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FKBP1A
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1A7X, 1B6C, 1BKF, 1BL4, 1D6O, 1D7H, 1D7I, 1D7J, 1EYM, 1F40, 1FAP, 1FKB, 1FKD, 1FKF, 1FKG, 1FKH, 1FKI, 1FKJ, 1FKR, 1FKS, 1FKT, 1J4H, 1J4I, 1J4R, 1NSG, 1QPF, 1QPL, 2DG3, 2DG4, 2DG9, 2FAP, 2FKE, 2PPN, 2PPO, 2PPP, 2RSE, 3FAP, 3H9R, 3MDY, 4DH0, 4FAP, 4IPX, 4N19, 4ODP, 4ODQ, 4ODR
Identifiers
Aliases	FKBP1A, FKBP-12, FKBP-1A, FKBP1, FKBP12, PKC12, PKCI2, PPIASE, FK506 binding protein 1A, FKBP prolyl isomerase 1A
External IDs	OMIM: 186945; MGI: 95541; HomoloGene: 105139; GeneCards: FKBP1A; OMA:FKBP1A - orthologs
Gene location (Human)
Chr.	Chromosome 20 (human)
End	1,393,164 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	151,403,612 bp
RNA expression pattern
	Top expressed in
	right lung; ; monocyte; ; upper lobe of left lung; ; right lobe of thyroid gland; ; left lobe of thyroid gland; ; nucleus accumbens; ; epithelium of colon; ; rectum; ; left uterine tube; ; smooth muscle tissue;
	Top expressed in
	lateral septal nucleus; ; olfactory tubercle; ; external carotid artery; ; internal carotid artery; ; dentate gyrus of hippocampal formation granule cell; ; subiculum; ; nucleus accumbens; ; anterior amygdaloid area; ; endocardial cushion; ; Gonadal ridge;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	calcium channel inhibitor activity; activin binding; isomerase activity; macrolide binding; peptidyl-prolyl cis-trans isomerase activity; signal transducer activity; protein binding; SMAD binding; transforming growth factor beta receptor binding; FK506 binding; enzyme binding; Hsp70 protein binding; type I transforming growth factor beta receptor binding; protein homodimerization activity; transmembrane transporter binding;
Cellular component	cytoplasm; terminal cisterna; Z discdkac; extracellular exosome; extrinsic component of organelle membrane; cytoplasmic side of membrane; ryanodine receptor complex; cytosol; membrane; sarcoplasmic reticulum; sarcoplasmic reticulum membrane; intracellular membrane-bounded organelle; axon terminus;
Biological process	SMAD protein complex assembly; amyloid fibril formation; regulation of activin receptor signaling pathway; protein maturation by protein folding; regulation of amyloid precursor protein catabolic process; protein peptidyl-prolyl isomerization; negative regulation of ryanodine-sensitive calcium-release channel activity; regulation of protein localization; calcium ion transmembrane transport; protein refolding; regulation of immune response; positive regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of release of sequestered calcium ion into cytosol; positive regulation of protein binding; positive regulation of protein ubiquitination; 'de novo' protein folding; transforming growth factor beta receptor signaling pathway; T cell activation; chaperone-mediated protein folding; supramolecular fiber organization; negative regulation of phosphoprotein phosphatase activity; protein folding; negative regulation of protein phosphorylation; heart morphogenesis; muscle contraction; response to iron ion; cytokine-mediated signaling pathway; response to caffeine; T cell proliferation; release of sequestered calcium ion into cytosol; ventricular cardiac muscle tissue morphogenesis; regulation of ryanodine-sensitive calcium-release channel activity; heart trabecula formation;
	Sources:Amigo / QuickGO
Orthologs
	2280
	14225
	ENSG00000088832
	ENSMUSG00000032966
	P62942
	P26883
	NM_054014; NM_000801; NM_001199786
NM_001302077; NM_001302078; NM_001302079; NM_001302080; NM_008019;
	NM_001355077; NM_001355078
	NP_000792; NP_001186715; NP_463460
NP_001289006; NP_001289007; NP_001289008; NP_001289009; NP_032045;
	NP_001342006; NP_001342007
	Wikidata
View/Edit Human	View/Edit Mouse

Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the FKBP1A gene.^[5] It is also commonly referred to as FKBP-12 or FKBP12 and is a member of a family of FK506-binding proteins (FKBPs).

Function

The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 (tacrolimus) and rapamycin (sirolimus). It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels including the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. Multiple alternatively spliced variants, encoding the same protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed.^[6]

Interactions

FKBP1A has been shown to interact with:

GLMN,^[7]^[8]
ITPR1^[9]^[10]
KIAA1303,^[11]^[12]
Mammalian target of rapamycin,^[11]^[12]^[13]^[14]^[15]^[16]
RYR1,^[17]^[18]^[19] and
TGF beta receptor 1.^[20]^[21]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000088832 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000032966 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ DiLella AG (Sep 1991). "Chromosomal assignment of the human immunophilin FKBP-12 gene". Biochemical and Biophysical Research Communications. 179 (3): 1427–33. doi:10.1016/0006-291X(91)91732-R. PMID 1930186.
^ "Entrez Gene: FKBP1A FK506 binding protein 1A, 12kDa".
^ Chambraud B, Radanyi C, Camonis JH, Shazand K, Rajkowski K, Baulieu EE (Dec 1996). "FAP48, a new protein that forms specific complexes with both immunophilins FKBP59 and FKBP12. Prevention by the immunosuppressant drugs FK506 and rapamycin". The Journal of Biological Chemistry. 271 (51): 32923–9. doi:10.1074/jbc.271.51.32923. PMID 8955134.
^ Neye H (Mar 2001). "Mutation of FKBP associated protein 48 (FAP48) at proline 219 disrupts the interaction with FKBP12 and FKBP52". Regulatory Peptides. 97 (2–3): 147–52. doi:10.1016/s0167-0115(00)00206-8. PMID 11164950. S2CID 20617551.
^ MacMillan D, Currie S, Bradley KN, Muir TC, McCarron JG (Dec 2005). "In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin". Journal of Cell Science. 118 (Pt 23): 5443–51. doi:10.1242/jcs.02657. PMID 16278292.
^ Cameron AM, Nucifora FC, Fung ET, Livingston DJ, Aldape RA, Ross CA, Snyder SH (Oct 1997). "FKBP12 binds the inositol 1,4,5-trisphosphate receptor at leucine-proline (1400-1401) and anchors calcineurin to this FK506-like domain". The Journal of Biological Chemistry. 272 (44): 27582–8. doi:10.1074/jbc.272.44.27582. PMID 9346894.
^ ^a ^b Jacinto E, Loewith R, Schmidt A, Lin S, Rüegg MA, Hall A, Hall MN (Nov 2004). "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive". Nature Cell Biology. 6 (11): 1122–8. doi:10.1038/ncb1183. PMID 15467718. S2CID 13831153.
^ ^a ^b Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (Jul 2004). "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Current Biology. 14 (14): 1296–302. Bibcode:2004CBio...14.1296D. doi:10.1016/j.cub.2004.06.054. PMID 15268862. S2CID 4658268.
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^ Luker KE, Smith MC, Luker GD, Gammon ST, Piwnica-Worms H, Piwnica-Worms D (Aug 2004). "Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12288–93. Bibcode:2004PNAS..10112288L. doi:10.1073/pnas.0404041101. PMC 514471. PMID 15284440.
^ Banaszynski LA, Liu CW, Wandless TJ (Apr 2005). "Characterization of the FKBP.rapamycin.FRB ternary complex". Journal of the American Chemical Society. 127 (13): 4715–21. doi:10.1021/ja043277y. PMID 15796538.
^ Sabers CJ, Martin MM, Brunn GJ, Williams JM, Dumont FJ, Wiederrecht G, Abraham RT (Jan 1995). "Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells". The Journal of Biological Chemistry. 270 (2): 815–22. doi:10.1074/jbc.270.2.815. PMID 7822316.
^ Avila G, Lee EH, Perez CF, Allen PD, Dirksen RT (Jun 2003). "FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes". The Journal of Biological Chemistry. 278 (25): 22600–8. doi:10.1074/jbc.M205866200. PMID 12704193.
^ Bultynck G, De Smet P, Rossi D, Callewaert G, Missiaen L, Sorrentino V, De Smedt H, Parys JB (Mar 2001). "Characterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor". The Biochemical Journal. 354 (Pt 2): 413–22. doi:10.1042/bj3540413. PMC 1221670. PMID 11171121.
^ Gaburjakova M, Gaburjakova J, Reiken S, Huang F, Marx SO, Rosemblit N, Marks AR (May 2001). "FKBP12 binding modulates ryanodine receptor channel gating". The Journal of Biological Chemistry. 276 (20): 16931–5. doi:10.1074/jbc.M100856200. PMID 11279144.
^ Wang T, Donahoe PK, Zervos AS (Jul 1994). "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science. 265 (5172): 674–6. Bibcode:1994Sci...265..674W. doi:10.1126/science.7518616. PMID 7518616.
^ Liu F, Ventura F, Doody J, Massagué J (Jul 1995). "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Molecular and Cellular Biology. 15 (7): 3479–86. doi:10.1128/mcb.15.7.3479. PMC 230584. PMID 7791754.

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Wang T, Donahoe PK, Zervos AS (Jul 1994). "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science. 265 (5172): 674–6. Bibcode:1994Sci...265..674W. doi:10.1126/science.7518616. PMID 7518616.
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Yang WM, Inouye CJ, Seto E (Jun 1995). "Cyclophilin A and FKBP12 interact with YY1 and alter its transcriptional activity". The Journal of Biological Chemistry. 270 (25): 15187–93. doi:10.1074/jbc.270.25.15187. PMID 7541038.
Kawamura A, Su MS (Jun 1995). "Interaction of FKBP12-FK506 with calcineurin A at the B subunit-binding domain". The Journal of Biological Chemistry. 270 (26): 15463–6. doi:10.1074/jbc.270.26.15463. PMID 7541044.
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