Peptidyl-prolyl cis-trans isomerase FKBP1A (FKBP1A)
The protein contains 108 amino acids for an estimated molecular weight of 11951 Da.
Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
'de novo' protein folding
Amyloid fibril formation
Calcium ion transmembrane transport
Chaperone-mediated protein folding
Cytokine-mediated signaling pathway
Extracellular fibril organization
Heart morphogenesis
Heart trabecula formation
Muscle contraction
Negative regulation of phosphoprotein phosphatase activity
Negative regulation of protein phosphatase type 2B activity
Negative regulation of protein phosphorylation
Negative regulation of transforming growth factor beta receptor signaling pathway
Negative regulation of transforming growth factor beta1 activation
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of protein binding
Positive regulation of protein ubiquitination
Protein folding
Protein maturation by protein folding
Protein peptidyl-prolyl isomerization
Protein refolding
Regulation of activin receptor signaling pathway
Regulation of amyloid precursor protein catabolic process
Regulation of immune response
Regulation of protein localization
Regulation of ryanodine-sensitive calcium-release channel activity
Release of sequestered calcium ion into cytosol
Response to caffeine
Response to iron ion
SMAD protein complex assembly
Supramolecular fiber organization
T cell activation
T cell proliferation
Transforming growth factor beta receptor signaling pathway
Ventricular cardiac muscle tissue morphogenesis
Cellular Component
Axon terminus
Cytoplasm
Cytoplasmic side of membrane
Cytosol
Endoplasmic reticulum membrane
Extracellular exosome
Extrinsic component of organelle membrane
Membrane
Ryanodine receptor complex
Sarcoplasmic reticulum
Sarcoplasmic reticulum membrane
Terminal cisterna
Z disc
Molecular Function
Activin binding
Enzyme binding
FK506 binding
Hsp70 protein binding
Ion channel binding
Macrolide binding
Obsolete signal transducer activity
Peptidyl-prolyl cis-trans isomerase activity
Protein homodimerization activity
SMAD binding
Transforming growth factor beta receptor binding
Type I transforming growth factor beta receptor binding
The reference OMIM entry for this protein is 186945
Fk506-binding protein 1a; fkbp1a
Fk506-binding protein 1; fkbp1
Fk506-binding protein, 12-kd; fkbp12
Fk506-binding protein, t-cell, 12-kd
Calstabin 1
DESCRIPTION
Immunophilins are a family of highly conserved proteins that bind with immunosuppressive drugs, such as FK506, rapamycin, and cyclosporin A (CsA). The 2 major types of immunophilins are FK506-binding proteins (FKBPs), most of which bind FK506 and rapamycin, and cyclophilins (e.g., PPIA; 123840), which bind CsA. Most FKBPs, including FKBP1A, exhibit peptidyl-prolyl cis/trans isomerase (PPIase; EC 5.2.1.8) activity. FKBPs are involved in numerous biologic processes, including protein folding, receptor signaling, protein trafficking, transcription, apoptosis, and T-cell activation (review by Kang et al., 2008).CLONING
Maki et al. (1990) isolated and sequenced DNA coding for FKBP from human peripheral blood T lymphocytes by using mixed 20-mer oligonucleotide probes synthesized on the basis of the sequence of bovine Fkbp. They found an ORF encoding 108 amino acids, the first 40 of which are identical to those of the bovine sequence. Analysis showed no significant sequence similarity to other proteins, including cyclophilin (PPIA; 123840). Southern blot analysis of human genomic DNA suggested the existence of only a few copies of the FKBP gene. This is in contrast to results indicating as many as 20 copies of the cyclophilin gene, as well as possible pseudogenes, in the mammalian genome. Standaert et al. (1990) likewise isolated a cDNA for FKBP and reported the derived amino acid sequence. The human FKBP cDNA sequence shares significant similarity with an ORF in the genome of Neisseria meningitidis. Peattie et al. (1994) identified 3 distinct mRNAs for FKBP12, designated A, B, and C, that result from differential splicing or polyadenylation. All 3 encode the same protein sequence.GENE FUNCTION
Jin et al. (1991) noted that the 12-kD FKBP is a cytosolic receptor for rapamycin and FK506, both of which are immunosuppressants. Wang et al. (1994) reported that in a yeast genetic screen, FKBP1 interacted with various type I receptors, including the TGF-beta type I receptor (190181). Deletion, point mutation, and coimmunoprecipitation studies demonstrated the specificity of this interaction, and competitive binding assays indicated that the type I receptor may be a natural ligand for FKBP1. Wang et al. (1994) concluded that FKBP1 may play a role in type I receptor-mediated signaling. - Reviews Kang et al. (2008) reviewed the molecular characteristics of FKBP family members, including FKBP1A, and the biologic functions of their ligands in performing neuroprotective and neurotrophic activities.MAPPING
Using PCR to amplify an intron-containing region of the gene in purified DNA isolated from human/rodent somatic cell hybrids, DiLella (1991) assigned the FKBP1 gene to human chromosome 20. DiLella et al. (1992) used fluorescence in situ hybridization to map the FKBP1 gene to chromosome 20p13.ANIMAL MODEL
To define the functions of FKBP12 in vivo, Shou et al. (1998) generated mutant mice deficient in Fkpb12 using embryonic stem (ES) cell technology. Fkbp12-deficient mice had normal skeletal muscle, but they had severe dilated cardiomyopathy and ventricular septal defects that mimicked a human congenital heart disorder, namely noncompaction of left ventricular myocardium (see 302060 for an X-linked form of myocardial noncompaction). About 9% of the mutants exhibited exencephaly secondary to a defect in neural tube closure. Physiologic studies demonstrated that Fkbp12 was dispensable for ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 186945 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed