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Protein

Inactive peptidyl-prolyl cis-trans isomerase FKBP6

Gene

FKBP6

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

Functioni

Co-chaperone required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Acts as a co-chaperone via its interaction with HSP90 and is required for the piRNA amplification process, the secondary piRNA biogenesis. May be required together with HSP90 in removal of 16 nucleotide ping-pong by-products from Piwi complexes, possibly facilitating turnover of Piwi complexes (By similarity).By similarity

Caution

Although it contains a PPIase FKBP-type domain, does not show peptidyl-prolyl cis-trans isomerase activity.Curated

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processDifferentiation, Meiosis, RNA-mediated gene silencing, Spermatogenesis

Enzyme and pathway databases

ReactomeiR-HSA-1221632 Meiotic synapsis
R-HSA-5601884 PIWI-interacting RNA (piRNA) biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Inactive peptidyl-prolyl cis-trans isomerase FKBP6
Short name:
Inactive PPIase FKBP6
Alternative name(s):
36 kDa FK506-binding protein
Short name:
36 kDa FKBP
Short name:
FKBP-36
FK506-binding protein 6
Short name:
FKBP-6
Immunophilin FKBP36
Gene namesi
Name:FKBP6
Synonyms:FKBP36
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000077800.11
HGNCiHGNC:3722 FKBP6
MIMi604839 gene
neXtProtiNX_O75344

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

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

FKBP6 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of FKBP6 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease (PubMed:9782077). A father and son with Williams-Beuren syndrome appear to have a common heterozygous deletion that includes FKBP6 gene. However, the haploinsufficiency for FKBP6 does not appear to preclude male fertility (PubMed:15770126).2 Publications
Defects in FKBP6 may be a cause of azoospermia. A study based on 323 patients with azoospermia or severe oligozoospermia suggested an association between FKBP6 variants and azoospermia (PubMed:17307919). However, other studies suggest that defects in FKBP6 are not a common cause of non-obstructive azoospermia (PubMed:16227348).2 Publications

Keywords - Diseasei

Williams-Beuren syndrome

Organism-specific databases

DisGeNETi8468
OpenTargetsiENSG00000077800
PharmGKBiPA28163

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000753291 – 327Inactive peptidyl-prolyl cis-trans isomerase FKBP6Add BLAST327

Proteomic databases

MaxQBiO75344
PaxDbiO75344
PeptideAtlasiO75344
PRIDEiO75344

PTM databases

iPTMnetiO75344
PhosphoSitePlusiO75344

Expressioni

Tissue specificityi

Detected in all tissues examined, with higher expression in testis, heart, skeletal muscle, liver, and kidney.

Gene expression databases

BgeeiENSG00000077800
CleanExiHS_FKBP6
ExpressionAtlasiO75344 baseline and differential
GenevisibleiO75344 HS

Organism-specific databases

HPAiHPA061109

Interactioni

Subunit structurei

Interacts (via TPR repeats) with HSP90 (By similarity). Interacts with HSP72/HSPA2 and CLTC. Interacts with GAPDH; leading to inhibit GAPDH catalytic activity.By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • Hsp90 protein binding Source: UniProtKB
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi114046, 38 interactors
IntActiO75344, 45 interactors
STRINGi9606.ENSP00000252037

Structurei

Secondary structure

1327
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi21 – 25Combined sources5
Turni26 – 28Combined sources3
Beta strandi30 – 44Combined sources15
Beta strandi47 – 50Combined sources4
Beta strandi56 – 64Combined sources9
Beta strandi72 – 74Combined sources3
Helixi93 – 100Combined sources8
Beta strandi107 – 112Combined sources6
Helixi114 – 116Combined sources3
Turni117 – 121Combined sources5
Turni124 – 126Combined sources3
Beta strandi133 – 143Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3B7XX-ray2.10A12-144[»]
ProteinModelPortaliO75344
SMRiO75344
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75344

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 143PPIase FKBP-typePROSITE-ProRule annotationAdd BLAST90
Repeati171 – 204TPR 1Add BLAST34
Repeati219 – 252TPR 2Add BLAST34
Repeati253 – 286TPR 3Add BLAST34

Sequence similaritiesi

Belongs to the FKBP6 family.Curated

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOGENOMiHOG000251594
HOVERGENiHBG051625
InParanoidiO75344
KOiK09572
OMAiCPPRIKP
OrthoDBiEOG091G0FWD
PhylomeDBiO75344
TreeFamiTF354214

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR023566 PPIase_FKBP
IPR001179 PPIase_FKBP_dom
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR019734 TPR_repeat
PANTHERiPTHR10516 PTHR10516, 1 hit
PfamiView protein in Pfam
PF00254 FKBP_C, 1 hit
SMARTiView protein in SMART
SM00028 TPR, 3 hits
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS50059 FKBP_PPIASE, 1 hit
PS50293 TPR_REGION, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75344-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGGSALNQGV LEGDDAPGQS LYERLSQRML DISGDRGVLK DVIREGAGDL
60 70 80 90 100
VAPDASVLVK YSGYLEHMDR PFDSNYFRKT PRLMKLGEDI TLWGMELGLL
110 120 130 140 150
SMRRGELARF LFKPNYAYGT LGCPPLIPPN TTVLFEIELL DFLDCAESDK
160 170 180 190 200
FCALSAEQQD QFPLQKVLKV AATEREFGNY LFRQNRFYDA KVRYKRALLL
210 220 230 240 250
LRRRSAPPEE QHLVEAAKLP VLLNLSFTYL KLDRPTIALC YGEQALIIDQ
260 270 280 290 300
KNAKALFRCG QACLLLTEYQ KARDFLVRAQ KEQPFNHDIN NELKKLASCY
310 320
RDYVDKEKEM WHRMFAPCGD GSTAGES
Length:327
Mass (Da):37,214
Last modified:November 1, 1998 - v1
Checksum:iC137FA629B676623
GO
Isoform 2 (identifier: O75344-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MGGSALNQGVLEGDDAPGQ → MSASSWPQNGMPPS

Note: No experimental confirmation available.
Show »
Length:322
Mass (Da):36,874
Checksum:iC3C697A7F1962706
GO
Isoform 3 (identifier: O75344-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     59-88: Missing.

Show »
Length:297
Mass (Da):33,553
Checksum:iBF5A6F2324830850
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti103R → Q in AAP97324 (Ref. 2) Curated1
Sequence conflicti123C → S in AAP97324 (Ref. 2) Curated1
Sequence conflicti136E → K in AAP97324 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070840183R → C Probable polymorphism. 1 PublicationCorresponds to variant dbSNP:rs147213094Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0420381 – 19MGGSA…DAPGQ → MSASSWPQNGMPPS in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_05425159 – 88Missing in isoform 3. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF038847 mRNA Translation: AAC64249.1
AF447060 mRNA Translation: AAP97324.1
AK302121 mRNA Translation: BAG63499.1
BC036817 mRNA Translation: AAH36817.1
AC005049 Genomic DNA No translation available.
AC073841 Genomic DNA No translation available.
CH471200 Genomic DNA Translation: EAW69684.1
CH471200 Genomic DNA Translation: EAW69686.1
CCDSiCCDS43595.1 [O75344-1]
CCDS47604.1 [O75344-2]
CCDS64670.1 [O75344-3]
RefSeqiNP_001128683.1, NM_001135211.2 [O75344-2]
NP_001268233.1, NM_001281304.1 [O75344-3]
NP_003593.3, NM_003602.4 [O75344-1]
UniGeneiHs.661266

Genome annotation databases

EnsembliENST00000252037; ENSP00000252037; ENSG00000077800 [O75344-1]
ENST00000413573; ENSP00000394952; ENSG00000077800 [O75344-3]
ENST00000431982; ENSP00000416277; ENSG00000077800 [O75344-2]
GeneIDi8468
KEGGihsa:8468
UCSCiuc003tya.4 human [O75344-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFKBP6_HUMAN
AccessioniPrimary (citable) accession number: O75344
Secondary accession number(s): B4DXT7
, G3V0I2, Q7Z4T4, Q9UDS0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 1, 1998
Last modified: April 25, 2018
This is version 166 of the entry and version 1 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, Reference proteome
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Main funding by: National Institutes of Health