Peptidyl-prolyl cis-trans isomerase FKBP8

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

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Entry

#Exp.

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Notes

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

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Q14318 (FKBP8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 18, 2012. Version 124. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Sequence length	412 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

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.9 Ref.11
Catalytic activity	Peptidylproline (omega=180) = peptidylproline (omega=0). Ref.10
Cofactor	Calcium. Ref.10
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 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.11 Ref.12 Ref.14 Ref.15 Ref.16
Subcellular location	Mitochondrion membrane; Single-pass membrane protein; Cytoplasmic side By similarity Ref.1 Ref.9.
Tissue specificity	Widely expressed. Highest levels seen in the brain.
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.

Keywords
Biological process	Apoptosis Host-virus interaction
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat TPR repeat Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Isomerase Rotamase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW intracellular signal transduction Traceable author statement PubMed 10197430. Source: ProtInc protein folding Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to endoplasmic reticulum membrane Inferred from Biological aspect of Ancestor. Source: RefGenome mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	FK506 binding Inferred from Biological aspect of Ancestor. Source: RefGenome peptidyl-prolyl cis-trans isomerase activity Inferred from Biological aspect of Ancestor. Source: RefGenome protein binding Inferred from physical interaction PubMed 20029029 Ref.16 PubMed 17082457. Source: IntAct
Complete GO annotation...

With	Entry	#Exp.	IntAct	Notes
EGFR	P00533	3	EBI-724839,EBI-297353
ZFYVE27	Q5T4F4	4	EBI-724839,EBI-3892947

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 412

412

Peptidyl-prolyl cis-trans isomerase FKBP8

PRO_0000075331

Transmembrane

390 – 410

Helical; Potential

Domain

120 – 204

PPIase FKBP-type

Repeat

221 – 254

TPR 1

Repeat

272 – 305

TPR 2

Repeat

306 – 339

TPR 3

Compositional bias

22 – 92

Glu-rich

Modified residue

322

Phosphotyrosine Ref.13

Modified residue

348

N6-acetyllysine Ref.17

Alternative sequence

183

G → GS in isoform 2.

VSP_034486

Natural variant

A → V.
Corresponds to variant rs11574806 [ dbSNP | Ensembl ].

VAR_044225

Sequence conflict

144

V → A in CAD98028. Ref.3

Sequence conflict

191

H → R in CAD98028. Ref.3

Sequence conflict

206

G → R in BAD96558. Ref.7

412

Helix Strand Turn

Details...

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified July 1, 2008. Version 2. Checksum: 887C25ADE71EBA8D Show »	FASTA	412	44,562
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 »	FASTA	413	44,649
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 PQGSRSPYIP PHAALCLEVT LKTAVDGPDL EMLTGQERVA LANRKRECGN AHYQRADFVL 250 260 270 280 290 300 AANSYDLAIK AITSSAKVDM TFEEEAQLLQ LKVKCLNNLA ASQLKLDHYR AALRSCSLVL 310 320 330 340 350 360 EHQPDNIKAL FRKGKVLAQQ GEYSEAIPIL RAALKLEPSN KTIHAELSKL VKKHAAQRST 370 380 390 400 410 ETALYRKMLG NPSRLPAKCP GKGAWSIPWK WLFGATAVAL GGVALSVVIA ARN « Hide

	« Hide 'large scale' referencesShow '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: 12510191] [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: 15105374] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Colon endothelium.
[4]	"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. Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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. Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 7543869] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-412 (ISOFORM 1).
[7]	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.
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 54-412 (ISOFORM 1). Tissue: Pancreas.
[9]	"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: 16176796] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]	"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: 15990872] [Abstract] Cited for: CATALYTIC ACTIVITY, COFACTOR.
[11]	"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: 15757646] [Abstract] Cited for: FUNCTION, ABSENCE OF DIRECT INTERACTION WITH CALCINEURIN.
[12]	"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: 15733859] [Abstract] Cited for: INTERACTION WITH BCL2.
[13]	"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: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-322, MASS SPECTROMETRY.
[14]	"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: 17090549] [Abstract] Cited for: INTERACTION WITH BCL2.
[15]	"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: 16844119] [Abstract] Cited for: INTERACTION WITH HCV NS5A.
[16]	"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: 18459960] [Abstract] Cited for: INTERACTION WITH ZFYVE27.
[17]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-348, MASS SPECTROMETRY.
[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: 21269460] [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: 16604427] [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.
+	Additional computationally mapped references.

EMBL
GenBank
DDBJ

AY225339 mRNA. Translation: AAO39020.1.
AY278607 mRNA. Translation: AAQ84561.1.
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.

IPI

IPI00640341.
IPI01011108.

RefSeq

NP_036313.3. NM_012181.3.

UniGene

Hs.173464.

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AWG	X-ray	1.60	A	90-205	[»]
2D9F	NMR	-	A	91-211	[»]
2F2D	NMR	-	A	92-210	[»]
2JWX	NMR	-	A	58-205	[»]
3EY6	X-ray	1.05	A	92-210	[»]

ProteinModelPortal

Q14318.

SMR

Q14318. Positions 58-370.

ModBase

Search...

IntAct

Q14318. 14 interactions.

MINT

MINT-1338555.

STRING

Q14318.

PhosphoSite

Q14318.

DMDM

193806337.

PRIDE

Q14318.

DNASU

23770.

StructuralBiologyKnowledgebase

Search...

Ensembl

ENST00000453489; ENSP00000388891; ENSG00000105701.

GeneID

23770.

KEGG

hsa:23770.

UCSC

uc002njj.1. human.
uc002njk.1. human.

CTD

23770.

GeneCards

GC19M018642.

HGNC

HGNC:3724. FKBP8.

HPA

CAB025346.

MIM

604840. gene.

neXtProt

NX_Q14318.

PharmGKB

PA28165.

GenAtlas

Search...

eggNOG

NOG256105.

GeneTree

ENSGT00550000074272.

HOVERGEN

HBG051626.

InParanoid

Q14318.

K09574.

OMA

PLEDFEV.

Pathway_Interaction_DB

nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.

ArrayExpress

Q14318.

Bgee

Q14318.

CleanEx

HS_FKBP8.

Genevestigator

Q14318.

GermOnline

ENSG00000105701. Homo sapiens.

Gene3D

G3DSA:1.10.150.160. Elongated_TPR_rpt_dom. 1 hit.
G3DSA:1.25.40.10. TPR-like_helical. 1 hit.

InterPro

IPR023114. Elongated_TPR_rpt_dom.
IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR001440. TPR-1.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
[Graphical view]

PANTHER

PTHR10516. PPIase_FKBP. 1 hit.

Pfam

PF00254. FKBP_C. 1 hit.
PF00515. TPR_1. 2 hits.
[Graphical view]

PROSITE

PS50059. FKBP_PPIASE. 1 hit.
PS50005. TPR. 2 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

EvolutionaryTrace

Q14318.

NextBio

46745.

SOURCE

Search...

Entry name

FKBP8_HUMAN

Accession

Primary (citable) accession number: Q14318
Secondary accession number(s): Q53GU3, Q7Z349, Q86YK6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 1, 2008
Last modified:	April 18, 2012
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.

Human chromosome 19

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

This entry describes 2 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