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P68106

- FKB1B_HUMAN

UniProt

P68106 - FKB1B_HUMAN

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Protein
Peptidyl-prolyl cis-trans isomerase FKBP1B
Gene
FKBP1B, FKBP12.6, FKBP1L, FKBP9, OTK4
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 activityi

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

Enzyme regulationi

Inhibited by both FK506 and rapamycin.

GO - Molecular functioni

  1. FK506 binding Source: BHF-UCL
  2. calcium channel inhibitor activity Source: BHF-UCL
  3. cyclic nucleotide binding Source: Ensembl
  4. ion channel binding Source: BHF-UCL
  5. peptidyl-prolyl cis-trans isomerase activity Source: BHF-UCL
  6. protein binding Source: IntAct
  7. receptor binding Source: BHF-UCL

GO - Biological processi

  1. 'de novo' protein folding Source: BHF-UCL
  2. T cell proliferation Source: Ensembl
  3. calcium ion transmembrane transport Source: GOC
  4. calcium-mediated signaling using intracellular calcium source Source: BHF-UCL
  5. cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
  6. chaperone-mediated protein folding Source: RefGenome
  7. cytosolic calcium ion homeostasis Source: BHF-UCL
  8. insulin secretion Source: Ensembl
  9. negative regulation of heart rate Source: BHF-UCL
  10. negative regulation of insulin secretion involved in cellular response to glucose stimulus Source: Ensembl
  11. negative regulation of protein phosphatase type 2B activity Source: BHF-UCL
  12. negative regulation of release of sequestered calcium ion into cytosol Source: BHF-UCL
  13. negative regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
  14. neuronal action potential propagation Source: Ensembl
  15. positive regulation of axon regeneration Source: Ensembl
  16. positive regulation of sequestering of calcium ion Source: BHF-UCL
  17. protein maturation by protein folding Source: BHF-UCL
  18. protein peptidyl-prolyl isomerization Source: BHF-UCL
  19. protein refolding Source: BHF-UCL
  20. regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: BHF-UCL
  21. regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: BHF-UCL
  22. regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
  23. release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: Ensembl
  24. response to glucose Source: Ensembl
  25. response to hydrogen peroxide Source: Ensembl
  26. response to redox state Source: BHF-UCL
  27. response to vitamin E Source: Ensembl
  28. smooth muscle contraction Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Rotamase

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP1B (EC:5.2.1.8)
Short name:
PPIase FKBP1B
Alternative name(s):
12.6 kDa FK506-binding protein
Short name:
12.6 kDa FKBP
Short name:
FKBP-12.6
FK506-binding protein 1B
Short name:
FKBP-1B
Immunophilin FKBP12.6
Rotamase
h-FKBP-12
Gene namesi
Name:FKBP1B
Synonyms:FKBP12.6, FKBP1L, FKBP9, OTK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:3712. FKBP1B.

Subcellular locationi

Cytoplasm By similarity. Sarcoplasmic reticulum By similarity

GO - Cellular componenti

  1. Z disc Source: BHF-UCL
  2. calcium channel complex Source: BHF-UCL
  3. cytoplasm Source: BHF-UCL
  4. cytosol Source: BHF-UCL
  5. membrane Source: BHF-UCL
  6. sarcoplasmic reticulum membrane Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Sarcoplasmic reticulum

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28154.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 108107Peptidyl-prolyl cis-trans isomerase FKBP1B
PRO_0000075295Add
BLAST

Proteomic databases

PaxDbiP68106.
PRIDEiP68106.

PTM databases

PhosphoSiteiP68106.

Expressioni

Tissue specificityi

Detected in heart muscle (at protein level). Isoform 1 and isoform 2 are ubiquitous with highest levels in brain and thymus.1 Publication

Gene expression databases

BgeeiP68106.
CleanExiHS_FKBP1B.
HS_FKBP9.
GenevestigatoriP68106.

Organism-specific databases

HPAiHPA051798.

Interactioni

Subunit structurei

Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with RYR2.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
RYR2Q927362EBI-6693977,EBI-1170425

Protein-protein interaction databases

BioGridi108571. 2 interactions.
DIPiDIP-48796N.
IntActiP68106. 4 interactions.
STRINGi9606.ENSP00000370373.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 97
Beta strandi22 – 3110
Beta strandi36 – 405
Turni41 – 444
Beta strandi47 – 504
Turni51 – 544
Helixi58 – 647
Beta strandi72 – 776
Helixi79 – 813
Turni82 – 865
Beta strandi89 – 913
Beta strandi98 – 10811

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1C9HX-ray2.00A2-108[»]
4C02X-ray2.17B1-108[»]
4IQ2X-ray1.70A/B2-108[»]
4IQCX-ray1.90A/B2-108[»]
ProteinModelPortaliP68106.
SMRiP68106. Positions 2-108.

Miscellaneous databases

EvolutionaryTraceiP68106.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 10889PPIase FKBP-type
Add
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0545.
HOGENOMiHOG000154887.
HOVERGENiHBG051623.
InParanoidiP68106.
KOiK09568.
OMAiCWIGSWR.
OrthoDBiEOG7ZGX5T.
PhylomeDBiP68106.
TreeFamiTF105291.

Family and domain databases

InterProiIPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 1 hit.
PfamiPF00254. FKBP_C. 1 hit.
[Graphical view]
PROSITEiPS50059. FKBP_PPIASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P68106-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MGVEIETISP GDGRTFPKKG QTCVVHYTGM LQNGKKFDSS RDRNKPFKFR    50
IGKQEVIKGF EEGAAQMSLG QRAKLTCTPD VAYGATGHPG VIPPNATLIF 100
DVELLNLE 108
Length:108
Mass (Da):11,783
Last modified:January 23, 2007 - v2
Checksum:iBAC2A25945F63AC4
GO
Isoform 2 (identifier: P68106-2) [UniParc] [UniParc]FASTAAdd to Basket

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

Show »
Length:80
Mass (Da):8,802
Checksum:i99C0A9C743984BA2
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei67 – 10842MSLGQ…LLNLE → LGPLSPLPICPHPC in isoform 2.
VSP_005184Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS1706.1.
CCDS33153.1. [P68106-2]
PIRiJC2188.
RefSeqiNP_004107.1. NM_004116.3. [P68106-1]
NP_473374.1. NM_054033.2. [P68106-2]
UniGeneiHs.709461.

Genome annotation databases

EnsembliENST00000380986; ENSP00000370373; ENSG00000119782. [P68106-1]
ENST00000380991; ENSP00000370379; ENSG00000119782. [P68106-2]
GeneIDi2281.
KEGGihsa:2281.
UCSCiuc002rer.3. human.
uc002res.3. human. [P68106-2]

Polymorphism databases

DMDMi61224185.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS1706.1.
CCDS33153.1. [P68106-2 ]
PIRi JC2188.
RefSeqi NP_004107.1. NM_004116.3. [P68106-1 ]
NP_473374.1. NM_054033.2. [P68106-2 ]
UniGenei Hs.709461.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1C9H X-ray 2.00 A 2-108 [» ]
4C02 X-ray 2.17 B 1-108 [» ]
4IQ2 X-ray 1.70 A/B 2-108 [» ]
4IQC X-ray 1.90 A/B 2-108 [» ]
ProteinModelPortali P68106.
SMRi P68106. Positions 2-108.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108571. 2 interactions.
DIPi DIP-48796N.
IntActi P68106. 4 interactions.
STRINGi 9606.ENSP00000370373.

Chemistry

BindingDBi P68106.
ChEMBLi CHEMBL2430.

PTM databases

PhosphoSitei P68106.

Polymorphism databases

DMDMi 61224185.

Proteomic databases

PaxDbi P68106.
PRIDEi P68106.

Protocols and materials databases

DNASUi 2281.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000380986 ; ENSP00000370373 ; ENSG00000119782 . [P68106-1 ]
ENST00000380991 ; ENSP00000370379 ; ENSG00000119782 . [P68106-2 ]
GeneIDi 2281.
KEGGi hsa:2281.
UCSCi uc002rer.3. human.
uc002res.3. human. [P68106-2 ]

Organism-specific databases

CTDi 2281.
GeneCardsi GC02P024272.
HGNCi HGNC:3712. FKBP1B.
HPAi HPA051798.
MIMi 600620. gene.
neXtProti NX_P68106.
PharmGKBi PA28154.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0545.
HOGENOMi HOG000154887.
HOVERGENi HBG051623.
InParanoidi P68106.
KOi K09568.
OMAi CWIGSWR.
OrthoDBi EOG7ZGX5T.
PhylomeDBi P68106.
TreeFami TF105291.

Miscellaneous databases

EvolutionaryTracei P68106.
GeneWikii FKBP1B.
GenomeRNAii 2281.
NextBioi 9275.
PROi P68106.
SOURCEi Search...

Gene expression databases

Bgeei P68106.
CleanExi HS_FKBP1B.
HS_FKBP9.
Genevestigatori P68106.

Family and domain databases

InterProi IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
[Graphical view ]
PANTHERi PTHR10516. PTHR10516. 1 hit.
Pfami PF00254. FKBP_C. 1 hit.
[Graphical view ]
PROSITEi PS50059. FKBP_PPIASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. 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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Brain.
  8. "PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts."
    Marx S.O., Reiken S., Hisamatsu Y., Jayaraman T., Burkhoff D., Rosemblit N., Marks A.R.
    Cell 101:365-376(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH RYR2; PP1; PP2A AKAP6 AND PKA, INTERACTION WITH RYR2, TISSUE SPECIFICITY.
  9. Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).

Entry informationi

Entry nameiFKB1B_HUMAN
AccessioniPrimary (citable) accession number: P68106
Secondary accession number(s): Q13664
, Q16645, Q53TM2, Q9BQ40
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 25, 2004
Last sequence update: January 23, 2007
Last modified: September 3, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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