FKBP6_MOUSE
ID FKBP6_MOUSE Reviewed; 327 AA.
AC Q91XW8; Q8C1Y1; Q91VB7; Q91Y30;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Inactive peptidyl-prolyl cis-trans isomerase FKBP6;
DE Short=Inactive PPIase FKBP6;
DE AltName: Full=36 kDa FK506-binding protein;
DE Short=36 kDa FKBP;
DE Short=FKBP-36;
DE AltName: Full=FK506-binding protein 6;
DE Short=FKBP-6;
DE AltName: Full=Immunophilin FKBP36;
GN Name=Fkbp6; Synonyms=Fkbp36;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Telencephalon, and Testis;
RA Guimiot F., Mas C., Levacher B., Bourgeois F., Simonneau M.;
RT "A murine homolog of the human FKBP6 gene, deleted in Williams-Beuren
RT syndrome, is expressed in the embryonic structures involved in sensory
RT cognition.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
RX PubMed=12764197; DOI=10.1126/science.1083022;
RA Crackower M.A., Kolas N.K., Noguchi J., Sarao R., Kikuchi K., Kaneko H.,
RA Kobayashi E., Kawai Y., Kozieradzki I., Landers R., Mo R., Hui C.C.,
RA Nieves E., Cohen P.E., Osborne L.R., Wada T., Kunieda T., Moens P.B.,
RA Penninger J.M.;
RT "Essential role of Fkbp6 in male fertility and homologous chromosome
RT pairing in meiosis.";
RL Science 300:1291-1295(2003).
RN [7]
RP FUNCTION.
RX PubMed=18408354; DOI=10.1262/jrd.19158;
RA Noguchi J., Ozawa M., Nakai M., Somfai T., Kikuchi K., Kaneko H.,
RA Kunieda T.;
RT "Affected homologous chromosome pairing and phosphorylation of testis
RT specific histone, H2AX, in male meiosis under FKBP6 deficiency.";
RL J. Reprod. Dev. 54:203-207(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HSP90, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF LYS-254.
RX PubMed=22902560; DOI=10.1016/j.molcel.2012.07.019;
RA Xiol J., Cora E., Koglgruber R., Chuma S., Subramanian S., Hosokawa M.,
RA Reuter M., Yang Z., Berninger P., Palencia A., Benes V., Penninger J.,
RA Sachidanandam R., Pillai R.S.;
RT "A role for Fkbp6 and the chaperone machinery in piRNA amplification and
RT transposon silencing.";
RL Mol. Cell 47:970-979(2012).
CC -!- FUNCTION: Co-chaperone required during spermatogenesis to repress
CC transposable elements and prevent their mobilization, which is
CC essential for the germline integrity. Acts via the piRNA metabolic
CC process, which mediates the repression of transposable elements during
CC meiosis by forming complexes composed of piRNAs and Piwi proteins and
CC govern the methylation and subsequent repression of transposons. Acts
CC as a co-chaperone via its interaction with HSP90 and is required for
CC the piRNA amplification process, the secondary piRNA biogenesis. May be
CC required together with HSP90 in removal of 16 nucleotide ping-pong by-
CC products from Piwi complexes, possibly facilitating turnover of Piwi
CC complexes. {ECO:0000269|PubMed:12764197, ECO:0000269|PubMed:18408354,
CC ECO:0000269|PubMed:22902560}.
CC -!- SUBUNIT: Interacts with HSP72/HSPA2 and CLTC. Interacts with GAPDH;
CC leading to inhibit GAPDH catalytic activity (By similarity). Interacts
CC (via TPR repeats) with HSP90. {ECO:0000250,
CC ECO:0000269|PubMed:22902560}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12764197,
CC ECO:0000269|PubMed:22902560}. Nucleus {ECO:0000269|PubMed:12764197}.
CC Chromosome {ECO:0000269|PubMed:12764197}. Note=Does not localize to pi-
CC bodies. Localizes to meiotic chromosome cores and regions of homologous
CC chromosome synapsis. {ECO:0000269|PubMed:12764197,
CC ECO:0000269|PubMed:22902560}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q91XW8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91XW8-2; Sequence=VSP_005185, VSP_005186;
CC Name=3;
CC IsoId=Q91XW8-3; Sequence=VSP_005185;
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:12764197}.
CC -!- DEVELOPMENTAL STAGE: Present in spermatocytes. Expression is lost as
CC cells exit prophase I. Not detected in spermatids (at protein level).
CC {ECO:0000269|PubMed:12764197}.
CC -!- DISRUPTION PHENOTYPE: Males mice are sterile and aspermic due to
CC abnormal pachytene spermatocytes, characterized by the appearance of
CC unusual inclusion bodies and dense compacted nuclei. Spermatocytes fail
CC to proceed beyond the pachytene stage due to abnormal pairing and
CC misalignments between homologous chromosomes, non-homologous partner
CC switches and autosynapsis of X chromosome cores in meiotic
CC spermatocytes. No other abnormalities are detected in any tissues of
CC males. Females mice are fertile (PubMed:12764197). Spermatocytes show
CC derepressed LINE-1 retrotransposon and reduced DNA methylation due to
CC deficient nuclear accumulation of Miwi2 (PubMed:22902560).
CC {ECO:0000269|PubMed:12764197, ECO:0000269|PubMed:22902560}.
CC -!- SIMILARITY: Belongs to the FKBP6 family. {ECO:0000305}.
CC -!- CAUTION: Although it contains a PPIase FKBP-type domain, does not show
CC peptidyl-prolyl cis-trans isomerase activity.
CC {ECO:0000305|PubMed:22902560}.
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DR EMBL; AY029192; AAK39645.1; -; mRNA.
DR EMBL; AF367709; AAK53411.1; -; mRNA.
DR EMBL; AF367710; AAK53412.1; -; mRNA.
DR EMBL; AF367711; AAK53413.1; -; mRNA.
DR EMBL; AK090036; BAC41058.1; -; mRNA.
DR EMBL; AC074359; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466529; EDL19373.1; -; Genomic_DNA.
DR EMBL; CH466529; EDL19374.1; -; Genomic_DNA.
DR EMBL; BC139092; AAI39093.1; -; mRNA.
DR EMBL; BC139097; AAI39098.1; -; mRNA.
DR CCDS; CCDS19738.1; -. [Q91XW8-3]
DR CCDS; CCDS80425.1; -. [Q91XW8-1]
DR CCDS; CCDS80426.1; -. [Q91XW8-2]
DR RefSeq; NP_001264820.1; NM_001277891.1. [Q91XW8-3]
DR RefSeq; NP_001264821.1; NM_001277892.1. [Q91XW8-1]
DR RefSeq; NP_001264822.1; NM_001277893.1. [Q91XW8-2]
DR RefSeq; NP_291049.1; NM_033571.3. [Q91XW8-3]
DR RefSeq; XP_011239215.1; XM_011240913.1. [Q91XW8-3]
DR RefSeq; XP_011239217.1; XM_011240915.1. [Q91XW8-2]
DR RefSeq; XP_017176679.1; XM_017321190.1.
DR AlphaFoldDB; Q91XW8; -.
DR SMR; Q91XW8; -.
DR BioGRID; 220490; 5.
DR STRING; 10090.ENSMUSP00000043193; -.
DR iPTMnet; Q91XW8; -.
DR PhosphoSitePlus; Q91XW8; -.
DR PaxDb; Q91XW8; -.
DR PRIDE; Q91XW8; -.
DR ProteomicsDB; 271895; -. [Q91XW8-1]
DR ProteomicsDB; 272920; -. [Q91XW8-2]
DR ProteomicsDB; 272921; -. [Q91XW8-3]
DR Antibodypedia; 7933; 277 antibodies from 29 providers.
DR DNASU; 94244; -.
DR Ensembl; ENSMUST00000044972; ENSMUSP00000043193; ENSMUSG00000040013. [Q91XW8-3]
DR Ensembl; ENSMUST00000201534; ENSMUSP00000144471; ENSMUSG00000040013. [Q91XW8-3]
DR Ensembl; ENSMUST00000201784; ENSMUSP00000144381; ENSMUSG00000040013. [Q91XW8-1]
DR Ensembl; ENSMUST00000201791; ENSMUSP00000144460; ENSMUSG00000040013. [Q91XW8-2]
DR GeneID; 94244; -.
DR KEGG; mmu:94244; -.
DR UCSC; uc008zyb.2; mouse. [Q91XW8-3]
DR UCSC; uc008zyc.2; mouse. [Q91XW8-2]
DR UCSC; uc008zyd.1; mouse. [Q91XW8-1]
DR CTD; 8468; -.
DR MGI; MGI:2137612; Fkbp6.
DR VEuPathDB; HostDB:ENSMUSG00000040013; -.
DR eggNOG; KOG0543; Eukaryota.
DR GeneTree; ENSGT00940000158514; -.
DR InParanoid; Q91XW8; -.
DR OMA; GCPPRIK; -.
DR OrthoDB; 1465346at2759; -.
DR PhylomeDB; Q91XW8; -.
DR TreeFam; TF354214; -.
DR BioGRID-ORCS; 94244; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Fkbp6; mouse.
DR PRO; PR:Q91XW8; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q91XW8; protein.
DR Bgee; ENSMUSG00000040013; Expressed in morula and 23 other tissues.
DR Genevisible; Q91XW8; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000795; C:synaptonemal complex; IDA:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0043046; P:DNA methylation involved in gamete generation; IMP:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IMP:UniProtKB.
DR GO; GO:0034587; P:piRNA metabolic process; IMP:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; ISO:MGI.
DR GO; GO:0006457; P:protein folding; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.10.50.40; -; 1.
DR InterPro; IPR042282; FKBP6/shu.
DR InterPro; IPR046357; PPIase_dom_sf.
DR InterPro; IPR001179; PPIase_FKBP_dom.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR46674; PTHR46674; 1.
DR Pfam; PF00254; FKBP_C; 1.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50059; FKBP_PPIASE; 1.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromosome; Cytoplasm; Differentiation; Meiosis;
KW Nucleus; Reference proteome; Repeat; RNA-mediated gene silencing;
KW Spermatogenesis; TPR repeat.
FT CHAIN 1..327
FT /note="Inactive peptidyl-prolyl cis-trans isomerase FKBP6"
FT /id="PRO_0000075330"
FT DOMAIN 54..143
FT /note="PPIase FKBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277"
FT REPEAT 171..204
FT /note="TPR 1"
FT REPEAT 219..252
FT /note="TPR 2"
FT REPEAT 253..286
FT /note="TPR 3"
FT VAR_SEQ 1..18
FT /note="MGGSTRDPGALEGAGILG -> MSVFSRLRNGIPPSRDDC (in isoform
FT 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|Ref.1"
FT /id="VSP_005185"
FT VAR_SEQ 157..196
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_005186"
FT MUTAGEN 254
FT /note="K->A: Abolishes interaction with HSP90."
FT /evidence="ECO:0000269|PubMed:22902560"
FT CONFLICT 19
FT /note="Q -> H (in Ref. 2; BAC41058)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 327 AA; 37125 MW; 9A2AE310DDC064CD CRC64;
MGGSTRDPGA LEGAGILGQS PYERLSQRML DISGDRGVLK DIIREGTGDT VTPDASVLVK
YSGYLEHMDK PFDSNCFRKT PRLMKLGEDI TLWGMELGLL SMRKGELARF LFKPAYAYGT
LGCPPLIPPN ATVLFEIELI DFLDSAESDK FCALSAEQQE QFPLQKVLKV AATEREFGNY
LFRQNRFCDA KVRYKRALLL LHRRLATCEE QHLVEPAVLL VLLNLSFVYL KLDRPAMALR
YGEQALLIDK RNAKALFRCG QACLLLTEYE RARDFLVRAQ KEQPCNHDIN NELKKLSSHY
RDYVDREREM CHRMFAPCGS RSSVGGN
