関: bHLH

WordNet

move in loops; "The bicycle looped around the tree"
anything with a round or oval shape (formed by a curve that is closed and does not intersect itself)
a flight maneuver; aircraft flies a complete circle in the vertical plane (同)loop-the-loop
an intrauterine device in the shape of a loop
a computer program that performs a series of instructions repeatedly until some specified condition is satisfied
an inner circle of advisors (especially under President Reagan); "hes no longer in the loop"
the basic pattern of the human fingerprint
make a loop in; "loop a rope" (同)intertwine
fasten or join with a loop; "He looped the watch through his belt"
fly loops, perform a loop; "the stunt pilot looped his plane"
pertaining to or constituting a base or basis; "a basic fact"; "the basic ingredients"; "basic changes in public opinion occur because of changes in priorities"
(usually plural) a necessary commodity for which demand is constant (同)staple
reduced to the simplest and most significant form possible without loss of generality; "a basic story line"; "a canonical syllable pattern" (同)canonic, canonical
serving as a base or starting point; "a basic course in Russian"; "basic training for raw recruits"; "a set of basic tools"; "an introductory art course" (同)introductory
of or denoting or of the nature of or containing a base
a curve that lies on the surface of a cylinder or cone and cuts the element at a constant angle (同)spiral
a popular programming language that is relatively easy to learn; an acronym for beginners all-purpose symbolic instruction code; no longer in general use
a statement of fundamental facts or principles (同)rudiments

PrepTutorEJDIC

(糸・ひも・針金などで作った)『輪』・輪状のもの;(輪状の)湾曲部・(宙返り飛行・スケートなどで描く)輪・ループ (ある条件が成立するまで繰り返し実行される，プログラム中に記述された一連の命令のこと)・仲間、影響｝を受け合う間柄・同列の立場・「keep誰々in the loop」として、「keep誰々informed：情報を（人）に絶えず提供し続ける、報告を（人）に欠かさない、（人）に逐次連絡する、（人）に常に通知する」・避妊リング; (鉄道・電線などの)環状線(loop line)・…‘を'輪にする,輪で囲む・…‘を'輪で結ぶ,輪で締める《+『up』+『名,』+『名』+『up』》・輪になる,輪を描く
『基礎の』,基本的な(fundamental) / 塩基性(アルカリ性)の
らせん / らせん形のもの
基本,基礎

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/09/03 03:30:16」(JST)

wiki en

A basic helix-loop-helix (bHLH) is a protein structural motif that characterizes a family of transcription factors.^[2]^[3]^[4] It should not be confused with the helix-turn-helix domain.

Structure[edit source | edit]

The motif is characterized by two α-helices connected by a loop. In general, transcription factors including this domain are dimeric, each with one helix containing basic amino acid residues that facilitate DNA binding.^[5] In general, one helix is smaller, and, due to the flexibility of the loop, allows dimerization by folding and packing against another helix. The larger helix typically contains the DNA-binding regions. bHLH proteins typically bind to a consensus sequence called an E-box, CANNTG.^[6] The canonical E-box is CACGTG (palindromic), however some bHLH transcription factors, notably those of the bHLH-PAS family, bind to related non-palindromic sequences, which are similar to the E-box.

Examples[edit source | edit]

Examples of transcription factors containing a bHLH include:

AhR
Beta2/NeuroD1
BMAL-1-CLOCK
C-Myc, N-Myc
MyoD
Myf5
Pho4
HIF
ICE1
NPAS1, NPAS3, MOP5
Scl, also known as Tal1
proneural bHLH genes like p-CaMKII, and pSer(336)NeuroD.
Scleraxis
Neurogenins
MAX
OLIG1, OLIG2

bHLH transcription factors are often important in development or cell activity. BMAL1-Clock is a core transcription complex in the molecular circadian clock. Other genes, like c-Myc and HIF-1, have been linked to cancer due to their effects on cell growth and metabolism.

Regulation[edit source | edit]

Since many bHLH transcription factors are heterodimeric, their activity is often highly regulated by the dimerization of the subunits. One subunit's expression or availability is often controlled, whereas the other subunit is constitutively expressed. Many of the known regulatory proteins, such as the Drosophila extramacrochaetae protein, have the helix-loop-helix structure but lack the basic region, making them unable to bind to DNA on their own. They are, however, able to form heterodimers with proteins that have the bHLH structure, and inactivate their abilities as transcription factors.^[7]

History[edit source | edit]

1989: Murre et al. showed that dimers of various bHLH proteins bind to a short DNA motif (later called E-Box).^[8] This E-box consists of the DNA sequence CANNTG, where N can be any nucleotide.^[6]

1994: Harrison's^[9] and Pabo's^[10] groups crystallize bHLH proteins bound to E-boxes, demonstrating that the parallel 4-helix bundle motif loop orients the basic sequences to interact with specific nucleotides in the major groove of the E-box.

1994: Wharton et al. identified asymmetric E-boxes bound by a subset of bHLH proteins with PAS domains (bHLH-PAS proteins), including Single-minded (Sim) and the aromatic hydrocarbon receptor.^[11]

1995: Semenza's group identifies hypoxia-inducible factor (HIF) as a bHLH-PAS heterodimer that binds a related asymmetric E-box.^[12]

2009: Grove, De Masi et al., identified novel short DNA motifs, bound by a subset of bHLH proteins, which they defined as "E-box-like sequences". These are in the form of CAYRMK, where Y stands for C or T, R is A or G, M is A or C and K is G or T.^[13]

Human proteins with helix-loop-helix DNA-binding domain[edit source | edit]

AHR; AHRR; ARNT^{[disambiguation needed]}; ARNT2; ARNTL; ARNTL2; ASCL1; ASCL2; ASCL3; ASCL4; ATOH1; ATOH7; ATOH8; BHLHB2; BHLHB3; BHLHB4; BHLHB5; BHLHB8; CLOCK; EPAS1; FERD3L; FIGLA; HAND1; HAND2; HES1; HES2; HES3; HES4; HES5; HES6; HES7; HEY1; HEY2; HIF1A; ID1; ID2; ID3; ID4; KIAA2018; LYL1; MASH1; MATH2; MAX; MESP1; MESP2; MIST1; MITF; MLX; MLXIP; MLXIPL; MNT; MSC; MSGN1; MXD1; MXD3; MXD4; MXI1; MYC; MYCL1; MYCL2; MYCN; MYF5; MYF6; MYOD1; MYOG; NCOA1; NCOA3; NEUROD1; NEUROD2; NEUROD4; NEUROD6; NEUROG1; NEUROG2; NEUROG3; NHLH1; NHLH2; NPAS1; NPAS2; NPAS3; OAF1; OLIG1; OLIG2; OLIG3; PTF1A; SCL; SCXB; SIM1; SIM2; SOHLH1; SOHLH2; SREBF1; SREBF2; TAL1; TAL2; TCF12; TCF15; TCF21; TCF3; TCF4; TCFL5; TFAP4; TFE3; TFEB; TFEC; TWIST1; TWIST2; USF1; USF2;

References[edit source | edit]

^ PDB 1x0o; Card PB, Erbel PJ, Gardner KH (October 2005). "Structural basis of ARNT PAS-B dimerization: use of a common beta-sheet interface for hetero- and homodimerization". J. Mol. Biol. 353 (3): 664–77. doi:10.1016/j.jmb.2005.08.043. PMID 16181639.
^ Murre C, Bain G, van Dijk MA, Engel I, Furnari BA, Massari ME, Matthews JR, Quong MW, Rivera RR, Stuiver MH (June 1994). "Structure and function of helix-loop-helix proteins". Biochim. Biophys. Acta 1218 (2): 129–35. doi:10.1016/0167-4781(94)90001-9. PMID 8018712.
^ Littlewood TD, Evan GI (1995). "Transcription factors 2: helix-loop-helix". Protein Profile 2 (6): 621–702. PMID 7553065.
^ Massari ME, Murre C (January 2000). "Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms". Mol. Cell. Biol. 20 (2): 429–40. doi:10.1128/MCB.20.2.429-440.2000. PMC 85097. PMID 10611221.
^ Lawrence Zipursky; Arnold Berk; Monty Krieger; Darnell, James E.; Lodish, Harvey F.; Kaiser, Chris; Matthew P Scott; Matsudaira, Paul T. McGill Lodish 5E Package - Molecular Cell Biology & McGill Activation Code. San Francisco: W. H. Freeman. ISBN 0-7167-8635-4.
^ ^a ^b Chaudhary J, Skinner MK (1999). "Basic helix-loop-helix proteins can act at the E-box within the serum response element of the c-fos promoter to influence hormone-induced promoter activation in Sertoli cells". Mol. Endocrinol. 13 (5): 774–86. doi:10.1210/me.13.5.774. PMID 10319327.
^ Cabrera CV, Alonso MC, Huikeshoven H (1994). "Regulation of scute function by extramacrochaete in vitro and in vivo". Development 120 (12): 3595–603. PMID 7821225.
^ Murre C, McCaw PS, Vaessin H et al. (1989). "Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence". Cell 58 (3): 537–44. doi:10.1016/0092-8674(89)90434-0. PMID 2503252.
^ Ellenberger T, Fass D, Arnaud M, Harrison SC (April 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.
^ Ma PC, Rould MA, Weintraub H, Pabo CO (May 1994). "Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation". Cell 77 (3): 451–9. doi:10.1016/0092-8674(94)90159-7. PMID 8181063.
^ Wharton KA, Franks RG, Kasai Y, Crews ST (December 1994). "Control of CNS midline transcription by asymmetric E-box-like elements: similarity to xenobiotic responsive regulation". Development 120 (12): 3563–9. PMID 7821222.
^ Wang GL, Jiang BH, Rue EA, Semenza GL (June 1995). "Hypoxia-inducible factor 1 is a basic helix-loop-helix-PAS heterodimer regulated by cellular O2 tension". Proc. Natl. Acad. Sci. U.S.A. 92 (12): 5510–4. doi:10.1073/pnas.92.12.5510. PMC 41725. PMID 7539918.
^ Grove C, De Masi F et al. (2009). "A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors". Cell 138 (2): 314–27. doi:10.1016/j.cell.2009.04.058. PMC 2774807. PMID 19632181.

External links[edit source | edit]

PDOC00038 in PROSITE
Basic Helix-Loop-Helix Transcription Factors at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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English Journal

Deficits in trace fear memory in a mouse model of the schizophrenia risk gene TCF4.

Brzózka MM, Rossner MJ.SourceMax-Planck-Institute of Experimental Medicine, Research Group 'Gene Expression and Signaling', Hermann-Rein-Str. 3, 37075 Göttingen, Germany; Ludwig-Maximilian-University Munich, Department of Psychiatry, Nussbaumstr. 7, 80336 München, Germany.
Behavioural brain research.Behav Brain Res.2013 Jan 15;237:348-56. doi: 10.1016/j.bbr.2012.10.001. Epub 2012 Oct 13.
The basic helix-loop-helix (bHLH) transcription factor TCF4 was confirmed in the combined analysis of several large genome-wide association studies (GWAS) as one of the rare highly replicated significant schizophrenia (SZ) susceptibility genes in large case-control cohorts. Focused genetic associati
PMID 23069005

Two single nucleotide polymorphisms in the human nescient helix-loop-helix 2 (NHLH2) gene reduce mRNA stability and DNA binding.

Al Rayyan N, Wankhade UD, Bush K, Good DJ.SourceDepartment of Human Nutrition, Foods and Exercise, Virginia Tech University, Blacksburg, VA 24061, USA.
Gene.Gene.2013 Jan 1;512(1):134-42. doi: 10.1016/j.gene.2012.09.068. Epub 2012 Sep 28.
Nescient helix-loop-helix-2 (NHLH2) is a basic helix-loop-helix transcription factor, which has been implicated, using mouse knockouts, in adult body weight regulation and fertility. A scan of the known single nucleotide polymorphisms (SNPs) in the NHLH2 gene revealed one in the 3' untranslated regi
PMID 23026212

Japanese Journal

Protein inhibitor of activated STAT, PIASy regulates α-smooth muscle actin expression by interacting with E12 in mesangial cells.

Torikoshi Kazuo,Abe Hideharu,Matsubara Takeshi,Hirano Takahiro,Ohshima Takayuki,Murakami Taichi,Araki Makoto,Mima Akira,Iehara Noriyuki,Fukatsu Atsushi,Kita Toru,Arai Hidenori,Doi Toshio
PloS one 7(7), 2012-07-19
… Recently, E-boxes and the class I basic helix-loop-helix proteins, such as E12 have been shown to regulateα-SMA expression. …
NAID 120004770223

An atypical bHLH protein encoded by POSITIVE REGULATOR OF GRAIN LENGTH 2 is involved in controlling grain length and weight of rice through interaction with a typical bHLH protein APG

Heang Dany,Sassa Hidenori
Breeding science 62(2), 133-141, 2012-06-01
NAID 10030434532

Overexpression of a basic helix-loop-helix gene Antagonist of PGL1 (APG) decreases grain length of rice

Heang Dany,Sassa Hidenori
Plant biotechnology 29(1), 65-69, 2012-03-25
… Previously we reported that three basic helix–loop–helix (bHLH) protein dimers are involved in regulating grain length of rice. …
NAID 10030561451

Related Pictures

★リンクテーブル★

リンク元	「bHLH」「ベーシック・ヘリックス・ループ・ヘリックス」「bHLH proteins」
拡張検索	「basic helix-loop-helix leucine zipper transcription factor」「basic helix-loop-helix transcription factor」
関連記事	「basic」「helix」「loop」

「bHLH」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

basic helix-loop-helix DNA-binding domain
	; Basic helix-loop-helix structural motif of ARNT. Two α-helices (blue) are connected by a short loop (red).
Identifiers
Symbol	bHLH
Pfam	PF00010
InterPro	IPR001092
SMART	SM00353
PROSITE	PDOC00038
SCOP	1mdy
SUPERFAMILY	1mdy
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary