Reviewed, UniProtKB/Swiss-Prot Q9XSH5 (FKBP5_SAIBB)

Names and origin

Protein names

Recommended name:
    FK506-binding protein 5
    EC=5.2.1.8
Alternative name(s):
    Peptidyl-prolyl cis-trans isomerase
    51 kDa FK506-binding immunophilin
    FKBP-51

Gene names

Name:	FKBP5
Synonyms:	FKBP51

Organism

Saimiri boliviensis boliviensis (Bolivian squirrel monkey)

Taxonomic identifier

39432 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Platyrrhini › Cebidae › Saimiriinae › Saimiri

Protein attributes

Sequence length	457 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP By similarity. Interacts with the glucocorticoid receptor and modulates its response to glucocorticoids.
Catalytic activity	Peptidylproline (omega=180) = peptidylproline (omega=0).
Enzyme regulation	Inhibited by FK506 but not cyclosporin.
Subunit structure	Part of a heteromultimeric cytoplasmic complex with HSP90, HSP70 and steroid receptors. Dissociates from the complex when NR3C1 binds glucocorticoid By similarity.
Subcellular location	Cytoplasm.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR By similarity.
Miscellaneous	The relative resistance of squirrel monkeys to glucocorticoids is associated with a high level of expression of FKBP5, but is also due to intrinsic differences between the human and the monkey proteins. Human FKBP5 has a much lower effect on glucocorticoid sensitivity.
Sequence similarities	Contains 2 PPIase FKBP-type domains. Contains 3 TPR repeats.

Ontologies

Keywords
Cellular component	Cytoplasm
Domain	Repeat TPR repeat
Molecular function	Chaperone Isomerase Rotamase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein folding Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	binding Inferred from electronic annotation. Source: InterPro peptidyl-prolyl cis-trans isomerase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 457

457

FK506-binding protein 5

PRO_0000075328

Regions

Domain

50 – 138

89

PPIase FKBP-type 1

Domain

165 – 251

87

PPIase FKBP-type 2

Repeat

268 – 301

34

TPR 1

Repeat

317 – 350

34

TPR 2

Repeat

351 – 384

34

TPR 3

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

445

1

Phosphoserine By similarity

Secondary structure

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457

Helix Strand Turn

Details...

Beta strand

34 – 36

3

Beta strand

52 – 56

5

Beta strand

77 – 80

4

Beta strand

83 – 86

4

Helix

88 – 92

5

Turn

94 – 96

3

Beta strand

103 – 106

4

Turn

115 – 117

3

Turn

119 – 121

3

Beta strand

129 – 138

10

Beta strand

144 – 154

11

Beta strand

167 – 176

10

Beta strand

179 – 189

11

Helix

193 – 196

4

Helix

200 – 206

7

Beta strand

214 – 219

6

Helix

221 – 223

3

Turn

231 – 234

4

Beta strand

241 – 251

11

Helix

256 – 258

3

Helix

261 – 280

20

Helix

284 – 298

15

Helix

306 – 329

24

Helix

333 – 346

14

Helix

351 – 363

13

Helix

367 – 379

13

Helix

385 – 417

33

Sequences

	Sequence		Length	Mass (Da)
	Q9XSH5-1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: DFF9E1D81F7759A8	FASTA	457	51,169
	10 20 30 40 50 60 MTTDEGAKNS RGNPAATVAE QGEDVTSKKD RGVLKIVKRV GHGEETPMIG DRVYVHYNGK 70 80 90 100 110 120 LANGKKFDSS HDRNEPFVFS IGKGQVIKAW DIGVATMKKG EICHLLCKPE YAYGATGSLP 130 140 150 160 170 180 KIPSNATLFF EVELLDFKGE DLLEDGGIIR RTKRRGEGYS NPNEGARVQI HLEGRCGGRV 190 200 210 220 230 240 FDCRDVAFTV GEGEDHDIPI GIDKALEKMQ REEQCILHLG PRYGFGEAGK PKFGIEPNAE 250 260 270 280 290 300 LIYEVTLKSF EKAKESWEMD TKEKLEQAAI VKEKGTVYFK GGKYVQAVIQ YGKIVSWLEM 310 320 330 340 350 360 EYGLSEKESK ASESFLLAAF LNLAMCYLKL REYTKAVECC DKALGLDSAN EKGLYRRGEA 370 380 390 400 410 420 QLLMNEFESA KGDFEKVLEV NPQNKAARLQ IFMCQKKAKE HNERDRRTYA NMFKKFAEQD 430 440 450 AKEEANKAMS KKTSEGVTNE KLTASHAVEE EKPEGHV

References

[1]	"Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding." Denny W.B., Valentine D.L., Reynolds P.D., Smith D.F., Scammell J.G. Endocrinology 141:4107-4113(2000) [PubMed: 11089542] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION. Tissue: B-cell.
[2]	"Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes." Sinars C.R., Cheung-Flynn J., Rimerman R.A., Scammell J.G., Smith D.F., Clardy J. Proc. Natl. Acad. Sci. U.S.A. 100:868-873(2003) [PubMed: 12538866] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-421, FUNCTION.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF140759 mRNA. Translation: AAD32678.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KT1	X-ray	2.80	A	1-457	[»]

ModBase

Search...

Phylogenomic databases

HOVERGEN

Q9XSH5.

Family and domain databases

InterPro

IPR001179. PPIase_FKBP.
IPR001440. TPR-1.
IPR011990. TPR-like_helical.
IPR013026. TPR_region.
IPR019734. TPR_repeat.
[Graphical view]

Gene3D

G3DSA:1.25.40.10. TPR-like_helical. 1 hit.

PANTHER

PTHR10516. PPIase_FKBP. 1 hit.

Pfam

PF00254. FKBP_C. 2 hits.
PF00515. TPR_1. 2 hits.
[Graphical view]

PROSITE

PS50059. FKBP_PPIASE. 2 hits.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

FKBP5_SAIBB

Accession

Primary (citable) accession number: Q9XSH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 16, 2004
Last sequence update:	November 1, 1999
Last modified:	November 24, 2009
This is version 54 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)