Q15672 (TWST1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Twist-related protein 1

Alternative name(s):
Class A basic helix-loop-helix protein 38
Short name=bHLHa38
H-twist

Gene names

Name:	TWIST1
Synonyms:	BHLHA38, TWIST

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	202 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a transcriptional regulator. Inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. This interaction probably involves the basic domains of both proteins. Also represses expression of proinflammatory cytokines such as TNFA and IL1B. Regulates cranial suture patterning and fusion. Activates transcription as a heterodimer with E proteins. Regulates gene expression differentially, depending on dimer composition. Homodimers induce expression of FGFR2 and POSTN while heterodimers repress FGFR2 and POSTN expression and induce THBS1 expression. Heterodimerization is also required for osteoblast differentiation. Ref.8
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein. Homodimer or heterodimer with E proteins such as TCF3. ID1 binds preferentially to TCF3 but does not interact efficiently with TWIST1 so ID1 levels control the amount of TCF3 available to dimerize with TWIST1 and thus determine the type of dimer formed By similarity.
Subcellular location	Nucleus.
Tissue specificity	Subset of mesodermal cells.
Involvement in disease	Saethre-Chotzen syndrome (SCS) [MIM:101400]: A craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.9 Ref.10 Robinow-Sorauf syndrome (RSS) [MIM:180750]: An autosomal dominant syndrome characterized by craniosynostosis, asymmetry of orbits, flat face, hypertelorism, a thin, long, and pointed nose, shallow orbits, strabismus, and broad great toes with a duplication of the distal phalanx. RSS is clinically similar to Saethre-Chotzen syndrome, with the most characteristic additional feature in Robinow-Sorauf syndrome being a bifid or partially duplicated hallux. Note: The disease is caused by mutations affecting the gene represented in this entry. Craniosynostosis 1 (CRS1) [MIM:123100]: Craniosynostosis consists of premature fusion of one or more cranial sutures, resulting in an abnormal head shape. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
Biological process	Differentiation Myogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Craniosynostosis Disease mutation
Ligand	DNA-binding
Molecular function	Activator Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aortic valve morphogenesis Inferred from mutant phenotype PubMed 20804746. Source: BHF-UCL apoptotic process Inferred from electronic annotation. Source: Compara cardiac neural crest cell migration involved in outflow tract morphogenesis Inferred from electronic annotation. Source: Compara cell proliferation involved in heart valve development Inferred from mutant phenotype PubMed 20804746. Source: BHF-UCL cellular response to hypoxia Inferred from mutant phenotype PubMed 18297062. Source: BHF-UCL cranial suture morphogenesis Traceable author statement PubMed 11001584. Source: BHF-UCL embryonic camera-type eye formation Inferred from mutant phenotype PubMed 17070479. Source: BHF-UCL embryonic cranial skeleton morphogenesis Inferred from mutant phenotype Ref.3Ref.9. Source: BHF-UCL embryonic digit morphogenesis Traceable author statement PubMed 11001584. Source: BHF-UCL embryonic forelimb morphogenesis Inferred from electronic annotation. Source: Compara embryonic hindlimb morphogenesis Inferred from electronic annotation. Source: Compara endocardial cushion morphogenesis Inferred from electronic annotation. Source: Compara eyelid development in camera-type eye Inferred from mutant phenotype PubMed 17070479. Source: BHF-UCL in utero embryonic development Inferred from electronic annotation. Source: Compara mitral valve morphogenesis Inferred from electronic annotation. Source: Compara muscle organ development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of DNA damage response, signal transduction by p53 class mediator Inferred from mutant phenotype PubMed 17690110. Source: BHF-UCL negative regulation of cellular senescence Inferred from mutant phenotype PubMed 17690110. Source: BHF-UCL negative regulation of double-strand break repair Inferred from mutant phenotype PubMed 17690110. Source: BHF-UCL negative regulation of histone acetylation Inferred from electronic annotation. Source: Compara negative regulation of histone phosphorylation Inferred from mutant phenotype PubMed 17690110. Source: BHF-UCL negative regulation of osteoblast differentiation Inferred from mutant phenotype PubMed 16888803. Source: BHF-UCL negative regulation of oxidative phosphorylation uncoupler activity Inferred from electronic annotation. Source: Compara negative regulation of peroxisome proliferator activated receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype PubMed 17003487. Source: BHF-UCL negative regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara negative regulation of skeletal muscle tissue development Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 17690110. Source: BHF-UCL negative regulation of tumor necrosis factor production Inferred from electronic annotation. Source: Compara neural tube closure Inferred from electronic annotation. Source: Compara neuron migration Inferred from electronic annotation. Source: Compara ossification Traceable author statement PubMed 11001584. Source: BHF-UCL osteoblast differentiation Inferred from electronic annotation. Source: Compara outer ear morphogenesis Traceable author statement PubMed 11001584. Source: BHF-UCL positive regulation of angiogenesis Non-traceable author statement PubMed 17987801. Source: BHF-UCL positive regulation of cell motility Inferred from mutant phenotype PubMed 17332325. Source: BHF-UCL positive regulation of endocardial cushion to mesenchymal transition involved in heart valve formation Inferred from electronic annotation. Source: Compara positive regulation of epithelial to mesenchymal transition Inferred from mutant phenotype PubMed 18297062. Source: BHF-UCL positive regulation of fatty acid beta-oxidation Inferred from mutant phenotype PubMed 20007935. Source: BHF-UCL positive regulation of interleukin-6 secretion Inferred from mutant phenotype PubMed 20007935. Source: BHF-UCL positive regulation of monocyte chemotactic protein-1 production Inferred from mutant phenotype PubMed 20007935. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 17332325. Source: BHF-UCL positive regulation of transcription regulatory region DNA binding Inferred from mutant phenotype PubMed 12270142. Source: BHF-UCL positive regulation of tumor necrosis factor production Inferred from mutant phenotype PubMed 20007935. Source: BHF-UCL regulation of bone mineralization Inferred from mutant phenotype PubMed 19597909. Source: BHF-UCL
Cellular_component	nucleus Inferred from direct assay PubMed 15545268. Source: UniProtKB
Molecular_function	E-box binding Inferred from direct assay PubMed 17332325PubMed 20804746. Source: BHF-UCL sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from direct assay PubMed 17332325. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ETS2	P15036	2	EBI-1797287,EBI-1646991
KAT2B	Q92831	2	EBI-1797287,EBI-477430
TP53	P04637	9	EBI-1797287,EBI-366083

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 202	202	Twist-related protein 1		PRO_0000127483
Regions
	Domain	108 – 159	52	bHLH
	Region	161 – 191	31	Sufficient for transactivation activity By similarity
	Compositional bias	80 – 98	19	Gly-rich
Natural variations
	Natural variant	31	1	S → G. Corresponds to variant rs1800126 [ dbSNP | Ensembl ].		VAR_014821
	Natural variant	84	1	G → S. Corresponds to variant rs2234705 [ dbSNP | Ensembl ].		VAR_014822
	Natural variant	119	1	Q → P in SCS. Ref.3		VAR_004495
	Natural variant	131	1	L → P in SCS. Ref.9		VAR_004496
	Natural variant	135	1	I → IAALRKII in SCS.		VAR_004497
	Natural variant	139	1	P → PKIIPTLP in SCS.		VAR_004498
	Natural variant	156	1	I → V in SCS; variant form with features overlapping Baller-Gerold syndrome. Ref.10		VAR_015219
	Natural variant	186	1	A → T in CRS1. Ref.11		VAR_034985
	Natural variant	188	1	S → L in CRS1. Ref.11		VAR_034986
Experimental info
	Sequence conflict	32	1	G → A in CAA67664. Ref.2
	Sequence conflict	36	1	G → A in CAA67664. Ref.2
	Sequence conflict	41	1	S → T in CAA62850. Ref.1
	Sequence conflict	41	1	S → T in CAA71821. Ref.4
	Sequence conflict	45	1	S → T in CAA62850. Ref.1
	Sequence conflict	45	1	S → T in CAA71821. Ref.4
	Sequence conflict	56	1	Missing in CAA62850. Ref.1
	Sequence conflict	56	1	Missing in CAA71821. Ref.4
	Sequence conflict	59	1	G → A in CAA67664. Ref.2
	Sequence conflict	92	1	G → GGGGG in CAA67664. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q15672 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 9394E4351BA1D081	FASTA	202	20,954
	10 20 30 40 50 60 MMQDVSSSPV SPADDSLSNS EEEPDRQQPP SGKRGGRKRR SSRRSAGGGA GPGGAAGGGV 70 80 90 100 110 120 GGGDEPGSPA QGKRGKKSAG CGGGGGAGGG GGSSSGGGSP QSYEELQTQR VMANVRERQR 130 140 150 160 170 180 TQSLNEAFAA LRKIIPTLPS DKLSKIQTLK LAARYIDFLY QVLQSDELDS KMASCSYVAH 190 200 ERLSYAFSVW RMEGAWSMSA SH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human twist gene: its expression is retained in adult mesodermally-derived tissues." Wang S.M., Coljee V.W., Pignolo R.J., Rotenberg M.O., Cristofalo V.J., Sierra F. Gene 187:83-92(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lung.
[2]	"The human H-twist gene is located at 7p21 and encodes a B-HLH protein that is 96% similar to its murine M-twist counterpart." Bourgeois P., Stoetzel C., Bolcato-Bellemin A.-L., Mattei M.-G., Perrin-Schmitt F. Mamm. Genome 7:915-917(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome." Howard T.D., Paznekas W.A., Green E.D., Chiang L.C., Ma N., Ortiz de Luna R.I., Delgado C.G., Gonzalez-Ramos M., Kline A.D., Jabs E.W. Nat. Genet. 15:36-41(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SCS PRO-119; ALA-ALA-LEU-ARG-LYS-ILE-ILE-135 INS AND LYS-ILE-ILE-PRO-THR-LEU-PRO-139 INS.
[4]	"Translocation breakpoint maps 5 kb 3-prime from TWIST in a patient affected with Saethre-Chotzen syndrome." Krebs I., Weis I., Hudler M., Rommens J.M., Roth H., Scherer S.W., Tsui L.-C., Fuchtbauer E.-M., Grzeschik K.-H., Tsuji K., Kunz J. Hum. Mol. Genet. 6:1079-1086(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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.
[8]	"Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity." Sosic D., Richardson J.A., Yu K., Ornitz D.M., Olson E.N. Cell 112:169-180(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Mutations of the TWIST gene in the Saethre-Chotzen syndrome." el Ghouzzi V., le Merrer M., Perrin-Schmitt F., Lajeunie E., Benit P., Renier D., Bourgeois P., Bolcato-Bellemin A.-L., Munnich A., Bonaventure J. Nat. Genet. 15:42-46(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SCS PRO-131 AND LYS-ILE-ILE-PRO-THR-LEU-PRO-139 INS.
[10]	"Another TWIST on Baller-Gerold syndrome." Seto M.L., Lee S.J., Sze R.W., Cunningham M.L. Am. J. Med. Genet. 104:323-330(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SCS VAL-156.
[11]	"Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations." Seto M.L., Hing A.V., Chang J., Hu M., Kapp-Simon K.A., Patel P.K., Burton B.K., Kane A.A., Smyth M.D., Hopper R., Ellenbogen R.G., Stevenson K., Speltz M.L., Cunningham M.L. Am. J. Med. Genet. A 143:678-686(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CRS1 THR-186 AND LEU-188.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X91662 Genomic DNA. Translation: CAA62850.1. X99268 mRNA. Translation: CAA67664.1. U80998 Genomic DNA. Translation: AAC50930.1. Y10871 Genomic DNA. Translation: CAA71821.1. AC003986 Genomic DNA. Translation: AAC60381.2. CH236948 Genomic DNA. Translation: EAL24279.1. BC036704 mRNA. Translation: AAH36704.1.
IPI	IPI00018907.
PIR	G01204.
RefSeq	NP_000465.1. NM_000474.3.
UniGene	Hs.66744.
3D structure databases
ProteinModelPortal	Q15672.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15672. 6 interactions.
STRING	9606.ENSP00000242261.
PTM databases
PhosphoSite	Q15672.
Polymorphism databases
DMDM	2498009.
Proteomic databases
PaxDb	Q15672.
PRIDE	Q15672.
Protocols and materials databases
DNASU	7291.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000242261; ENSP00000242261; ENSG00000122691.
GeneID	7291.
KEGG	hsa:7291.
UCSC	uc003sum.3. human.
Organism-specific databases
CTD	7291.
GeneCards	GC07M019121.
HGNC	HGNC:12428. TWIST1.
MIM	101400. phenotype. 123100. phenotype. 180750. phenotype. 601622. gene.
neXtProt	NX_Q15672.
Orphanet	35099. Isolated brachycephaly. 35093. Isolated scaphocephaly. 794. Saethre-Chotzen syndrome.
PharmGKB	PA37088.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG258515.
HOGENOM	HOG000261629.
InParanoid	Q15672.
KO	K09069.
OMA	MMQDVSS.
PhylomeDB	Q15672.
Gene expression databases
Bgee	Q15672.
CleanEx	HS_TWIST1.
Genevestigator	Q15672.
GermOnline	ENSG00000122691. Homo sapiens.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. IPR015789. Twist_related. [Graphical view]
PANTHER	PTHR23349:SF6. PTHR23349:SF6. 1 hit.
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TWIST1. human.
GenomeRNAi	7291.
NextBio	28507.
SOURCE	Search...

Entry information

Entry name

TWST1_HUMAN

Accession

Primary (citable) accession number: Q15672
Secondary accession number(s): A4D128, Q92487, Q99804

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 143 of the entry and version 1 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.