Reviewed, UniProtKB/Swiss-Prot P62942 (FKB1A_HUMAN)

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):
    FK506-binding protein 1A
      Short name=FKBP-1A
    Rotamase
    Immunophilin FKBP12
      Short name=12 kDa FKBP
      Short name=FKBP-12

Gene names

Name:	FKBP1A
Synonyms:	FKBP1, FKBP12

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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	May play a role in modulation of ryanodine receptor isoform-1 (RYR-1), a component of the calcium release channel of skeletal muscle sarcoplasmic reticulum. There are four molecules of FKBP12 per skeletal muscle RYR. 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.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the FKBP-type PPIase family. FKBP1 subfamily. Contains 1 PPIase FKBP-type domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Molecular function	Isomerase Rotamase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	'de novo' protein folding Traceable author statement. Source: UniProtKB T cell activation Ref.2 Non-traceable author statement. Source: UniProtKB negative regulation of protein phosphatase type 2B activity Inferred from direct assay. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype. Source: UniProtKB protein maturation via protein folding Traceable author statement. Source: UniProtKB protein refolding Traceable author statement. Source: UniProtKB regulation of immune response Ref.10 Inferred from mutant phenotype. Source: UniProtKB regulation of ryanodine-sensitive calcium-release channel activity Inferred from direct assay. Source: UniProtKB ventricular cardiac muscle morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytosol Ref.9 Inferred from direct assay. Source: UniProtKB terminal cisterna Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	peptidyl-prolyl cis-trans isomerase activity Ref.2 Ref.9 Ref.10 Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB receptor activity Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FRAP1	P42345	1	EBI-1027571,EBI-359260

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 108

107

Peptidyl-prolyl cis-trans isomerase FKBP1A

PRO_0000075289

Regions

Domain

20 – 108

89

PPIase FKBP-type

Experimental info

Sequence conflict

60

1

W → R in CAG28541. Ref.6

Sequence conflict

91

1

I → V in CAG28541. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

108

Helix Strand Turn

Details...

Beta strand

3 – 9

7

Beta strand

22 – 31

10

Beta strand

36 – 39

4

Helix

40 – 43

4

Beta strand

47 – 50

4

Helix

58 – 64

7

Beta strand

72 – 77

6

Helix

79 – 81

3

Turn

82 – 86

5

Turn

89 – 91

3

Sequences

	Sequence		Length	Mass (Da)
	P62942-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 9CC8493C802540B4	FASTA	108	11,951
	10 20 30 40 50 60 MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFM LGKQEVIRGW 70 80 90 100 EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPHATLVF DVELLKLE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complementary DNA encoding the human T-cell FK506-binding protein, a peptidylprolyl cis-trans isomerase distinct from cyclophilin." Maki N., Sekiguchi F., Nishimaki J., Miwa K., Hayano T., Takahashi N., Suzuki M. Proc. Natl. Acad. Sci. U.S.A. 87:5440-5443(1990) [PubMed: 1695378] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning and overexpression of the human FK506-binding protein FKBP." Standaert R.F., Galat A., Verdine G.L., Schreiber S.L. Nature 346:671-674(1990) [PubMed: 1696686] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Exon organization of the human FKBP-12 gene: correlation with structural and functional protein domains." Dilella A.G., Craig R.J. Biochemistry 30:8512-8517(1991) [PubMed: 1716149] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Three distinct messenger RNAs can encode the human immunosuppressant-binding protein FKBP12." Peattie D.A., Hsiao K., Benasutti M., Lippke J.A. Gene 150:251-257(1994) [PubMed: 7529739] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Placenta.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Placenta.
[9]	"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: 1701173] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-52.
[10]	"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: 2477715] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-17.
[11]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-14. Tissue: Platelet.
[12]	"Proton and nitrogen sequential assignments and secondary structure determination of the human FK506 and rapamycin binding protein." Rosen M.K., Michnick S.W., Karplus M., Schreiber S.L. Biochemistry 30:4774-4789(1991) [PubMed: 1709363] [Abstract] Cited for: STRUCTURE BY NMR.
[13]	"Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin." Michnick S.W., Rosen M.K., Wandless T.J., Karplus M., Schreiber S.L. Science 252:836-839(1991) [PubMed: 1709301] [Abstract] Cited for: STRUCTURE BY NMR.
[14]	"Solution structure of FK506 bound to FKBP-12." Lepre C.A., Thomson J.A., Moore J.M. FEBS Lett. 302:89-96(1992) [PubMed: 1375171] [Abstract] Cited for: STRUCTURE BY NMR.
[15]	"1H, 13C, and 15N assignments and secondary structure of the FK506 binding protein when bound to ascomycin." Xu R.X., Nettesheim D., Olejniczak E.T., Meadows R., Gemmecker G., Fesik S.W. Biopolymers 33:535-550(1993) [PubMed: 7682113] [Abstract] Cited for: STRUCTURE BY NMR OF COMPLEX WITH ASCOMYCIN.
[16]	"Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex." van Duyne G.D., Standaert R.F., Karplus P.A., Schreiber S.L., Clardy J. Science 252:839-842(1991) [PubMed: 1709302] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
[17]	"Atomic structure of the rapamycin human immunophilin FKBP-12 complex." van Duyne G.D., Standaert R.F., Schreiber S.L., Clardy J. J. Am. Chem. Soc. 113:7433-7434(1991) Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
[18]	"Atomic structures of the human immunophilin FKBP-12 complexes with FK506 and rapamycin." van Duyne G.D., Standaert R.F., Karplus P.A., Schreiber S.L., Clardy J. J. Mol. Biol. 229:105-124(1993) [PubMed: 7678431] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS).
[19]	"X-ray structures of small ligand-FKBP complexes provide an estimate for hydrophobic interaction energies." Burkhard P., Taylor P., Walkinshaw M.D. J. Mol. Biol. 295:953-962(2000) [PubMed: 10656803] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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, AL109658 Genomic DNA. Translation: CAH72382.1.
AL109658, AL136531 Genomic DNA. Translation: CAI22728.1.
BC001925 mRNA. Translation: AAH01925.3.
BC005147 mRNA. Translation: AAH05147.1.

PIR

A35780. I65284.

RefSeq

NP_000792.1.
NP_463460.1.

UniGene

Hs.471933

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A7X	X-ray	2.00	A/B	1-108	[»]
1B6C	X-ray	2.60	A/C/E/G	1-108	[»]
1BKF	X-ray	1.60	A	1-108	[»]
1BL4	X-ray	1.90	A/B	1-108	[»]
1D6O	X-ray	1.85	A/B	1-108	[»]
1D7H	X-ray	1.90	A/B	1-108	[»]
1D7I	X-ray	1.90	A/B	1-108	[»]
1D7J	X-ray	1.85	A/B	1-108	[»]
1EYM	X-ray	2.00	A/B	1-108	[»]
1F40	NMR	-	A	1-108	[»]
1FAP	X-ray	2.70	A	1-108	[»]
1FKB	X-ray	1.70	A	1-108	[»]
1FKD	X-ray	1.72	A	1-108	[»]
1FKF	X-ray	1.70	A	1-108	[»]
1FKG	X-ray	2.00	A	1-108	[»]
1FKH	X-ray	1.95	A	1-108	[»]
1FKI	X-ray	2.20	A/B	1-108	[»]
1FKJ	X-ray	1.70	A	1-108	[»]
1FKR	NMR	-	A	1-108	[»]
1FKS	NMR	-	A	1-108	[»]
1FKT	NMR	-	A	1-108	[»]
1J4H	X-ray	1.80	A	1-108	[»]
1J4I	X-ray	1.80	A	1-108	[»]
1J4R	X-ray	1.80	A/B/D	1-108	[»]
1NSG	X-ray	2.20	A	1-108	[»]
1QPF	X-ray	2.50	A/D	1-108	[»]
1QPL	X-ray	2.90	A/C	1-108	[»]
1TCO	X-ray	2.50	C	1-108	[»]
2DG3	X-ray	1.70	A	1-108	[»]
2DG4	X-ray	1.70	A	1-108	[»]
2DG9	X-ray	1.70	A	1-108	[»]
2FAP	X-ray	2.20	A	1-108	[»]
2FKE	X-ray	1.72	A	1-108	[»]
2PPN	X-ray	0.92	A	2-108	[»]
2PPO	X-ray	1.29	A	2-108	[»]
2PPP	X-ray	0.94	A	2-108	[»]
3FAP	X-ray	1.85	A	1-108	[»]
4FAP	X-ray	2.80	A	1-108	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P62942.

PTM databases

PhosphoSite

P62942.

Genome annotation databases

Ensembl

ENSG00000088832. Homo sapiens. [Contig view]

GeneID

2280.

KEGG

hsa:2280.

Organism-specific databases

H-InvDB

HIX0015564.

HGNC

HGNC:3711. FKBP1A.

HPA

CAB004639.

MIM

186945. gene.

PharmGKB

PA28153.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P62942.

Gene expression databases

ArrayExpress

P62942.

CleanEx

HS_FKBP1A.

GermOnline

ENSG00000088832. Homo sapiens.

Family and domain databases

InterPro

IPR001179. PPIase_FKBP.
[Graphical view]

PANTHER

PTHR10516. PPIase_FKBP. 1 hit.

Pfam

PF00254. FKBP_C. 1 hit.
[Graphical view]

PROSITE

PS50059. FKBP_PPIASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00337. Pimecrolimus.
DB00877. Sirolimus.
DB00864. Tacrolimus.

LinkHub

P62942.

NextBio

9269.

SOURCE

Search...

Entry information

Entry name

FKB1A_HUMAN

Accession

Primary (citable) accession number: P62942
Secondary accession number(s): P20071 , Q4VC47, Q6FGD9, Q6LEU3, Q9H103, Q9H566

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 31, 2004
Last sequence update:	January 23, 2007
Last modified:	November 25, 2008
This is version 52 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)