Scleraxis

protein
Name = scleraxis homolog A (mouse)
caption =


width =
HGNCid = 24312
Symbol = SCXA
AltSymbols =
EntrezGene = 333927
OMIM = 609067
RefSeq =
UniProt = Q7RTU7
PDB =
ECnumber =
Chromosome = 8
Arm = q
Band = 24.3
LocusSupplementaryData = protein
Name = scleraxis homolog B (mouse)
caption =


width =
HGNCid = 32322
Symbol = SCXB
AltSymbols =
EntrezGene = 642658
OMIM =
RefSeq = XM_926116
UniProt =
PDB =
ECnumber =
Chromosome = 8
Arm = q
Band = 24.3
LocusSupplementaryData =

The scleraxis protein is a member of the basic-helix-loop-helix (bHLH) superfamily of transcription factors.cite journal | author = Cserjesi P, Brown D, Ligon KL, Lyons GE, Copeland NG, Gilbert DJ, Jenkins NA, Olson EN | title = Scleraxis: a basic helix-loop-helix protein that prefigures skeletal formation during mouse embryogenesis | journal = Development | volume = 121 | issue = 4 | pages = 1099–110 | year = 1995 | pmid = 7743923 | doi = | url = http://dev.biologists.org/cgi/content/abstract/121/4/1099 | issn = ] Currently two genes (gene|SCXA and gene|SCXB respectively) have been identified to code for identical scleraxis proteins.

Function

It is thought that early scleraxis expressing progenitor cells lead to the eventual formation of tendon tissue and other muscle attachments. Scleraxis is involved in mesoderm formation and is expressed in the syndetomal (embryonic tissues that develop into tendon and blood vessels) compartment of developing somites (primitive segments or compartments of embryos).cite journal | author = Brent AE, Schweitzer R, Tabin CJ | title = A somitic compartment of tendon progenitors | journal = Cell | volume = 113 | issue = 2 | pages = 235–48 | year = 2003 | pmid = 12705871 | doi = 10.1016/S0092-8674(03)00268-X | issn = ]

Background

bHLH transcription factors have been shown to have a wide array of functions in developmental processes.cite journal | author = Kadesch T | title = Consequences of heteromeric interactions among helix-loop-helix proteins | journal = Cell Growth Differ. | volume = 4 | issue = 1 | pages = 49–55 | year = 1993 | pmid = 8424906 | doi = | issn = | url = http://dev.biologists.org/cgi/content/abstract/121/4/1099 ] More precisely, they have critical roles in the control of cellular differentiation, proliferation and regulation of oncogenesis.cite journal | author = Olson EN, Klein WH | title = bHLH factors in muscle development: dead lines and commitments, what to leave in and what to leave out | journal = Genes Dev. | volume = 8 | issue = 1 | pages = 1–8 | year = 1994 | pmid = 8288123 | doi = 10.1101/gad.8.1.1 | issn = ] cite journal | author = Jan YN, Jan LY | title = Functional gene cassettes in development | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 90 | issue = 18 | pages = 8305–7 | year = 1993 | pmid = 8378299 | doi = 10.1073/pnas.90.18.8305 | issn = ] To date, 242 eukaryotic proteins belonging to the HLH superfamily have been reported. They have varied expression patterns in all eukaryotes from yeast to humans.cite journal | author = Atchley WR, Fitch WM | title = A natural classification of the basic helix-loop-helix class of transcription factors | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 10 | pages = 5172–6 | year = 1997 | pmid = 9144210 | doi = 10.1073/pnas.94.10.5172 | issn = ]

Structurally, bHLH proteins are characterised by a “highly conserved domain containing a stretch of basic amino acids adjacent to two amphipathic α-helices separated by a loop”.cite journal | author = Wilson-Rawls J, Rhee JM, Rawls A | title = Paraxis is a basic helix-loop-helix protein that positively regulates transcription through binding to specific E-box elements | journal = J. Biol. Chem. | volume = 279 | issue = 36 | pages = 37685–92 | year = 2004 | pmid = 15226298 | doi = 10.1074/jbc.M401319200 | issn = ] cite journal | author = Ellenberger T, Fass D, Arnaud M, Harrison SC | title = Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer | journal = Genes Dev. | volume = 8 | issue = 8 | pages = 970–80 | year = 1994 | pmid = 7926781 | doi = 10.1101/gad.8.8.970 | issn = ]

These helices have important functional properties, forming part of the DNA binding and transcription activating domains. With respect to scleraxis, the bHLH region spans amino acid residues 78 to 131. A proline rich region is also predicted to lie between residues 161-170. A stretch of basic residues, which aids in DNA binding, is found closer to the N terminal end of scleraxis.cite journal | author = Wolf C, Thisse C, Stoetzel C, Thisse B, Gerlinger P, Perrin-Schmitt F | title = The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the Xenopus X-twi and the Drosophila twist genes | journal = Dev. Biol. | volume = 143 | issue = 2 | pages = 363–73 | year = 1991 | pmid = 1840517 | doi = 10.1016/0012-1606(91)90086-I | issn = ]

HLH proteins that lack this basic domain have been shown to negatively regulate the activities of bHLH proteins and are called inhibitors of differentiation (Id).cite journal | author = Jen Y, Manova K, Benezra R | title = Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis | journal = Dev. Dyn. | volume = 207 | issue = 3 | pages = 235–52 | year = 1996 | pmid = 8922523 | doi = 10.1002/(SICI)1097-0177(199611)207:3<235::AID-AJA1>3.0.CO;2-I | issn = | doilabel = 10.1002/(SICI)1097-0177(199611)207:3235::AID-AJA13.0.CO;2-I ] Basic HLH proteins function normally as dimers and bind to a specific hexanucleotide DNA sequence (CAANTG) known as an E-box thus switching on the expression of various genes involved in cellular development and survival.

References