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Protein

Fibronectin type III domain-containing protein 5

Gene

FNDC5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Irisin: Contrary to mouse, may not be involved in the beneficial effects of muscular exercise, nor in the induction of browning of human white adipose tissue.1 Publication

Caution

It is uncertain whether Met-1 or Met-76 is the initiator. Transcript evidence available at present time points at Met-76. In this short version of the protein, the signal peptide cannot be predicted and the irisin peptide is severely truncated. The first initiation codon corresponds to a non-AUG site, an N-terminal ATA codon. This initiation codon has been annotated as it is in good Kozak context and it is conserved in other primates, including gibbon, chimpanzee and gorilla. Although the existence of such a form has not been demonstrated in human, western blot analysis following endurance exercise shows the presence of an irisin peptide of similar size in human and mouse plasma (PubMed:22237023), suggesting the existence of full-length irisin in human, at least in some tissues. However, expression from Met-1 may be less efficient than that from Met-76 (PubMed:24040023).2 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHormone

Names & Taxonomyi

Protein namesi
Recommended name:
Fibronectin type III domain-containing protein 5
Alternative name(s):
Fibronectin type III repeat-containing protein 2
Cleaved into the following chain:
Gene namesi
Name:FNDC5
Synonyms:FRCP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000160097.15
HGNCiHGNC:20240 FNDC5
MIMi611906 gene
neXtProtiNX_Q8NAU1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 152ExtracellularSequence analysisAdd BLAST121
Transmembranei153 – 173HelicalSequence analysisAdd BLAST21
Topological domaini174 – 212CytoplasmicSequence analysisAdd BLAST39

Keywords - Cellular componenti

Cell membrane, Membrane, Peroxisome, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi252995
OpenTargetsiENSG00000160097
PharmGKBiPA134924607

Polymorphism and mutation databases

DMDMi403314395

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000032897132 – 212Fibronectin type III domain-containing protein 5Add BLAST181
ChainiPRO_000041585732 – 143IrisinAdd BLAST112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi39N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi84N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

The extracellular domain is cleaved and released from the cell membrane.
N-Glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8NAU1
PeptideAtlasiQ8NAU1
PRIDEiQ8NAU1
ProteomicsDBi72700
72701 [Q8NAU1-2]
72702 [Q8NAU1-3]
72703 [Q8NAU1-4]

PTM databases

iPTMnetiQ8NAU1
PhosphoSitePlusiQ8NAU1

Expressioni

Tissue specificityi

Widely expressed, with highest levels in heart. Very low expression, if any, in colon, pancreas and spleen.1 Publication

Inductioni

Has been shown to be up-regulated some twofold by muscular exercise at the mRNA and protein level; this effect has been suggested to be mediated by PPARGC1A (PubMed:22237023). However, up-regulation upon exercise could not be reproduced, at least not at the mRNA level (PubMed:24040023).2 Publications

Gene expression databases

BgeeiENSG00000160097 Expressed in 155 organ(s), highest expression level in quadriceps femoris
CleanExiHS_FNDC5
ExpressionAtlasiQ8NAU1 baseline and differential

Organism-specific databases

HPAiHPA051290

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi128948, 11 interactors
STRINGi9606.ENSP00000362570

Structurei

Secondary structure

1212
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8NAU1
SMRiQ8NAU1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 127Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST92

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi210 – 212Microbody targeting signalSequence analysis3

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IESX Eukaryota
ENOG410YC2F LUCA
GeneTreeiENSGT00390000004923
HOGENOMiHOG000082536
HOVERGENiHBG067308
InParanoidiQ8NAU1
TreeFamiTF325415

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR013783 Ig-like_fold
PfamiView protein in Pfam
PF00041 fn3, 1 hit
SMARTiView protein in SMART
SM00060 FN3, 1 hit
SUPFAMiSSF49265 SSF49265, 1 hit
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8NAU1-1) [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
        10         20         30         40         50
MHPGSPSAWP PRARAALRLW LGCVCFALVQ ADSPSAPVNV TVRHLKANSA
60 70 80 90 100
VVSWDVLEDE VVIGFAISQQ KKDVRMLRFI QEVNTTTRSC ALWDLEEDTE
110 120 130 140 150
YIVHVQAISI QGQSPASEPV LFKTPREAEK MASKNKDEVT MKEMGRNQQL
160 170 180 190 200
RTGEVLIIVV VLFMWAGVIA LFCRQYDIIK DNEPNNNKEK TKSASETSTP
210
EHQGGGLLRS KI
Length:212
Mass (Da):23,659
Last modified:September 5, 2012 - v3
Checksum:iC4A066452A05A134
GO
Isoform 2 (identifier: Q8NAU1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     180-181: KD → EA
     182-212: Missing.

Note: No experimental confirmation available.
Show »
Length:181
Mass (Da):20,281
Checksum:i36BEE521AFABE5A6
GO
Isoform 3 (identifier: Q8NAU1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.
     212-212: I → VRARPGPGWATLCLMLW

Note: No experimental confirmation available.
Show »
Length:153
Mass (Da):17,323
Checksum:i4DA2ABEAC5B4D934
GO
Isoform 4 (identifier: Q8NAU1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.

Note: No experimental confirmation available.
Show »
Length:137
Mass (Da):15,527
Checksum:i1045BF9CE29A41E4
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MRR6A0A0A0MRR6_HUMAN
Fibronectin type III domain-contain...
FNDC5
212Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0328601 – 75Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST75
Alternative sequenceiVSP_032861180 – 181KD → EA in isoform 2. 1 Publication2
Alternative sequenceiVSP_032862182 – 212Missing in isoform 2. 1 PublicationAdd BLAST31
Alternative sequenceiVSP_032863212I → VRARPGPGWATLCLMLW in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK092102 mRNA Translation: BAC03806.1
AC114493 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07499.1
CH471059 Genomic DNA Translation: EAX07502.1
CH471059 Genomic DNA Translation: EAX07500.1
BC062297 mRNA Translation: AAH62297.1
BX537781 mRNA Translation: CAD97840.1
BF221649 mRNA No translation available.
CCDSiCCDS369.2 [Q8NAU1-1]
CCDS65483.1 [Q8NAU1-3]
RefSeqiNP_001165411.2, NM_001171940.1 [Q8NAU1-2]
NP_001165412.1, NM_001171941.2 [Q8NAU1-3]
NP_715637.2, NM_153756.2 [Q8NAU1-1]
UniGeneiHs.524234

Genome annotation databases

EnsembliENST00000496770; ENSP00000476320; ENSG00000160097 [Q8NAU1-3]
ENST00000640867; ENSP00000491708; ENSG00000160097 [Q8NAU1-1]
GeneIDi252995
KEGGihsa:252995
UCSCiuc001bwg.5 human [Q8NAU1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK092102 mRNA Translation: BAC03806.1
AC114493 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07499.1
CH471059 Genomic DNA Translation: EAX07502.1
CH471059 Genomic DNA Translation: EAX07500.1
BC062297 mRNA Translation: AAH62297.1
BX537781 mRNA Translation: CAD97840.1
BF221649 mRNA No translation available.
CCDSiCCDS369.2 [Q8NAU1-1]
CCDS65483.1 [Q8NAU1-3]
RefSeqiNP_001165411.2, NM_001171940.1 [Q8NAU1-2]
NP_001165412.1, NM_001171941.2 [Q8NAU1-3]
NP_715637.2, NM_153756.2 [Q8NAU1-1]
UniGeneiHs.524234

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LSDX-ray2.28A/B/C/D/E/F/G/H33-130[»]
ProteinModelPortaliQ8NAU1
SMRiQ8NAU1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128948, 11 interactors
STRINGi9606.ENSP00000362570

PTM databases

iPTMnetiQ8NAU1
PhosphoSitePlusiQ8NAU1

Polymorphism and mutation databases

DMDMi403314395

Proteomic databases

PaxDbiQ8NAU1
PeptideAtlasiQ8NAU1
PRIDEiQ8NAU1
ProteomicsDBi72700
72701 [Q8NAU1-2]
72702 [Q8NAU1-3]
72703 [Q8NAU1-4]

Protocols and materials databases

DNASUi252995
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000496770; ENSP00000476320; ENSG00000160097 [Q8NAU1-3]
ENST00000640867; ENSP00000491708; ENSG00000160097 [Q8NAU1-1]
GeneIDi252995
KEGGihsa:252995
UCSCiuc001bwg.5 human [Q8NAU1-1]

Organism-specific databases

CTDi252995
DisGeNETi252995
EuPathDBiHostDB:ENSG00000160097.15
GeneCardsiFNDC5
HGNCiHGNC:20240 FNDC5
HPAiHPA051290
MIMi611906 gene
neXtProtiNX_Q8NAU1
OpenTargetsiENSG00000160097
PharmGKBiPA134924607
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IESX Eukaryota
ENOG410YC2F LUCA
GeneTreeiENSGT00390000004923
HOGENOMiHOG000082536
HOVERGENiHBG067308
InParanoidiQ8NAU1
TreeFamiTF325415

Miscellaneous databases

ChiTaRSiFNDC5 human
GenomeRNAii252995
PROiPR:Q8NAU1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160097 Expressed in 155 organ(s), highest expression level in quadriceps femoris
CleanExiHS_FNDC5
ExpressionAtlasiQ8NAU1 baseline and differential

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR013783 Ig-like_fold
PfamiView protein in Pfam
PF00041 fn3, 1 hit
SMARTiView protein in SMART
SM00060 FN3, 1 hit
SUPFAMiSSF49265 SSF49265, 1 hit
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFNDC5_HUMAN
AccessioniPrimary (citable) accession number: Q8NAU1
Secondary accession number(s): A6NMC9
, D3DPQ6, Q6P6D9, Q7Z676
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: September 5, 2012
Last modified: September 12, 2018
This is version 131 of the entry and version 3 of the sequence. See 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 1
    Human chromosome 1: 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
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Main funding by: National Institutes of Health

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