Scleraxis

scleraxis homolog A (mouse)
Identifiers
Symbol	SCXA
Entrez	333927
HUGO	24312
OMIM	609067
UniProt	Q7RTU7
Other data
Locus	Chr. 8 q24.3

scleraxis homolog B (mouse)
Identifiers
Symbol	SCXB
Entrez	642658
HUGO	32322
RefSeq	XM_926116
Other data
Locus	Chr. 8 q24.3

The scleraxis protein is a member of the basic helix-loop-helix (bHLH) superfamily of transcription factors.^[1] Currently two genes (SCXA and 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.^[1] 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).^[2]

Background

bHLH transcription factors have been shown to have a wide array of functions in developmental processes.^[3] More precisely, they have critical roles in the control of cellular differentiation, proliferation and regulation of oncogenesis.^[3]^[4]^[5] 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.^[6]

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”.^[7]^[8]

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.^[1]^[9]

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).^[10] 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

1 2 3 Cserjesi P, Brown D, Ligon KL, Lyons GE, Copeland NG, Gilbert DJ, Jenkins NA, Olson EN (1995). "Scleraxis: a basic helix-loop-helix protein that prefigures skeletal formation during mouse embryogenesis". Development 121 (4): 1099–110. PMID 7743923.
↑ Brent AE, Schweitzer R, Tabin CJ (2003). "A somitic compartment of tendon progenitors". Cell 113 (2): 235–48. doi:10.1016/S0092-8674(03)00268-X. PMID 12705871.
1 2 Kadesch T (1993). "Consequences of heteromeric interactions among helix-loop-helix proteins". Cell Growth Differ. 4 (1): 49–55. PMID 8424906.
↑ Olson EN, Klein WH (1994). "bHLH factors in muscle development: dead lines and commitments, what to leave in and what to leave out". Genes Dev. 8 (1): 1–8. doi:10.1101/gad.8.1.1. PMID 8288123.
↑ Jan YN, Jan LY (1993). "Functional gene cassettes in development". Proc. Natl. Acad. Sci. U.S.A. 90 (18): 8305–7. doi:10.1073/pnas.90.18.8305. PMC 47343. PMID 8378299.
↑ Atchley WR, Fitch WM (1997). "A natural classification of the basic helix–loop–helix class of transcription factors". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 5172–6. doi:10.1073/pnas.94.10.5172. PMC 24651. PMID 9144210.
↑ Wilson-Rawls J, Rhee JM, Rawls A (2004). "Paraxis is a basic helix-loop-helix protein that positively regulates transcription through binding to specific E-box elements". J. Biol. Chem. 279 (36): 37685–92. doi:10.1074/jbc.M401319200. PMID 15226298.
↑ Ellenberger T, Fass D, Arnaud M, Harrison SC (1994). "Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer". Genes Dev. 8 (8): 970–80. doi:10.1101/gad.8.8.970. PMID 7926781.
↑ Wolf C, Thisse C, Stoetzel C, Thisse B, Gerlinger P, Perrin-Schmitt F (1991). "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". Dev. Biol. 143 (2): 363–73. doi:10.1016/0012-1606(91)90086-I. PMID 1840517.
↑ Jen Y, Manova K, Benezra R (1996). "Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis". Dev. Dyn. 207 (3): 235–52. doi:10.1002/(SICI)1097-0177(199611)207:3<235::AID-AJA1>3.0.CO;2-I. PMID 8922523.

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

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