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O75344 (FKBP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:FKBP6
Synonyms:FKBP36
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length327 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Interacts (via TPR repeats) with HSP90 By similarity. Interacts with HSP72/HSPA2 and CLTC. Interacts with GAPDH; leading to inhibit GAPDH catalytic activity. Ref.10 Ref.11

Subcellular location

Cytoplasmcytosol By similarity. Nucleus By similarity. Chromosome By similarity. Note: Does not localize to pi-bodies. Localizes to meiotic chromosome cores and regions of homologous chromosome synapsis By similarity.

Tissue specificity

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

Involvement in disease

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 (Ref.1). 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 (Ref.7). Ref.7

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 (Ref.9). However, other studies suggest that defects in FKBP6 are not a common cause of non-obstructive azoospermia (Ref.8).

Sequence similarities

Belongs to the FKBP6 family.

Contains 1 PPIase FKBP-type domain.

Contains 3 TPR repeats.

Caution

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

Ontologies

Keywords
   Biological processDifferentiation
Meiosis
RNA-mediated gene silencing
Spermatogenesis
   Cellular componentChromosome
Cytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseWilliams-Beuren syndrome
   DomainRepeat
TPR repeat
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA methylation involved in gamete generation

Inferred from sequence or structural similarity. Source: UniProtKB

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

gene silencing by RNA

Inferred from sequence or structural similarity. Source: UniProtKB

meiotic nuclear division

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-proline modification

Inferred from Biological aspect of Ancestor. Source: RefGenome

piRNA metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein folding

Inferred from sequence or structural similarity. Source: UniProtKB

spermatogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

synaptonemal complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionFK506 binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Hsp90 protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-prolyl cis-trans isomerase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O75344-1)

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.
Isoform 2 (identifier: O75344-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MGGSALNQGVLEGDDAPGQ → MSASSWPQNGMPPS
Note: No experimental confirmation available.
Isoform 3 (identifier: O75344-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 327327Inactive peptidyl-prolyl cis-trans isomerase FKBP6
PRO_0000075329

Regions

Domain54 – 14390PPIase FKBP-type
Repeat171 – 20434TPR 1
Repeat219 – 25234TPR 2
Repeat253 – 28634TPR 3

Natural variations

Alternative sequence1 – 1919MGGSA…DAPGQ → MSASSWPQNGMPPS in isoform 2.
VSP_042038
Alternative sequence59 – 8830Missing in isoform 3.
VSP_054251
Natural variant1831R → C Probable polymorphism. Ref.8
VAR_070840

Experimental info

Sequence conflict1031R → Q in AAP97324. Ref.2
Sequence conflict1231C → S in AAP97324. Ref.2
Sequence conflict1361E → K in AAP97324. Ref.2

Secondary structure

....................... 327
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: C137FA629B676623

FASTA32737,214
        10         20         30         40         50         60 
MGGSALNQGV LEGDDAPGQS LYERLSQRML DISGDRGVLK DVIREGAGDL VAPDASVLVK 

        70         80         90        100        110        120 
YSGYLEHMDR PFDSNYFRKT PRLMKLGEDI TLWGMELGLL SMRRGELARF LFKPNYAYGT 

       130        140        150        160        170        180 
LGCPPLIPPN TTVLFEIELL DFLDCAESDK FCALSAEQQD QFPLQKVLKV AATEREFGNY 

       190        200        210        220        230        240 
LFRQNRFYDA KVRYKRALLL LRRRSAPPEE QHLVEAAKLP VLLNLSFTYL KLDRPTIALC 

       250        260        270        280        290        300 
YGEQALIIDQ KNAKALFRCG QACLLLTEYQ KARDFLVRAQ KEQPFNHDIN NELKKLASCY 

       310        320 
RDYVDKEKEM WHRMFAPCGD GSTAGES 

« Hide

Isoform 2 [UniParc].

Checksum: C3C697A7F1962706
Show »

FASTA32236,874
Isoform 3 [UniParc].

Checksum: BF5A6F2324830850
Show »

FASTA29733,553

References

« Hide 'large scale' references
[1]"A novel human gene FKBP6 is deleted in Williams syndrome."
Meng X., Lu X., Morris C.A., Keating M.T.
Genomics 52:130-137(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Testis.
[2]Zan Q., Guo J.H., Yu L.
Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[4]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[7]"Autosomal dominant inheritance of Williams-Beuren syndrome in a father and son with haploinsufficiency for FKBP6."
Metcalfe K., Simeonov E., Beckett W., Donnai D., Tassabehji M.
Clin. Dysmorphol. 14:61-65(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN WBS.
[8]"Mutations in the chromosome pairing gene FKBP6 are not a common cause of non-obstructive azoospermia."
Westerveld G.H., Repping S., Lombardi M.P., van der Veen F.
Mol. Hum. Reprod. 11:673-675(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CYS-183, POSSIBLE INVOLVEMENT IN AZOOSPERMIA.
[9]"Mutation screening of the FKBP6 gene and its association study with spermatogenic impairment in idiopathic infertile men."
Zhang W., Zhang S., Xiao C., Yang Y., Zhoucun A.
Reproduction 133:511-516(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN AZOOSPERMIA.
[10]"FKBP36 forms complexes with clathrin and Hsp72 in spermatocytes."
Jarczowski F., Fischer G., Edlich F.
Biochemistry 47:6946-6952(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HSPA2 AND CLTC.
[11]"FKBP36 is an inherent multifunctional glyceraldehyde-3-phosphate dehydrogenase inhibitor."
Jarczowski F., Jahreis G., Erdmann F., Schierhorn A., Fischer G., Edlich F.
J. Biol. Chem. 284:766-773(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GAPDH.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS43595.1. [O75344-1]
CCDS47604.1. [O75344-2]
RefSeqNP_001128683.1. NM_001135211.2. [O75344-2]
NP_001268233.1. NM_001281304.1. [O75344-3]
NP_003593.3. NM_003602.4. [O75344-1]
UniGeneHs.661266.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3B7XX-ray2.10A12-144[»]
ProteinModelPortalO75344.
SMRO75344. Positions 19-315.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114046. 4 interactions.
IntActO75344. 2 interactions.
MINTMINT-1460144.
STRING9606.ENSP00000252037.

PTM databases

PhosphoSiteO75344.

Proteomic databases

PaxDbO75344.
PRIDEO75344.

Protocols and materials databases

DNASU8468.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252037; ENSP00000252037; ENSG00000077800. [O75344-1]
ENST00000413573; ENSP00000394952; ENSG00000077800.
ENST00000431982; ENSP00000416277; ENSG00000077800. [O75344-2]
ENST00000572911; ENSP00000458784; ENSG00000262532. [O75344-1]
ENST00000574089; ENSP00000459768; ENSG00000262532. [O75344-2]
GeneID8468.
KEGGhsa:8468.
UCSCuc003tya.2. human. [O75344-1]
uc011kew.1. human. [O75344-2]

Organism-specific databases

CTD8468.
GeneCardsGC07P072742.
H-InvDBHIX0006777.
HIX0078779.
HIX0114828.
HGNCHGNC:3722. FKBP6.
HPAHPA043046.
MIM604839. gene.
neXtProtNX_O75344.
Orphanet904. Williams syndrome.
PharmGKBPA28163.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0545.
HOGENOMHOG000251594.
HOVERGENHBG051625.
InParanoidO75344.
KOK09572.
OMAEREMCHR.
PhylomeDBO75344.
TreeFamTF354214.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.

Gene expression databases

ArrayExpressO75344.
BgeeO75344.
CleanExHS_FKBP6.
GenevestigatorO75344.

Family and domain databases

Gene3D1.25.40.10. 1 hit.
InterProIPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
[Graphical view]
PANTHERPTHR10516. PTHR10516. 1 hit.
PfamPF00254. FKBP_C. 1 hit.
[Graphical view]
PROSITEPS50059. FKBP_PPIASE. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFKBP6. human.
EvolutionaryTraceO75344.
GenomeRNAi8468.
NextBio31692.
PROO75344.
SOURCESearch...

Entry information

Entry nameFKBP6_HUMAN
AccessionPrimary (citable) accession number: O75344
Secondary accession number(s): B4DXT7 expand/collapse secondary AC list , G3V0I2, Q7Z4T4, Q9UDS0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 1, 1998
Last modified: July 9, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM