Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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

Keywordsi

Molecular functionDevelopmental protein, DNA-binding, Repressor
Biological processDifferentiation, Transcription, Transcription regulation

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
Proteomesi
  • UP000005640 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
  • nucleolus Source: HPA
  • nucleus Source: UniProtKB

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_072927109L → P in FFDD3. 1 Publication1
Ablepharon-macrostomia syndrome (AMS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital ectodermal dysplasia characterized by absent eyelids, macrostomia, microtia, redundant skin, sparse hair, dysmorphic nose and ears, variable abnormalities of the nipples, genitalia, fingers, and hands, largely normal intellectual and motor development, and poor growth.
See also OMIM:200110
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07467575E → K in AMS; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065049Ensembl.1
Barber-Say syndrome (BBRSAY)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare ectodermal dysplasia characterized by ectropion, macrostomia, ear abnormalities, broad nasal bridge, bulbous nose, redundant skin, hypertrichosis, dental abnormalities, and variable other features.
See also OMIM:209885
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07467475E → A in BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065048Ensembl.1
Natural variantiVAR_07467675E → Q in BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065049Ensembl.1
Natural variantiVAR_07467778R → RQR in BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 Publication1

Keywords - Diseasei

Disease mutation, Ectodermal dysplasia

Organism-specific databases

DisGeNETi117581.
MalaCardsiTWIST2.
MIMi200110. phenotype.
209885. phenotype.
227260. phenotype.
OpenTargetsiENSG00000233608.
Orphaneti1807. Focal facial dermal dysplasia type III.
PharmGKBiPA134973713.

Polymorphism and mutation databases

BioMutaiTWIST2.
DMDMi32699724.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001274891 – 160Twist-related protein 2Add BLAST160

Proteomic databases

PaxDbiQ8WVJ9.
PeptideAtlasiQ8WVJ9.
PRIDEiQ8WVJ9.

PTM databases

iPTMnetiQ8WVJ9.
PhosphoSitePlusiQ8WVJ9.

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

BgeeiENSG00000233608.
CleanExiHS_TWIST2.
ExpressionAtlasiQ8WVJ9. baseline and differential.
GenevisibleiQ8WVJ9. HS.

Organism-specific databases

HPAiHPA062870.

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi125591. 9 interactors.
IntActiQ8WVJ9. 9 interactors.
STRINGi9606.ENSP00000405176.

Structurei

3D structure databases

ProteinModelPortaliQ8WVJ9.
SMRiQ8WVJ9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini66 – 117bHLHPROSITE-ProRule annotationAdd BLAST52

Phylogenomic databases

eggNOGiKOG4447. Eukaryota.
ENOG4111QFU. LUCA.
GeneTreeiENSGT00760000119097.
HOGENOMiHOG000261629.
HOVERGENiHBG019071.
InParanoidiQ8WVJ9.
KOiK09069.
OMAiDNKMSSC.
OrthoDBiEOG091G07PB.
PhylomeDBiQ8WVJ9.
TreeFamiTF315153.

Family and domain databases

CDDicd00083. HLH. 1 hit.
Gene3Di4.10.280.10. 1 hit.
InterProiView protein in InterPro
IPR011598. bHLH_dom.
IPR015789. Twist-related.
PANTHERiPTHR23349:SF82. PTHR23349:SF82. 1 hit.
PfamiView protein in Pfam
PF00010. HLH. 1 hit.
SMARTiView protein in SMART
SM00353. HLH. 1 hit.
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiView protein in PROSITE
PS50888. BHLH. 1 hit.

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)DescriptionActionsGraphical viewLength
Sequence conflicti31R → L no nucleotide entry (PubMed:11062344).Curated1
Sequence conflicti109L → V no nucleotide entry (PubMed:11062344).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07467475E → A in BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065048Ensembl.1
Natural variantiVAR_07467575E → K in AMS; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065049Ensembl.1
Natural variantiVAR_07467675E → Q in BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065049Ensembl.1
Natural variantiVAR_07467778R → RQR in BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 Publication1
Natural variantiVAR_072927109L → P in FFDD3. 1 Publication1

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.
UniGeneiHs.422585.
Hs.745035.

Genome annotation databases

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

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 one 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.

Entry informationi

Entry nameiTWST2_HUMAN
AccessioniPrimary (citable) accession number: Q8WVJ9
Secondary accession number(s): Q3SYL6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 11, 2003
Last sequence update: March 1, 2002
Last modified: May 10, 2017
This is version 139 of the entry and version 1 of the sequence. See 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