FKBP1B

FKBP1B
Identifiers
Aliases	FKBP1B, FKBP12.6, FKBP1L, OTK4, PKBP1L, PPIase, FK506 binding protein 1B, FKBP prolyl isomerase 1B
External IDs	OMIM: 600620; MGI: 1336205; HomoloGene: 68380; GeneCards: FKBP1B; OMA:FKBP1B - orthologs
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1C9H, 3J8E, 4C02, 4IQ2, 4IQC
Enzyme activity
Gene location (Human)
Chr.	Chromosome 2 (human)
End	24,063,681 bp
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)
End	4,891,591 bp
RNA expression pattern
	Top expressed in
	nucleus accumbens; ; caudate nucleus; ; putamen; ; hippocampus proper; ; anterior cingulate cortex; ; temporal lobe; ; amygdala; ; dorsolateral prefrontal cortex; ; right frontal lobe; ; superior frontal gyrus;
	Top expressed in
	trigeminal ganglion; ; barrel cortex; ; spinal ganglia; ; islet of Langerhans; ; facial motor nucleus; ; lumbar spinal ganglion; ; motor neuron; ; substantia nigra; ; CA3 field; ; medulla oblongata;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	ryanodine-sensitive calcium-release channel activity; calcium channel inhibitor activity; transmembrane transporter binding; FK506 binding; isomerase activity; peptidyl-prolyl cis-trans isomerase activity; protein binding; signaling receptor binding; cyclic nucleotide binding;
Cellular component	cytoplasm; calcium channel complex; intracellular membrane-bounded organelle; membrane; sarcoplasmic reticulum; Z discdkac; sarcoplasmic reticulum membrane; cytosol;
Biological process	smooth muscle contraction; regulation of ryanodine-sensitive calcium-release channel activity; release of sequestered calcium ion into cytosol; regulation of cardiac conduction; release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; regulation of cytosolic calcium ion concentration; regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; positive regulation of cytosolic calcium ion concentration; cell communication by electrical coupling involved in cardiac conduction; negative regulation of insulin secretion involved in cellular response to glucose stimulus; insulin secretion; response to glucose; positive regulation of axon regeneration; protein maturation by protein folding; response to organic substance; negative regulation of heart rate; response to vitamin E; regulation of heart rate; negative regulation of ryanodine-sensitive calcium-release channel activity; response to redox state; T cell proliferation; ion transmembrane transport; positive regulation of sequestering of calcium ion; neuronal action potential propagation; protein refolding; negative regulation of release of sequestered calcium ion into cytosol; regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; 'de novo' protein folding; calcium-mediated signaling using intracellular calcium source; response to hydrogen peroxide; chaperone-mediated protein folding; protein peptidyl-prolyl isomerization; negative regulation of phosphoprotein phosphatase activity;
	Sources:Amigo / QuickGO
Orthologs
	2281
	14226
	ENSG00000119782
	ENSMUSG00000020635
	P68106
	Q9Z2I2
	NM_004116; NM_054033; NM_001322963; NM_001322964
	NM_016863; NM_001378816; NM_001378817; NM_001378818
	NP_001309892; NP_001309893; NP_004107; NP_473374
	NP_058559; NP_001365745; NP_001365746; NP_001365747
	Wikidata
View/Edit Human	View/Edit Mouse

Peptidyl-prolyl cis-trans isomerase FKBP1B is an enzyme that in humans is encoded by the FKBP1B gene.^[5]^[6]

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 is highly similar to the FK506-binding protein 1A. Its physiological role is thought to be in excitation-contraction coupling in cardiac muscle. There are two alternatively spliced transcript variants of this gene encoding different isoforms.^[6]

Clinical significance

Defective interaction between FKB1B and the ryanodine receptor is thought to be a potential mechanism underlying the arrhythmias seen in those with the genetic condition catecholaminergic polymorphic ventricular tachycardia.^[7]

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000119782 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020635 – 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.
↑ Arakawa H, Nagase H, Hayashi N, Fujiwara T, Ogawa M, Shin S, et al. (April 1994). "Molecular cloning and expression of a novel human gene that is highly homologous to human FK506-binding protein 12kDa (hFKBP-12) and characterization of two alternatively spliced transcripts". Biochemical and Biophysical Research Communications. 200 (2): 836–843. Bibcode:1994BBRC..200..836A. doi:10.1006/bbrc.1994.1527. PMID 7513996.
1 2 "Entrez Gene: FKBP1B FK506 binding protein 1B, 12.6 kDa".
↑ Venetucci L, Denegri M, Napolitano C, Priori SG (October 2012). "Inherited calcium channelopathies in the pathophysiology of arrhythmias". Nature Reviews. Cardiology. 9 (10): 561–575. doi:10.1038/nrcardio.2012.93. PMID 22733215. S2CID 24883043.

Schiene-Fischer C, Yu C (April 2001). "Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases". FEBS Letters. 495 (1–2): 1–6. Bibcode:2001FEBSL.495....1S. doi:10.1016/S0014-5793(01)02326-2. PMID 11322937. S2CID 42263861.
Lam E, Martin MM, Timerman AP, Sabers C, Fleischer S, Lukas T, et al. (November 1995). "A novel FK506 binding protein can mediate the immunosuppressive effects of FK506 and is associated with the cardiac ryanodine receptor". The Journal of Biological Chemistry. 270 (44): 26511–26522. doi:10.1074/jbc.270.44.26511. PMID 7592869.
Noguchi N, Takasawa S, Nata K, Tohgo A, Kato I, Ikehata F, et al. (February 1997). "Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes". The Journal of Biological Chemistry. 272 (6): 3133–3136. doi:10.1074/jbc.272.6.3133. PMID 9013543.
Deivanayagam CC, Carson M, Thotakura A, Narayana SV, Chodavarapu RS (March 2000). "Structure of FKBP12.6 in complex with rapamycin". Acta Crystallographica. Section D, Biological Crystallography. 56 (Pt 3): 266–271. doi:10.1107/S0907444999016571. PMID 10713512.
Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, et al. (May 2000). "PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts". Cell. 101 (4): 365–376. doi:10.1016/S0092-8674(00)80847-8. PMID 10830164. S2CID 6496567.
Jeyakumar LH, Ballester L, Cheng DS, McIntyre JO, Chang P, Olivey HE, et al. (March 2001). "FKBP binding characteristics of cardiac microsomes from diverse vertebrates". Biochemical and Biophysical Research Communications. 281 (4): 979–986. Bibcode:2001BBRC..281..979J. doi:10.1006/bbrc.2001.4444. PMID 11237759.
George CH, Sorathia R, Bertrand BM, Lai FA (March 2003). "In situ modulation of the human cardiac ryanodine receptor (hRyR2) by FKBP12.6". The Biochemical Journal. 370 (Pt 2): 579–589. doi:10.1042/BJ20021433. PMC 1223191. PMID 12443530.
Masumiya H, Wang R, Zhang J, Xiao B, Chen SR (February 2003). "Localization of the 12.6-kDa FK506-binding protein (FKBP12.6) binding site to the NH2-terminal domain of the cardiac Ca2+ release channel (ryanodine receptor)". The Journal of Biological Chemistry. 278 (6): 3786–3792. doi:10.1074/jbc.M210962200. PMID 12446682.
Tiso N, Salamon M, Bagattin A, Danieli GA, Argenton F, Bortolussi M (December 2002). "The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations". Biochemical and Biophysical Research Communications. 299 (4): 594–598. Bibcode:2002BBRC..299..594T. doi:10.1016/S0006-291X(02)02689-X. PMID 12459180.
George CH, Higgs GV, Mackrill JJ, Lai FA (August 2003). "Dysregulated ryanodine receptors mediate cellular toxicity: restoration of normal phenotype by FKBP12.6". The Journal of Biological Chemistry. 278 (31): 28856–28864. doi:10.1074/jbc.M212440200. PMID 12754204.
Nishanian TG, Waldman T (October 2004). "Interaction of the BMPR-IA tumor suppressor with a developmentally relevant splicing factor". Biochemical and Biophysical Research Communications. 323 (1): 91–97. Bibcode:2004BBRC..323...91N. doi:10.1016/j.bbrc.2004.08.060. PMID 15351706.
Maalej A, Mbarki F, Rebai A, Karray F, Jouida J, Abid M, et al. (May 2004). "Evidence of association between FKBP1B and thyroid autoimmune disorders in a large Tunisian family". Autoimmunity. 37 (3): 237–239. doi:10.1080/08916930410001702478. PMID 15497458. S2CID 31963934.
Zissimopoulos S, Lai FA (February 2005). "Interaction of FKBP12.6 with the cardiac ryanodine receptor C-terminal domain". The Journal of Biological Chemistry. 280 (7): 5475–5485. doi:10.1074/jbc.M412954200. PMID 15591045.
Aizawa Y, Ueda K, Komura S, Washizuka T, Chinushi M, Inagaki N, et al. (March 2005). "A novel mutation in FKBP12.6 binding region of the human cardiac ryanodine receptor gene (R2401H) in a Japanese patient with catecholaminergic polymorphic ventricular tachycardia". International Journal of Cardiology. 99 (2): 343–345. doi:10.1016/j.ijcard.2003.11.050. PMID 15749201.
Wehrens XH, Lehnart SE, Reiken S, van der Nagel R, Morales R, Sun J, et al. (July 2005). "Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure". Proceedings of the National Academy of Sciences of the United States of America. 102 (27): 9607–9612. Bibcode:2005PNAS..102.9607W. doi:10.1073/pnas.0500353102. PMC 1172237. PMID 15972811.

This article on a gene on human chromosome 2 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000119782 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020635 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7513996-5] Arakawa H, Nagase H, Hayashi N, Fujiwara T, Ogawa M, Shin S, et al. (April 1994). "Molecular cloning and expression of a novel human gene that is highly homologous to human FK506-binding protein 12kDa (hFKBP-12) and characterization of two alternatively spliced transcripts". Biochemical and Biophysical Research Communications. 200 (2): 836–843. Bibcode:1994BBRC..200..836A. doi:10.1006/bbrc.1994.1527. PMID 7513996.

[entrez-6] 1 2 "Entrez Gene: FKBP1B FK506 binding protein 1B, 12.6 kDa".

[7] Venetucci L, Denegri M, Napolitano C, Priori SG (October 2012). "Inherited calcium channelopathies in the pathophysiology of arrhythmias". Nature Reviews. Cardiology. 9 (10): 561–575. doi:10.1038/nrcardio.2012.93. PMID 22733215. S2CID 24883043.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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FKBP1B

Function

Clinical significance

References

Further reading