ID FGF14_HUMAN Reviewed; 247 AA. AC Q92915; Q86YN7; Q96QX6; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 24-JAN-2024, entry version 188. DE RecName: Full=Fibroblast growth factor 14; DE Short=FGF-14; DE AltName: Full=Fibroblast growth factor homologous factor 4; DE Short=FHF-4; GN Name=FGF14; Synonyms=FHF4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Retina; RX PubMed=8790420; DOI=10.1073/pnas.93.18.9850; RA Smallwood P.M., Munoz-Sanjuan I., Tong P., Macke J.P., Hendry S.H., RA Gilbert D.J., Copeland N.G., Jenkins N.A., Nathans J.; RT "Fibroblast growth factor (FGF) homologous factors: new members of the FGF RT family implicated in nervous system development."; RL Proc. Natl. Acad. Sci. U.S.A. 93:9850-9857(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Brain; RA Bonner T.I.; RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=12364586; DOI=10.1073/pnas.182412499; RA Chumakov I., Blumenfeld M., Guerassimenko O., Cavarec L., Palicio M., RA Abderrahim H., Bougueleret L., Barry C., Tanaka H., La Rosa P., Puech A., RA Tahri N., Cohen-Akenine A., Delabrosse S., Lissarrague S., Picard F.-P., RA Maurice K., Essioux L., Millasseau P., Grel P., Debailleul V., Simon A.-M., RA Caterina D., Dufaure I., Malekzadeh K., Belova M., Luan J.-J., Bouillot M., RA Sambucy J.-L., Primas G., Saumier M., Boubkiri N., Martin-Saumier S., RA Nasroune M., Peixoto H., Delaye A., Pinchot V., Bastucci M., Guillou S., RA Chevillon M., Sainz-Fuertes R., Meguenni S., Aurich-Costa J., Cherif D., RA Gimalac A., Van Duijn C., Gauvreau D., Ouellette G., Fortier I., RA Raelson J., Sherbatich T., Riazanskay N., Rogaev E., Raeymaekers P., RA Aerssens J., Konings F., Luyten W., Macciardi F., Sham P.C., Straub R.E., RA Weinberger D.R., Cohen N., Cohen D.; RT "Genetic and physiological data implicating the new human gene G72 and the RT gene for D-amino acid oxidase in schizophrenia."; RL Proc. Natl. Acad. Sci. U.S.A. 99:13675-13680(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [6] RP INTERACTION WITH SCN8A. RX PubMed=26900580; DOI=10.1002/acn3.276; RA Wagnon J.L., Barker B.S., Hounshell J.A., Haaxma C.A., Shealy A., Moss T., RA Parikh S., Messer R.D., Patel M.K., Meisler M.H.; RT "Pathogenic mechanism of recurrent mutations of SCN8A in epileptic RT encephalopathy."; RL Ann. Clin. Transl. Neurol. 3:114-123(2016). RN [7] RP VARIANT SCA27A SER-145. RX PubMed=12489043; DOI=10.1086/345488; RA van Swieten J.C., Brusse E., de Graaf B.M., Krieger E., van de Graaf R., RA de Koning I., Maat-Kievit A., Leegwater P., Dooijes D., Oostra B.A., RA Heutink P.; RT "A mutation in the fibroblast growth factor 14 gene is associated with RT autosomal dominant cerebellar (sic) ataxia."; RL Am. J. Hum. Genet. 72:191-199(2003). RN [8] RP ERRATUM OF PUBMED:12489043. RA van Swieten J.C., Brusse E., de Graaf B.M., Krieger E., van de Graaf R., RA de Koning I., Maat-Kievit A., Leegwater P., Dooijes D., Oostra B.A., RA Heutink P.; RL Am. J. Hum. Genet. 72:1078-1078(2003). RN [9] RP VARIANT CYS-42. RX PubMed=15470364; DOI=10.1038/sj.ejhg.5201286; RA Dalski A., Atici J., Kreuz F.R., Hellenbroich Y., Schwinger E., Zuehlke C.; RT "Mutation analysis in the fibroblast growth factor 14 gene: frameshift RT mutation and polymorphisms in patients with inherited ataxias."; RL Eur. J. Hum. Genet. 13:118-120(2005). RN [10] RP VARIANT [LARGE SCALE ANALYSIS] CYS-44 (ISOFORM 2). RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [11] RP VARIANT SCA27A 147-GLU--THR-247 DEL, AND INVOLVEMENT IN SCA27A. RX PubMed=32162847; DOI=10.1002/acn3.51005; RA Piarroux J., Riant F., Humbertclaude V., Remerand G., Hadjadj J., Rejou F., RA Coubes C., Pinson L., Meyer P., Roubertie A.; RT "FGF14-related episodic ataxia: delineating the phenotype of Episodic RT Ataxia type 9."; RL Ann. Clin. Transl. Neurol. 7:565-572(2020). RN [12] RP INVOLVEMENT IN SCA27B. RX PubMed=36493768; DOI=10.1016/j.ajhg.2022.11.015; RA Rafehi H., Read J., Szmulewicz D.J., Davies K.C., Snell P., Fearnley L.G., RA Scott L., Thomsen M., Gillies G., Pope K., Bennett M.F., Munro J.E., RA Ngo K.J., Chen L., Wallis M.J., Butler E.G., Kumar K.R., Wu K.H., RA Tomlinson S.E., Tisch S., Malhotra A., Lee-Archer M., Dolzhenko E., RA Eberle M.A., Roberts L.J., Fogel B.L., Brueggemann N., Lohmann K., RA Delatycki M.B., Bahlo M., Lockhart P.J.; RT "An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant RT adult-onset ataxia SCA50/ATX-FGF14."; RL Am. J. Hum. Genet. 110:105-119(2023). RN [13] RP INVOLVEMENT IN SCA27B. RX PubMed=36516086; DOI=10.1056/nejmoa2207406; RA Pellerin D., Danzi M.C., Wilke C., Renaud M., Fazal S., Dicaire M.J., RA Scriba C.K., Ashton C., Yanick C., Beijer D., Rebelo A., Rocca C., RA Jaunmuktane Z., Sonnen J.A., Lariviere R., Genis D., Molina Porcel L., RA Choquet K., Sakalla R., Provost S., Robertson R., Allard-Chamard X., RA Tetreault M., Reiling S.J., Nagy S., Nishadham V., Purushottam M., RA Vengalil S., Bardhan M., Nalini A., Chen Z., Mathieu J., Massie R., RA Chalk C.H., Lafontaine A.L., Evoy F., Rioux M.F., Ragoussis J., RA Boycott K.M., Dube M.P., Duquette A., Houlden H., Ravenscroft G., RA Laing N.G., Lamont P.J., Saporta M.A., Schuele R., Schoels L., La Piana R., RA Synofzik M., Zuchner S., Brais B.; RT "Deep intronic FGF14 GAA repeat expansion in late-onset cerebellar RT ataxia."; RL N. Engl. J. Med. 388:128-141(2023). CC -!- FUNCTION: Probably involved in nervous system development and function. CC -!- SUBUNIT: Interacts with SCN8A (PubMed:26900580). CC {ECO:0000269|PubMed:26900580}. CC -!- INTERACTION: CC Q92915; P05067: APP; NbExp=3; IntAct=EBI-10489272, EBI-77613; CC Q92915-2; Q13085-4: ACACA; NbExp=3; IntAct=EBI-12836320, EBI-12562760; CC Q92915-2; Q92843: BCL2L2; NbExp=3; IntAct=EBI-12836320, EBI-707714; CC Q92915-2; P35222: CTNNB1; NbExp=3; IntAct=EBI-12836320, EBI-491549; CC Q92915-2; Q15438: CYTH1; NbExp=3; IntAct=EBI-12836320, EBI-997830; CC Q92915-2; Q08426: EHHADH; NbExp=3; IntAct=EBI-12836320, EBI-2339219; CC Q92915-2; Q9NWN3: FBXO34; NbExp=3; IntAct=EBI-12836320, EBI-719816; CC Q92915-2; Q14318: FKBP8; NbExp=3; IntAct=EBI-12836320, EBI-724839; CC Q92915-2; Q9BWH2: FUNDC2; NbExp=3; IntAct=EBI-12836320, EBI-714482; CC Q92915-2; Q99525: H4C7; NbExp=3; IntAct=EBI-12836320, EBI-10294329; CC Q92915-2; P35452-2: HOXD12; NbExp=3; IntAct=EBI-12836320, EBI-17244356; CC Q92915-2; P27338: MAOB; NbExp=3; IntAct=EBI-12836320, EBI-3911344; CC Q92915-2; Q14D33: RTP5; NbExp=3; IntAct=EBI-12836320, EBI-10217913; CC Q92915-2; Q9UQD0: SCN8A; NbExp=3; IntAct=EBI-12836320, EBI-2682072; CC Q92915-2; Q14683: SMC1A; NbExp=3; IntAct=EBI-12836320, EBI-80690; CC Q92915-2; Q17RD7: SYT16; NbExp=3; IntAct=EBI-12836320, EBI-10238936; CC Q92915-2; P49638: TTPA; NbExp=3; IntAct=EBI-12836320, EBI-10210710; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q92915-1; Sequence=Displayed; CC Name=2; Synonyms=Isoform 1B; CC IsoId=Q92915-2; Sequence=VSP_029051; CC -!- TISSUE SPECIFICITY: Nervous system. CC -!- DISEASE: Spinocerebellar ataxia 27A (SCA27A) [MIM:193003]: A form of CC spinocerebellar ataxia, a clinically and genetically heterogeneous CC group of cerebellar disorders. Patients show progressive incoordination CC of gait and often poor coordination of hands, speech and eye movements, CC due to degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCA27A is an autosomal dominant, slowly CC progressive form characterized by gait disturbances, ataxia with CC tremor, dysarthria, orofacial dyskinesia, gaze-evoked nystagmus, and CC learning disabilities. There is significant variability, and patients CC show various combinations of neurologic features. CC {ECO:0000269|PubMed:12489043, ECO:0000269|PubMed:32162847}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Spinocerebellar ataxia 27B, late-onset (SCA27B) [MIM:620174]: CC A form of spinocerebellar ataxia, a clinically and genetically CC heterogeneous group of cerebellar disorders. Patients show progressive CC incoordination of gait and often poor coordination of hands, speech and CC eye movements, due to degeneration of the cerebellum with variable CC involvement of the brainstem and spinal cord. SCA27B is an autosomal CC dominant, slowly progressive form characterized by the onset of gait CC and appendicular ataxia in adulthood. {ECO:0000269|PubMed:36493768, CC ECO:0000269|PubMed:36516086}. Note=The disease is caused by variants CC affecting the gene represented in this entry. SCA27B is caused by CC GAA(n) trinucleotide repeat expansions with a size above 250 repeats in CC FGF14 intron 1. Expansions ranging from 250 to 300 repeats are CC pathogenic albeit with reduced penetrance, whereas those above 300 are CC fully penetrant. {ECO:0000269|PubMed:36493768, CC ECO:0000269|PubMed:36516086}. CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U66200; AAB18916.1; -; mRNA. DR EMBL; AY188178; AAO31806.1; -; mRNA. DR EMBL; AE014293; AAN16025.1; -; Genomic_DNA. DR EMBL; AL160153; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL512629; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591909; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL356263; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC100920; AAI00921.1; -; mRNA. DR EMBL; BC100921; AAI00922.1; -; mRNA. DR EMBL; BC100922; AAI00923.1; -; mRNA. DR CCDS; CCDS9500.1; -. [Q92915-2] DR CCDS; CCDS9501.1; -. [Q92915-1] DR RefSeq; NP_004106.1; NM_004115.3. [Q92915-1] DR RefSeq; NP_787125.1; NM_175929.2. [Q92915-2] DR AlphaFoldDB; Q92915; -. DR SMR; Q92915; -. DR BioGRID; 108550; 42. DR IntAct; Q92915; 18. DR STRING; 9606.ENSP00000365301; -. DR BindingDB; Q92915; -. DR ChEMBL; CHEMBL4739699; -. DR iPTMnet; Q92915; -. DR PhosphoSitePlus; Q92915; -. DR BioMuta; FGF14; -. DR DMDM; 2494463; -. DR MassIVE; Q92915; -. DR PaxDb; 9606-ENSP00000365301; -. DR PeptideAtlas; Q92915; -. DR ProteomicsDB; 75600; -. [Q92915-1] DR ProteomicsDB; 75601; -. [Q92915-2] DR Antibodypedia; 35193; 234 antibodies from 34 providers. DR DNASU; 2259; -. DR Ensembl; ENST00000376131.9; ENSP00000365301.3; ENSG00000102466.17. [Q92915-2] DR Ensembl; ENST00000376143.5; ENSP00000365313.4; ENSG00000102466.17. [Q92915-1] DR GeneID; 2259; -. DR KEGG; hsa:2259; -. DR MANE-Select; ENST00000376143.5; ENSP00000365313.4; NM_004115.4; NP_004106.1. DR UCSC; uc001vpe.3; human. [Q92915-1] DR AGR; HGNC:3671; -. DR CTD; 2259; -. DR DisGeNET; 2259; -. DR GeneCards; FGF14; -. DR HGNC; HGNC:3671; FGF14. DR HPA; ENSG00000102466; Tissue enhanced (brain, cervix). DR MalaCards; FGF14; -. DR MIM; 193003; phenotype. DR MIM; 601515; gene. DR MIM; 620174; phenotype. DR neXtProt; NX_Q92915; -. DR OpenTargets; ENSG00000102466; -. DR Orphanet; 98764; Spinocerebellar ataxia type 27. DR PharmGKB; PA28110; -. DR VEuPathDB; HostDB:ENSG00000102466; -. DR eggNOG; KOG3885; Eukaryota. DR GeneTree; ENSGT00940000156984; -. DR HOGENOM; CLU_081609_2_0_1; -. DR InParanoid; Q92915; -. DR OMA; KRINSPH; -. DR OrthoDB; 5348469at2759; -. DR PhylomeDB; Q92915; -. DR TreeFam; TF317805; -. DR PathwayCommons; Q92915; -. DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation. DR SignaLink; Q92915; -. DR SIGNOR; Q92915; -. DR BioGRID-ORCS; 2259; 7 hits in 1151 CRISPR screens. DR ChiTaRS; FGF14; human. DR GeneWiki; FGF14; -. DR GenomeRNAi; 2259; -. DR Pharos; Q92915; Tbio. DR PRO; PR:Q92915; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q92915; Protein. DR Bgee; ENSG00000102466; Expressed in secondary oocyte and 137 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0008083; F:growth factor activity; TAS:ProtInc. DR GO; GO:0008201; F:heparin binding; IDA:MGI. DR GO; GO:0017080; F:sodium channel regulator activity; IBA:GO_Central. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0007254; P:JNK cascade; IPI:MGI. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. 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:SF18; FIBROBLAST GROWTH FACTOR 14; 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; Q92915; HS. PE 1: Evidence at protein level; KW Alternative splicing; Disease variant; Growth factor; Neurodegeneration; KW Nucleus; Reference proteome; Spinocerebellar ataxia; KW Triplet repeat expansion. FT CHAIN 1..247 FT /note="Fibroblast growth factor 14" FT /id="PRO_0000147610" FT REGION 1..38 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 214..247 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 13..29 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 222..247 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..64 FT /note="MAAAIASGLIRQKRQAREQHWDRPSASRRRSSPSKNRGLCNGNLVDIFSKVR FT IFGLKKRRLRRQ -> MVKPVPLFRRTDFKLLLCNHKDLFFLRVSKLLDCFSPKSMWFL FT WNIFSKGTHMLQCLCGKSLKKNKNPT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2" FT /id="VSP_029051" FT VARIANT 42 FT /note="G -> C (in dbSNP:rs141304687)" FT /evidence="ECO:0000269|PubMed:15470364" FT /id="VAR_022735" FT VARIANT 145 FT /note="F -> S (in SCA27A; dbSNP:rs104894393)" FT /evidence="ECO:0000269|PubMed:12489043" FT /id="VAR_022736" FT VARIANT 147..247 FT /note="Missing (in SCA27A)" FT /evidence="ECO:0000269|PubMed:32162847" FT /id="VAR_087533" FT VARIANT Q92915-2:44 FT /note="W -> C (in a colorectal cancer)" FT /evidence="ECO:0000305" FT /id="VAR_082821" SQ SEQUENCE 247 AA; 27702 MW; 427C3373198B967E CRC64; MAAAIASGLI RQKRQAREQH WDRPSASRRR SSPSKNRGLC NGNLVDIFSK VRIFGLKKRR LRRQDPQLKG IVTRLYCRQG YYLQMHPDGA LDGTKDDSTN STLFNLIPVG LRVVAIQGVK TGLYIAMNGE GYLYPSELFT PECKFKESVF ENYYVIYSSM LYRQQESGRA WFLGLNKEGQ AMKGNRVKKT KPAAHFLPKP LEVAMYREPS LHDVGETVPK PGVTPSKSTS ASAIMNGGKP VNKSKTT //