Q14318 (FKBP8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	412 AA.
Sequence status	Complete.
Protein existence	Evidence 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.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.

Ontologies

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
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process 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 virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to 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_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
Complete GO annotation...

Binary interactions

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

Alternative products

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 412

412

Peptidyl-prolyl cis-trans isomerase FKBP8

PRO_0000075331

Regions

Transmembrane

390 – 410

21

Helical; Potential

Domain

120 – 204

85

PPIase FKBP-type

Repeat

221 – 254

34

TPR 1

Repeat

272 – 305

34

TPR 2

Repeat

306 – 339

34

TPR 3

Compositional bias

22 – 92

71

Glu-rich

Natural variations

Alternative sequence

183

1

G → GS in isoform 2.

VSP_034486

Natural variant

87

1

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

VAR_044225

Experimental info

Sequence conflict

144

1

V → A in CAD98028. Ref.3

Sequence conflict

191

1

H → R in CAD98028. Ref.3

Sequence conflict

206

1

G → R in BAD96558. Ref.7

Secondary structure

1

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412

Helix Strand Turn

Details...

Beta strand

67 – 73

7

Beta strand

94 – 108

15

Beta strand

121 – 131

11

Beta strand

136 – 146

11

Turn

147 – 150

4

Helix

154 – 157

4

Helix

160 – 162

3

Beta strand

168 – 173

6

Helix

175 – 177

3

Helix

180 – 182

3

Turn

185 – 187

3

Beta strand

190 – 192

3

Beta strand

194 – 204

11

Beta strand

208 – 211

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 2008. Version 2. Checksum: 887C25ADE71EBA8D	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
	Isoform 2 [UniParc]. Checksum: 0C32331CCBE5E4D9	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

References

	« 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] [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]	"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.
[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. , 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].
[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. , 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].
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZFYVE27.
[17]	"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].
[18]	"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.
[19]	"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.
[20]	"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.

Cross-references

Sequence databases

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.

3D structure databases

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.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14318. 17 interactions.

MINT

MINT-1338555.

STRING

9606.ENSP00000222308.

PTM databases

PhosphoSite

Q14318.

Polymorphism databases

DMDM

193806337.

Proteomic databases

PaxDb

Q14318.

PRIDE

Q14318.

Protocols and materials databases

DNASU

23770.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222308; ENSP00000222308; ENSG00000105701.
ENST00000596558; ENSP00000472302; ENSG00000105701.
ENST00000597960; ENSP00000471700; ENSG00000105701.

GeneID

23770.

KEGG

hsa:23770.

UCSC

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

Organism-specific databases

CTD

23770.

GeneCards

GC19M018642.

HGNC

HGNC:3724. FKBP8.

HPA

CAB025346.

MIM

604840. gene.

neXtProt

NX_Q14318.

PharmGKB

PA28165.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG256105.

HOVERGEN

HBG051626.

InParanoid

Q14318.

KO

K09574.

Enzyme and pathway databases

Pathway_Interaction_DB

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

Gene expression databases

ArrayExpress

Q14318.

Bgee

Q14318.

CleanEx

HS_FKBP8.

Genevestigator

Q14318.

GermOnline

ENSG00000105701. Homo sapiens.

Family and domain databases

Gene3D

1.10.150.160. 1 hit.
1.25.40.10. 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. PTHR10516. 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...

Other

ChiTaRS

FKBP8. human.

EvolutionaryTrace

Q14318.

GenomeRNAi

23770.

NextBio

46745.

SOURCE

Search...

Entry information

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:	May 1, 2013
This is version 134 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.