EFHC1_HUMAN
ID EFHC1_HUMAN Reviewed; 640 AA.
AC Q5JVL4; B4DMU3; F5GZD8; Q5XKM4; Q6E1U7; Q6E1U8; Q8WUL2; Q9NVW6;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=EF-hand domain-containing protein 1;
DE AltName: Full=Myoclonin-1;
GN Name=EFHC1 {ECO:0000312|HGNC:HGNC:16406};
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 2), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 557-640 (ISOFORM 1), FUNCTION, INTERACTION WITH CACNA1E, TISSUE
RP SPECIFICITY, VARIANTS EJM1 THR-77; ASN-210; HIS-221; LEU-229 AND TYR-253,
RP CHARACTERIZATION OF VARIANTS EJM1 THR-77; ASN-210; HIS-221; LEU-229 AND
RP TYR-253, VARIANTS TRP-159; HIS-182 AND LEU-619, AND CHARACTERIZATION OF
RP VARIANTS TRP-159; HIS-182 AND LEU-619.
RX PubMed=15258581; DOI=10.1038/ng1393;
RA Suzuki T., Delgado-Escueta A.V., Aguan K., Alonso M.E., Shi J., Hara Y.,
RA Nishida M., Numata T., Medina M.T., Takeuchi T., Morita R., Bai D.,
RA Ganesh S., Sugimoto Y., Inazawa J., Bailey J.N., Ochoa A., Jara-Prado A.,
RA Rasmussen A., Ramos-Peek J., Cordova S., Rubio-Donnadieu F., Inoue Y.,
RA Osawa M., Kaneko S., Oguni H., Mori Y., Yamakawa K.;
RT "Mutations in EFHC1 cause juvenile myoclonic epilepsy.";
RL Nat. Genet. 36:842-849(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ILE-285
RP AND LEU-619.
RC TISSUE=Kidney;
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 [5]
RP INVOLVEMENT IN JAE1, AND VARIANTS TRP-159; VAL-174; HIS-182; LEU-229;
RP TYR-259; HIS-294; SER-394 AND THR-448.
RX PubMed=17159113; DOI=10.1212/01.wnl.0000250254.67042.1b;
RA Stogmann E., Lichtner P., Baumgartner C., Bonelli S., Assem-Hilger E.,
RA Leutmezer F., Schmied M., Hotzy C., Strom T.M., Meitinger T., Zimprich F.,
RA Zimprich A.;
RT "Idiopathic generalized epilepsy phenotypes associated with different EFHC1
RT mutations.";
RL Neurology 67:2029-2031(2006).
RN [6]
RP INVOLVEMENT IN EJM1, VARIANTS EJM1 LEU-229 AND TRP-353, AND VARIANT
RP HIS-182.
RX PubMed=17634063; DOI=10.1111/j.1528-1167.2007.01173.x;
RA Annesi F., Gambardella A., Michelucci R., Bianchi A., Marini C.,
RA Canevini M.P., Capovilla G., Elia M., Buti D., Chifari R., Striano P.,
RA Rocca F.E., Castellotti B., Cali F., Labate A., Lepiane E., Besana D.,
RA Sofia V., Tabiadon G., Tortorella G., Vigliano P., Vignoli A., Beccaria F.,
RA Annesi G., Striano S., Aguglia U., Guerrini R., Quattrone A.;
RT "Mutational analysis of EFHC1 gene in Italian families with juvenile
RT myoclonic epilepsy.";
RL Epilepsia 48:1686-1690(2007).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ALPHA-TUBULIN.
RX PubMed=19734894; DOI=10.1038/nn.2390;
RA de Nijs L., Leon C., Nguyen L., Loturco J.J., Delgado-Escueta A.V.,
RA Grisar T., Lakaye B.;
RT "EFHC1 interacts with microtubules to regulate cell division and cortical
RT development.";
RL Nat. Neurosci. 12:1266-1274(2009).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EJM1 ASN-210;
RP HIS-221; LEU-229 AND TYR-253, AND CHARACTERIZATION OF VARIANTS TRP-159 AND
RP LEU-619.
RX PubMed=22926142; DOI=10.1093/hmg/dds356;
RA de Nijs L., Wolkoff N., Coumans B., Delgado-Escueta A.V., Grisar T.,
RA Lakaye B.;
RT "Mutations of EFHC1, linked to juvenile myoclonic epilepsy, disrupt radial
RT and tangential migrations during brain development.";
RL Hum. Mol. Genet. 21:5106-5117(2012).
RN [9]
RP VARIANT EJM1 LEU-229, AND POSSIBLE INVOLVEMENT IN INTRACTABLE EPILEPSY OF
RP INFANCY.
RX PubMed=22690745; DOI=10.1111/j.1528-1167.2012.03536.x;
RA Berger I., Dor T., Halvardson J., Edvardson S., Shaag A., Feuk L.,
RA Elpeleg O.;
RT "Intractable epilepsy of infancy due to homozygous mutation in the EFHC1
RT gene.";
RL Epilepsia 53:1436-1440(2012).
RN [10]
RP VARIANTS EJM1 CYS-118; GLN-153 AND CYS-182.
RX PubMed=22727576; DOI=10.1016/j.seizure.2012.05.016;
RA Jara-Prado A., Martinez-Juarez I.E., Ochoa A., Gonzalez V.M.,
RA Fernandez-Gonzalez-Aragon M.C., Lopez-Ruiz M., Medina M.T., Bailey J.N.,
RA Delgado-Escueta A.V., Alonso M.E.;
RT "Novel Myoclonin1/EFHC1 mutations in Mexican patients with juvenile
RT myoclonic epilepsy.";
RL Seizure 21:550-554(2012).
RN [11]
RP VARIANTS EJM1 ARG-89; LEU-229; LYS-322; TRP-353; CYS-355; TRP-372; GLU-378;
RP CYS-436; HIS-485; SER-519; LEU-556; SER-619 AND CYS-631, CHARACTERIZATION
RP OF VARIANTS EJM1 ARG-89; LYS-322; TRP-353; CYS-355; TRP-372; GLU-378;
RP CYS-436; HIS-485; SER-519; LEU-556; SER-619 AND CYS-631, VARIANTS TRP-159;
RP HIS-182; CYS-221; HIS-294; THR-448 AND LEU-619, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=28370826; DOI=10.1002/humu.23221;
RA Raju P.K., Satishchandra P., Nayak S., Iyer V., Sinha S., Anand A.;
RT "Microtubule-associated defects caused by EFHC1 mutations in juvenile
RT myoclonic epilepsy.";
RL Hum. Mutat. 38:816-826(2017).
CC -!- FUNCTION: Microtubule-associated protein which regulates cell division
CC and neuronal migration during cortical development. Necessary for
CC mitotic spindle organization (PubMed:19734894, PubMed:28370826).
CC Necessary for radial and tangential cell migration during brain
CC development, possibly acting as a regulator of cell morphology and
CC process formation during migration (PubMed:22926142). May enhance
CC calcium influx through CACNA1E and stimulate programmed cell death
CC (PubMed:15258581). Microtubule inner protein (MIP) part of the dynein-
CC decorated doublet microtubules (DMTs) in cilia axoneme, which is
CC required for motile cilia beating (By similarity).
CC {ECO:0000250|UniProtKB:E1BKH1, ECO:0000269|PubMed:15258581,
CC ECO:0000269|PubMed:19734894, ECO:0000269|PubMed:22926142,
CC ECO:0000269|PubMed:28370826}.
CC -!- SUBUNIT: Interacts with the C-terminus of CACNA1E (PubMed:15258581).
CC Interacts with alpha-tubulin (PubMed:19734894).
CC {ECO:0000269|PubMed:15258581, ECO:0000269|PubMed:19734894}.
CC -!- INTERACTION:
CC Q5JVL4; Q8TAV5: C11orf45; NbExp=3; IntAct=EBI-743105, EBI-12810853;
CC Q5JVL4; Q9H1P6: C20orf85; NbExp=3; IntAct=EBI-743105, EBI-12155483;
CC Q5JVL4; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-743105, EBI-739580;
CC Q5JVL4; Q6P656: CFAP161; NbExp=5; IntAct=EBI-743105, EBI-11901329;
CC Q5JVL4; Q9NX63: CHCHD3; NbExp=3; IntAct=EBI-743105, EBI-743375;
CC Q5JVL4; Q5JST6: EFHC2; NbExp=6; IntAct=EBI-743105, EBI-2349927;
CC Q5JVL4; Q9NRA8: EIF4ENIF1; NbExp=9; IntAct=EBI-743105, EBI-301024;
CC Q5JVL4; Q8IXW7: FMR1; NbExp=3; IntAct=EBI-743105, EBI-11976595;
CC Q5JVL4; O75293: GADD45B; NbExp=5; IntAct=EBI-743105, EBI-448187;
CC Q5JVL4; Q8NHY3: GAS2L2; NbExp=3; IntAct=EBI-743105, EBI-7960826;
CC Q5JVL4; Q08379: GOLGA2; NbExp=3; IntAct=EBI-743105, EBI-618309;
CC Q5JVL4; Q9NSC5: HOMER3; NbExp=3; IntAct=EBI-743105, EBI-748420;
CC Q5JVL4; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-743105, EBI-8638439;
CC Q5JVL4; Q9UKT9: IKZF3; NbExp=13; IntAct=EBI-743105, EBI-747204;
CC Q5JVL4; Q9NV31: IMP3; NbExp=3; IntAct=EBI-743105, EBI-747481;
CC Q5JVL4; Q13352: ITGB3BP; NbExp=3; IntAct=EBI-743105, EBI-712105;
CC Q5JVL4; Q8WVF5: KCTD4; NbExp=6; IntAct=EBI-743105, EBI-741463;
CC Q5JVL4; O14901: KLF11; NbExp=3; IntAct=EBI-743105, EBI-948266;
CC Q5JVL4; P19012: KRT15; NbExp=3; IntAct=EBI-743105, EBI-739566;
CC Q5JVL4; P05783: KRT18; NbExp=3; IntAct=EBI-743105, EBI-297888;
CC Q5JVL4; O95678: KRT75; NbExp=3; IntAct=EBI-743105, EBI-2949715;
CC Q5JVL4; P25791-3: LMO2; NbExp=3; IntAct=EBI-743105, EBI-11959475;
CC Q5JVL4; Q9BV99: LRRC61; NbExp=3; IntAct=EBI-743105, EBI-2350424;
CC Q5JVL4; Q7Z304: MAMDC2; NbExp=3; IntAct=EBI-743105, EBI-8456413;
CC Q5JVL4; Q8WWY6: MBD3L1; NbExp=3; IntAct=EBI-743105, EBI-12516603;
CC Q5JVL4; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-743105, EBI-8487781;
CC Q5JVL4; Q5JXC2: MIIP; NbExp=3; IntAct=EBI-743105, EBI-2801965;
CC Q5JVL4; Q6NTE8: MRNIP; NbExp=3; IntAct=EBI-743105, EBI-2857471;
CC Q5JVL4; Q9H019: MTFR1L; NbExp=3; IntAct=EBI-743105, EBI-2824497;
CC Q5JVL4; P16083: NQO2; NbExp=3; IntAct=EBI-743105, EBI-358466;
CC Q5JVL4; Q9NQ35: NRIP3; NbExp=3; IntAct=EBI-743105, EBI-10311735;
CC Q5JVL4; Q7Z3B4: NUP54; NbExp=3; IntAct=EBI-743105, EBI-741048;
CC Q5JVL4; O43482: OIP5; NbExp=3; IntAct=EBI-743105, EBI-536879;
CC Q5JVL4; P26367: PAX6; NbExp=3; IntAct=EBI-743105, EBI-747278;
CC Q5JVL4; P40424: PBX1; NbExp=3; IntAct=EBI-743105, EBI-301611;
CC Q5JVL4; P40425: PBX2; NbExp=3; IntAct=EBI-743105, EBI-348489;
CC Q5JVL4; Q6P1K2: PMF1; NbExp=3; IntAct=EBI-743105, EBI-713832;
CC Q5JVL4; Q6MZQ0: PRR5L; NbExp=3; IntAct=EBI-743105, EBI-1567866;
CC Q5JVL4; Q15293: RCN1; NbExp=3; IntAct=EBI-743105, EBI-948278;
CC Q5JVL4; Q04864: REL; NbExp=7; IntAct=EBI-743105, EBI-307352;
CC Q5JVL4; Q04864-2: REL; NbExp=6; IntAct=EBI-743105, EBI-10829018;
CC Q5JVL4; Q9UFD9: RIMBP3; NbExp=3; IntAct=EBI-743105, EBI-10182375;
CC Q5JVL4; Q5SSQ6-2: SAPCD1; NbExp=3; IntAct=EBI-743105, EBI-13072754;
CC Q5JVL4; P59797: SELENOV; NbExp=3; IntAct=EBI-743105, EBI-10216195;
CC Q5JVL4; Q9NR46: SH3GLB2; NbExp=3; IntAct=EBI-743105, EBI-749607;
CC Q5JVL4; Q8ND83: SLAIN1; NbExp=3; IntAct=EBI-743105, EBI-10269374;
CC Q5JVL4; O95863: SNAI1; NbExp=3; IntAct=EBI-743105, EBI-1045459;
CC Q5JVL4; O60504: SORBS3; NbExp=3; IntAct=EBI-743105, EBI-741237;
CC Q5JVL4; Q9UM82: SPATA2; NbExp=3; IntAct=EBI-743105, EBI-744066;
CC Q5JVL4; Q96PV0: SYNGAP1; NbExp=3; IntAct=EBI-743105, EBI-2682386;
CC Q5JVL4; P15884: TCF4; NbExp=7; IntAct=EBI-743105, EBI-533224;
CC Q5JVL4; P15884-3: TCF4; NbExp=6; IntAct=EBI-743105, EBI-13636688;
CC Q5JVL4; Q969V4: TEKT1; NbExp=3; IntAct=EBI-743105, EBI-10180409;
CC Q5JVL4; Q8IYF3-3: TEX11; NbExp=6; IntAct=EBI-743105, EBI-11523345;
CC Q5JVL4; Q08117-2: TLE5; NbExp=3; IntAct=EBI-743105, EBI-11741437;
CC Q5JVL4; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-743105, EBI-11952721;
CC Q5JVL4; Q12933: TRAF2; NbExp=6; IntAct=EBI-743105, EBI-355744;
CC Q5JVL4; Q15654: TRIP6; NbExp=3; IntAct=EBI-743105, EBI-742327;
CC Q5JVL4; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-743105, EBI-10241197;
CC Q5JVL4; Q6PF05: TTC23L; NbExp=3; IntAct=EBI-743105, EBI-8656864;
CC Q5JVL4; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-743105, EBI-2514383;
CC Q5JVL4; P61758: VBP1; NbExp=3; IntAct=EBI-743105, EBI-357430;
CC Q5JVL4; Q92558: WASF1; NbExp=3; IntAct=EBI-743105, EBI-1548747;
CC Q5JVL4; Q9P202: WHRN; NbExp=3; IntAct=EBI-743105, EBI-310886;
CC Q5JVL4; P13994: YJU2B; NbExp=3; IntAct=EBI-743105, EBI-716093;
CC Q5JVL4; O96006: ZBED1; NbExp=6; IntAct=EBI-743105, EBI-740037;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:22926142}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:19734894,
CC ECO:0000269|PubMed:22926142}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000269|PubMed:28370826}. Cytoplasm, cytoskeleton, cilium axoneme
CC {ECO:0000250|UniProtKB:E1BKH1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5JVL4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5JVL4-2; Sequence=VSP_015894, VSP_015895;
CC Name=3;
CC IsoId=Q5JVL4-3; Sequence=VSP_046107;
CC -!- TISSUE SPECIFICITY: Widely expressed. Not detected in lymphocytes.
CC {ECO:0000269|PubMed:15258581}.
CC -!- DISEASE: Juvenile myoclonic epilepsy 1 (EJM1) [MIM:254770]: A subtype
CC of idiopathic generalized epilepsy. Patients have afebrile seizures
CC only, with onset in adolescence (rather than in childhood) and
CC myoclonic jerks which usually occur after awakening and are triggered
CC by sleep deprivation and fatigue. {ECO:0000269|PubMed:15258581,
CC ECO:0000269|PubMed:17634063, ECO:0000269|PubMed:22690745,
CC ECO:0000269|PubMed:22727576, ECO:0000269|PubMed:22926142,
CC ECO:0000269|PubMed:28370826}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Juvenile absence epilepsy 1 (JAE1) [MIM:607631]: A subtype of
CC idiopathic generalized epilepsy characterized by onset occurring around
CC puberty, absence seizures, generalized tonic-clonic seizures (GTCS),
CC GTCS on awakening, and myoclonic seizures.
CC {ECO:0000269|PubMed:17159113, ECO:0000305|PubMed:17159113}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- DISEASE: Note=Mutation Leu-229 may be a cause of intractable epilepsy
CC of infancy. Affected individuals have seizures of multiple type,
CC manifested as tonic, clonic, and myoclonic seizures in the neonatal
CC period, and as tonic seizures activated frequently by sleep, and
CC repeated frequent myoclonic seizures in later infancy. The seizures are
CC unresponsive to numerous antiepileptic drugs, and infants die in the
CC first years of life. Although heterozygosity for Leu-229 has been
CC associated with relatively benign forms of epilepsy in adolescence,
CC homozygosity for the same mutation has much more severe consequences.
CC {ECO:0000269|PubMed:22690745}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to intron retention.
CC {ECO:0000305}.
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DR EMBL; AY608689; AAT67418.1; -; mRNA.
DR EMBL; AY608690; AAT67419.1; -; mRNA.
DR EMBL; AK001328; BAA91628.1; -; mRNA.
DR EMBL; AK297632; BAG60005.1; -; mRNA.
DR EMBL; AL049611; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020210; AAH20210.1; -; mRNA.
DR CCDS; CCDS4942.1; -. [Q5JVL4-1]
DR CCDS; CCDS55021.1; -. [Q5JVL4-3]
DR RefSeq; NP_001165891.1; NM_001172420.1. [Q5JVL4-3]
DR RefSeq; NP_060570.2; NM_018100.3. [Q5JVL4-1]
DR AlphaFoldDB; Q5JVL4; -.
DR SMR; Q5JVL4; -.
DR BioGRID; 125313; 77.
DR IntAct; Q5JVL4; 76.
DR MINT; Q5JVL4; -.
DR STRING; 9606.ENSP00000360107; -.
DR iPTMnet; Q5JVL4; -.
DR PhosphoSitePlus; Q5JVL4; -.
DR BioMuta; EFHC1; -.
DR DMDM; 74762202; -.
DR jPOST; Q5JVL4; -.
DR MassIVE; Q5JVL4; -.
DR MaxQB; Q5JVL4; -.
DR PaxDb; Q5JVL4; -.
DR PeptideAtlas; Q5JVL4; -.
DR PRIDE; Q5JVL4; -.
DR ProteomicsDB; 25004; -.
DR ProteomicsDB; 63338; -. [Q5JVL4-1]
DR ProteomicsDB; 63339; -. [Q5JVL4-2]
DR Antibodypedia; 30907; 170 antibodies from 23 providers.
DR DNASU; 114327; -.
DR Ensembl; ENST00000371068.11; ENSP00000360107.4; ENSG00000096093.16. [Q5JVL4-1]
DR Ensembl; ENST00000538167.2; ENSP00000444521.1; ENSG00000096093.16. [Q5JVL4-3]
DR Ensembl; ENST00000636489.1; ENSP00000489998.1; ENSG00000096093.16. [Q5JVL4-3]
DR Ensembl; ENST00000636954.1; ENSP00000489966.1; ENSG00000096093.16. [Q5JVL4-3]
DR GeneID; 114327; -.
DR KEGG; hsa:114327; -.
DR MANE-Select; ENST00000371068.11; ENSP00000360107.4; NM_018100.4; NP_060570.2.
DR UCSC; uc003pap.5; human. [Q5JVL4-1]
DR CTD; 114327; -.
DR DisGeNET; 114327; -.
DR GeneCards; EFHC1; -.
DR HGNC; HGNC:16406; EFHC1.
DR HPA; ENSG00000096093; Tissue enhanced (fallopian).
DR MalaCards; EFHC1; -.
DR MIM; 254770; phenotype.
DR MIM; 607631; phenotype.
DR MIM; 608815; gene.
DR neXtProt; NX_Q5JVL4; -.
DR OpenTargets; ENSG00000096093; -.
DR Orphanet; 1941; Juvenile absence epilepsy.
DR Orphanet; 307; Juvenile myoclonic epilepsy.
DR PharmGKB; PA27654; -.
DR VEuPathDB; HostDB:ENSG00000096093; -.
DR eggNOG; KOG0043; Eukaryota.
DR GeneTree; ENSGT00530000063528; -.
DR HOGENOM; CLU_1001001_0_0_1; -.
DR InParanoid; Q5JVL4; -.
DR OMA; EDTYASC; -.
DR PhylomeDB; Q5JVL4; -.
DR TreeFam; TF314504; -.
DR PathwayCommons; Q5JVL4; -.
DR SignaLink; Q5JVL4; -.
DR SIGNOR; Q5JVL4; -.
DR BioGRID-ORCS; 114327; 7 hits in 1070 CRISPR screens.
DR ChiTaRS; EFHC1; human.
DR GeneWiki; EFHC1; -.
DR GenomeRNAi; 114327; -.
DR Pharos; Q5JVL4; Tbio.
DR PRO; PR:Q5JVL4; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q5JVL4; protein.
DR Bgee; ENSG00000096093; Expressed in bronchial epithelial cell and 185 other tissues.
DR ExpressionAtlas; Q5JVL4; baseline and differential.
DR Genevisible; Q5JVL4; HS.
DR GO; GO:0005879; C:axonemal microtubule; ISS:UniProtKB.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008022; F:protein C-terminus binding; ISS:UniProtKB.
DR GO; GO:0021795; P:cerebral cortex cell migration; IMP:UniProtKB.
DR GO; GO:0060285; P:cilium-dependent cell motility; IBA:GO_Central.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB.
DR GO; GO:0007052; P:mitotic spindle organization; IMP:UniProtKB.
DR GO; GO:0051302; P:regulation of cell division; IMP:UniProtKB.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR006602; DM10_dom.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR040193; EFHC1/EFHC2/EFHB.
DR PANTHER; PTHR12086; PTHR12086; 1.
DR Pfam; PF06565; DUF1126; 3.
DR SMART; SM00676; DM10; 3.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS51336; DM10; 3.
DR PROSITE; PS50222; EF_HAND_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cytoplasm; Cytoskeleton;
KW Disease variant; Epilepsy; Reference proteome; Repeat.
FT CHAIN 1..640
FT /note="EF-hand domain-containing protein 1"
FT /id="PRO_0000073877"
FT DOMAIN 93..198
FT /note="DM10 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00665"
FT DOMAIN 239..359
FT /note="DM10 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00665"
FT DOMAIN 416..520
FT /note="DM10 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00665"
FT DOMAIN 574..609
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..45
FT /note="Required for its localization in the mitotic spindle
FT and interaction with alpha-tubulin"
FT /evidence="ECO:0000269|PubMed:19734894"
FT REGION 535..554
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 537..554
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..21
FT /note="MVSNPVHGLPFLPGTSFKDST -> ML (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046107"
FT VAR_SEQ 243..278
FT /note="LRFYAIWDDTDSMYGECRTYIIHYYLMDDTVEIREV -> SDIGTTIGLLIS
FT KCDLHLLAKGLGSCIGNYFETLQL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15258581"
FT /id="VSP_015894"
FT VAR_SEQ 279..640
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15258581"
FT /id="VSP_015895"
FT VARIANT 77
FT /note="P -> T (in EJM1; associated with H-221; reduces
FT substantially the cell death effect; reduces partly the
FT calcium influx; binds to CACNA1E; dbSNP:rs149055334)"
FT /evidence="ECO:0000269|PubMed:15258581"
FT /id="VAR_023619"
FT VARIANT 89
FT /note="H -> R (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis; dbSNP:rs543160745)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079772"
FT VARIANT 118
FT /note="R -> C (in EJM1; dbSNP:rs764096785)"
FT /evidence="ECO:0000269|PubMed:22727576"
FT /id="VAR_072108"
FT VARIANT 153
FT /note="R -> Q (in EJM1; unknown pathological significance;
FT dbSNP:rs745600475)"
FT /evidence="ECO:0000269|PubMed:22727576"
FT /id="VAR_072109"
FT VARIANT 159
FT /note="R -> W (no effect on cell death; binds to CACNA1E as
FT the wild type protein; does not affect subcellular
FT location; dbSNP:rs3804506)"
FT /evidence="ECO:0000269|PubMed:15258581,
FT ECO:0000269|PubMed:17159113, ECO:0000269|PubMed:22926142,
FT ECO:0000269|PubMed:28370826"
FT /id="VAR_023620"
FT VARIANT 174
FT /note="I -> V (associated with susceptibility to JAE1;
FT dbSNP:rs137852779)"
FT /evidence="ECO:0000269|PubMed:17159113"
FT /id="VAR_043154"
FT VARIANT 182
FT /note="R -> C (in EJM1; unknown pathological significance;
FT dbSNP:rs200191497)"
FT /evidence="ECO:0000269|PubMed:22727576"
FT /id="VAR_072110"
FT VARIANT 182
FT /note="R -> H (benign variant; no effect on cell death;
FT binds to CACNA1E; dbSNP:rs3804505)"
FT /evidence="ECO:0000269|PubMed:15258581,
FT ECO:0000269|PubMed:17159113, ECO:0000269|PubMed:17634063,
FT ECO:0000269|PubMed:28370826"
FT /id="VAR_023621"
FT VARIANT 210
FT /note="D -> N (in EJM1; reduces substantially the cell
FT death effect; reduces partly the calcium influx; normally
FT binds to CACNA1E; does not affect subcellular location;
FT results in impaired cell migration; dbSNP:rs137852777)"
FT /evidence="ECO:0000269|PubMed:15258581,
FT ECO:0000269|PubMed:22926142"
FT /id="VAR_023622"
FT VARIANT 221
FT /note="R -> C (in dbSNP:rs139197513)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079773"
FT VARIANT 221
FT /note="R -> H (in EJM1; associated with T-77; reduces
FT substantially the cell death effect; reduces partly the
FT calcium influx; normally binds to CACNA1E; does not affect
FT subcellular location; results in impaired cell migration;
FT dbSNP:rs79761183)"
FT /evidence="ECO:0000269|PubMed:15258581,
FT ECO:0000269|PubMed:22926142"
FT /id="VAR_023623"
FT VARIANT 229
FT /note="F -> L (in EJM1; uncertain pathological
FT significance; also found at homozygosity in neonatal
FT intractable epilepsy; reduces substantially the cell death
FT effect; reduces significantly the calcium influx; normally
FT binds to CACNA1E; does not affect subcellular location;
FT results in impaired cell migration; dbSNP:rs137852776)"
FT /evidence="ECO:0000269|PubMed:15258581,
FT ECO:0000269|PubMed:17159113, ECO:0000269|PubMed:17634063,
FT ECO:0000269|PubMed:22690745, ECO:0000269|PubMed:22926142,
FT ECO:0000269|PubMed:28370826"
FT /id="VAR_023624"
FT VARIANT 253
FT /note="D -> Y (in EJM1; reduces substantially the cell
FT death effect; reduces partly the calcium influx; normally
FT binds to CACNA1E; does not affect subcellular location;
FT results in impaired cell migration; dbSNP:rs137852778)"
FT /evidence="ECO:0000269|PubMed:15258581,
FT ECO:0000269|PubMed:22926142"
FT /id="VAR_023625"
FT VARIANT 259
FT /note="C -> Y (associated with susceptibility to JAE1;
FT dbSNP:rs137852780)"
FT /evidence="ECO:0000269|PubMed:17159113"
FT /id="VAR_043155"
FT VARIANT 285
FT /note="R -> I (in dbSNP:rs17851771)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026531"
FT VARIANT 294
FT /note="R -> H (in dbSNP:rs1570624)"
FT /evidence="ECO:0000269|PubMed:17159113,
FT ECO:0000269|PubMed:28370826"
FT /id="VAR_043156"
FT VARIANT 322
FT /note="E -> K (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079774"
FT VARIANT 353
FT /note="R -> W (in EJM1; no effect on protein expression; no
FT effect on the spindle pole localization; defective mitotic
FT spindle organization; defective cytokinesis;
FT dbSNP:rs527295360)"
FT /evidence="ECO:0000269|PubMed:17634063,
FT ECO:0000269|PubMed:28370826"
FT /id="VAR_043157"
FT VARIANT 355
FT /note="Y -> C (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis; dbSNP:rs767833659)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079775"
FT VARIANT 357
FT /note="E -> K (in dbSNP:rs505760)"
FT /id="VAR_048666"
FT VARIANT 372
FT /note="R -> W (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis; dbSNP:rs371151471)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079776"
FT VARIANT 378
FT /note="K -> E (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079777"
FT VARIANT 394
FT /note="A -> S (in a sporadic case of unclassified
FT epilepsy)"
FT /evidence="ECO:0000269|PubMed:17159113"
FT /id="VAR_043158"
FT VARIANT 436
FT /note="R -> C (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis; dbSNP:rs377286138)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079778"
FT VARIANT 448
FT /note="M -> T (in dbSNP:rs1266787)"
FT /evidence="ECO:0000269|PubMed:17159113,
FT ECO:0000269|PubMed:28370826"
FT /id="VAR_043159"
FT VARIANT 485
FT /note="Y -> H (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis; dbSNP:rs779322943)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079779"
FT VARIANT 519
FT /note="N -> S (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis; dbSNP:rs527539103)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079780"
FT VARIANT 556
FT /note="V -> L (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis; dbSNP:rs772265107)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079781"
FT VARIANT 619
FT /note="I -> L (no effect on cell death; normally binds to
FT CACNA1E; does not affect subcellular location;
FT dbSNP:rs17851770)"
FT /evidence="ECO:0000269|PubMed:15258581,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:22926142,
FT ECO:0000269|PubMed:28370826"
FT /id="VAR_023626"
FT VARIANT 619
FT /note="I -> S (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis; dbSNP:rs142458862)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079782"
FT VARIANT 631
FT /note="Y -> C (in EJM1; no effect on protein expression;
FT defective mitotic spindle organization; defective
FT cytokinesis; dbSNP:rs574948354)"
FT /evidence="ECO:0000269|PubMed:28370826"
FT /id="VAR_079783"
FT CONFLICT 140
FT /note="N -> D (in Ref. 2; BAG60005)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="A -> T (in Ref. 2; BAA91628)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 640 AA; 73990 MW; 08F9E8BFEC42FCF3 CRC64;
MVSNPVHGLP FLPGTSFKDS TKTAFHRSQT LSYRNGYAIV RRPTVGIGGD RLQFNQLSQA
ELDELASKAP VLTYGQPKQA PPADFIPAHV AFDKKVLKFD AYFQEDVPMS TEEQYRIRQV
NIYYYLEDDS MSVIEPVVEN SGILQGKLIK RQRLAKNDRG DHYHWKDLNR GINITIYGKT
FRVVDCDQFT QVFLESQGIE LNPPEKMALD PYTELRKQPL RKYVTPSDFD QLKQFLTFDK
QVLRFYAIWD DTDSMYGECR TYIIHYYLMD DTVEIREVHE RNDGRDPFPL LMNRQRVPKV
LVENAKNFPQ CVLEISDQEV LEWYTAKDFI VGKSLTILGR TFFIYDCDPF TRRYYKEKFG
ITDLPRIDVS KREPPPVKQE LPPYNGFGLV EDSAQNCFAL IPKAPKKDVI KMLVNDNKVL
RYLAVLESPI PEDKDRRFVF SYFLATDMIS IFEPPVRNSG IIGGKYLGRT KVVKPYSTVD
NPVYYGPSDF FIGAVIEVFG HRFIILDTDE YVLKYMESNA AQYSPEALAS IQNHVRKREA
PAPEAESKQT EKDPGVQELE ALIDTIQKQL KDHSCKDNIR EAFQIYDKEA SGYVDRDMFF
KICESLNVPV DDSLVKELIR MCSHGEGKIN YYNFVRAFSN
