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Protein

Peptidyl-prolyl cis-trans isomerase FKBP1A

Gene

FKBP1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

Peptidylproline (omega=180) = peptidylproline (omega=0).2 Publications

Activity regulationi

Inhibited by both FK506 and rapamycin.

GO - Molecular functioni

  • activin binding Source: BHF-UCL
  • FK506 binding Source: BHF-UCL
  • ion channel binding Source: BHF-UCL
  • macrolide binding Source: BHF-UCL
  • peptidyl-prolyl cis-trans isomerase activity Source: BHF-UCL
  • SMAD binding Source: BHF-UCL
  • transforming growth factor beta receptor binding Source: BHF-UCL
  • type I transforming growth factor beta receptor binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionIsomerase, Rotamase

Enzyme and pathway databases

BRENDAi5.2.1.8 2681
ReactomeiR-HSA-2025928 Calcineurin activates NFAT
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-3645790 TGFBR2 Kinase Domain Mutants in Cancer
R-HSA-3656532 TGFBR1 KD Mutants in Cancer
R-HSA-3656535 TGFBR1 LBD Mutants in Cancer
SignaLinkiP62942
SIGNORiP62942

Protein family/group databases

TCDBi8.A.11.1.2 the immunophilin-like prolyl:peptidyl isomerase regulator (i-ppi) family

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP1A (EC:5.2.1.82 Publications)
Short name:
PPIase FKBP1A
Alternative name(s):
12 kDa FK506-binding protein
Short name:
12 kDa FKBP
Short name:
FKBP-12
Calstabin-1
FK506-binding protein 1A
Short name:
FKBP-1A
Immunophilin FKBP12
Rotamase
Gene namesi
Name:FKBP1A
Synonyms:FKBP1, FKBP12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000088832.14
HGNCiHGNC:3711 FKBP1A
MIMi186945 gene
neXtProtiNX_P62942

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Sarcoplasmic reticulum

Pathology & Biotechi

Organism-specific databases

DisGeNETi2280
OpenTargetsiENSG00000088832
PharmGKBiPA28153

Chemistry databases

ChEMBLiCHEMBL1902
DrugBankiDB04094 4-Hydroxy-2-Butanone
DB02888 FKB-001
DB01951 Gpi-1046
DB05814 GPI-1485
DB03338 Heptyl-Beta-D-Glucopyranoside
DB02311 Methyl Methylsulfinylmethyl Sulfide
DB08231 MYRISTIC ACID
DB00337 Pimecrolimus
DB00877 Sirolimus
DB00864 Tacrolimus
GuidetoPHARMACOLOGYi2609

Polymorphism and mutation databases

BioMutaiFKBP1A

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved3 Publications
ChainiPRO_00000752892 – 108Peptidyl-prolyl cis-trans isomerase FKBP1AAdd BLAST107

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei53N6-acetyllysine; alternateBy similarity1
Modified residuei53N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP62942
MaxQBiP62942
PaxDbiP62942
PeptideAtlasiP62942
PRIDEiP62942
ProteomicsDBi57456
TopDownProteomicsiP62942

PTM databases

iPTMnetiP62942
PhosphoSitePlusiP62942

Miscellaneous databases

PMAP-CutDBiP62942

Expressioni

Gene expression databases

BgeeiENSG00000088832 Expressed in 231 organ(s), highest expression level in caudate nucleus
CleanExiHS_FKBP1A
ExpressionAtlasiP62942 baseline and differential
GenevisibleiP62942 HS

Organism-specific databases

HPAiCAB004639
HPA051798

Interactioni

Subunit structurei

Interacts with TGFBR1; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation (PubMed:9233797). Interacts with ACVR1B and SMAD7 (PubMed:16720724). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Interacts directly with RYR2 and RYR3 (PubMed:10358090, PubMed:22100703). Interacts with GLMN; rapamycin and FK506 abolish the interaction with GLMN in a dose dependent manner (PubMed:8955134). Interacts directly with RYR1 (By similarity).By similarity6 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108570, 62 interactors
CORUMiP62942
DIPiDIP-29710N
IntActiP62942, 18 interactors
MINTiP62942
STRINGi9606.ENSP00000371138

Chemistry databases

BindingDBiP62942

Structurei

Secondary structure

1108
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP62942
SMRiP62942
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62942

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 108PPIase FKBP-typePROSITE-ProRule annotationAdd BLAST89

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0544 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOVERGENiHBG051623
InParanoidiP62942
KOiK09568
OMAiRVIAGWD
PhylomeDBiP62942
TreeFamiTF105291

Family and domain databases

InterProiView protein in InterPro
IPR023566 PPIase_FKBP
IPR001179 PPIase_FKBP_dom
PANTHERiPTHR10516 PTHR10516, 1 hit
PfamiView protein in Pfam
PF00254 FKBP_C, 1 hit
PROSITEiView protein in PROSITE
PS50059 FKBP_PPIASE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

P62942-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFM
60 70 80 90 100
LGKQEVIRGW EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPHATLVF

DVELLKLE
Length:108
Mass (Da):11,951
Last modified:January 23, 2007 - v2
Checksum:i9CC8493C802540B4
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WZM5A0A087WZM5_HUMAN
Peptidylprolyl isomerase
FKBP1A
129Annotation score:
Q1JUQ5Q1JUQ5_HUMAN
Peptidylprolyl isomerase
FKBP1A FKBP12-Exip2
92Annotation score:
Q5W0X3Q5W0X3_HUMAN
Peptidylprolyl isomerase
FKBP1A
103Annotation score:
Q1JUQ3Q1JUQ3_HUMAN
FK506 binding protein12
FKBP1A FKBP12-Exin
37Annotation score:
A0A087WTS4A0A087WTS4_HUMAN
Peptidyl-prolyl cis-trans isomerase...
FKBP1A
97Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60W → R in CAG28541 (Ref. 6) Curated1
Sequence conflicti91I → V in CAG28541 (Ref. 6) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34539 mRNA Translation: AAA35844.1
M92423, M92422 Genomic DNA Translation: AAA58476.1
M93060 Genomic DNA No translation available.
X55741 Genomic DNA Translation: CAA39272.1
M80199 Genomic DNA Translation: AAA58472.1
X52220 mRNA Translation: CAA36462.1
BT007066 mRNA Translation: AAP35729.1
CR407613 mRNA Translation: CAG28541.1
CR542168 mRNA Translation: CAG46965.1
AL136531 Genomic DNA No translation available.
AL109658 Genomic DNA No translation available.
CH471133 Genomic DNA Translation: EAX10633.1
CH471133 Genomic DNA Translation: EAX10634.1
CH471133 Genomic DNA Translation: EAX10635.1
BC001925 mRNA Translation: AAH01925.3
BC005147 mRNA Translation: AAH05147.1
CCDSiCCDS13014.1
PIRiI65284 A35780
RefSeqiNP_000792.1, NM_000801.4
NP_463460.1, NM_054014.3
UniGeneiHs.471933
Hs.700839

Genome annotation databases

EnsembliENST00000381719; ENSP00000371138; ENSG00000088832
ENST00000400137; ENSP00000383003; ENSG00000088832
GeneIDi2280
KEGGihsa:2280
UCSCiuc002wey.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34539 mRNA Translation: AAA35844.1
M92423, M92422 Genomic DNA Translation: AAA58476.1
M93060 Genomic DNA No translation available.
X55741 Genomic DNA Translation: CAA39272.1
M80199 Genomic DNA Translation: AAA58472.1
X52220 mRNA Translation: CAA36462.1
BT007066 mRNA Translation: AAP35729.1
CR407613 mRNA Translation: CAG28541.1
CR542168 mRNA Translation: CAG46965.1
AL136531 Genomic DNA No translation available.
AL109658 Genomic DNA No translation available.
CH471133 Genomic DNA Translation: EAX10633.1
CH471133 Genomic DNA Translation: EAX10634.1
CH471133 Genomic DNA Translation: EAX10635.1
BC001925 mRNA Translation: AAH01925.3
BC005147 mRNA Translation: AAH05147.1
CCDSiCCDS13014.1
PIRiI65284 A35780
RefSeqiNP_000792.1, NM_000801.4
NP_463460.1, NM_054014.3
UniGeneiHs.471933
Hs.700839

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A7XX-ray2.00A/B2-108[»]
1B6CX-ray2.60A/C/E/G2-108[»]
1BKFX-ray1.60A2-108[»]
1BL4X-ray1.90A/B2-108[»]
1D6OX-ray1.85A/B2-108[»]
1D7HX-ray1.90A/B2-108[»]
1D7IX-ray1.90A/B2-108[»]
1D7JX-ray1.85A/B2-108[»]
1EYMX-ray2.00A/B2-108[»]
1F40NMR-A2-108[»]
1FAPX-ray2.70A2-108[»]
1FKBX-ray1.70A2-108[»]
1FKDX-ray1.72A2-108[»]
1FKFX-ray1.70A2-108[»]
1FKGX-ray2.00A2-108[»]
1FKHX-ray1.95A2-108[»]
1FKIX-ray2.20A/B2-108[»]
1FKJX-ray1.70A2-108[»]
1FKRNMR-A2-108[»]
1FKSNMR-A2-108[»]
1FKTNMR-A2-108[»]
1J4HX-ray1.80A2-108[»]
1J4IX-ray1.80A2-108[»]
1J4RX-ray1.80A/B/D2-108[»]
1NSGX-ray2.20A2-108[»]
1QPFX-ray2.50A/D2-108[»]
1QPLX-ray2.90A/C2-108[»]
2DG3X-ray1.70A2-108[»]
2DG4X-ray1.70A2-108[»]
2DG9X-ray1.70A2-108[»]
2FAPX-ray2.20A2-108[»]
2FKEX-ray1.72A2-108[»]
2ND5NMR-A1-108[»]
2PPNX-ray0.92A2-108[»]
2PPOX-ray1.29A2-108[»]
2PPPX-ray0.94A2-108[»]
2RSENMR-A2-108[»]
3FAPX-ray1.85A2-108[»]
3H9RX-ray2.35B1-108[»]
3MDYX-ray2.05B/D1-108[»]
4DH0X-ray2.10A2-108[»]
4FAPX-ray2.80A2-108[»]
4IPXX-ray1.70A2-108[»]
4N19X-ray1.20A2-108[»]
4ODPX-ray1.75A85-97[»]
4ODQX-ray2.00A85-97[»]
4ODRX-ray1.93A/B85-97[»]
5I7PX-ray2.00A2-84[»]
A98-108[»]
5I7QX-ray1.90A2-84[»]
A97-108[»]
ProteinModelPortaliP62942
SMRiP62942
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108570, 62 interactors
CORUMiP62942
DIPiDIP-29710N
IntActiP62942, 18 interactors
MINTiP62942
STRINGi9606.ENSP00000371138

Chemistry databases

BindingDBiP62942
ChEMBLiCHEMBL1902
DrugBankiDB04094 4-Hydroxy-2-Butanone
DB02888 FKB-001
DB01951 Gpi-1046
DB05814 GPI-1485
DB03338 Heptyl-Beta-D-Glucopyranoside
DB02311 Methyl Methylsulfinylmethyl Sulfide
DB08231 MYRISTIC ACID
DB00337 Pimecrolimus
DB00877 Sirolimus
DB00864 Tacrolimus
GuidetoPHARMACOLOGYi2609

Protein family/group databases

TCDBi8.A.11.1.2 the immunophilin-like prolyl:peptidyl isomerase regulator (i-ppi) family

PTM databases

iPTMnetiP62942
PhosphoSitePlusiP62942

Polymorphism and mutation databases

BioMutaiFKBP1A

Proteomic databases

EPDiP62942
MaxQBiP62942
PaxDbiP62942
PeptideAtlasiP62942
PRIDEiP62942
ProteomicsDBi57456
TopDownProteomicsiP62942

Protocols and materials databases

DNASUi2280
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381719; ENSP00000371138; ENSG00000088832
ENST00000400137; ENSP00000383003; ENSG00000088832
GeneIDi2280
KEGGihsa:2280
UCSCiuc002wey.4 human

Organism-specific databases

CTDi2280
DisGeNETi2280
EuPathDBiHostDB:ENSG00000088832.14
GeneCardsiFKBP1A
HGNCiHGNC:3711 FKBP1A
HPAiCAB004639
HPA051798
MIMi186945 gene
neXtProtiNX_P62942
OpenTargetsiENSG00000088832
PharmGKBiPA28153
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0544 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOVERGENiHBG051623
InParanoidiP62942
KOiK09568
OMAiRVIAGWD
PhylomeDBiP62942
TreeFamiTF105291

Enzyme and pathway databases

BRENDAi5.2.1.8 2681
ReactomeiR-HSA-2025928 Calcineurin activates NFAT
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-3645790 TGFBR2 Kinase Domain Mutants in Cancer
R-HSA-3656532 TGFBR1 KD Mutants in Cancer
R-HSA-3656535 TGFBR1 LBD Mutants in Cancer
SignaLinkiP62942
SIGNORiP62942

Miscellaneous databases

EvolutionaryTraceiP62942
GeneWikiiFKBP1A
GenomeRNAii2280
PMAP-CutDBiP62942
PROiPR:P62942
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000088832 Expressed in 231 organ(s), highest expression level in caudate nucleus
CleanExiHS_FKBP1A
ExpressionAtlasiP62942 baseline and differential
GenevisibleiP62942 HS

Family and domain databases

InterProiView protein in InterPro
IPR023566 PPIase_FKBP
IPR001179 PPIase_FKBP_dom
PANTHERiPTHR10516 PTHR10516, 1 hit
PfamiView protein in Pfam
PF00254 FKBP_C, 1 hit
PROSITEiView protein in PROSITE
PS50059 FKBP_PPIASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFKB1A_HUMAN
AccessioniPrimary (citable) accession number: P62942
Secondary accession number(s): D3DVW6
, P20071, Q4VC47, Q6FGD9, Q6LEU3, Q9H103, Q9H566
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 162 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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