Reviewed, UniProtKB/Swiss-Prot P68106 (FKB1B_HUMAN)

Names and origin

Protein names

Recommended name:
    Peptidyl-prolyl cis-trans isomerase FKBP1B
      Short name=PPIase FKBP1B
    EC=5.2.1.8
Alternative name(s):
    FK506-binding protein 1B
      Short name=FKBP-1B
    Rotamase
    Immunophilin FKBP12.6
      Short name=12.6 kDa FKBP
      Short name=FKBP-12.6
    h-FKBP-12

Gene names

Name:	FKBP1B
Synonyms:	FKBP12.6, FKBP1L, FKBP9, OTK4

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	108 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Associates with the ryanodine receptor (RYR-2) in cardiac muscle sarcoplasmic reticulum and may play a unique physiological role in excitation-contraction coupling in cardiac muscle. There are four molecules of FKBP12.6 per heart muscle RYR. Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Catalytic activity	Peptidylproline (omega=180) = peptidylproline (omega=0).
Enzyme regulation	Inhibited by both FK506 and rapamycin.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Ubiquitous for both isoforms with highest levels in brain and thymus.
Sequence similarities	Belongs to the FKBP-type PPIase family. FKBP1 subfamily. Contains 1 PPIase FKBP-type domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Molecular function	Isomerase Rotamase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	'de novo' protein folding Traceable author statement. Source: UniProtKB muscle contraction Non-traceable author statement. Source: UniProtKB negative regulation of heart rate Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein phosphatase type 2B activity Ref.2 Inferred from direct assay. Source: UniProtKB protein maturation by protein folding Traceable author statement. Source: UniProtKB protein refolding Traceable author statement. Source: UniProtKB regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Inferred from sequence or structural similarity. Source: UniProtKB regulation of ryanodine-sensitive calcium-release channel activity Ref.2 Inferred from mutant phenotype. Source: UniProtKB response to redox state Inferred from direct assay. Source: UniProtKB
Cellular component	calcium channel complex Inferred from direct assay. Source: UniProtKB cytosol Ref.2 Inferred by curator. Source: UniProtKB
Molecular function	FK506 binding Ref.2 Inferred from direct assay. Source: UniProtKB peptidyl-prolyl cis-trans isomerase activity Ref.2 Inferred from direct assay. Source: UniProtKB receptor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P68106-1)

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: P68106-2)

The sequence of this isoform differs from the canonical sequence as follows:
     67-108: MSLGQRAKLTCTPDVAYGATGHPGVIPPNATLIFDVELLNLE → LGPLSPLPICPHPC

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 108

107

Peptidyl-prolyl cis-trans isomerase FKBP1B

PRO_0000075295

Regions

Domain

20 – 108

89

PPIase FKBP-type

Natural variations

Alternative sequence

67 – 108

42

MSLGQ…LLNLE → LGPLSPLPICPHPC in isoform 2.

VSP_005184

Secondary structure

1

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108

Helix Strand Turn

Details...

Beta strand

3 – 9

7

Beta strand

22 – 31

10

Beta strand

36 – 39

4

Turn

40 – 44

5

Beta strand

47 – 50

4

Turn

51 – 54

4

Helix

58 – 65

8

Beta strand

72 – 77

6

Helix

79 – 81

3

Turn

82 – 86

5

Turn

89 – 91

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: BAC2A25945F63AC4	FASTA	108	11,783
	10 20 30 40 50 60 MGVEIETISP GDGRTFPKKG QTCVVHYTGM LQNGKKFDSS RDRNKPFKFR IGKQEVIKGF 70 80 90 100 EEGAAQMSLG QRAKLTCTPD VAYGATGHPG VIPPNATLIF DVELLNLE
	Isoform 2 [UniParc] [UniParc]. Checksum: 99C0A9C743984BA2	FASTA	80	8,802
	10 20 30 40 50 60 MGVEIETISP GDGRTFPKKG QTCVVHYTGM LQNGKKFDSS RDRNKPFKFR IGKQEVIKGF 70 80 EEGAAQLGPL SPLPICPHPC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of a novel human gene that is highly homologous to human FK506-binding protein 12kDa (hFKBP-12) and characterization of two alternatively spliced transcripts." Arakawa H., Nagase H., Hayashi N., Fujiwara T., Ogawa M., Shin S., Nakamura Y. Biochem. Biophys. Res. Commun. 200:836-843(1994) [PubMed: 7513996] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Fetal brain.
[2]	"A novel FK506 binding protein can mediate the immunosuppressive effects of FK506 and is associated with the cardiac ryanodine receptor." Lam E., Martin M.M., Timerman A.P., Sabers C., Fleischer S., Lukas T., Abraham R.T., O'Keefe S.J., O'Neill E.A., Wiederrecht G.J. J. Biol. Chem. 270:26511-26522(1995) [PubMed: 7592869] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain and Heart muscle.
[3]	"FKBP9: an alternative splice variant of the FK506-binding protein FKBP12.6 expressed in the human heart." Seidler T., Kussebi N., Prestle J. Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"Genomic organization, chromosomal localization, and promoter of human gene for FK506-binding protein 12.6." Nakazawa T., Takasawa S., Noguchi N., Nata K., Tohgo A., Mori M., Nakagawara K., Akiyama T., Ikeda T., Yamauchi A., Takahashi I., Yoshikawa T., Okamoto H. Gene 360:55-64(2005) [PubMed: 16122887] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 2). Tissue: Brain.
[8]	"Structure of FKBP12.6 in complex with rapamycin." Deivanayagam C.C., Carson M., Thotakura A., Narayana S.V., Chodavarapu R.S. Acta Crystallogr. D 56:266-271(2000) [PubMed: 10713512] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

S69815 mRNA. Translation: AAB30684.1.
D38037 mRNA. Translation: BAA07232.1.
L37086 mRNA. Translation: AAC37581.1.
S69800 mRNA. Translation: AAB30685.1.
AF322070 mRNA. Translation: AAK11191.1.
AB190793 Genomic DNA. Translation: BAE44300.1.
AC008073 Genomic DNA. Translation: AAY14663.1.
CH471053 Genomic DNA. Translation: EAX00769.1.
BC002614 mRNA. Translation: AAH02614.1.

IPI

IPI00073704.
IPI00396151.

PIR

JC2188.

RefSeq

NP_004107.1.
NP_473374.1.

UniGene

Hs.709461

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C9H	X-ray	2.00	A	2-108	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P68106.

Proteomic databases

PRIDE

P68106.

Genome annotation databases

Ensembl

ENST00000380986; ENSP00000370373; ENSG00000119782; Homo sapiens. [Genome view]
ENST00000380991; ENSP00000370379; ENSG00000119782; Homo sapiens. [Genome view]
ENST00000421839; ENSP00000397444; ENSG00000119782; Homo sapiens. [Genome view]
ENST00000438630; ENSP00000416349; ENSG00000119782; Homo sapiens. [Genome view]
ENST00000452109; ENSP00000406593; ENSG00000119782; Homo sapiens. [Genome view]

GeneID

2281.

KEGG

hsa:2281.

UCSC

uc002rer.1. human.
uc002res.1. human.

Organism-specific databases

CTD

2281.

GeneCards

GC02P024184.

H-InvDB

HIX0001871.

HGNC

HGNC:3712. FKBP1B.

MIM

600620. gene.

PharmGKB

PA28154.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P68106.

HOVERGEN

P68106.

OMA

MNDELQI.

Enzyme and pathway databases

BRENDA

5.2.1.8. 247.

Gene expression databases

ArrayExpress

P68106.

CleanEx

HS_FKBP1B.
HS_FKBP9.

Genevestigator

P68106.

GermOnline

ENSG00000119782. Homo sapiens.

Family and domain databases

InterPro

IPR001179. PPIase_FKBP.
[Graphical view]

PANTHER

PTHR10516. PPIase_FKBP. 1 hit.

Pfam

PF00254. FKBP_C. 1 hit.
[Graphical view]

PROSITE

PS50059. FKBP_PPIASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

9275.

SOURCE

Search...

Entry information

Entry name

FKB1B_HUMAN

Accession

Primary (citable) accession number: P68106
Secondary accession number(s): Q13664 , Q16645, Q53TM2, Q9BQ40

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2004
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 58 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.