ID   FGF4_MOUSE              Reviewed;         202 AA.
AC   P11403; P15657; Q542N0;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2012, sequence version 2.
DT   24-JAN-2024, entry version 168.
DE   RecName: Full=Fibroblast growth factor 4 {ECO:0000312|MGI:MGI:95518};
DE            Short=FGF-4 {ECO:0000312|MGI:MGI:95518};
DE   AltName: Full=Heparin-binding growth factor 4;
DE            Short=HBGF-4 {ECO:0000250|UniProtKB:P08620};
DE   AltName: Full=K-fibroblast growth factor;
DE   Flags: Precursor;
GN   Name=Fgf4 {ECO:0000312|MGI:MGI:95518};
GN   Synonyms=Fgf-4 {ECO:0000312|MGI:MGI:95518}, Kfgf
GN   {ECO:0000312|MGI:MGI:95518};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2740210; DOI=10.1093/nar/17.11.4037;
RA   Dickson C.;
RT   "The mouse homologue of hst/k-FGF: sequence, genome organization and
RT   location relative to int-2.";
RL   Nucleic Acids Res. 17:4037-4045(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2318343; DOI=10.1016/0012-1606(90)90211-z;
RA   Hebert J.M., Basilico C., Goldfarb M., Haub O., Martin G.R.;
RT   "Isolation of cDNAs encoding four mouse FGF family members and
RT   characterization of their expression patterns during embryogenesis.";
RL   Dev. Biol. 138:454-463(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   FUNCTION.
RX   PubMed=8898217; DOI=10.1242/dev.122.10.3035;
RA   Chen Y., Bei M., Woo I., Satokata I., Maas R.;
RT   "Msx1 controls inductive signaling in mammalian tooth morphogenesis.";
RL   Development 122:3035-3044(1996).
CC   -!- FUNCTION: Plays an important role in the regulation of embryonic
CC       development, cell proliferation, and cell differentiation. Is essential
CC       for survival of the postimplantation mouse embryo. Required for normal
CC       limb and cardiac valve development during embryogenesis. May play a
CC       role in embryonic molar tooth bud development via inducing the
CC       expression of MSX1, MSX2 and MSX1-mediated expression of SDC1 in dental
CC       mesenchyme cells (PubMed:8898217). {ECO:0000269|PubMed:8898217}.
CC   -!- SUBUNIT: Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between
CC       fibroblast growth factors (FGFs) and their receptors is increased by
CC       heparan sulfate glycosaminoglycans that function as coreceptors (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in the blastocyst inner cell mass and
CC       later in distinct embryonic tissues.
CC   -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC       {ECO:0000305}.
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DR   EMBL; X14849; CAA32967.1; -; Genomic_DNA.
DR   EMBL; M30642; AAA37619.1; -; mRNA.
DR   EMBL; AK082814; BAC38631.1; -; mRNA.
DR   EMBL; AC149593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC161763; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466531; EDL18271.1; -; Genomic_DNA.
DR   EMBL; BC104312; AAI04313.1; -; mRNA.
DR   EMBL; BC104313; AAI04314.1; -; mRNA.
DR   CCDS; CCDS22052.1; -.
DR   PIR; S04741; TVMSHS.
DR   RefSeq; NP_034332.2; NM_010202.6.
DR   AlphaFoldDB; P11403; -.
DR   SMR; P11403; -.
DR   BioGRID; 199649; 3.
DR   STRING; 10090.ENSMUSP00000056752; -.
DR   iPTMnet; P11403; -.
DR   PhosphoSitePlus; P11403; -.
DR   PaxDb; 10090-ENSMUSP00000056752; -.
DR   PeptideAtlas; P11403; -.
DR   Antibodypedia; 2159; 505 antibodies from 39 providers.
DR   DNASU; 14175; -.
DR   Ensembl; ENSMUST00000060336.5; ENSMUSP00000056752.5; ENSMUSG00000050917.6.
DR   GeneID; 14175; -.
DR   KEGG; mmu:14175; -.
DR   UCSC; uc009kqq.1; mouse.
DR   AGR; MGI:95518; -.
DR   CTD; 2249; -.
DR   MGI; MGI:95518; Fgf4.
DR   VEuPathDB; HostDB:ENSMUSG00000050917; -.
DR   eggNOG; KOG3885; Eukaryota.
DR   GeneTree; ENSGT00940000158825; -.
DR   HOGENOM; CLU_081609_4_0_1; -.
DR   InParanoid; P11403; -.
DR   OMA; YESHTYP; -.
DR   OrthoDB; 2883843at2759; -.
DR   PhylomeDB; P11403; -.
DR   TreeFam; TF317805; -.
DR   Reactome; R-MMU-109704; PI3K Cascade.
DR   Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-MMU-190322; FGFR4 ligand binding and activation.
DR   Reactome; R-MMU-190372; FGFR3c ligand binding and activation.
DR   Reactome; R-MMU-190373; FGFR1c ligand binding and activation.
DR   Reactome; R-MMU-190375; FGFR2c ligand binding and activation.
DR   Reactome; R-MMU-5654219; Phospholipase C-mediated cascade: FGFR1.
DR   Reactome; R-MMU-5654221; Phospholipase C-mediated cascade, FGFR2.
DR   Reactome; R-MMU-5654227; Phospholipase C-mediated cascade, FGFR3.
DR   Reactome; R-MMU-5654228; Phospholipase C-mediated cascade, FGFR4.
DR   Reactome; R-MMU-5654687; Downstream signaling of activated FGFR1.
DR   Reactome; R-MMU-5654688; SHC-mediated cascade:FGFR1.
DR   Reactome; R-MMU-5654689; PI-3K cascade:FGFR1.
DR   Reactome; R-MMU-5654693; FRS-mediated FGFR1 signaling.
DR   Reactome; R-MMU-5654695; PI-3K cascade:FGFR2.
DR   Reactome; R-MMU-5654699; SHC-mediated cascade:FGFR2.
DR   Reactome; R-MMU-5654700; FRS-mediated FGFR2 signaling.
DR   Reactome; R-MMU-5654704; SHC-mediated cascade:FGFR3.
DR   Reactome; R-MMU-5654706; FRS-mediated FGFR3 signaling.
DR   Reactome; R-MMU-5654710; PI-3K cascade:FGFR3.
DR   Reactome; R-MMU-5654712; FRS-mediated FGFR4 signaling.
DR   Reactome; R-MMU-5654719; SHC-mediated cascade:FGFR4.
DR   Reactome; R-MMU-5654720; PI-3K cascade:FGFR4.
DR   Reactome; R-MMU-5654726; Negative regulation of FGFR1 signaling.
DR   Reactome; R-MMU-5654727; Negative regulation of FGFR2 signaling.
DR   Reactome; R-MMU-5654732; Negative regulation of FGFR3 signaling.
DR   Reactome; R-MMU-5654733; Negative regulation of FGFR4 signaling.
DR   Reactome; R-MMU-5658623; FGFRL1 modulation of FGFR1 signaling.
DR   Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   BioGRID-ORCS; 14175; 4 hits in 77 CRISPR screens.
DR   PRO; PR:P11403; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; P11403; Protein.
DR   Bgee; ENSMUSG00000050917; Expressed in molar enamel organ and 55 other cell types or tissues.
DR   ExpressionAtlas; P11403; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005104; F:fibroblast growth factor receptor binding; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR   GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR   GO; GO:0006915; P:apoptotic process; IGI:MGI.
DR   GO; GO:0060561; P:apoptotic process involved in morphogenesis; IGI:MGI.
DR   GO; GO:0001502; P:cartilage condensation; IGI:MGI.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR   GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR   GO; GO:0060591; P:chondroblast differentiation; ISO:MGI.
DR   GO; GO:0060363; P:cranial suture morphogenesis; IDA:MGI.
DR   GO; GO:0035116; P:embryonic hindlimb morphogenesis; IGI:MGI.
DR   GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
DR   GO; GO:1904019; P:epithelial cell apoptotic process; IGI:MGI.
DR   GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISO:MGI.
DR   GO; GO:0010463; P:mesenchymal cell proliferation; ISO:MGI.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IGI:MGI.
DR   GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IDA:MGI.
DR   GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI.
DR   GO; GO:2000648; P:positive regulation of stem cell proliferation; IGI:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR   GO; GO:2000544; P:regulation of endothelial cell chemotaxis to fibroblast growth factor; ISO:MGI.
DR   GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR   GO; GO:0035019; P:somatic stem cell population maintenance; IGI:MGI.
DR   GO; GO:0019827; P:stem cell population maintenance; IGI:MGI.
DR   GO; GO:0072089; P:stem cell proliferation; IGI:MGI.
DR   CDD; cd00058; FGF; 1.
DR   Gene3D; 2.80.10.50; -; 1.
DR   InterPro; IPR002209; Fibroblast_GF_fam.
DR   InterPro; IPR008996; IL1/FGF.
DR   PANTHER; PTHR11486; FIBROBLAST GROWTH FACTOR; 1.
DR   PANTHER; PTHR11486:SF31; FIBROBLAST GROWTH FACTOR 4; 1.
DR   Pfam; PF00167; FGF; 1.
DR   PRINTS; PR00263; HBGFFGF.
DR   PRINTS; PR00262; IL1HBGF.
DR   SMART; SM00442; FGF; 1.
DR   SUPFAM; SSF50353; Cytokine; 1.
DR   PROSITE; PS00247; HBGF_FGF; 1.
DR   Genevisible; P11403; MM.
PE   2: Evidence at transcript level;
KW   Developmental protein; Differentiation; Growth factor; Mitogen;
KW   Proto-oncogene; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..29
FT                   /evidence="ECO:0000255"
FT   CHAIN           30..202
FT                   /note="Fibroblast growth factor 4"
FT                   /id="PRO_0000008954"
FT   CONFLICT        167
FT                   /note="S -> A (in Ref. 1; CAA32967)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   202 AA;  21919 MW;  62D4563AF7D9AA31 CRC64;
     MAKRGPTTGT LLPRVLLALV VALADRGTAA PNGTRHAELG HGWDGLVARS LARLPVAAQP
     PQAAVRSGAG DYLLGLKRLR RLYCNVGIGF HLQVLPDGRI GGVHADTRDS LLELSPVQRG
     VVSIFGVASR FFVAMSSRGK LFGVPFFTDE CKFKEILLPN NYNAYESYAY PGMFMALSKN
     GRTKKGNRVS PTMKVTHFLP RL
//