Reviewed, UniProtKB/Swiss-Prot Q15672 (TWST1_HUMAN)

Names and origin

Protein names

Recommended name:
    Twist-related protein 1
Alternative name(s):
    H-twist

Gene names

Name:	TWIST1
Synonyms:	TWIST

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	202 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probable transcription factor, which seems to be involved in the negative regulation of cellular determination and in the differentiation of several lineages including myogenesis, osteogenesis, and neurogenesis. 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 By similarity. Also represses expression of proinflammatory cytokines such as TNFA and IL1B.
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein. Homodimer By similarity.
Subcellular location	Nucleus.
Tissue specificity	Subset of mesodermal cells.
Involvement in disease	Defects in TWIST1 are a cause of Saethre-Chotzen syndrome (SCS) [MIM:101400]; also known as acrocephalosyndactyly type 3 (ACS3). SCS is a craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly. Defects in TWIST1 are the cause of Robinow-Sorauf syndrome (RSS) [MIM:180750]; also known as craniosynostosis-bifid hallux syndrome. RSS is an autosomal dominant defect characterized by minor skull and limb anomalies which is very similar to Saethre-Chotzen syndrome. Defects in TWIST1 are the cause of craniosynostosis type 1 (CRS1) [MIM:123100]. Craniosynostosis consists of premature fusion of one or more cranial sutures, resulting in an abnormal head shape.
Sequence similarities	Contains 1 basic helix-loop-helix (bHLH) domain.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Craniosynostosis Disease mutation
Ligand	DNA-binding
Molecular function	Developmental protein
Gene Ontology (GO)
Biological process	negative regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc skeletal system development Ref.3 Traceable author statement. Source: ProtInc
Cellular component	nucleus Inferred from electronic annotation. Source: InterPro
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW enzyme inhibitor activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct transcription regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ETS2	P15036	2	EBI-1797287,EBI-1646991

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	121 – 160	40	Helix-loop-helix motif
	DNA binding	108 – 120	13	Basic motif
	Compositional bias	80 – 98	19	Gly-rich
Natural variations
	Natural variant	31	1	S → G: dbSNP rs1800126.		VAR_014821
	Natural variant	84	1	G → S: dbSNP rs2234705.		VAR_014822
	Natural variant	119	1	Q → P in SCS.		VAR_004495
	Natural variant	131	1	L → P in SCS.		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.		VAR_015219
	Natural variant	186	1	A → T in CRS1.		VAR_034985
	Natural variant	188	1	S → L in CRS1.		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 Ref.1 Ref.4
	Sequence conflict	45	1	S → T Ref.1 Ref.4
	Sequence conflict	56	1	Missing Ref.1 Ref.4
	Sequence conflict	59	1	G → A in CAA67664. Ref.2
	Sequence conflict	92	1	G → GGGGG Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q15672-1 [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: 9073070] [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: 8995765] [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: 8988166] [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: 9215678] [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: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"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: 12553906] [Abstract] Cited for: FUNCTION.
[8]	"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: 8988167] [Abstract] Cited for: VARIANTS SCS PRO-131 AND LYS-ILE-ILE-PRO-THR-LEU-PRO-139 INS.
[9]	"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: 11754069] [Abstract] Cited for: VARIANT SCS VAL-156.
[10]	"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: 17343269] [Abstract] Cited for: VARIANTS CRS1 THR-186 AND LEU-188.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. BC036704 mRNA. Translation: AAH36704.1.
PIR	G01204.
RefSeq	NP_000465.1.
UniGene	Hs.644998 Hs.66744
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15672.
Genome annotation databases
Ensembl	ENSG00000122691. Homo sapiens. [Contig view]
GeneID	7291.
KEGG	hsa:7291.
Organism-specific databases
H-InvDB	HIX0025484.
HGNC	HGNC:12428. TWIST1.
MIM	101400. phenotype. 123100. phenotype. 180750. phenotype. 601622. gene.
Orphanet	1531. Craniosynostosis. 3106. Robinow-Sorauf syndrome. 794. Saethre-Chotzen syndrome.
PharmGKB	PA37088.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q15672.
HOVERGEN	Q15672.
Gene expression databases
ArrayExpress	Q15672.
CleanEx	HS_TWIST1.
GermOnline	ENSG00000122691. Homo sapiens.
Family and domain databases
InterPro	IPR001092. HLH_basic. IPR011598. HLH_DNA_bd. IPR015789. Twist. [Graphical view]
Gene3D	G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
PANTHER	PTHR23349:SF6. Twist. 1 hit.
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
PROSITE	PS50888. HLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	28507.
SOURCE	Search...

Entry information

Entry name

TWST1_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	November 25, 2008
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)