TWIST2

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

DNA binding Source: UniProtKB-KW
protein dimerization activity Source: InterPro

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cell differentiation Source: UniProtKB-KW
multicellular organism development Source: UniProtKB-KW
negative regulation of apoptotic process Source: Ensembl
negative regulation of osteoblast differentiation
Source: UniProtKB
Inferred from direct assayⁱ
- 11062344
negative regulation of transcription, DNA-templated Source: UniProtKB
positive regulation of cell migration
Source: BHF-UCL
Inferred from genetic interactionⁱ
- 24171926

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Developmental protein, DNA-binding, Repressor
Biological process	Differentiation, Transcription, Transcription regulation

Enzyme and pathway databases

Reactomeⁱ	R-HSA-8878166 Transcriptional regulation by RUNX2
SIGNORⁱ	Q8WVJ9

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
Organismⁱ	Homo sapiens (Human)Imported
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 2

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000233608.3
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:20670 TWIST2
MIMⁱ	607556 gene
neXtProtⁱ	NX_Q8WVJ9

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.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_072927	109	L → P in FFDD3. 1 Publication		1

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.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_074675	75	E → K in AMS; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065049EnsemblClinVar.		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.

Keywords - Diseaseⁱ

Disease mutation, Ectodermal dysplasia

Organism-specific databases

DisGeNET More...DisGeNETⁱ	117581
MalaCards human disease database More...MalaCardsⁱ	TWIST2
MIMⁱ	200110 phenotype 209885 phenotype 227260 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000233608
Orphanetⁱ	920 Ablepharon macrostomia syndrome 1231 Barber-Say syndrome 1807 Focal facial dermal dysplasia type III
PharmGKBⁱ	PA134973713

Polymorphism and mutation databases

BioMutaⁱ	TWIST2
DMDMⁱ	32699724

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000127489	1 – 160	Twist-related protein 2Add BLAST		160

Proteomic databases

PaxDbⁱ	Q8WVJ9
PeptideAtlas More...PeptideAtlasⁱ	Q8WVJ9
PRIDEⁱ	Q8WVJ9
ProteomicsDBⁱ	74799

PTM databases

iPTMnetⁱ	Q8WVJ9
PhosphoSitePlusⁱ	Q8WVJ9

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

Bgeeⁱ	ENSG00000233608 Expressed in 140 organ(s), highest expression level in endocervix
CleanExⁱ	HS_TWIST2
ExpressionAtlasⁱ	Q8WVJ9 baseline and differential
Genevisibleⁱ	Q8WVJ9 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA062870

HPAⁱ

HPA062870

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

With	Entry	#Exp.	IntAct
CCM2	Q9BSQ5	3	EBI-1797313,EBI-1573056
ETS2	P15036	2	EBI-1797313,EBI-1646991
TCF12	Q99081	3	EBI-1797313,EBI-722877
TCF4	P15884	3	EBI-1797313,EBI-533224

GO - Molecular functionⁱ

protein dimerization activity Source: InterPro

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	125591, 10 interactors
IntActⁱ	Q8WVJ9, 9 interactors
STRINGⁱ	9606.ENSP00000405176

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q8WVJ9
SMRⁱ	Q8WVJ9
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	66 – 117	bHLHPROSITE-ProRule annotationAdd BLAST		52

Phylogenomic databases

eggNOGⁱ	KOG4447 Eukaryota ENOG4111QFU LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119097
HOGENOMⁱ	HOG000261629
HOVERGENⁱ	HBG019071
InParanoidⁱ	Q8WVJ9
KEGG Orthology (KO) More...KOⁱ	K09069
OMAⁱ	DNKMSSC
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G07PB
PhylomeDBⁱ	Q8WVJ9
TreeFamⁱ	TF315153

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00010 HLH, 1 hit
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit
SUPFAMⁱ	SSF47459 SSF47459, 1 hit
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Q8WVJ9-1 [UniParc]FASTA Add 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 key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	31	R → L no nucleotide entry (PubMed:11062344).Curated		1
Sequence conflictⁱ	109	L → V no nucleotide entry (PubMed:11062344).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_074674	75	E → A in BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065048EnsemblClinVar.	1
Natural variantⁱVAR_074675	75	E → K in AMS; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065049EnsemblClinVar.	1
Natural variantⁱVAR_074676	75	E → Q in BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs796065049EnsemblClinVar.	1
Natural variantⁱVAR_074677	78	R → RQR in BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type. 1 Publication	1
Natural variantⁱVAR_072927	109	L → P in FFDD3. 1 Publication	1

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS46558.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001258822.1, NM_001271893.3 NP_476527.1, NM_057179.2
UniGeneⁱ	Hs.422585 Hs.745035

Genome annotation databases

Ensemblⁱ	ENST00000448943; ENSP00000405176; ENSG00000233608 ENST00000612363; ENSP00000482581; ENSG00000233608
GeneIDⁱ	117581
KEGGⁱ	hsa:117581
UCSC genome browser More...UCSCⁱ	uc010znx.2 human

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q8WVJ9	Twist-related protein 2		RAT		160	UniRef100_Q8WVJ9
Uncharacterized protein		SHEEP		161
Twist homolog 2 (Drosophila), isoform CRA_a		HUMAN		160
TWIST2 isoform 1		PANTR		160
twist-related protein 2		TARSY		160
+32

Protein	Similar proteins		Species	Score	Length	Source
Q8WVJ9	Twist-related protein 2		MOUSE		160	UniRef90_Q9D030
Twist-related protein 2		RAT		160
Uncharacterized protein (Fragment)		SARHA		161
Uncharacterized protein		ANOCA		161
Twist family bHLH transcription factor 2		MONDO		161
+122

Protein	Similar proteins		Species	Score	Length	Source
Q8WVJ9	Twist-related protein 2		MOUSE		160	UniRef50_Q9D030
Twist-related protein 2		RAT		160
Uncharacterized protein (Fragment)		SARHA		161
Twist family bHLH transcription factor 2		MONDO		161
Uncharacterized protein		ANOCA		161
+150

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
CCDSⁱ	CCDS46558.1
RefSeqⁱ	NP_001258822.1, NM_001271893.3 NP_476527.1, NM_057179.2
UniGeneⁱ	Hs.422585 Hs.745035

3D structure databases

ProteinModelPortalⁱ	Q8WVJ9
SMRⁱ	Q8WVJ9
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	125591, 10 interactors
IntActⁱ	Q8WVJ9, 9 interactors
STRINGⁱ	9606.ENSP00000405176

PTM databases

iPTMnetⁱ	Q8WVJ9
PhosphoSitePlusⁱ	Q8WVJ9

Polymorphism and mutation databases

BioMutaⁱ	TWIST2
DMDMⁱ	32699724

Proteomic databases

PaxDbⁱ	Q8WVJ9
PeptideAtlasⁱ	Q8WVJ9
PRIDEⁱ	Q8WVJ9
ProteomicsDBⁱ	74799

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	117581
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000448943; ENSP00000405176; ENSG00000233608 ENST00000612363; ENSP00000482581; ENSG00000233608
GeneIDⁱ	117581
KEGGⁱ	hsa:117581
UCSCⁱ	uc010znx.2 human

Organism-specific databases

CTDⁱ	117581
DisGeNETⁱ	117581
EuPathDBⁱ	HostDB:ENSG00000233608.3
GeneCardsⁱ	TWIST2
HGNCⁱ	HGNC:20670 TWIST2
HPAⁱ	HPA062870
MalaCardsⁱ	TWIST2
MIMⁱ	200110 phenotype 209885 phenotype 227260 phenotype 607556 gene
neXtProtⁱ	NX_Q8WVJ9
OpenTargetsⁱ	ENSG00000233608
Orphanetⁱ	920 Ablepharon macrostomia syndrome 1231 Barber-Say syndrome 1807 Focal facial dermal dysplasia type III
PharmGKBⁱ	PA134973713
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG4447 Eukaryota ENOG4111QFU LUCA
GeneTreeⁱ	ENSGT00760000119097
HOGENOMⁱ	HOG000261629
HOVERGENⁱ	HBG019071
InParanoidⁱ	Q8WVJ9
KOⁱ	K09069
OMAⁱ	DNKMSSC
OrthoDBⁱ	EOG091G07PB
PhylomeDBⁱ	Q8WVJ9
TreeFamⁱ	TF315153

Enzyme and pathway databases

Reactomeⁱ	R-HSA-8878166 Transcriptional regulation by RUNX2
SIGNORⁱ	Q8WVJ9

Miscellaneous databases

GeneWikiⁱ	TWIST2
GenomeRNAiⁱ	117581
Protein Ontology More...PROⁱ	PR:Q8WVJ9
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000233608 Expressed in 140 organ(s), highest expression level in endocervix
CleanExⁱ	HS_TWIST2
ExpressionAtlasⁱ	Q8WVJ9 baseline and differential
Genevisibleⁱ	Q8WVJ9 HS

Family and domain databases

CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf
Pfamⁱ	View protein in Pfam PF00010 HLH, 1 hit
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit
SUPFAMⁱ	SSF47459 SSF47459, 1 hit
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	TWST2_HUMAN
Accessionⁱ	Q8WVJ9Primary (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:	November 7, 2018
	This is version 148 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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UniProtKB - Q8WVJ9 (TWST2_HUMAN)

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Twist-related protein 2

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Other locations

Nucleus

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ