	371	1	K → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	372	1	P → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	373	1	K → A or G: Reduced nuclear translocation. Ref.11
	Mutagenesis	375	1	T → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	376	1	K → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	377	1	M → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	378	1	K → G: No effect on nuclear translocation. Ref.11
	Mutagenesis	379	1	T → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	380	1	K → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	381	1	L → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	382	1	R → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	383	1	T → A: No effect on nuclear translocation. Ref.11
	Mutagenesis	385	1	P → A: Reduced nuclear translocation. Ref.11
	Mutagenesis	386	1	Y → A: Reduced nuclear translocation. Ref.11
	Sequence conflict	183 – 184	2	IH → RI in BAA07909. Ref.7
	Sequence conflict	453	1	V → F in AAB62397. Ref.8
	Sequence conflict	453	1	V → F in CAA05055. Ref.8
	Sequence conflict	526	1	A → G in AAB62397. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform SIM2 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: A100880541A74E6B	FASTA	667	73,219
	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
	Isoform SIM2S [UniParc]. Checksum: 8C68F4B8FD2823B0	FASTA	570	63,523
	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 VPSYEGGSGL LVGKVGGLRT 550 560 570 AGSRSSHGGG WQMETEPSRF GQTCPLSASK

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
+	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.
IPI	IPI00029105. IPI00220895.
PIR	A58520. I78525. I78526.
RefSeq	NP_005060.1. NM_005069.3. NP_033664.2. NM_009586.2.
UniGene	Hs.146186.
3D structure databases
ProteinModelPortal	Q14190.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14190. 1 interaction.
STRING	9606.ENSP00000290399.
PTM databases
PhosphoSite	Q14190.
Polymorphism databases
DMDM	2851630.
Proteomic databases
PaxDb	Q14190.
PRIDE	Q14190.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000290399; ENSP00000290399; ENSG00000159263. ENST00000430056; ENSP00000404176; ENSG00000159263.
GeneID	6493.
KEGG	hsa:6493.
UCSC	uc002yvq.3. human. uc002yvr.2. human.
Organism-specific databases
CTD	6493.
GeneCards	GC21P038071.
HGNC	HGNC:10883. SIM2.
HPA	HPA029295.
MIM	600892. gene.
neXtProt	NX_Q14190.
PharmGKB	PA35783.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG310284.
HOVERGEN	HBG003936.
InParanoid	Q14190.
KO	K09100.
OMA	KKPMLPA.
OrthoDB	EOG43N7CB.
PhylomeDB	Q14190.
Gene expression databases
Bgee	Q14190.
CleanEx	HS_SIM2.
Genevestigator	Q14190.
GermOnline	ENSG00000159263. Homo sapiens.
Family and domain databases
InterPro	IPR011598. bHLH_dom. IPR001610. PAC. IPR000014. PAS. IPR013767. PAS_fold. IPR013655. PAS_fold_3. 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]
SMART	SM00353. HLH. 1 hit. SM00086. PAC. 1 hit. SM00091. PAS. 2 hits. [Graphical view]
PROSITE	PS50888. BHLH. 1 hit. PS50113. PAC. False negative. PS50112. PAS. 2 hits. PS51302. SIM_C. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6493.
NextBio	25235.
SOURCE	Search...

Entry information

Entry name

SIM2_HUMAN

Accession

Primary (citable) accession number: Q14190
Secondary accession number(s): O60766 , Q15470, Q15471, Q15472, Q15473, Q16532, Q2TBD8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 135 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.