UniProtKB - Q8NAU1 (FNDC5_HUMAN)
Protein
Fibronectin type III domain-containing protein 5
Gene
FNDC5
Organism
Homo sapiens (Human)
Status
Functioni
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
- hormone activity Source: UniProtKB-KW
GO - Biological processi
- positive regulation of brown fat cell differentiation Source: UniProtKB
- response to muscle activity Source: UniProtKB
Keywordsi
Molecular function | Hormone |
Enzyme and pathway databases
PathwayCommonsi | Q8NAU1 |
Names & Taxonomyi
Protein namesi | Recommended name: Fibronectin type III domain-containing protein 5Alternative name(s): Fibronectin type III repeat-containing protein 2 Cleaved into the following chain: |
Gene namesi | Name:FNDC5 Synonyms:FRCP2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20240, FNDC5 |
MIMi | 611906, gene |
neXtProti | NX_Q8NAU1 |
VEuPathDBi | HostDB:ENSG00000160097.15 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication
Peroxisome
- Peroxisome membrane By similarity; Single-pass type I membrane protein By similarity
Note: Imported in peroxisomes through the PEX5 receptor pathway.By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
Extracellular region or secreted
- extracellular region Source: UniProtKB
Peroxisome
- peroxisomal membrane Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 32 – 152 | ExtracellularSequence analysisAdd BLAST | 121 | |
Transmembranei | 153 – 173 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 174 – 212 | CytoplasmicSequence analysisAdd BLAST | 39 |
Keywords - Cellular componenti
Cell membrane, Membrane, Peroxisome, SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 252995 |
OpenTargetsi | ENSG00000160097 |
PharmGKBi | PA134924607 |
Miscellaneous databases
Pharosi | Q8NAU1, Tbio |
Genetic variation databases
BioMutai | FNDC5 |
DMDMi | 403314395 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 31 | Sequence analysisAdd BLAST | 31 | |
ChainiPRO_0000328971 | 32 – 212 | Fibronectin type III domain-containing protein 5Add BLAST | 181 | |
ChainiPRO_0000415857 | 32 – 143 | IrisinAdd BLAST | 112 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 39 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 84 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
The extracellular domain is cleaved and released from the cell membrane.
N-Glycosylated.By similarity
Keywords - PTMi
GlycoproteinProteomic databases
jPOSTi | Q8NAU1 |
MassIVEi | Q8NAU1 |
PaxDbi | Q8NAU1 |
PeptideAtlasi | Q8NAU1 |
PRIDEi | Q8NAU1 |
ProteomicsDBi | 72700 [Q8NAU1-1] 72701 [Q8NAU1-2] 72702 [Q8NAU1-3] 72703 [Q8NAU1-4] |
PTM databases
GlyGeni | Q8NAU1, 2 sites |
iPTMneti | Q8NAU1 |
PhosphoSitePlusi | Q8NAU1 |
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
Bgeei | ENSG00000160097, Expressed in quadriceps femoris and 174 other tissues |
ExpressionAtlasi | Q8NAU1, baseline and differential |
Organism-specific databases
HPAi | ENSG00000160097, Tissue enhanced (skeletal muscle, tongue) |
Interactioni
GO - Molecular functioni
- hormone activity Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 128948, 13 interactors |
IntActi | Q8NAU1, 8 interactors |
STRINGi | 9606.ENSP00000362570 |
Miscellaneous databases
RNActi | Q8NAU1, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q8NAU1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 36 – 127 | Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST | 92 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 210 – 212 | Microbody targeting signalSequence analysis | 3 |
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QQCU, Eukaryota |
GeneTreei | ENSGT00390000004923 |
HOGENOMi | CLU_089166_2_0_1 |
InParanoidi | Q8NAU1 |
OrthoDBi | 1198350at2759 |
TreeFami | TF325415 |
Family and domain databases
CDDi | cd00063, FN3, 1 hit |
Gene3Di | 2.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR003961, FN3_dom IPR036116, FN3_sf IPR032073, FNDC5_C IPR013783, Ig-like_fold |
Pfami | View protein in Pfam PF16066, DUF4808, 1 hit PF00041, fn3, 1 hit |
SMARTi | View protein in SMART SM00060, FN3, 1 hit |
SUPFAMi | SSF49265, SSF49265, 1 hit |
PROSITEi | View protein in PROSITE PS50853, FN3, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8NAU1-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0A0MRR6 | A0A0A0MRR6_HUMAN | Fibronectin type III domain-contain... | FNDC5 | 212 | Annotation score: | ||
A0A3B3ITP1 | A0A3B3ITP1_HUMAN | Fibronectin type III domain-contain... | FNDC5 | 201 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_032860 | 1 – 75 | Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST | 75 | |
Alternative sequenceiVSP_032861 | 180 – 181 | KD → EA in isoform 2. 1 Publication | 2 | |
Alternative sequenceiVSP_032862 | 182 – 212 | Missing in isoform 2. 1 PublicationAdd BLAST | 31 | |
Alternative sequenceiVSP_032863 | 212 | I → VRARPGPGWATLCLMLW in isoform 3. 1 Publication | 1 |
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. |
CCDSi | CCDS369.2 [Q8NAU1-1] CCDS65483.1 [Q8NAU1-3] |
RefSeqi | NP_001165411.2, NM_001171940.1 [Q8NAU1-2] NP_001165412.1, NM_001171941.2 [Q8NAU1-3] NP_715637.2, NM_153756.2 [Q8NAU1-1] |
Genome annotation databases
Ensembli | ENST00000496770; ENSP00000476320; ENSG00000160097 [Q8NAU1-3] |
GeneIDi | 252995 |
KEGGi | hsa:252995 |
UCSCi | uc001bwg.5, human [Q8NAU1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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. |
CCDSi | CCDS369.2 [Q8NAU1-1] CCDS65483.1 [Q8NAU1-3] |
RefSeqi | NP_001165411.2, NM_001171940.1 [Q8NAU1-2] NP_001165412.1, NM_001171941.2 [Q8NAU1-3] NP_715637.2, NM_153756.2 [Q8NAU1-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4LSD | X-ray | 2.28 | A/B/C/D/E/F/G/H | 33-130 | [»] | |
SMRi | Q8NAU1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 128948, 13 interactors |
IntActi | Q8NAU1, 8 interactors |
STRINGi | 9606.ENSP00000362570 |
PTM databases
GlyGeni | Q8NAU1, 2 sites |
iPTMneti | Q8NAU1 |
PhosphoSitePlusi | Q8NAU1 |
Genetic variation databases
BioMutai | FNDC5 |
DMDMi | 403314395 |
Proteomic databases
jPOSTi | Q8NAU1 |
MassIVEi | Q8NAU1 |
PaxDbi | Q8NAU1 |
PeptideAtlasi | Q8NAU1 |
PRIDEi | Q8NAU1 |
ProteomicsDBi | 72700 [Q8NAU1-1] 72701 [Q8NAU1-2] 72702 [Q8NAU1-3] 72703 [Q8NAU1-4] |
Protocols and materials databases
Antibodypediai | 54866, 192 antibodies |
DNASUi | 252995 |
Genome annotation databases
Ensembli | ENST00000496770; ENSP00000476320; ENSG00000160097 [Q8NAU1-3] |
GeneIDi | 252995 |
KEGGi | hsa:252995 |
UCSCi | uc001bwg.5, human [Q8NAU1-1] |
Organism-specific databases
CTDi | 252995 |
DisGeNETi | 252995 |
GeneCardsi | FNDC5 |
HGNCi | HGNC:20240, FNDC5 |
HPAi | ENSG00000160097, Tissue enhanced (skeletal muscle, tongue) |
MIMi | 611906, gene |
neXtProti | NX_Q8NAU1 |
OpenTargetsi | ENSG00000160097 |
PharmGKBi | PA134924607 |
VEuPathDBi | HostDB:ENSG00000160097.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QQCU, Eukaryota |
GeneTreei | ENSGT00390000004923 |
HOGENOMi | CLU_089166_2_0_1 |
InParanoidi | Q8NAU1 |
OrthoDBi | 1198350at2759 |
TreeFami | TF325415 |
Enzyme and pathway databases
PathwayCommonsi | Q8NAU1 |
Miscellaneous databases
BioGRID-ORCSi | 252995, 3 hits in 784 CRISPR screens |
ChiTaRSi | FNDC5, human |
GenomeRNAii | 252995 |
Pharosi | Q8NAU1, Tbio |
PROi | PR:Q8NAU1 |
RNActi | Q8NAU1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000160097, Expressed in quadriceps femoris and 174 other tissues |
ExpressionAtlasi | Q8NAU1, baseline and differential |
Family and domain databases
CDDi | cd00063, FN3, 1 hit |
Gene3Di | 2.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR003961, FN3_dom IPR036116, FN3_sf IPR032073, FNDC5_C IPR013783, Ig-like_fold |
Pfami | View protein in Pfam PF16066, DUF4808, 1 hit PF00041, fn3, 1 hit |
SMARTi | View protein in SMART SM00060, FN3, 1 hit |
SUPFAMi | SSF49265, SSF49265, 1 hit |
PROSITEi | View protein in PROSITE PS50853, FN3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | FNDC5_HUMAN | |
Accessioni | Q8NAU1Primary (citable) accession number: Q8NAU1 Secondary accession number(s): A6NMC9 Q7Z676 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 8, 2008 |
Last sequence update: | September 5, 2012 | |
Last modified: | February 10, 2021 | |
This is version 145 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references