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Q8WVJ9 (TWST2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Twist-related protein 2
Alternative name(s):
Class A basic helix-loop-helix protein 39
Short name=bHLHa39
Dermis-expressed protein 1
Short name=Dermo-1
Gene names
Name:TWIST2
Synonyms:BHLHA39, DERMO1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length160 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds to the E-box consensus sequence 5'-CANNTG-3' as a heterodimer and inhibits transcriptional activation by MYOD1, MYOG, MEF2A and MEF2C. Also represses expression of proinflammatory cytokines such as TNFA and IL1B. Involved in postnatal glycogen storage and energy metabolism By similarity. Inhibits the premature or ectopic differentiation of preosteoblast cells during osteogenesis, possibly by changing the internal signal transduction response of osteoblasts to external growth factors. Ref.1 UniProtKB Q9D030

Subunit structure

Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with TCF3/E12. Also interacts with MEF2C By similarity. UniProtKB Q9D030

Subcellular location

Nucleus. Cytoplasm. Note: Mainly nuclear during embryonic development. Cytoplasmic in adult tissues. Ref.1

Tissue specificity

In the embryo, highly expressed in chondrogenic cells. In embryonic skin, expressed in the undifferentiated mesenchymal layer beneath the epidermis which later develops into the dermis. Expressed in early myeloid cells but not in lymphoid cells in the liver. Expression also detected in the secretory ependymal epithelium of the choroid plexus primordium. In the adult, expressed in secreting glandular tissues and tubules. Ref.1

Involvement in disease

Focal facial dermal dysplasia 3, Setleis type (FFDD3) [MIM:227260]: A form of focal facial dermal dysplasia, a group of developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFDD3 is characterized by distinctive bitemporal scar-like depressions resembling forceps marks, and additional facial features, including a coarse and leonine appearance, absent eyelashes on both lids or multiple rows on the upper lids, absent Meibomian glands, slanted eyebrows, chin clefting, and hypo- or hyperpigmentation of the skin. Histologically, the bitemporal lesion is an ectodermal dysplasia with near absence of subcutaneous fat, suggesting insufficient migration of neural crest cells into the frontonasal process and the first branchial arch.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Sequence similarities

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

Ontologies

Keywords
   Biological processDifferentiation
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DiseaseEctodermal dysplasia
   LigandDNA-binding
   Molecular functionDevelopmental protein
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcornea development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

embryonic cranial skeleton morphogenesis

Inferred from electronic annotation. Source: Ensembl

face morphogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of DNA binding

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of myeloid cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoblast differentiation

Inferred from direct assay Ref.1. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of keratinocyte proliferation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

nucleus

Inferred from direct assay Ref.1. Source: UniProtKB

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA polymerase II transcription factor binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

chromatin binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 18598946. Source: IntAct

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ETS2P150362EBI-1797313,EBI-1646991

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 160160Twist-related protein 2
PRO_0000127489

Regions

Domain66 – 11752bHLH

Experimental info

Sequence conflict311R → L no nucleotide entry Ref.1
Sequence conflict1091L → V no nucleotide entry Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q8WVJ9 [UniParc].

Last modified March 1, 2002. Version 1.
Checksum: 8F44750916940C0A

FASTA16018,124
        10         20         30         40         50         60 
MEEGSSSPVS PVDSLGTSEE ELERQPKRFG RKRRYSKKSS EDGSPTPGKR GKKGSPSAQS 

        70         80         90        100        110        120 
FEELQSQRIL ANVRERQRTQ SLNEAFAALR KIIPTLPSDK LSKIQTLKLA ARYIDFLYQV 

       130        140        150        160 
LQSDEMDNKM TSCSYVAHER LSYAFSVWRM EGAWSMSASH 

« Hide

References

« Hide 'large scale' references
[1]"Human Dermo-1 has attributes similar to twist in early bone development."
Lee M.S., Lowe G., Flanagan S., Kuchler K., Glackin C.A.
Bone 27:591-602(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Bone.
[2]"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].
Tissue: Brain, Lung and Pancreas.
[3]"Homozygous nonsense mutations in TWIST2 cause Setleis syndrome."
Tukel T., Sosic D., Al-Gazali L.I., Erazo M., Casasnovas J., Franco H.L., Richardson J.A., Olson E.N., Cadilla C.L., Desnick R.J.
Am. J. Hum. Genet. 87:289-296(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FFDD3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC017907 mRNA. Translation: AAH17907.1.
BC033168 mRNA. Translation: AAH33168.1.
BC103755 mRNA. Translation: AAI03756.1.
CCDSCCDS46558.1.
RefSeqNP_001258822.1. NM_001271893.3.
NP_476527.1. NM_057179.2.
XP_006712305.1. XM_006712242.1.
UniGeneHs.422585.
Hs.745035.

3D structure databases

ProteinModelPortalQ8WVJ9.
SMRQ8WVJ9. Positions 67-125.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125591. 4 interactions.
IntActQ8WVJ9. 2 interactions.

PTM databases

PhosphoSiteQ8WVJ9.

Polymorphism databases

DMDM32699724.

Proteomic databases

PaxDbQ8WVJ9.
PRIDEQ8WVJ9.

Protocols and materials databases

DNASU117581.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000448943; ENSP00000405176; ENSG00000233608.
GeneID117581.
KEGGhsa:117581.
UCSCuc010znx.2. human.

Organism-specific databases

CTD117581.
GeneCardsGC02P239757.
HGNCHGNC:20670. TWIST2.
MIM227260. phenotype.
607556. gene.
neXtProtNX_Q8WVJ9.
Orphanet79133. Focal facial dermal dysplasia type I.
PharmGKBPA134973713.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG258515.
HOGENOMHOG000261629.
HOVERGENHBG019071.
KOK09069.
OMADNKMSSC.
OrthoDBEOG7TJ3M9.
PhylomeDBQ8WVJ9.
TreeFamTF315153.

Gene expression databases

BgeeQ8WVJ9.
CleanExHS_TWIST2.
GenevestigatorQ8WVJ9.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
[Graphical view]
PfamPF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTWIST2.
GenomeRNAi117581.
NextBio80218.
PROQ8WVJ9.
SOURCESearch...

Entry information

Entry nameTWST2_HUMAN
AccessionPrimary (citable) accession number: Q8WVJ9
Secondary accession number(s): Q3SYL6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 11, 2003
Last sequence update: March 1, 2002
Last modified: July 9, 2014
This is version 114 of the entry and version 1 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 chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM