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Fibroblast growth factor 12 (FGF-12) (Fibroblast growth factor homologous factor 1) (FHF-1) (Myocyte-activating factor)

 FGF12_HUMAN             Reviewed;         243 AA.
P61328; B2R6B7; B2R976; O35339; P70376; Q8TBG5; Q92912; Q93001;
10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
10-MAY-2004, sequence version 1.
25-OCT-2017, entry version 136.
RecName: Full=Fibroblast growth factor 12;
Short=FGF-12;
AltName: Full=Fibroblast growth factor homologous factor 1;
Short=FHF-1;
AltName: Full=Myocyte-activating factor;
Name=FGF12; Synonyms=FGF12B, FHF1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Retina;
PubMed=8790420; DOI=10.1073/pnas.93.18.9850;
Smallwood P.M., Munoz-Sanjuan I., Tong P., Macke J.P., Hendry S.H.,
Gilbert D.J., Copeland N.G., Jenkins N.A., Nathans J.;
"Fibroblast growth factor (FGF) homologous factors: new members of the
FGF family implicated in nervous system development.";
Proc. Natl. Acad. Sci. U.S.A. 93:9850-9857(1996).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
TISSUE=Heart;
PubMed=10049777; DOI=10.1006/bbrc.1999.0178;
Kok L.D.S., Tsui S.K.W., Waye M.M.Y., Liew C.C., Lee C.-Y.,
Fung K.-P.;
"Cloning and characterization of a cDNA encoding a novel fibroblast
growth factor preferentially expressed in human heart.";
Biochem. Biophys. Res. Commun. 255:717-721(1999).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
TISSUE=Hippocampus, and Thalamus;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
FUNCTION, INVOLVEMENT IN EIEE47, VARIANT EIEE47 HIS-114,
CHARACTERIZATION OF VARIANT EIEE47 HIS-114, AND MUTAGENESIS OF
ARG-114.
PubMed=27164707; DOI=10.1212/WNL.0000000000002752;
Siekierska A., Isrie M., Liu Y., Scheldeman C., Vanthillo N.,
Lagae L., de Witte P.A., Van Esch H., Goldfarb M., Buyse G.M.;
"Gain-of-function FHF1 mutation causes early-onset epileptic
encephalopathy with cerebellar atrophy.";
Neurology 86:2162-2170(2016).
-!- FUNCTION: Involved in nervous system development and function.
Involved in the positive regulation of voltage-gated sodium
channel activity. Promotes neuronal excitability by elevating the
voltage dependence of neuronal sodium channel SCN8A fast
inactivation. {ECO:0000269|PubMed:27164707}.
-!- SUBUNIT: Interacts with the C-terminal region of SCN9A.
{ECO:0000250}.
-!- INTERACTION:
P38432:COIL; NbExp=3; IntAct=EBI-6657662, EBI-945751;
Q9UI36-2:DACH1; NbExp=3; IntAct=EBI-6657662, EBI-10186082;
P32321:DCTD; NbExp=3; IntAct=EBI-6657662, EBI-739870;
Q9Y3R0-3:GRIP1; NbExp=4; IntAct=EBI-10699759, EBI-12193965;
Q13422:IKZF1; NbExp=3; IntAct=EBI-6657662, EBI-745305;
Q9BRK4:LZTS2; NbExp=3; IntAct=EBI-6657662, EBI-741037;
Q14524:SCN5A; NbExp=4; IntAct=EBI-10699759, EBI-726858;
Q14592:ZNF460; NbExp=3; IntAct=EBI-6657662, EBI-2555738;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1; Synonyms=FGF-12A;
IsoId=P61328-1; Sequence=Displayed;
Name=2; Synonyms=FGF-12B;
IsoId=P61328-2; Sequence=VSP_010222;
-!- TISSUE SPECIFICITY: Brain, eye and testis; highly expressed in
embryonic retina, olfactory epithelium, olfactory bulb, and in a
segmental pattern of the body wall; in adult olfactory bulb, less
in cerebellum, deep cerebellar nuclei, cortex and multiple
midbrain structures.
-!- DISEASE: Epileptic encephalopathy, early infantile, 47 (EIEE47)
[MIM:617166]: A form of epileptic encephalopathy, a heterogeneous
group of severe childhood onset epilepsies characterized by
refractory seizures, neurodevelopmental impairment, and poor
prognosis. Development is normal prior to seizure onset, after
which cognitive and motor delays become apparent.
{ECO:0000269|PubMed:27164707}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the heparin-binding growth factors family.
{ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; U66197; AAB18913.1; -; mRNA.
EMBL; U76381; AAB18786.3; -; mRNA.
EMBL; AK125307; BAG54181.1; -; mRNA.
EMBL; AK313671; BAG36423.1; -; mRNA.
EMBL; AK312513; BAG35414.1; -; mRNA.
EMBL; CH471052; EAW78084.1; -; Genomic_DNA.
EMBL; BC022524; AAH22524.1; -; mRNA.
CCDS; CCDS3301.1; -. [P61328-1]
CCDS; CCDS46983.1; -. [P61328-2]
PIR; JG0184; JG0184.
RefSeq; NP_004104.3; NM_004113.5. [P61328-2]
RefSeq; NP_066360.1; NM_021032.4. [P61328-1]
UniGene; Hs.390250; -.
PDB; 1Q1U; X-ray; 1.70 A; A=67-206.
PDB; 4JQ0; X-ray; 3.84 A; A=1-243.
PDBsum; 1Q1U; -.
PDBsum; 4JQ0; -.
DisProt; DP00770; -.
ProteinModelPortal; P61328; -.
SMR; P61328; -.
BioGrid; 108548; 61.
DIP; DIP-59850N; -.
IntAct; P61328; 20.
STRING; 9606.ENSP00000413496; -.
iPTMnet; P61328; -.
PhosphoSitePlus; P61328; -.
BioMuta; FGF12; -.
DMDM; 47117683; -.
EPD; P61328; -.
PaxDb; P61328; -.
PeptideAtlas; P61328; -.
PRIDE; P61328; -.
DNASU; 2257; -.
Ensembl; ENST00000445105; ENSP00000393686; ENSG00000114279. [P61328-2]
Ensembl; ENST00000450716; ENSP00000397635; ENSG00000114279. [P61328-2]
Ensembl; ENST00000454309; ENSP00000413496; ENSG00000114279. [P61328-1]
GeneID; 2257; -.
KEGG; hsa:2257; -.
UCSC; uc003fsx.4; human. [P61328-1]
CTD; 2257; -.
DisGeNET; 2257; -.
EuPathDB; HostDB:ENSG00000114279.13; -.
GeneCards; FGF12; -.
HGNC; HGNC:3668; FGF12.
HPA; HPA071557; -.
MalaCards; FGF12; -.
MIM; 601513; gene.
MIM; 617166; phenotype.
neXtProt; NX_P61328; -.
OpenTargets; ENSG00000114279; -.
PharmGKB; PA28108; -.
eggNOG; KOG3885; Eukaryota.
eggNOG; ENOG4111IPH; LUCA.
GeneTree; ENSGT00760000118859; -.
HOVERGEN; HBG007580; -.
InParanoid; P61328; -.
KO; K04358; -.
OMA; YSSEVFT; -.
OrthoDB; EOG091G0NAY; -.
PhylomeDB; P61328; -.
TreeFam; TF330751; -.
Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
SIGNOR; P61328; -.
ChiTaRS; FGF12; human.
EvolutionaryTrace; P61328; -.
GeneWiki; FGF12; -.
GenomeRNAi; 2257; -.
PRO; PR:P61328; -.
Proteomes; UP000005640; Chromosome 3.
Bgee; ENSG00000114279; -.
CleanEx; HS_FGF12; -.
ExpressionAtlas; P61328; baseline and differential.
Genevisible; P61328; HS.
GO; GO:0005615; C:extracellular space; TAS:ProtInc.
GO; GO:0005622; C:intracellular; IEA:GOC.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0008083; F:growth factor activity; TAS:ProtInc.
GO; GO:0008201; F:heparin binding; IDA:MGI.
GO; GO:0044325; F:ion channel binding; ISS:BHF-UCL.
GO; GO:0017080; F:sodium channel regulator activity; ISS:BHF-UCL.
GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; NAS:BHF-UCL.
GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
GO; GO:0007268; P:chemical synaptic transmission; IEA:Ensembl.
GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IEA:InterPro.
GO; GO:0007507; P:heart development; TAS:ProtInc.
GO; GO:0007254; P:JNK cascade; IPI:MGI.
GO; GO:2001258; P:negative regulation of cation channel activity; IEA:Ensembl.
GO; GO:0007399; P:nervous system development; TAS:ProtInc.
GO; GO:0050905; P:neuromuscular process; IEA:Ensembl.
GO; GO:0010765; P:positive regulation of sodium ion transport; IEA:Ensembl.
GO; GO:0003254; P:regulation of membrane depolarization; IEA:Ensembl.
GO; GO:0098908; P:regulation of neuronal action potential; IMP:UniProtKB.
GO; GO:1902305; P:regulation of sodium ion transmembrane transport; ISS:BHF-UCL.
GO; GO:2000649; P:regulation of sodium ion transmembrane transporter activity; ISS:BHF-UCL.
GO; GO:1905150; P:regulation of voltage-gated sodium channel activity; IMP:UniProtKB.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
CDD; cd00058; FGF; 1.
InterPro; IPR028254; FGF12.
InterPro; IPR002209; Fibroblast_GF_fam.
InterPro; IPR008996; IL1/FGF.
PANTHER; PTHR11486; PTHR11486; 1.
PANTHER; PTHR11486:SF17; PTHR11486:SF17; 1.
Pfam; PF00167; FGF; 1.
PRINTS; PR00263; HBGFFGF.
SMART; SM00442; FGF; 1.
SUPFAM; SSF50353; SSF50353; 1.
PROSITE; PS00247; HBGF_FGF; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome;
Disease mutation; Epilepsy; Growth factor; Nucleus;
Reference proteome.
CHAIN 1 243 Fibroblast growth factor 12.
/FTId=PRO_0000147604.
MOTIF 11 38 Bipartite nuclear localization signal.
{ECO:0000255}.
VAR_SEQ 1 66 MAAAIASSLIRQKRQARESNSDRVSASKRRSSPSKDGRSLC
ERHVLGVFSKVRFCSGRKRPVRRRP -> MESK (in
isoform 2). {ECO:0000303|PubMed:10049777,
ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:15489334}.
/FTId=VSP_010222.
VARIANT 114 114 R -> H (in EIEE47; increased function in
positive regulation of SCN8A voltage-
dependent sodium channel activity).
{ECO:0000269|PubMed:27164707}.
/FTId=VAR_076507.
MUTAGEN 114 114 R->A: Gain of function, affects voltage
dependence of SCN8A fast inactivation.
{ECO:0000269|PubMed:27164707}.
MUTAGEN 114 114 R->G: Gain of function, affects voltage
dependence of SCN8A fast inactivation.
{ECO:0000269|PubMed:27164707}.
CONFLICT 190 190 K -> E (in Ref. 2; AAB18786).
{ECO:0000305}.
CONFLICT 211 211 P -> Q (in Ref. 5; AAH22524).
{ECO:0000305}.
CONFLICT 229 243 TPTMNGGKVVNQDST -> HHHDGGKL (in Ref. 2;
AAB18786). {ECO:0000305}.
STRAND 73 79 {ECO:0000244|PDB:1Q1U}.
TURN 80 82 {ECO:0000244|PDB:1Q1U}.
STRAND 83 87 {ECO:0000244|PDB:1Q1U}.
STRAND 93 97 {ECO:0000244|PDB:1Q1U}.
HELIX 102 104 {ECO:0000244|PDB:1Q1U}.
STRAND 106 112 {ECO:0000244|PDB:1Q1U}.
STRAND 115 120 {ECO:0000244|PDB:1Q1U}.
TURN 121 123 {ECO:0000244|PDB:1Q1U}.
STRAND 126 129 {ECO:0000244|PDB:1Q1U}.
STRAND 135 140 {ECO:0000244|PDB:1Q1U}.
HELIX 143 145 {ECO:0000244|PDB:1Q1U}.
STRAND 147 152 {ECO:0000244|PDB:1Q1U}.
TURN 153 155 {ECO:0000244|PDB:1Q1U}.
STRAND 156 165 {ECO:0000244|PDB:1Q1U}.
TURN 167 169 {ECO:0000244|PDB:1Q1U}.
STRAND 172 174 {ECO:0000244|PDB:1Q1U}.
STRAND 181 183 {ECO:0000244|PDB:1Q1U}.
HELIX 186 188 {ECO:0000244|PDB:1Q1U}.
HELIX 194 196 {ECO:0000244|PDB:1Q1U}.
STRAND 198 202 {ECO:0000244|PDB:1Q1U}.
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


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