FKBP8_HUMAN
ID FKBP8_HUMAN Reviewed; 412 AA.
AC Q14318; C8C9T5; Q53GU3; Q7Z349; Q86YK6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP8;
DE Short=PPIase FKBP8;
DE EC=5.2.1.8;
DE AltName: Full=38 kDa FK506-binding protein;
DE Short=38 kDa FKBP;
DE Short=FKBP-38;
DE Short=hFKBP38;
DE AltName: Full=FK506-binding protein 8;
DE Short=FKBP-8;
DE AltName: Full=FKBPR38;
DE AltName: Full=Rotamase;
GN Name=FKBP8; Synonyms=FKBP38;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH BCL2 AND
RP BCL2L1/BCLXL, AND SUBCELLULAR LOCATION.
RX PubMed=12510191; DOI=10.1038/ncb894;
RA Shirane M., Nakayama K.I.;
RT "Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and
RT inhibits apoptosis.";
RL Nat. Cell Biol. 5:28-37(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=15105374; DOI=10.1242/dev.01122;
RA Bulgakov O.V., Eggenschwiler J.T., Hong D.-H., Anderson K.V., Li T.;
RT "FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural
RT tissues.";
RL Development 131:2149-2159(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION, INTERACTION
RP WITH BCL2L1, AND TISSUE SPECIFICITY.
RC TISSUE=Retinal pigment epithelium;
RX PubMed=18385096; DOI=10.1167/iovs.07-1121;
RA Chen Y., Sternberg P., Cai J.;
RT "Characterization of a Bcl-XL-interacting protein FKBP8 and its splice
RT variant in human RPE cells.";
RL Invest. Ophthalmol. Vis. Sci. 49:1721-1727(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-412 (ISOFORM 1).
RX PubMed=7543869; DOI=10.1016/0378-1119(95)00216-s;
RA Lam E., Martin M., Wiederrecht G.;
RT "Isolation of a cDNA encoding a novel human FK506-binding protein homolog
RT containing leucine zipper and tetratricopeptide repeat motifs.";
RL Gene 160:297-302(1995).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-412 (ISOFORM 2).
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 54-412 (ISOFORM 1).
RC TISSUE=Pancreas;
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 [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16176796; DOI=10.1016/j.bbrc.2005.09.023;
RA Kang C.B., Feng L., Chia J., Yoon H.S.;
RT "Molecular characterization of FK-506 binding protein 38 and its potential
RT regulatory role on the anti-apoptotic protein Bcl-2.";
RL Biochem. Biophys. Res. Commun. 337:30-38(2005).
RN [11]
RP CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=15990872; DOI=10.1038/sj.emboj.7600739;
RA Edlich F., Weiwad M., Erdmann F., Fanghaenel J., Jarczowski F.,
RA Rahfeld J.-U., Fischer G.;
RT "Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin.";
RL EMBO J. 24:2688-2699(2005).
RN [12]
RP FUNCTION, AND ABSENCE OF DIRECT INTERACTION WITH CALCINEURIN.
RX PubMed=15757646; DOI=10.1016/j.febslet.2004.12.098;
RA Weiwad M., Edlich F., Erdmann F., Jarczowski F., Kilka S., Dorn M.,
RA Pechstein A., Fischer G.;
RT "A reassessment of the inhibitory capacity of human FKBP38 on
RT calcineurin.";
RL FEBS Lett. 579:1591-1596(2005).
RN [13]
RP INTERACTION WITH BCL2.
RX PubMed=15733859; DOI=10.1016/j.febslet.2005.01.053;
RA Kang C.B., Tai J., Chia J., Yoon H.S.;
RT "The flexible loop of Bcl-2 is required for molecular interaction with
RT immunosuppressant FK-506 binding protein 38 (FKBP38).";
RL FEBS Lett. 579:1469-1476(2005).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [15]
RP INTERACTION WITH BCL2.
RX PubMed=17090549; DOI=10.1074/jbc.m606181200;
RA Portier B.P., Taglialatela G.;
RT "Bcl-2 localized at the nuclear compartment induces apoptosis after
RT transient overexpression.";
RL J. Biol. Chem. 281:40493-40502(2006).
RN [16]
RP INTERACTION WITH HCV NS5A (MICROBIAL INFECTION).
RX PubMed=16844119; DOI=10.1016/j.febslet.2006.07.002;
RA Wang J., Tong W., Zhang X., Chen L., Yi Z., Pan T., Hu Y., Xiang L.,
RA Yuan Z.;
RT "Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and
RT inhibits apoptosis in Huh7 hepatoma cells.";
RL FEBS Lett. 580:4392-4400(2006).
RN [17]
RP INTERACTION WITH ZFYVE27.
RX PubMed=18459960; DOI=10.1111/j.1365-2443.2008.01194.x;
RA Shirane M., Ogawa M., Motoyama J., Nakayama K.I.;
RT "Regulation of apoptosis and neurite extension by FKBP38 is required for
RT neural tube formation in the mouse.";
RL Genes Cells 13:635-651(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP UBIQUITINATION AT LYS-249; LYS-271; LYS-273; LYS-284; LYS-307; LYS-314;
RP LYS-334; LYS-340; LYS-348; LYS-351 AND LYS-352.
RX PubMed=25621951; DOI=10.1038/ncb3097;
RA Cunningham C.N., Baughman J.M., Phu L., Tea J.S., Yu C., Coons M.,
RA Kirkpatrick D.S., Bingol B., Corn J.E.;
RT "USP30 and parkin homeostatically regulate atypical ubiquitin chains on
RT mitochondria.";
RL Nat. Cell Biol. 17:160-169(2015).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [22]
RP STRUCTURE BY NMR OF 92-210.
RX PubMed=16604427; DOI=10.1007/s10858-006-0018-6;
RA Maestre-Martinez M., Edlich F., Jarczowski F., Weiwad M., Fischer G.,
RA Luecke C.;
RT "Solution structure of the FK506-binding domain of human FKBP38.";
RL J. Biomol. NMR 34:197-202(2006).
RN [23]
RP STRUCTURE BY NMR OF 91-205.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-047, an FKBP domain from human cDNA.";
RL Submitted (JUN-2006) to the PDB data bank.
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 90-205.
RG Structural genomics consortium (SGC);
RT "Structure of the human FK-506 binding protein 8.";
RL Submitted (OCT-2006) to the PDB data bank.
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF 92-210, METAL-BINDING SITES, AND
RP MUTAGENESIS OF ASP-149 AND ASP-151.
RX PubMed=20140889; DOI=10.1002/jmr.1020;
RA Maestre-Martinez M., Haupt K., Edlich F., Neumann P., Parthier C.,
RA Stubbs M.T., Fischer G., Lucke C.;
RT "A charge-sensitive loop in the FKBP38 catalytic domain modulates Bcl-2
RT binding.";
RL J. Mol. Recognit. 24:23-34(2011).
CC -!- FUNCTION: Constitutively inactive PPiase, which becomes active when
CC bound to calmodulin and calcium. Seems to act as a chaperone for BCL2,
CC targets it to the mitochondria and modulates its phosphorylation state.
CC The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the
CC binding of BCL2 to its targets. The active form of FKBP8 may therefore
CC play a role in the regulation of apoptosis.
CC {ECO:0000269|PubMed:12510191, ECO:0000269|PubMed:15757646,
CC ECO:0000269|PubMed:16176796}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-peptidylproline (omega=180) = [protein]-
CC peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA-
CC COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833,
CC ChEBI:CHEBI:83834; EC=5.2.1.8;
CC Evidence={ECO:0000269|PubMed:15990872};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:15990872};
CC -!- SUBUNIT: Homomultimers or heteromultimers (Potential). Forms
CC heterodimer with calmodulin. When activated by calmodulin and calcium,
CC interacts with the BH4 domain of BCL2 and weakly with BCL2L1/BCLX
CC isoform Bcl-X(L). Does not bind and inhibit calcineurin. Interacts with
CC ZFYVE27; may negatively regulate ZFYVE27 phosphorylation.
CC {ECO:0000269|PubMed:12510191, ECO:0000269|PubMed:15733859,
CC ECO:0000269|PubMed:17090549, ECO:0000269|PubMed:18385096,
CC ECO:0000269|PubMed:18459960, ECO:0000305}.
CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C/HCV protein
CC NS5A. {ECO:0000269|PubMed:16844119}.
CC -!- INTERACTION:
CC Q14318; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-724839, EBI-11343438;
CC Q14318; P11912: CD79A; NbExp=3; IntAct=EBI-724839, EBI-7797864;
CC Q14318; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-724839, EBI-7062247;
CC Q14318; P25025: CXCR2; NbExp=3; IntAct=EBI-724839, EBI-2835281;
CC Q14318; P49447: CYB561; NbExp=3; IntAct=EBI-724839, EBI-8646596;
CC Q14318; Q53TN4: CYBRD1; NbExp=3; IntAct=EBI-724839, EBI-8637742;
CC Q14318; Q15125: EBP; NbExp=3; IntAct=EBI-724839, EBI-3915253;
CC Q14318; P00533: EGFR; NbExp=4; IntAct=EBI-724839, EBI-297353;
CC Q14318; Q9GZT9: EGLN1; NbExp=6; IntAct=EBI-724839, EBI-1174818;
CC Q14318; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-724839, EBI-18535450;
CC Q14318; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-724839, EBI-781551;
CC Q14318; Q8TBP5: FAM174A; NbExp=3; IntAct=EBI-724839, EBI-18636064;
CC Q14318; Q92915-2: FGF14; NbExp=3; IntAct=EBI-724839, EBI-12836320;
CC Q14318; O75344: FKBP6; NbExp=2; IntAct=EBI-724839, EBI-744771;
CC Q14318; Q14318: FKBP8; NbExp=3; IntAct=EBI-724839, EBI-724839;
CC Q14318; P07900: HSP90AA1; NbExp=7; IntAct=EBI-724839, EBI-296047;
CC Q14318; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-724839, EBI-10266796;
CC Q14318; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-724839, EBI-373355;
CC Q14318; O00623: PEX12; NbExp=3; IntAct=EBI-724839, EBI-594836;
CC Q14318; P26678: PLN; NbExp=3; IntAct=EBI-724839, EBI-692836;
CC Q14318; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-724839, EBI-10192441;
CC Q14318; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-724839, EBI-17589229;
CC Q14318; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-724839, EBI-17247926;
CC Q14318; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-724839, EBI-18159983;
CC Q14318; Q9BS91: SLC35A5; NbExp=3; IntAct=EBI-724839, EBI-18915901;
CC Q14318; P78383: SLC35B1; NbExp=3; IntAct=EBI-724839, EBI-12147661;
CC Q14318; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-724839, EBI-8638294;
CC Q14318; Q8TBM7: TMEM254; NbExp=3; IntAct=EBI-724839, EBI-11956809;
CC Q14318; Q9BTV4: TMEM43; NbExp=3; IntAct=EBI-724839, EBI-721293;
CC Q14318; Q96B21: TMEM45B; NbExp=3; IntAct=EBI-724839, EBI-3923061;
CC Q14318; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-724839, EBI-11742770;
CC Q14318; Q9H3N1: TMX1; NbExp=3; IntAct=EBI-724839, EBI-1051115;
CC Q14318; O95159: ZFPL1; NbExp=3; IntAct=EBI-724839, EBI-718439;
CC Q14318; Q5T4F4: ZFYVE27; NbExp=4; IntAct=EBI-724839, EBI-3892947;
CC Q14318; O39474: NS5A; Xeno; NbExp=16; IntAct=EBI-724839, EBI-7016711;
CC Q14318; C5E526: PB1; Xeno; NbExp=5; IntAct=EBI-724839, EBI-12577179;
CC Q14318; P03431: PB1; Xeno; NbExp=5; IntAct=EBI-724839, EBI-2547514;
CC Q14318; Q1K9H5: PB1; Xeno; NbExp=5; IntAct=EBI-724839, EBI-6050669;
CC Q14318; Q5EP37: PB1; Xeno; NbExp=3; IntAct=EBI-724839, EBI-12577201;
CC Q14318; PRO_0000037551 [Q9WMX2]; Xeno; NbExp=11; IntAct=EBI-724839, EBI-6863748;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16176796}.
CC Mitochondrion membrane {ECO:0000305}; Single-pass membrane protein;
CC Cytoplasmic side {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion membrane
CC {ECO:0000269|PubMed:12510191, ECO:0000269|PubMed:18385096}; Single-pass
CC membrane protein; Cytoplasmic side {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Mitochondrion membrane
CC {ECO:0000269|PubMed:18385096}; Single-pass membrane protein;
CC Cytoplasmic side {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q14318-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14318-2; Sequence=VSP_034486;
CC Name=3;
CC IsoId=Q14318-3; Sequence=VSP_047717;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels seen in the brain.
CC Highly abundant in the retina. {ECO:0000269|PubMed:18385096}.
CC -!- PTM: Ubiquitinated by PRKN during mitophagy, leading to its degradation
CC and enhancement of mitophagy. Deubiquitinated by USP30.
CC {ECO:0000269|PubMed:25621951}.
CC -!- MISCELLANEOUS: Binds the immunosuppressant FK506 only in its
CC calmodulin/calcium activated form.
CC -!- MISCELLANEOUS: [Isoform 3]: Interacts with BCL2L1/BCLX. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-58 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB00102.1; Type=Miscellaneous discrepancy; Note=The first part of the cDNA maps to the same locus, but in opposite orientation.; Evidence={ECO:0000305};
CC Sequence=AAH09966.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD98028.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FKBP8ID40579ch19p13.html";
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DR EMBL; AY225339; AAO39020.1; -; mRNA.
DR EMBL; AY278607; AAQ84561.1; -; mRNA.
DR EMBL; GQ372970; ACU65096.1; -; mRNA.
DR EMBL; BX538124; CAD98028.1; ALT_INIT; mRNA.
DR EMBL; BX647405; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC005387; AAC28753.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84709.1; -; Genomic_DNA.
DR EMBL; L37033; AAB00102.1; ALT_SEQ; mRNA.
DR EMBL; AK222838; BAD96558.1; -; mRNA.
DR EMBL; BC009966; AAH09966.1; ALT_INIT; mRNA.
DR CCDS; CCDS32961.1; -. [Q14318-2]
DR CCDS; CCDS77266.1; -. [Q14318-1]
DR RefSeq; NP_001295302.1; NM_001308373.1. [Q14318-1]
DR RefSeq; NP_036313.3; NM_012181.4. [Q14318-2]
DR RefSeq; XP_011526165.1; XM_011527863.1.
DR PDB; 2AWG; X-ray; 1.60 A; A=90-205.
DR PDB; 2D9F; NMR; -; A=91-211.
DR PDB; 2F2D; NMR; -; A=92-210.
DR PDB; 2MF9; NMR; -; A=58-205.
DR PDB; 3EY6; X-ray; 1.05 A; A=92-210.
DR PDB; 5MGX; X-ray; 2.18 A; E/F/G/H=91-380.
DR PDBsum; 2AWG; -.
DR PDBsum; 2D9F; -.
DR PDBsum; 2F2D; -.
DR PDBsum; 2MF9; -.
DR PDBsum; 3EY6; -.
DR PDBsum; 5MGX; -.
DR AlphaFoldDB; Q14318; -.
DR BMRB; Q14318; -.
DR SMR; Q14318; -.
DR BioGRID; 117270; 514.
DR CORUM; Q14318; -.
DR DIP; DIP-42200N; -.
DR ELM; Q14318; -.
DR IntAct; Q14318; 134.
DR MINT; Q14318; -.
DR STRING; 9606.ENSP00000476767; -.
DR GuidetoPHARMACOLOGY; 3177; -.
DR iPTMnet; Q14318; -.
DR MetOSite; Q14318; -.
DR PhosphoSitePlus; Q14318; -.
DR SwissPalm; Q14318; -.
DR BioMuta; FKBP8; -.
DR DMDM; 193806337; -.
DR EPD; Q14318; -.
DR jPOST; Q14318; -.
DR MassIVE; Q14318; -.
DR MaxQB; Q14318; -.
DR PaxDb; Q14318; -.
DR PeptideAtlas; Q14318; -.
DR PRIDE; Q14318; -.
DR ProteomicsDB; 59962; -. [Q14318-1]
DR ProteomicsDB; 59963; -. [Q14318-2]
DR ProteomicsDB; 7612; -.
DR Antibodypedia; 28073; 414 antibodies from 34 providers.
DR DNASU; 23770; -.
DR Ensembl; ENST00000222308.8; ENSP00000222308.4; ENSG00000105701.16. [Q14318-1]
DR Ensembl; ENST00000596558.6; ENSP00000472302.1; ENSG00000105701.16. [Q14318-1]
DR Ensembl; ENST00000597960.7; ENSP00000471700.1; ENSG00000105701.16. [Q14318-2]
DR Ensembl; ENST00000608443.6; ENSP00000476767.1; ENSG00000105701.16. [Q14318-2]
DR GeneID; 23770; -.
DR KEGG; hsa:23770; -.
DR MANE-Select; ENST00000608443.6; ENSP00000476767.1; NM_012181.5; NP_036313.3. [Q14318-2]
DR UCSC; uc002njj.2; human. [Q14318-1]
DR CTD; 23770; -.
DR DisGeNET; 23770; -.
DR GeneCards; FKBP8; -.
DR HGNC; HGNC:3724; FKBP8.
DR HPA; ENSG00000105701; Low tissue specificity.
DR MIM; 604840; gene.
DR neXtProt; NX_Q14318; -.
DR OpenTargets; ENSG00000105701; -.
DR PharmGKB; PA28165; -.
DR VEuPathDB; HostDB:ENSG00000105701; -.
DR eggNOG; KOG0543; Eukaryota.
DR GeneTree; ENSGT00940000156705; -.
DR HOGENOM; CLU_013615_1_3_1; -.
DR InParanoid; Q14318; -.
DR OMA; RRDQHNE; -.
DR OrthoDB; 787673at2759; -.
DR PhylomeDB; Q14318; -.
DR TreeFam; TF105295; -.
DR BRENDA; 5.2.1.8; 2681.
DR PathwayCommons; Q14318; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SABIO-RK; Q14318; -.
DR SignaLink; Q14318; -.
DR SIGNOR; Q14318; -.
DR BioGRID-ORCS; 23770; 23 hits in 1076 CRISPR screens.
DR ChiTaRS; FKBP8; human.
DR EvolutionaryTrace; Q14318; -.
DR GeneWiki; FKBP8; -.
DR GenomeRNAi; 23770; -.
DR Pharos; Q14318; Tbio.
DR PRO; PR:Q14318; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q14318; protein.
DR Bgee; ENSG00000105701; Expressed in right frontal lobe and 174 other tissues.
DR ExpressionAtlas; Q14318; baseline and differential.
DR Genevisible; Q14318; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005740; C:mitochondrial envelope; IBA:GO_Central.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA.
DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0044183; F:protein folding chaperone; IMP:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:CAFA.
DR GO; GO:0048665; P:neuron fate specification; IEA:Ensembl.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.10.50.40; -; 1.
DR InterPro; IPR046357; PPIase_dom_sf.
DR InterPro; IPR001179; PPIase_FKBP_dom.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR013105; TPR_2.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF00254; FKBP_C; 1.
DR Pfam; PF07719; TPR_2; 1.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50059; FKBP_PPIASE; 1.
DR PROSITE; PS50005; TPR; 2.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Calcium;
KW Host-virus interaction; Isomerase; Isopeptide bond; Membrane;
KW Metal-binding; Mitochondrion; Phosphoprotein; Reference proteome; Repeat;
KW Rotamase; TPR repeat; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..412
FT /note="Peptidyl-prolyl cis-trans isomerase FKBP8"
FT /id="PRO_0000075331"
FT TRANSMEM 390..410
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 120..204
FT /note="PPIase FKBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277"
FT REPEAT 221..254
FT /note="TPR 1"
FT REPEAT 272..305
FT /note="TPR 2"
FT REPEAT 306..339
FT /note="TPR 3"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..53
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 149
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 151
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 249
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 271
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 273
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 284
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 307
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 314
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 334
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 340
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 348
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 351
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 352
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT VAR_SEQ 98..256
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18385096"
FT /id="VSP_047717"
FT VAR_SEQ 183
FT /note="G -> GS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005, ECO:0000303|Ref.8"
FT /id="VSP_034486"
FT VARIANT 87
FT /note="A -> V (in dbSNP:rs11574806)"
FT /id="VAR_044225"
FT MUTAGEN 149
FT /note="D->N: Abolishes calcium-binding and reduces affinity
FT for BCL2; when associated with Asn-151."
FT /evidence="ECO:0000269|PubMed:20140889"
FT MUTAGEN 151
FT /note="D->N: Abolishes calcium-binding and reduces affinity
FT for BCL2; when associated with Asn-149."
FT /evidence="ECO:0000269|PubMed:20140889"
FT CONFLICT 144
FT /note="V -> A (in Ref. 4; CAD98028)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="H -> R (in Ref. 4; CAD98028)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="G -> R (in Ref. 8; BAD96558)"
FT /evidence="ECO:0000305"
FT STRAND 94..108
FT /evidence="ECO:0007829|PDB:3EY6"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:2MF9"
FT STRAND 121..131
FT /evidence="ECO:0007829|PDB:3EY6"
FT STRAND 136..146
FT /evidence="ECO:0007829|PDB:3EY6"
FT TURN 147..150
FT /evidence="ECO:0007829|PDB:2MF9"
FT HELIX 154..157
FT /evidence="ECO:0007829|PDB:3EY6"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:3EY6"
FT STRAND 168..173
FT /evidence="ECO:0007829|PDB:3EY6"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:3EY6"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:3EY6"
FT TURN 185..187
FT /evidence="ECO:0007829|PDB:3EY6"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:2F2D"
FT STRAND 194..204
FT /evidence="ECO:0007829|PDB:3EY6"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:5MGX"
FT HELIX 214..233
FT /evidence="ECO:0007829|PDB:5MGX"
FT HELIX 237..252
FT /evidence="ECO:0007829|PDB:5MGX"
FT HELIX 261..284
FT /evidence="ECO:0007829|PDB:5MGX"
FT HELIX 288..301
FT /evidence="ECO:0007829|PDB:5MGX"
FT HELIX 306..319
FT /evidence="ECO:0007829|PDB:5MGX"
FT HELIX 322..335
FT /evidence="ECO:0007829|PDB:5MGX"
FT HELIX 340..354
FT /evidence="ECO:0007829|PDB:5MGX"
SQ SEQUENCE 412 AA; 44562 MW; 887C25ADE71EBA8D CRC64;
MASCAEPSEP SAPLPAGVPP LEDFEVLDGV EDAEGEEEEE EEEEEEDDLS ELPPLEDMGQ
PPAEEAEQPG ALAREFLAAM EPEPAPAPAP EEWLDILGNG LLRKKTLVPG PPGSSRPVKG
QVVTVHLQTS LENGTRVQEE PELVFTLGDC DVIQALDLSV PLMDVGETAM VTADSKYCYG
PQGRSPYIPP HAALCLEVTL KTAVDGPDLE MLTGQERVAL ANRKRECGNA HYQRADFVLA
ANSYDLAIKA ITSSAKVDMT FEEEAQLLQL KVKCLNNLAA SQLKLDHYRA ALRSCSLVLE
HQPDNIKALF RKGKVLAQQG EYSEAIPILR AALKLEPSNK TIHAELSKLV KKHAAQRSTE
TALYRKMLGN PSRLPAKCPG KGAWSIPWKW LFGATAVALG GVALSVVIAA RN
