Q9NSA1 (FGF21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fibroblast growth factor 21
Short name=FGF-21

Gene names

Name:	FGF21
ORF Names:	UNQ3115/PRO10196

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	209 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	Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Ref.7 Ref.8
Subunit structure	Interacts (via C-terminus) with KLB; this interaction is direct. Interacts with FGFR4. Ref.7 Ref.9 Ref.10
Subcellular location	Secreted Potential.
Sequence similarities	Belongs to the heparin-binding growth factors family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Growth factor
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell signaling Traceable author statement Ref.1. Source: ProtInc positive regulation of ERK1 and ERK2 cascade Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of glucose import Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of low-density lipoprotein particle receptor biosynthetic process Non-traceable author statement PubMed 22378787. Source: BHF-UCL regulation of low-density lipoprotein particle clearance Non-traceable author statement PubMed 22378787. Source: BHF-UCL signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	extracellular region Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	Ref.6
	Chain	29 – 209	181	Fibroblast growth factor 21		PRO_0000008994
Natural variations
	Natural variant	141	1	G → S. Ref.3 Corresponds to variant rs41308776 [ dbSNP | Ensembl ].		VAR_055375
	Natural variant	174	1	L → P. Ref.3 Corresponds to variant rs739320 [ dbSNP | Ensembl ].		VAR_049064
Experimental info
	Sequence conflict	23	1	Missing in AAQ89444. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9NSA1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 27925C52A0023823	FASTA	209	22,300
	10 20 30 40 50 60 MDSDETGFEH SGLWVSVLAG LLLGACQAHP IPDSSPLLQF GGQVRQRYLY TDDAQQTEAH 70 80 90 100 110 120 LEIREDGTVG GAADQSPESL LQLKALKPGV IQILGVKTSR FLCQRPDGAL YGSLHFDPEA 130 140 150 160 170 180 CSFRELLLED GYNVYQSEAH GLPLHLPGNK SPHRDPAPRG PARFLPLPGL PPALPEPPGI 190 200 LAPQPPDVGS SDPLSMVGPS QGRSPSYAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a novel FGF, FGF-21, preferentially expressed in the liver." Nishimura T., Nakatake Y., Konishi M., Itoh N. Biochim. Biophys. Acta 1492:203-206(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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].
[3]	NIEHS SNPs program Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-141 AND PRO-174.
[4]	Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: Lung.
[6]	"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 29-43.
[7]	"FGF-21 as a novel metabolic regulator." Kharitonenkov A., Shiyanova T.L., Koester A., Ford A.M., Micanovic R., Galbreath E.J., Sandusky G.E., Hammond L.J., Moyers J.S., Owens R.A., Gromada J., Brozinick J.T., Hawkins E.D., Wroblewski V.J., Li D.-S., Mehrbod F., Jaskunas S.R., Shanafelt A.B. J. Clin. Invest. 115:1627-1635(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FGFR4 AND KLB.
[8]	"Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21." Kurosu H., Choi M., Ogawa Y., Dickson A.S., Goetz R., Eliseenkova A.V., Mohammadi M., Rosenblatt K.P., Kliewer S.A., Kuro-o M. J. Biol. Chem. 282:26687-26695(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"C-terminal tail of FGF19 determines its specificity toward Klotho co-receptors." Wu X., Lemon B., Li X., Gupte J., Weiszmann J., Stevens J., Hawkins N., Shen W., Lindberg R., Chen J.-L., Tian H., Li Y. J. Biol. Chem. 283:33304-33309(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KLB.
[10]	"Different roles of N- and C- termini in the functional activity of FGF21." Micanovic R., Raches D.W., Dunbar J.D., Driver D.A., Bina H.A., Dickinson C.D., Kharitonenkov A. J. Cell. Physiol. 219:227-234(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KLB.
[11]	"Fibroblast growth factor signalling: from development to cancer." Turner N., Grose R. Nat. Rev. Cancer 10:116-129(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB021975 mRNA. Translation: BAA99415.1. AY359086 mRNA. Translation: AAQ89444.1. DQ847413 Genomic DNA. Translation: ABI75345.1. CH471177 Genomic DNA. Translation: EAW52402.1. BC018404 mRNA. Translation: AAH18404.1.
IPI	IPI00017149.
RefSeq	NP_061986.1. NM_019113.2.
UniGene	Hs.283015.
3D structure databases
ProteinModelPortal	Q9NSA1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NSA1. 3 interactions.
STRING	9606.ENSP00000222157.
Polymorphism databases
DMDM	13626703.
Proteomic databases
PaxDb	Q9NSA1.
PRIDE	Q9NSA1.
Protocols and materials databases
DNASU	26291.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000222157; ENSP00000222157; ENSG00000105550. ENST00000593756; ENSP00000471477; ENSG00000105550.
GeneID	26291.
KEGG	hsa:26291.
UCSC	uc002pkn.1. human.
Organism-specific databases
CTD	26291.
GeneCards	GC19P049259.
HGNC	HGNC:3678. FGF21.
MIM	609436. gene.
neXtProt	NX_Q9NSA1.
PharmGKB	PA28117.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG311125.
HOGENOM	HOG000112572.
HOVERGEN	HBG051612.
InParanoid	Q9NSA1.
KO	K04358.
OMA	AHRSPES.
OrthoDB	EOG4T1HNJ.
PhylomeDB	Q9NSA1.
Gene expression databases
Bgee	Q9NSA1.
CleanEx	HS_FGF21.
Genevestigator	Q9NSA1.
GermOnline	ENSG00000105550. Homo sapiens.
Family and domain databases
InterPro	IPR008996. Cytokine_IL1-like. IPR017338. Fibroblast_GF_15/19/21. IPR002209. GF_heparin-bd. IPR002348. IL1_HBGF. [Graphical view]
PANTHER	PTHR11486. PTHR11486. 1 hit.
Pfam	PF00167. FGF. 1 hit. [Graphical view]
PIRSF	PIRSF037961. FGF-19_FGF-21. 1 hit.
PRINTS	PR00263. HBGFFGF. PR00262. IL1HBGF.
SMART	SM00442. FGF. 1 hit. [Graphical view]
SUPFAM	SSF50353. Cytok_IL1_like. 1 hit.
PROSITE	PS00247. HBGF_FGF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	26291.
NextBio	48635.
SOURCE	Search...

Entry information

Entry name

FGF21_HUMAN

Accession

Primary (citable) accession number: Q9NSA1
Secondary accession number(s): Q8N683

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 104 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.