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Protein

Twist-related protein 2

Gene

TWIST2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:TWIST2
Synonyms:BHLHA39, DERMO1
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:20670. TWIST2.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication
  • Cytoplasm 1 Publication

  • Note: Mainly nuclear during embryonic development. Cytoplasmic in adult tissues.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • transcription factor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Focal facial dermal dysplasia 3, Setleis type (FFDD3)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:227260
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti109 – 1091L → P in FFDD3. 1 Publication
VAR_072927

Keywords - Diseasei

Disease mutation, Ectodermal dysplasia

Organism-specific databases

MIMi227260. phenotype.
Orphaneti1807. Focal facial dermal dysplasia type III.
PharmGKBiPA134973713.

Polymorphism and mutation databases

BioMutaiTWIST2.
DMDMi32699724.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 160160Twist-related protein 2PRO_0000127489Add
BLAST

Proteomic databases

PaxDbiQ8WVJ9.
PRIDEiQ8WVJ9.

PTM databases

PhosphoSiteiQ8WVJ9.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiQ8WVJ9.
CleanExiHS_TWIST2.
ExpressionAtlasiQ8WVJ9. baseline and differential.
GenevisibleiQ8WVJ9. HS.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
CCM2Q9BSQ53EBI-1797313,EBI-1573056
ETS2P150362EBI-1797313,EBI-1646991
TCF12Q990813EBI-1797313,EBI-722877
TCF4P158843EBI-1797313,EBI-533224

Protein-protein interaction databases

BioGridi125591. 6 interactions.
IntActiQ8WVJ9. 7 interactions.
STRINGi9606.ENSP00000405176.

Structurei

3D structure databases

ProteinModelPortaliQ8WVJ9.
SMRiQ8WVJ9. Positions 67-125.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini66 – 11752bHLHPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG258515.
GeneTreeiENSGT00760000119097.
HOGENOMiHOG000261629.
HOVERGENiHBG019071.
InParanoidiQ8WVJ9.
KOiK09069.
OMAiDNKMSSC.
OrthoDBiEOG7TJ3M9.
PhylomeDBiQ8WVJ9.
TreeFamiTF315153.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8WVJ9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEEGSSSPVS PVDSLGTSEE ELERQPKRFG RKRRYSKKSS EDGSPTPGKR
60 70 80 90 100
GKKGSPSAQS FEELQSQRIL ANVRERQRTQ SLNEAFAALR KIIPTLPSDK
110 120 130 140 150
LSKIQTLKLA ARYIDFLYQV LQSDEMDNKM TSCSYVAHER LSYAFSVWRM
160
EGAWSMSASH
Length:160
Mass (Da):18,124
Last modified:March 1, 2002 - v1
Checksum:i8F44750916940C0A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti31 – 311R → L no nucleotide entry (PubMed:11062344).Curated
Sequence conflicti109 – 1091L → V no nucleotide entry (PubMed:11062344).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti109 – 1091L → P in FFDD3. 1 Publication
VAR_072927

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC017907 mRNA. Translation: AAH17907.1.
BC033168 mRNA. Translation: AAH33168.1.
BC103755 mRNA. Translation: AAI03756.1.
CCDSiCCDS46558.1.
RefSeqiNP_001258822.1. NM_001271893.3.
NP_476527.1. NM_057179.2.
XP_006712305.1. XM_006712242.2.
UniGeneiHs.422585.
Hs.745035.

Genome annotation databases

EnsembliENST00000448943; ENSP00000405176; ENSG00000233608.
ENST00000612363; ENSP00000482581; ENSG00000233608.
GeneIDi117581.
KEGGihsa:117581.
UCSCiuc010znx.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC017907 mRNA. Translation: AAH17907.1.
BC033168 mRNA. Translation: AAH33168.1.
BC103755 mRNA. Translation: AAI03756.1.
CCDSiCCDS46558.1.
RefSeqiNP_001258822.1. NM_001271893.3.
NP_476527.1. NM_057179.2.
XP_006712305.1. XM_006712242.2.
UniGeneiHs.422585.
Hs.745035.

3D structure databases

ProteinModelPortaliQ8WVJ9.
SMRiQ8WVJ9. Positions 67-125.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125591. 6 interactions.
IntActiQ8WVJ9. 7 interactions.
STRINGi9606.ENSP00000405176.

PTM databases

PhosphoSiteiQ8WVJ9.

Polymorphism and mutation databases

BioMutaiTWIST2.
DMDMi32699724.

Proteomic databases

PaxDbiQ8WVJ9.
PRIDEiQ8WVJ9.

Protocols and materials databases

DNASUi117581.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000448943; ENSP00000405176; ENSG00000233608.
ENST00000612363; ENSP00000482581; ENSG00000233608.
GeneIDi117581.
KEGGihsa:117581.
UCSCiuc010znx.2. human.

Organism-specific databases

CTDi117581.
GeneCardsiGC02P239757.
HGNCiHGNC:20670. TWIST2.
MIMi227260. phenotype.
607556. gene.
neXtProtiNX_Q8WVJ9.
Orphaneti1807. Focal facial dermal dysplasia type III.
PharmGKBiPA134973713.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG258515.
GeneTreeiENSGT00760000119097.
HOGENOMiHOG000261629.
HOVERGENiHBG019071.
InParanoidiQ8WVJ9.
KOiK09069.
OMAiDNKMSSC.
OrthoDBiEOG7TJ3M9.
PhylomeDBiQ8WVJ9.
TreeFamiTF315153.

Miscellaneous databases

GeneWikiiTWIST2.
GenomeRNAii117581.
NextBioi80218.
PROiQ8WVJ9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8WVJ9.
CleanExiHS_TWIST2.
ExpressionAtlasiQ8WVJ9. baseline and differential.
GenevisibleiQ8WVJ9. HS.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: Bone1 Publication.
  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: BrainImported, LungImported and Pancreas.
  3. Cited for: INVOLVEMENT IN FFDD3.
  4. "Setleis syndrome: clinical, molecular and structural studies of the first TWIST2 missense mutation."
    Rosti R.O., Uyguner Z.O., Nazarenko I., Bekerecioglu M., Cadilla C.L., Ozgur H., Lee B.H., Aggarwal A.K., Pehlivan S., Desnick R.J.
    Clin. Genet. 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT FFDD3 PRO-109.

Entry informationi

Entry nameiTWST2_HUMAN
AccessioniPrimary (citable) accession number: Q8WVJ9
Secondary accession number(s): Q3SYL6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2003
Last sequence update: March 1, 2002
Last modified: July 22, 2015
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.