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Q14318 (FKBP8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Peptidyl-prolyl cis-trans isomerase FKBP8

Short name=PPIase FKBP8
EC=5.2.1.8
Alternative name(s):
38 kDa FK506-binding protein
Short name=38 kDa FKBP
Short name=FKBP-38
Short name=hFKBP38
FK506-binding protein 8
Short name=FKBP-8
FKBPR38
Rotamase
Gene names
Name:FKBP8
Synonyms:FKBP38
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length412 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis. Ref.1 Ref.10 Ref.12

Catalytic activity

Peptidylproline (omega=180) = peptidylproline (omega=0). Ref.11

Cofactor

Calcium. Ref.11

Subunit structure

Homomultimers or heteromultimers Potential. Forms heterodimer with calmodulin. When activated by calmodulin and calcium, interacts with the BH4 domain of BCL2 and weakly with BCL2L1/BCLX isoform Bcl-X(L) Does not bind and inhibit calcineurin. Interacts with HCV NS5A. Interacts with ZFYVE27; may negatively regulate ZFYVE27 phosphorylation. Ref.1 Ref.3 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17

Subcellular location

Isoform 1: Mitochondrion membrane; Single-pass membrane protein; Cytoplasmic side Ref.1 Ref.3 Ref.10.

Isoform 3: Mitochondrion membrane; Single-pass membrane protein; Cytoplasmic side Ref.1 Ref.3 Ref.10.

Tissue specificity

Widely expressed. Highest levels seen in the brain. Highly abundant in the retina. Ref.3

Miscellaneous

Binds the immunosuppressant FK506 only in its calmodulin/calcium activated form.

Sequence similarities

Contains 1 PPIase FKBP-type domain.

Contains 3 TPR repeats.

Caution

It is uncertain whether Met-1 or Met-58 is the initiator.

Sequence caution

The sequence AAB00102.1 differs from that shown. Reason: The first part of the cDNA maps to the same locus, but in opposite orientation.

The sequence AAH09966.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAD98028.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processApoptosis
Host-virus interaction
   Cellular componentMembrane
Mitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
TPR repeat
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
   Molecular functionIsomerase
Rotamase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Traceable author statement PubMed 10197430. Source: ProtInc

peptidyl-proline modification

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein folding

Inferred from electronic annotation. Source: UniProtKB-KW

protein peptidyl-prolyl isomerization

Inferred from Biological aspect of Ancestor. Source: GOC

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentintegral component of endoplasmic reticulum membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

mitochondrial envelope

Inferred from Biological aspect of Ancestor. Source: RefGenome

mitochondrial membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionFK506 binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

identical protein binding

Inferred from physical interaction PubMed 17024179. Source: IntAct

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptidyl-prolyl cis-trans isomerase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14318-1)

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: Q14318-2)

The sequence of this isoform differs from the canonical sequence as follows:
     183-183: G → GS
Isoform 3 (identifier: Q14318-3)

The sequence of this isoform differs from the canonical sequence as follows:
     98-256: Missing.
Note: Interacts with BCL2L1/BCLX.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 412412Peptidyl-prolyl cis-trans isomerase FKBP8
PRO_0000075331

Regions

Transmembrane390 – 41021Helical; Potential
Domain120 – 20485PPIase FKBP-type
Repeat221 – 25434TPR 1
Repeat272 – 30534TPR 2
Repeat306 – 33934TPR 3
Compositional bias22 – 9271Glu-rich

Sites

Metal binding1491Calcium
Metal binding1511Calcium

Natural variations

Alternative sequence98 – 256159Missing in isoform 3.
VSP_047717
Alternative sequence1831G → GS in isoform 2.
VSP_034486
Natural variant871A → V.
Corresponds to variant rs11574806 [ dbSNP | Ensembl ].
VAR_044225

Experimental info

Mutagenesis1491D → N: Abolishes calcium-binding and reduces affinity for BCL2; when associated with Asn-151. Ref.22
Mutagenesis1511D → N: Abolishes calcium-binding and reduces affinity for BCL2; when associated with Asn-149. Ref.22
Sequence conflict1441V → A in CAD98028. Ref.4
Sequence conflict1911H → R in CAD98028. Ref.4
Sequence conflict2061G → R in BAD96558. Ref.8

Secondary structure

............................ 412
Helix Strand Turn

Details...

Sequences

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

Last modified July 1, 2008. Version 2.
Checksum: 887C25ADE71EBA8D

FASTA41244,562
        10         20         30         40         50         60 
MASCAEPSEP SAPLPAGVPP LEDFEVLDGV EDAEGEEEEE EEEEEEDDLS ELPPLEDMGQ 

        70         80         90        100        110        120 
PPAEEAEQPG ALAREFLAAM EPEPAPAPAP EEWLDILGNG LLRKKTLVPG PPGSSRPVKG 

       130        140        150        160        170        180 
QVVTVHLQTS LENGTRVQEE PELVFTLGDC DVIQALDLSV PLMDVGETAM VTADSKYCYG 

       190        200        210        220        230        240 
PQGRSPYIPP HAALCLEVTL KTAVDGPDLE MLTGQERVAL ANRKRECGNA HYQRADFVLA 

       250        260        270        280        290        300 
ANSYDLAIKA ITSSAKVDMT FEEEAQLLQL KVKCLNNLAA SQLKLDHYRA ALRSCSLVLE 

       310        320        330        340        350        360 
HQPDNIKALF RKGKVLAQQG EYSEAIPILR AALKLEPSNK TIHAELSKLV KKHAAQRSTE 

       370        380        390        400        410 
TALYRKMLGN PSRLPAKCPG KGAWSIPWKW LFGATAVALG GVALSVVIAA RN 

« Hide

Isoform 2 [UniParc].

Checksum: 0C32331CCBE5E4D9
Show »

FASTA41344,649
Isoform 3 [UniParc].

Checksum: F899112DC6BF5118
Show »

FASTA25327,545

References

« Hide 'large scale' references
[1]"Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis."
Shirane M., Nakayama K.I.
Nat. Cell Biol. 5:28-37(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH BCL2 AND BCL2L1/BCLXL, SUBCELLULAR LOCATION.
[2]"FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues."
Bulgakov O.V., Eggenschwiler J.T., Hong D.-H., Anderson K.V., Li T.
Development 131:2149-2159(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Characterization of a Bcl-XL-interacting protein FKBP8 and its splice variant in human RPE cells."
Chen Y., Sternberg P., Cai J.
Invest. Ophthalmol. Vis. Sci. 49:1721-1727(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION, INTERACTION WITH BCL2L1, TISSUE SPECIFICITY.
Tissue: Retinal pigment epithelium.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Colon endothelium.
[5]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"Isolation of a cDNA encoding a novel human FK506-binding protein homolog containing leucine zipper and tetratricopeptide repeat motifs."
Lam E., Martin M., Wiederrecht G.
Gene 160:297-302(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-412 (ISOFORM 1).
[8]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-412 (ISOFORM 2).
Tissue: Liver.
[9]"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] OF 54-412 (ISOFORM 1).
Tissue: Pancreas.
[10]"Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2."
Kang C.B., Feng L., Chia J., Yoon H.S.
Biochem. Biophys. Res. Commun. 337:30-38(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]"Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin."
Edlich F., Weiwad M., Erdmann F., Fanghaenel J., Jarczowski F., Rahfeld J.-U., Fischer G.
EMBO J. 24:2688-2699(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, COFACTOR.
[12]"A reassessment of the inhibitory capacity of human FKBP38 on calcineurin."
Weiwad M., Edlich F., Erdmann F., Jarczowski F., Kilka S., Dorn M., Pechstein A., Fischer G.
FEBS Lett. 579:1591-1596(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ABSENCE OF DIRECT INTERACTION WITH CALCINEURIN.
[13]"The flexible loop of Bcl-2 is required for molecular interaction with immunosuppressant FK-506 binding protein 38 (FKBP38)."
Kang C.B., Tai J., Chia J., Yoon H.S.
FEBS Lett. 579:1469-1476(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BCL2.
[14]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Bcl-2 localized at the nuclear compartment induces apoptosis after transient overexpression."
Portier B.P., Taglialatela G.
J. Biol. Chem. 281:40493-40502(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BCL2.
[16]"Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells."
Wang J., Tong W., Zhang X., Chen L., Yi Z., Pan T., Hu Y., Xiang L., Yuan Z.
FEBS Lett. 580:4392-4400(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HCV NS5A.
[17]"Regulation of apoptosis and neurite extension by FKBP38 is required for neural tube formation in the mouse."
Shirane M., Ogawa M., Motoyama J., Nakayama K.I.
Genes Cells 13:635-651(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZFYVE27.
[18]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Solution structure of the FK506-binding domain of human FKBP38."
Maestre-Martinez M., Edlich F., Jarczowski F., Weiwad M., Fischer G., Luecke C.
J. Biomol. NMR 34:197-202(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 92-210.
[20]"Solution structure of RSGI RUH-047, an FKBP domain from human cDNA."
RIKEN structural genomics initiative (RSGI)
Submitted (JUN-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 91-205.
[21]"Structure of the human FK-506 binding protein 8."
Structural genomics consortium (SGC)
Submitted (OCT-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 90-205.
[22]"A charge-sensitive loop in the FKBP38 catalytic domain modulates Bcl-2 binding."
Maestre-Martinez M., Haupt K., Edlich F., Neumann P., Parthier C., Stubbs M.T., Fischer G., Lucke C.
J. Mol. Recognit. 24:23-34(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF 92-210, METAL-BINDING SITES, MUTAGENESIS OF ASP-149 AND ASP-151.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY225339 mRNA. Translation: AAO39020.1.
AY278607 mRNA. Translation: AAQ84561.1.
GQ372970 mRNA. Translation: ACU65096.1.
BX538124 mRNA. Translation: CAD98028.1. Different initiation.
BX647405 mRNA. No translation available.
AC005387 Genomic DNA. Translation: AAC28753.1.
CH471106 Genomic DNA. Translation: EAW84709.1.
L37033 mRNA. Translation: AAB00102.1. Sequence problems.
AK222838 mRNA. Translation: BAD96558.1.
BC009966 mRNA. Translation: AAH09966.1. Different initiation.
RefSeqNP_036313.3. NM_012181.3.
UniGeneHs.173464.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2AWGX-ray1.60A90-205[»]
2D9FNMR-A91-211[»]
2F2DNMR-A92-210[»]
2MF9NMR-A58-205[»]
3EY6X-ray1.05A92-210[»]
ProteinModelPortalQ14318.
SMRQ14318. Positions 58-371.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117270. 70 interactions.
IntActQ14318. 23 interactions.
MINTMINT-1338555.
STRING9606.ENSP00000222308.

PTM databases

PhosphoSiteQ14318.

Polymorphism databases

DMDM193806337.

Proteomic databases

PaxDbQ14318.
PRIDEQ14318.

Protocols and materials databases

DNASU23770.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222308; ENSP00000222308; ENSG00000105701. [Q14318-1]
ENST00000596558; ENSP00000472302; ENSG00000105701. [Q14318-1]
ENST00000597960; ENSP00000471700; ENSG00000105701. [Q14318-2]
ENST00000608443; ENSP00000476767; ENSG00000105701. [Q14318-2]
ENST00000610101; ENSP00000476586; ENSG00000105701. [Q14318-3]
GeneID23770.
KEGGhsa:23770.
UCSCuc002njj.1. human. [Q14318-2]
uc002njk.1. human. [Q14318-1]

Organism-specific databases

CTD23770.
GeneCardsGC19M018642.
HGNCHGNC:3724. FKBP8.
HPACAB025346.
HPA045177.
MIM604840. gene.
neXtProtNX_Q14318.
PharmGKBPA28165.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG256105.
HOVERGENHBG051626.
InParanoidQ14318.
KOK09574.
OrthoDBEOG70S75T.
PhylomeDBQ14318.
TreeFamTF105295.

Gene expression databases

ArrayExpressQ14318.
BgeeQ14318.
CleanExHS_FKBP8.
GenevestigatorQ14318.

Family and domain databases

Gene3D1.10.150.160. 1 hit.
1.25.40.10. 1 hit.
InterProIPR023114. Elongated_TPR_rpt_dom.
IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR001440. TPR_1.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERPTHR10516. PTHR10516. 1 hit.
PfamPF00254. FKBP_C. 1 hit.
PF00515. TPR_1. 2 hits.
[Graphical view]
PROSITEPS50059. FKBP_PPIASE. 1 hit.
PS50005. TPR. 2 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFKBP8. human.
EvolutionaryTraceQ14318.
GeneWikiFKBP8.
GenomeRNAi23770.
NextBio35483698.
PROQ14318.
SOURCESearch...

Entry information

Entry nameFKBP8_HUMAN
AccessionPrimary (citable) accession number: Q14318
Secondary accession number(s): C8C9T5 expand/collapse secondary AC list , Q53GU3, Q7Z349, Q86YK6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 1, 2008
Last modified: April 16, 2014
This is version 145 of the entry and version 2 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 19

Human chromosome 19: entries, gene names and cross-references to MIM