FK506結合タンパク質

関: FK506-binding protein、tacrolimus-binding protein

関: FK-binding proteins

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/18 08:50:59」(JST)

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上記の図と同じ方向から見たタンパク質

FKBPあるいはFK506結合タンパク質（エフケイ506けつごうタンパクしつ）は、プロリルイソメラーゼ活性を持ち、シクロフィリンと機能的に類似しているがアミノ酸配列の点では類似していないタンパク質ファミリーである^[1]。FKBP類は、酵母からヒトまで多くの真核生物において同定されており、プロリン残基を含むタンパク質のためのタンパク質フォールディングシャペロンとして機能している。シクロフィリンと共に、FKBP類はイムノフィリンファミリーに属している^[2]。

FKBP12は、臓器移植後の患者や自己免疫疾患の患者に対して用いられる免疫抑制剤のタクロリムス（FK506）に結合することで重要である^[3]。タクロリムスは、シクロフィリンに結合する免疫抑制剤シクロスポリンよりも臓器拒絶を減少させることが明らかにされている^[4]。FKBP-タクロリムス複合体とシクロスポリン-シクロフィリン複合体はどちらもカルシニューリンと呼ばれるホスファターゼ（脱リン酸化酵素）を阻害することによって、T-リンパ球シグナル伝達経路におけるシグナルを妨げる^[5]。この治療的役割はプロリルイソメラーゼ活性とは関係していない。

生物学研究ツールとして

FKBPは通常は二量体を形成しないが、FK506の誘導体であるFK1012の存在下で二量化する。このためFKBPは、タンパク質の局在やシグナル伝達経路、タンパク質の活性化などを制御するために使用される化学誘導二量体形成法のための有用ツールとなっている^[6]。

例

FKBPファミリーのタンパク質をコードしているヒト遺伝子には以下のものがある。

AIP; AIPL1
FKBP1A; FKBP1B; FKBP2; FKBP3; en:FKBP5; FKBP6; FKBP7; FKBP8; FKBP9; FKBP9L; FKBP10; FKBP11; FKBP14; FKBP15; FKBP52
LOC541473;

脚注

^ Siekierka JJ, Hung SH, Poe M, Lin CS, Sigal NH (October 1989). "A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin". Nature 341 (6244): 755–7. doi:10.1038/341755a0. PMID 2477714. Cite uses deprecated parameters (help)
^ Balbach J, Schmid FX (2000). “Proline isomerization and its catalysis in protein folding”. In Pain RH. Mechanisms of protein folding (2nd ed.). Oxford: Oxford University Press. pp. 212–237. ISBN 0-19-963789-X.
^ Wang T, Donahoe PK, Zervos AS (July 1994). "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". サイエンス 265 (5172): 674–6. doi:10.1126/science.7518616. PMID 7518616. Cite uses deprecated parameters (help)
^ Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, van Hooff J, Christiaans M, Morales JM, Andres A, Johnson RW, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JL, Talbot D, Pohanka E (August 1997). "Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group". Transplantation 64 (3): 436–43. doi:10.1097/00007890-199708150-00012. PMID 9275110. Cite uses deprecated parameters (help)
^ Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL (August 1991). "Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes". Cell 66 (4): 807–15. doi:10.1016/0092-8674(91)90124-H. PMID 1715244. Cite uses deprecated parameters (help)
^ Fegan, A; White, B; Carlson, JC; Wagner, CR (2010 Jun 9). "Chemically controlled protein assembly: techniques and applications.". en:Chemical Reviews 110 (6): 3315–36. PMID 20353181. Cite uses deprecated parameters (help); Check date values in: |date= (help)

外部リンク

Anti-rejection drugs

この項目は、生化学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:化学、プロジェクト:生命科学／Portal:化学、Portal:生物学）。

wiki en

[Wiki en表示]

An illustration of the same protein in the same orientation

FKBP, or FK506 binding protein, is a family of proteins that have prolyl isomerase activity and are related to the cyclophilins in function, though not in amino acid sequence.^[1] FKBPs have been identified in many eukaryotes from yeast to humans and function as protein folding chaperones for proteins containing proline residues. Along with cyclophilin, FKBPs belong to the immunophilin family.^[2]

FKBP12 is notable in humans for binding the immunosuppressant molecule tacrolimus (originally designated FK506), which is used in treating patients after organ transplant and patients suffering from autoimmune disorders.^[3] Tacrolimus has been found to reduce episodes of organ rejection over a related treatment, the drug ciclosporin, which binds cyclophilin.^[4] Both the FKBP-tacrolimus complex and the ciclosporin-cyclophilin complex inhibit a phosphatase called calcineurin, thus blocking signal transduction in the T-lymphocyte transduction pathway.^[5] This therapeutic role is not related to prolyl isomerase activity.

Use as a biological research tool

FKBP does not normally form a dimer but will dimerize in the presence of FK1012, a derivative of the drug FK506. This has made it a useful tool for chemically induced dimerization applications where it can be used to manipulate protein localization, signalling pathways and protein activation.^[6]

Examples

Human genes encoding proteins in this family include:

AIP; AIPL1
FKBP1A; FKBP1B; FKBP2; FKBP3; FKBP5; FKBP6; FKBP7; FKBP8; FKBP9; FKBP9L; FKBP10; FKBP11; FKBP14; FKBP15; FKBP52
LOC541473;

References

^ Siekierka JJ, Hung SH, Poe M, Lin CS, Sigal NH (October 1989). "A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin". Nature 341 (6244): 755–7. doi:10.1038/341755a0. PMID 2477714.
^ Balbach J, Schmid FX (2000). "Proline isomerization and its catalysis in protein folding". In Pain RH. Mechanisms of protein folding (2nd ed.). Oxford: Oxford University Press. pp. 212–237. ISBN 0-19-963789-X.
^ Wang T, Donahoe PK, Zervos AS (July 1994). "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science 265 (5172): 674–6. doi:10.1126/science.7518616. PMID 7518616.
^ Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, van Hooff J, Christiaans M, Morales JM, Andres A, Johnson RW, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JL, Talbot D, Pohanka E (August 1997). "Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group". Transplantation 64 (3): 436–43. doi:10.1097/00007890-199708150-00012. PMID 9275110.
^ Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL (August 1991). "Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes". Cell 66 (4): 807–15. doi:10.1016/0092-8674(91)90124-H. PMID 1715244.
^ Fegan, A; White, B; Carlson, JC; Wagner, CR (Jun 9, 2010). "Chemically controlled protein assembly: techniques and applications.". Chemical reviews 110 (6): 3315–36. doi:10.1021/cr8002888. PMID 20353181.

External links

Anti-rejection drugs

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Related Pictures

★リンクテーブル★

リンク元	「FK506結合タンパク質」「tacrolimus-binding protein」「FK506-binding protein」

「FK506結合タンパク質」

FKBP-type peptidyl-prolyl cis-trans isomerase
	The human protein FKBP12 bound to FK506 (tacrolimus). The protein surface is colored by hydrophobicity; the deep cleft in which the ligand is bound is hydrophobic.
Identifiers
Symbol	FKBP_C
Pfam	PF00254
InterPro	IPR001179
PROSITE	PDOC00426
SCOP	1fkb
SUPERFAMILY	1fkb
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

利用可能な蛋白質構造:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

FKBP-type peptidyl-prolyl cis-trans isomerase
	FK506（タクロリムス）と結合したヒトFKBP12タンパク質。このタンパク質の表面は疎水性によって色付けされており、リガンドが存在する深い窪みは疎水性である。
識別子
略号	FKBP_C
Pfam	PF00254
InterPro	IPR001179
PROSITE	PDOC00426
SCOP	1fkb
SUPERFAMILY	1fkb
利用可能な蛋白質構造:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary