ID FGF12_HUMAN Reviewed; 243 AA.
AC P61328; B2R6B7; B2R976; O35339; P70376; Q8TBG5; Q92912; Q93001;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 27-MAR-2024, entry version 174.
DE RecName: Full=Fibroblast growth factor 12;
DE Short=FGF-12;
DE AltName: Full=Fibroblast growth factor homologous factor 1;
DE Short=FHF-1;
DE AltName: Full=Myocyte-activating factor;
GN Name=FGF12; Synonyms=FGF12B, FHF1;
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=Heart;
RX PubMed=10049777; DOI=10.1006/bbrc.1999.0178;
RA Kok L.D.S., Tsui S.K.W., Waye M.M.Y., Liew C.C., Lee C.-Y., Fung K.-P.;
RT "Cloning and characterization of a cDNA encoding a novel fibroblast growth
RT factor preferentially expressed in human heart.";
RL Biochem. Biophys. Res. Commun. 255:717-721(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Hippocampus, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 FUNCTION, INVOLVEMENT IN DEE47, VARIANT DEE47 HIS-114, CHARACTERIZATION OF
RP VARIANT DEE47 HIS-114, AND MUTAGENESIS OF ARG-114.
RX PubMed=27164707; DOI=10.1212/wnl.0000000000002752;
RA Siekierska A., Isrie M., Liu Y., Scheldeman C., Vanthillo N., Lagae L.,
RA de Witte P.A., Van Esch H., Goldfarb M., Buyse G.M.;
RT "Gain-of-function FHF1 mutation causes early-onset epileptic encephalopathy
RT with cerebellar atrophy.";
RL Neurology 86:2162-2170(2016).
CC -!- FUNCTION: Involved in nervous system development and function. Involved
CC in the positive regulation of voltage-gated sodium channel activity.
CC Promotes neuronal excitability by elevating the voltage dependence of
CC neuronal sodium channel SCN8A fast inactivation.
CC {ECO:0000269|PubMed:27164707}.
CC -!- SUBUNIT: Interacts with the C-terminal region of SCN9A. {ECO:0000250}.
CC -!- INTERACTION:
CC P61328; P38432: COIL; NbExp=3; IntAct=EBI-6657662, EBI-945751;
CC P61328; Q9UI36-2: DACH1; NbExp=3; IntAct=EBI-6657662, EBI-10186082;
CC P61328; P32321: DCTD; NbExp=3; IntAct=EBI-6657662, EBI-739870;
CC P61328; Q13422: IKZF1; NbExp=3; IntAct=EBI-6657662, EBI-745305;
CC P61328; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-6657662, EBI-741037;
CC P61328; Q14592: ZNF460; NbExp=3; IntAct=EBI-6657662, EBI-2555738;
CC P61328-2; Q5HYN5: CT45A1; NbExp=3; IntAct=EBI-10699759, EBI-12051833;
CC P61328-2; Q9UI36-2: DACH1; NbExp=3; IntAct=EBI-10699759, EBI-10186082;
CC P61328-2; Q9Y3R0-3: GRIP1; NbExp=3; IntAct=EBI-10699759, EBI-12193965;
CC P61328-2; Q9NYW8: RBAK; NbExp=3; IntAct=EBI-10699759, EBI-1210429;
CC P61328-2; Q2KHN1: RNF151; NbExp=3; IntAct=EBI-10699759, EBI-12002474;
CC P61328-2; Q8TA86: RP9; NbExp=3; IntAct=EBI-10699759, EBI-630339;
CC P61328-2; Q14524: SCN5A; NbExp=4; IntAct=EBI-10699759, EBI-726858;
CC P61328-2; Q96MF2: STAC3; NbExp=3; IntAct=EBI-10699759, EBI-745680;
CC P61328-2; Q9NVV9: THAP1; NbExp=3; IntAct=EBI-10699759, EBI-741515;
CC P61328-2; Q15937: ZNF79; NbExp=3; IntAct=EBI-10699759, EBI-10237274;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=FGF-12A;
CC IsoId=P61328-1; Sequence=Displayed;
CC Name=2; Synonyms=FGF-12B;
CC IsoId=P61328-2; Sequence=VSP_010222;
CC -!- TISSUE SPECIFICITY: Brain, eye and testis; highly expressed in
CC embryonic retina, olfactory epithelium, olfactory bulb, and in a
CC segmental pattern of the body wall; in adult olfactory bulb, less in
CC cerebellum, deep cerebellar nuclei, cortex and multiple midbrain
CC structures.
CC -!- DISEASE: Developmental and epileptic encephalopathy 47 (DEE47)
CC [MIM:617166]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. {ECO:0000269|PubMed:27164707}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
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DR EMBL; U66197; AAB18913.1; -; mRNA.
DR EMBL; U76381; AAB18786.3; -; mRNA.
DR EMBL; AK125307; BAG54181.1; -; mRNA.
DR EMBL; AK313671; BAG36423.1; -; mRNA.
DR EMBL; AK312513; BAG35414.1; -; mRNA.
DR EMBL; CH471052; EAW78084.1; -; Genomic_DNA.
DR EMBL; BC022524; AAH22524.1; -; mRNA.
DR CCDS; CCDS3301.1; -. [P61328-1]
DR CCDS; CCDS46983.1; -. [P61328-2]
DR PIR; JG0184; JG0184.
DR RefSeq; NP_004104.3; NM_004113.5. [P61328-2]
DR RefSeq; NP_066360.1; NM_021032.4. [P61328-1]
DR PDB; 1Q1U; X-ray; 1.70 A; A=67-206.
DR PDB; 4JQ0; X-ray; 3.84 A; A=1-243.
DR PDBsum; 1Q1U; -.
DR PDBsum; 4JQ0; -.
DR AlphaFoldDB; P61328; -.
DR SMR; P61328; -.
DR BioGRID; 108548; 80.
DR DIP; DIP-59850N; -.
DR IntAct; P61328; 21.
DR STRING; 9606.ENSP00000413496; -.
DR iPTMnet; P61328; -.
DR PhosphoSitePlus; P61328; -.
DR BioMuta; FGF12; -.
DR DMDM; 47117683; -.
DR MassIVE; P61328; -.
DR PaxDb; 9606-ENSP00000413496; -.
DR PeptideAtlas; P61328; -.
DR ProteomicsDB; 57295; -. [P61328-1]
DR ProteomicsDB; 57296; -. [P61328-2]
DR Pumba; P61328; -.
DR ABCD; P61328; 1 sequenced antibody.
DR Antibodypedia; 33876; 289 antibodies from 32 providers.
DR DNASU; 2257; -.
DR Ensembl; ENST00000445105.7; ENSP00000393686.1; ENSG00000114279.15. [P61328-2]
DR Ensembl; ENST00000450716.5; ENSP00000397635.1; ENSG00000114279.15. [P61328-2]
DR Ensembl; ENST00000454309.7; ENSP00000413496.2; ENSG00000114279.15. [P61328-1]
DR Ensembl; ENST00000683451.2; ENSP00000508366.1; ENSG00000114279.15. [P61328-2]
DR Ensembl; ENST00000683935.1; ENSP00000507098.1; ENSG00000114279.15. [P61328-2]
DR GeneID; 2257; -.
DR KEGG; hsa:2257; -.
DR MANE-Select; ENST00000445105.7; ENSP00000393686.1; NM_004113.6; NP_004104.3. [P61328-2]
DR UCSC; uc003fsx.4; human. [P61328-1]
DR AGR; HGNC:3668; -.
DR DisGeNET; 2257; -.
DR GeneCards; FGF12; -.
DR GeneReviews; FGF12; -.
DR HGNC; HGNC:3668; FGF12.
DR HPA; ENSG00000114279; Tissue enriched (heart).
DR MalaCards; FGF12; -.
DR MIM; 601513; gene.
DR MIM; 617166; phenotype.
DR neXtProt; NX_P61328; -.
DR OpenTargets; ENSG00000114279; -.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA28108; -.
DR VEuPathDB; HostDB:ENSG00000114279; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000155929; -.
DR HOGENOM; CLU_081609_2_0_1; -.
DR InParanoid; P61328; -.
DR OMA; HEIGDKA; -.
DR OrthoDB; 5348469at2759; -.
DR PhylomeDB; P61328; -.
DR TreeFam; TF330751; -.
DR PathwayCommons; P61328; -.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR SignaLink; P61328; -.
DR SIGNOR; P61328; -.
DR BioGRID-ORCS; 2257; 10 hits in 1146 CRISPR screens.
DR ChiTaRS; FGF12; human.
DR EvolutionaryTrace; P61328; -.
DR GeneWiki; FGF12; -.
DR GenomeRNAi; 2257; -.
DR Pharos; P61328; Tbio.
DR PRO; PR:P61328; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P61328; Protein.
DR Bgee; ENSG00000114279; Expressed in right atrium auricular region and 133 other cell types or tissues.
DR ExpressionAtlas; P61328; baseline and differential.
DR Genevisible; P61328; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0045202; C:synapse; IEA:GOC.
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; ISS:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; ISS:BHF-UCL.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; NAS:BHF-UCL.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0007268; P:chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; TAS:ProtInc.
DR GO; GO:0007254; P:JNK cascade; IPI:MGI.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0050905; P:neuromuscular process; IEA:Ensembl.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IEA:Ensembl.
DR GO; GO:0098908; P:regulation of neuronal action potential; IMP:UniProtKB.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; ISS:BHF-UCL.
DR GO; GO:2000649; P:regulation of sodium ion transmembrane transporter activity; ISS:BHF-UCL.
DR GO; GO:1905150; P:regulation of voltage-gated sodium channel activity; IMP:UniProtKB.
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:SF17; FIBROBLAST GROWTH FACTOR 12; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant; Epilepsy;
KW Growth factor; Nucleus; Reference proteome.
FT CHAIN 1..243
FT /note="Fibroblast growth factor 12"
FT /id="PRO_0000147604"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 216..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 11..38
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 15..39
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 223..243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..66
FT /note="MAAAIASSLIRQKRQARESNSDRVSASKRRSSPSKDGRSLCERHVLGVFSKV
FT RFCSGRKRPVRRRP -> MESK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10049777,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_010222"
FT VARIANT 114
FT /note="R -> H (in DEE47; increased function in positive
FT regulation of SCN8A voltage-dependent sodium channel
FT activity; dbSNP:rs886039903)"
FT /evidence="ECO:0000269|PubMed:27164707"
FT /id="VAR_076507"
FT MUTAGEN 114
FT /note="R->A: Gain of function, affects voltage dependence
FT of SCN8A fast inactivation."
FT /evidence="ECO:0000269|PubMed:27164707"
FT MUTAGEN 114
FT /note="R->G: Gain of function, affects voltage dependence
FT of SCN8A fast inactivation."
FT /evidence="ECO:0000269|PubMed:27164707"
FT CONFLICT 190
FT /note="K -> E (in Ref. 2; AAB18786)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="P -> Q (in Ref. 5; AAH22524)"
FT /evidence="ECO:0000305"
FT CONFLICT 229..243
FT /note="TPTMNGGKVVNQDST -> HHHDGGKL (in Ref. 2; AAB18786)"
FT /evidence="ECO:0000305"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:1Q1U"
FT TURN 80..82
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:1Q1U"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:1Q1U"
FT TURN 121..123
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:1Q1U"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:1Q1U"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 156..165
FT /evidence="ECO:0007829|PDB:1Q1U"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:1Q1U"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:1Q1U"
FT HELIX 194..196
FT /evidence="ECO:0007829|PDB:1Q1U"
FT STRAND 198..202
FT /evidence="ECO:0007829|PDB:1Q1U"
SQ SEQUENCE 243 AA; 27399 MW; 773ED10B5BDD033C CRC64;
MAAAIASSLI RQKRQARESN SDRVSASKRR SSPSKDGRSL CERHVLGVFS KVRFCSGRKR
PVRRRPEPQL KGIVTRLFSQ QGYFLQMHPD GTIDGTKDEN SDYTLFNLIP VGLRVVAIQG
VKASLYVAMN GEGYLYSSDV FTPECKFKES VFENYYVIYS STLYRQQESG RAWFLGLNKE
GQIMKGNRVK KTKPSSHFVP KPIEVCMYRE PSLHEIGEKQ GRSRKSSGTP TMNGGKVVNQ
DST
//
