Reviewed, UniProtKB/Swiss-Prot Q14318 (FKBP8_HUMAN)

Names and origin

Protein names

Recommended name:
    FK506-binding protein 8
    EC=5.2.1.8
Alternative name(s):
    Peptidyl-prolyl cis-trans isomerase
      Short name=PPIase
      Short name=Rotamase
    38 kDa FK506-binding protein
      Short name=hFKBP38
    FKBPR38

Gene names

Name:	FKBP8
Synonyms:	FKBP38

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	412 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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).
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.
Subcellular location	Mitochondrion membrane; Single-pass membrane protein; Cytoplasmic side By similarity.
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: Miscellaneous discrepancy. The first part of the cDNA maps to the same locus, but in opposite orientation.

Ontologies

Keywords
Biological process	Apoptosis Host-virus interaction
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat TPR repeat Transmembrane
Ligand	Calcium
Molecular function	Isomerase Rotamase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW intracellular signaling cascade Traceable author statement. Source: ProtInc protein folding Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-prolyl cis-trans isomerase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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

FK506-binding protein 8

PRO_0000075331

Regions

Transmembrane

390 – 410

21

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

Amino acid modifications

Modified residue

322

1

Phosphotyrosine Ref.13

Natural variations

Alternative sequence

183

1

G → GS in isoform 2.

VSP_034486

Natural variant

87

1

A → V: dbSNP rs11574806.

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.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

412

Helix Strand Turn

Details...

Beta strand

36 – 51

16

Beta strand

64 – 73

10

Beta strand

79 – 89

11

Helix

97 – 102

6

Helix

103 – 105

3

Beta strand

111 – 116

6

Helix

118 – 120

3

Turn

121 – 125

5

Turn

128 – 130

3

Beta strand

137 – 147

11

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. 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: 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]	Bloecker H., Boecher M., Mewes H.-W., Weil B., Amid C., Osanger A., Fobo G., Han M., Wiemann S. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases 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: 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. , 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: 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: PPIASE 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]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[17]	"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.
[18]	"Solution structure of 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.
[19]	"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

EMBLGenBankDDBJ

AY225339 mRNA. Translation: AAO39020.1.
AY278607 mRNA. Translation: AAQ84561.1.
BX538124 mRNA. Translation: CAD98028.1. Different initiation.
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

IPI00328161.
IPI00640341.

RefSeq

NP_036313.3.

UniGene

Hs.173464

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14318. 2 interactions.

PTM databases

PhosphoSite

Q14318.

Proteomic databases

PRIDE

Q14318.

Genome annotation databases

Ensembl

ENSG00000105701. Homo sapiens. [Contig view]

GeneID

23770.

KEGG

hsa:23770.

UCSC

uc002njk.1. human.

Organism-specific databases

GeneCards

GC19M018503.

HGNC

HGNC:3724. FKBP8.

HPA

HPA007054.

MIM

604840. gene.

PharmGKB

PA28165.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q14318.

OMA

Q14318. KVDMTFE.

Enzyme and pathway databases

BRENDA

5.2.1.8. 247.

Pathway_Interaction_DB

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

Gene expression databases

ArrayExpress

Q14318.

Bgee

Q14318.

CleanEx

HS_FKBP8.

GermOnline

ENSG00000105701. Homo sapiens.

Family and domain databases

InterPro

IPR001179. PPIase_FKBP.
IPR001440. TPR-1.
IPR011990. TPR-like_helical.
IPR013026. TPR_region.
IPR019734. TPR_repeat.
[Graphical view]

Gene3D

G3DSA:1.25.40.10. TPR-like_helical. 1 hit.

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...

Other Resources

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:	July 7, 2009
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)