P18203 (FKB1A_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP1A
Short name=PPIase FKBP1A
EC=5.2.1.8

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 names

Name:	FKBP1A
Synonyms:	FKBP1

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	108 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. 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.
Catalytic activity	Peptidylproline (omega=180) = peptidylproline (omega=0).
Enzyme regulation	Inhibited by both FK506 and rapamycin.
Subunit structure	Interacts with TGFBR1; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with ACVR1B and SMAD7. Interacts directly with RYR1, RYR2 and RYR3. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) By similarity.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the FKBP-type PPIase family. FKBP1 subfamily. Contains 1 PPIase FKBP-type domain.
Caution	Was originally (Ref.2) thought to be protein kinase C inhibitor 2 (PKCI-2 or 12 kDa inhibitor of protein kinase C), but has since been experimentally shown not to inhibit protein kinase C (Ref.8 and Ref.10).

Ontologies

Keywords
Cellular component	Cytoplasm
Molecular function	Isomerase Rotamase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell activation Non-traceable author statement Ref.4. Source: BHF-UCL negative regulation of protein phosphatase type 2B activity Inferred from sequence or structural similarity. Source: RefGenome protein folding Inferred from electronic annotation. Source: UniProtKB-KW regulation of ryanodine-sensitive calcium-release channel activity Inferred from sequence or structural similarity. Source: RefGenome
Cellular_component	axon Inferred from sequence or structural similarity. Source: RefGenome cytosol Inferred from direct assay Ref.4. Source: BHF-UCL sarcoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: RefGenome
Molecular_function	FK506 binding Inferred from sequence or structural similarity. Source: RefGenome peptidyl-prolyl cis-trans isomerase activity Inferred from direct assay Ref.4. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.2 Ref.3 Ref.4 Ref.5

Chain

2 – 108

107

Peptidyl-prolyl cis-trans isomerase FKBP1A

PRO_0000075288

Regions

Domain

20 – 108

89

PPIase FKBP-type

Amino acid modifications

Modified residue

9

1

Phosphoserine By similarity

Secondary structure

1

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108

Helix Strand Turn

Details...

Beta strand

3 – 9

7

Beta strand

22 – 31

10

Beta strand

36 – 40

5

Turn

41 – 44

4

Beta strand

47 – 50

4

Beta strand

53 – 56

4

Helix

58 – 65

8

Beta strand

72 – 77

6

Helix

79 – 81

3

Turn

82 – 86

5

Turn

89 – 91

3

Beta strand

98 – 107

10

Sequences

	Sequence		Length	Mass (Da)
	P18203 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 9CD0F1278039C5B4	FASTA	108	11,910
	10 20 30 40 50 60 MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFV LGKQEVIRGW 70 80 90 100 EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPNATLIF DVELLKLE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of 954 bovine full-CDS cDNA sequences." Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L. BMC Genomics 6:166-166(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]	"Amino acid sequence of a 12-kDa inhibitor of protein kinase C." Mozier N.M., Zuercher-Neely H.A., Guido D.M., Mathews W.R., Heinrikson R.L., Fraser E.D., Walsh M.P., Pearson J.D. Eur. J. Biochem. 194:19-23(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-108. Tissue: Brain.
[3]	"Complete amino acid sequence of the FK506 and rapamycin binding protein, FKBP, isolated from calf thymus." Lane W.S., Galat A., Harding M.W., Schreiber S.L. J. Protein Chem. 10:151-160(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-108. Tissue: Thymus.
[4]	"The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase." Siekierka J.J., Widerrecht G., Greulich H., Boulton D., Hung S.H.Y., Cryan J., Hodges P.J., Sigal N.H. J. Biol. Chem. 265:21011-21015(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-87.
[5]	"A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase." Harding M.W., Galat A., Uehling D.E., Schreiber S.L. Nature 341:758-760(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-41.
[6]	"The peptidyl-prolyl isomerase, FK506-binding protein, is most likely the 12 kd endogenous inhibitor 2 of protein kinase C." Goebl M.G. Cell 64:1051-1052(1991) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTITY OF FKBP AND PKCI-2.
[7]	"FK506 and protein kinase C." Tropschug A.M., Hofmann R. Nature 351:195-195(1991) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTITY OF FKBP AND PKCI-2.
[8]	"The peptidyl-prolyl isomerase, FK506-binding protein, is not identical to protein kinase C inhibitor 2." Goebl M. Cell 66:423-423(1991) [PubMed] [Europe PMC] [Abstract] Cited for: SHOWS THAT THE PROTEIN IS NOT AN INHIBITOR OF PROTEIN KINASE C.
[9]	"Retraction concerning amino acid sequence of a 12-kDa inhibitor of protein kinase C. Mistaken identity of a protein kinase C inhibitor." Walsh M.P. Eur. J. Biochem. 200:811-811(1991) [PubMed] [Europe PMC] [Abstract] Cited for: SHOWS THAT THE PROTEIN IS NOT AN INHIBITOR OF PROTEIN KINASE C.
[10]	"Relationship of FKBP to PKCI-2." Albers M.W., Liu J., Schreiber S.L. Nature 351:527-527(1991) [PubMed] [Europe PMC] [Abstract] Cited for: SHOWS THAT THE PROTEIN IS NOT AN INHIBITOR OF PROTEIN KINASE C.
[11]	"Solution structure of the major binding protein for the immunosuppressant FK506." Moore J.M., Peattie D.A., Fitzgibbon M.J., Thomson J.A. Nature 351:248-250(1991) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[12]	"X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex." Griffith J.P., Kim J.L., Kim E.E., Sintchak M.D., Thomson J.A., Fitzgibbon M.J., Fleming M.A., Caron P.R., Hsiao K., Navia M.A. Cell 82:507-522(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH CALCINEURIN B.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BT021075 mRNA. Translation: AAX09092.1.

IPI

IPI00698916.

PIR

A61431.

RefSeq

NP_001030533.1. NM_001035456.1.

UniGene

Bt.63982.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FKK	X-ray	2.20	A	2-107	[»]
1FKL	X-ray	1.70	A	2-107	[»]
1TCO	X-ray	2.50	C	2-108	[»]

ProteinModelPortal

P18203.

SMR

P18203. Positions 2-108.

ModBase

Search...

Proteomic databases

PaxDb

P18203.

PRIDE

P18203.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSBTAT00000010928; ENSBTAP00000010928; ENSBTAG00000008303.

GeneID

614795.

KEGG

bta:614795.

Organism-specific databases

CTD

2280.

Phylogenomic databases

eggNOG

COG0545.

GeneTree

ENSGT00550000074272.

HOVERGEN

HBG051623.

InParanoid

P18203.

KO

K09568.

OMA

GNRSAGK.

OrthoDB

EOG42NJ1X.

Gene expression databases

ArrayExpress

P18203.

Family and domain databases

InterPro

IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
[Graphical view]

PANTHER

PTHR10516. PTHR10516. 1 hit.

Pfam

PF00254. FKBP_C. 1 hit.
[Graphical view]

PROSITE

PS50059. FKBP_PPIASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P18203.

EvolutionaryTrace

P18203.

NextBio

20899293.

Entry information

Entry name

FKB1A_BOVIN

Accession

Primary (citable) accession number: P18203
Secondary accession number(s): Q5E945

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program