Q9NWM8 (FKB14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP14
Short name=PPIase FKBP14
EC=5.2.1.8

Alternative name(s):
22 kDa FK506-binding protein
Short name=22 kDa FKBP
Short name=FKBP-22
FK506-binding protein 14
Short name=FKBP-14
Rotamase

Gene names

Name:	FKBP14
Synonyms:	FKBP22
ORF Names:	UNQ322/PRO381

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	211 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	PPIases accelerate the folding of proteins during protein synthesis.
Catalytic activity	Peptidylproline (omega=180) = peptidylproline (omega=0).
Subcellular location	Endoplasmic reticulum lumen Ref.5.
Involvement in disease	Ehlers-Danlos syndrome, with progressive kyphoscoliosis, myopathy, and hearing loss (EDSKMH) [MIM:614557]: A syndrome with features of Ehlers-Danlos syndrome types VIA and VIB on the one hand, and the collagen VI-related congenital myopathies Ullrich congenital muscular dystrophy and Bethlem myopathy on the other hand. Clinically, this disorder is characterized by the following features: severe generalized hypotonia at birth with marked muscle weakness that improve in infancy; early-onset progressive kyphoscoliosis; joint hypermobility without contractures; hyperelastic skin with follicular hyperkeratosis, easy bruising, and occasional abnormal scarring; myopathy; hearing impairment, which is predominantly sensorineural; normal ratio of lysyl pyridinoline to hydroxylysyl pyridinoline (LP/HP) in urine. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
Sequence similarities	Contains 2 EF-hand domains. Contains 1 PPIase FKBP-type domain.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Disease	Deafness Ehlers-Danlos syndrome
Domain	Repeat Signal
Ligand	Calcium Metal-binding
Molecular function	Isomerase Rotamase
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome protein folding Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum lumen Traceable author statement. Source: Reactome membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	FK506 binding Inferred from Biological aspect of Ancestor. Source: RefGenome calcium ion binding Inferred from electronic annotation. Source: InterPro peptidyl-prolyl cis-trans isomerase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.4

Chain

20 – 211

192

Peptidyl-prolyl cis-trans isomerase FKBP14

PRO_0000025521

Regions

Domain

45 – 135

91

PPIase FKBP-type

Domain

135 – 170

36

EF-hand 1

Domain

179 – 211

33

EF-hand 2

Calcium binding

148 – 159

12

1 Potential

Calcium binding

192 – 203

12

2 Potential

Motif

208 – 211

4

Prevents secretion from ER Potential

Amino acid modifications

Glycosylation

176

1

N-linked (GlcNAc...) Potential

Secondary structure

1

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211

Helix Strand Turn

Details...

Helix

19 – 21

3

Beta strand

28 – 33

6

Beta strand

47 – 56

10

Turn

57 – 59

3

Beta strand

62 – 65

4

Helix

66 – 69

4

Turn

70 – 72

3

Beta strand

75 – 78

4

Helix

86 – 91

6

Beta strand

100 – 105

6

Helix

107 – 109

3

Turn

110 – 114

5

Beta strand

125 – 135

11

Sequences

	Sequence		Length	Mass (Da)
	Q9NWM8 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 858184954FE10029	FASTA	211	24,172
	10 20 30 40 50 60 MRLFLWNAVL TLFVTSLIGA LIPEPEVKIE VLQKPFICHR KTKGGDLMLV HYEGYLEKDG 70 80 90 100 110 120 SLFHSTHKHN NGQPIWFTLG ILEALKGWDQ GLKGMCVGEK RKLIIPPALG YGKEGKGKIP 130 140 150 160 170 180 PESTLIFNID LLEIRNGPRS HESFQEMDLN DDWKLSKDEV KAYLKKEFEK HGAVVNESHH 190 200 210 DALVEDIFDK EDEDKDGFIS AREFTYKHDE L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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]. Tissue: Kidney.
[4]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-34.
[5]	"Mutations in FKBP14 cause a variant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss." Baumann M., Giunta C., Krabichler B., Ruschendorf F., Zoppi N., Colombi M., Bittner R.E., Quijano-Roy S., Muntoni F., Cirak S., Schreiber G., Zou Y., Hu Y., Romero N.B., Carlier R.Y., Amberger A., Deutschmann A., Straub V. , Rohrbach M., Steinmann B., Rostasy K., Karall D., Bonnemann C.G., Zschocke J., Fauth C. Am. J. Hum. Genet. 90:201-216(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN EDSKMH, SUBCELLULAR LOCATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY358643 mRNA. Translation: AAQ89006.1.
AK000738 mRNA. Translation: BAA91351.1.
BC005206 mRNA. Translation: AAH05206.1.

IPI

IPI00017331.

RefSeq

NP_060416.1. NM_017946.3.

UniGene

Hs.390838.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4DIP	X-ray	1.82	A/B/C/D/E/F/G/H/I/J	19-138	[»]

ProteinModelPortal

Q9NWM8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NWM8. 1 interaction.

STRING

9606.ENSP00000222803.

PTM databases

PhosphoSite

Q9NWM8.

Polymorphism databases

DMDM

23821568.

Proteomic databases

PaxDb

Q9NWM8.

PRIDE

Q9NWM8.

Protocols and materials databases

DNASU

55033.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222803; ENSP00000222803; ENSG00000106080.

GeneID

55033.

KEGG

hsa:55033.

UCSC

uc003tal.1. human.

Organism-specific databases

CTD

55033.

GeneCards

GC07M030050.

HGNC

HGNC:18625. FKBP14.

HPA

HPA013329.
HPA026829.

MIM

614505. gene.
614557. phenotype.

neXtProt

NX_Q9NWM8.

Orphanet

300179. Ehlers-Danlos syndrome, kyphoscoliotic and deafness type.

PharmGKB

PA38608.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0545.

HOGENOM

HOG000154887.

HOVERGEN

HBG051623.

InParanoid

Q9NWM8.

KO

K09577.

OMA

EVKIYLK.

OrthoDB

EOG45B1GJ.

PhylomeDB

Q9NWM8.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

Q9NWM8.

Bgee

Q9NWM8.

CleanEx

HS_FKBP14.

Genevestigator

Q9NWM8.

GermOnline

ENSG00000106080. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
[Graphical view]

PANTHER

PTHR10516. PTHR10516. 1 hit.

Pfam

PF13499. EF_hand_5. 1 hit.
PF00254. FKBP_C. 1 hit.
[Graphical view]

SMART

SM00054. EFh. 2 hits.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 2 hits.
PS00014. ER_TARGET. 1 hit.
PS50059. FKBP_PPIASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9NWM8.

ChEMBL

CHEMBL2342.

GenomeRNAi

55033.

NextBio

58455.

SOURCE

Search...

Entry information

Entry name

FKB14_HUMAN

Accession

Primary (citable) accession number: Q9NWM8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2002
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 113 of the entry and version 1 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.