Full text data of SPTAN1
SPTAN1
(NEAS, SPTA2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Spectrin alpha chain, non-erythrocytic 1 (Alpha-II spectrin; Fodrin alpha chain; Spectrin, non-erythroid alpha subunit)
Spectrin alpha chain, non-erythrocytic 1 (Alpha-II spectrin; Fodrin alpha chain; Spectrin, non-erythroid alpha subunit)
hRBCD
IPI00413728
IPI00413728 Splice Isoform 1 Of Spectrin alpha chain, brain Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic Isoform 1, 2 or 3 found at its expected molecular weight found at molecular weight
IPI00413728 Splice Isoform 1 Of Spectrin alpha chain, brain Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic Isoform 1, 2 or 3 found at its expected molecular weight found at molecular weight
UniProt
Q13813
ID SPTN1_HUMAN Reviewed; 2472 AA.
AC Q13813; Q13186; Q15324; Q16606; Q59EF1; Q5VXV5; Q5VXV6; Q7Z6M5;
read moreAC Q9P0V0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 3.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=Spectrin alpha chain, non-erythrocytic 1;
DE AltName: Full=Alpha-II spectrin;
DE AltName: Full=Fodrin alpha chain;
DE AltName: Full=Spectrin, non-erythroid alpha subunit;
GN Name=SPTAN1; Synonyms=NEAS, SPTA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-1300.
RX PubMed=2307671;
RA Moon R.T., McMahon A.P.;
RT "Generation of diversity in nonerythroid spectrins. Multiple
RT polypeptides are predicted by sequence analysis of cDNAs encompassing
RT the coding region of human nonerythroid alpha-spectrin.";
RL J. Biol. Chem. 265:4427-4433(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Fetal brain;
RX PubMed=10625438; DOI=10.1021/bi991458k;
RA Cianci C.D., Zhang Z., Pradhan D., Morrow J.S.;
RT "Brain and muscle express a unique alternative transcript of alphaII
RT spectrin.";
RL Biochemistry 38:15721-15730(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Kato S.;
RT "Human full-length cDNA starting with the capped site sequence.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Aorta;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 157-168; 970-981; 990-1002; 1608-1619; 2138-2155
RP AND 2455-2467, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 676-1595 (ISOFORM 1), AND VARIANT
RP THR-1300.
RC TISSUE=Lung;
RX PubMed=3691949;
RA McMahon A.P., Moon R.T.;
RT "Structure and evolution of a non-erythroid spectrin, human alpha-
RT fodrin.";
RL Biochem. Soc. Trans. 15:804-807(1987).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 676-1595 (ISOFORM 1), AND VARIANT
RP THR-1300.
RX PubMed=3038643; DOI=10.1111/j.1432-0436.1987.tb00052.x;
RA McMahon A.P., Giebelhaus D.H., Champion J.E., Bailes J.A., Lacey S.,
RA Carritt B., Henchman S.K., Moon R.T.;
RT "cDNA cloning, sequencing and chromosome mapping of a non-erythroid
RT spectrin, human alpha-fodrin.";
RL Differentiation 34:68-78(1987).
RN [10]
RP ERRATUM.
RA McMahon A.P., Giebelhaus D.H., Champion J.E., Bailes J.A., Lacey S.,
RA Carritt B., Henchman S.K., Moon R.T.;
RL Differentiation 34:241-241(1987).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 811-1529 (ISOFORMS 1/2), AND
RP MUTAGENESIS.
RX PubMed=8993318; DOI=10.1021/bi962034i;
RA Stabach P.R., Cianci C.D., Glantz S.B., Zhang Z., Morrow J.S.;
RT "Site-directed mutagenesis of alpha II spectrin at codon 1175
RT modulates its mu-calpain susceptibility.";
RL Biochemistry 36:57-65(1997).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1073-1349.
RA Murakami N., Speed W.C., Seaman M.I., Zychowski R.L., Wetterberg L.,
RA Pakstis A.J., Kidd J.R., Kidd K.K.;
RT "Association and linkage analyses of the nonerythroid alpha-spectrin
RT (SPTAN1) gene on chromosome 9q34 with a large Swedish kindred.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2059-2433 (ISOFORMS 1/2/3).
RC TISSUE=Fetal liver;
RX PubMed=7607240; DOI=10.1111/j.1432-1033.1995.0658h.x;
RA Lundberg S., Bjoerk J., Loefvenberg L., Backman L.;
RT "Cloning, expression and characterization of two putative calcium-
RT binding sites in human non-erythroid alpha-spectrin.";
RL Eur. J. Biochem. 230:658-665(1995).
RN [14]
RP INTERACTION WITH ACP1.
RX PubMed=11971983; DOI=10.1128/MCB.22.10.3527-3536.2002;
RA Nicolas G., Fournier C.M., Galand C., Malbert-Colas L., Bournier O.,
RA Kroviarski Y., Bourgeois M., Camonis J.H., Dhermy D., Grandchamp B.,
RA Lecomte M.-C.;
RT "Tyrosine phosphorylation regulates alpha II spectrin cleavage by
RT calpain.";
RL Mol. Cell. Biol. 22:3527-3536(2002).
RN [15]
RP INTERACTION WITH EMD.
RX PubMed=15328537; DOI=10.1371/journal.pbio.0020231;
RA Holaska J.M., Kowalski A.K., Wilson K.L.;
RT "Emerin caps the pointed end of actin filaments: evidence for an actin
RT cortical network at the nuclear inner membrane.";
RL PLoS Biol. 2:1354-1362(2004).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1217, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [17]
RP INTERACTION WITH TRPC4.
RX PubMed=18048348; DOI=10.1074/jbc.M709729200;
RA Odell A.F., Van Helden D.F., Scott J.L.;
RT "The spectrin cytoskeleton influences the surface expression and
RT activation of human transient receptor potential channel 4 channels.";
RL J. Biol. Chem. 283:4395-4407(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1041 AND TYR-1176, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-637; LYS-1519; LYS-2052 AND
RP LYS-2421, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-982; SER-999; SER-1217
RP AND SER-1647, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1217, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 1172-1210 IN COMPLEX WITH
RP CALM.
RX PubMed=16945920; DOI=10.1074/jbc.M604613200;
RA Simonovic M., Zhang Z., Cianci C.D., Steitz T.A., Morrow J.S.;
RT "Structure of the calmodulin alphaII-spectrin complex provides insight
RT into the regulation of cell plasticity.";
RL J. Biol. Chem. 281:34333-34340(2006).
RN [27]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-904; SER-1017; TRP-1794 AND
RP ASN-1918.
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.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [28]
RP VARIANTS EIEE5 GLU-2202 DEL AND MET-2303 INS, AND CHARACTERIZATION OF
RP VARIANTS EIEE5 GLU-2202 DEL AND MET-2303 INS.
RX PubMed=20493457; DOI=10.1016/j.ajhg.2010.04.013;
RA Saitsu H., Tohyama J., Kumada T., Egawa K., Hamada K., Okada I.,
RA Mizuguchi T., Osaka H., Miyata R., Furukawa T., Haginoya K.,
RA Hoshino H., Goto T., Hachiya Y., Yamagata T., Saitoh S., Nagai T.,
RA Nishiyama K., Nishimura A., Miyake N., Komada M., Hayashi K.,
RA Hirai S., Ogata K., Kato M., Fukuda A., Matsumoto N.;
RT "Dominant-negative mutations in alpha-II spectrin cause West syndrome
RT with severe cerebral hypomyelination, spastic quadriplegia, and
RT developmental delay.";
RL Am. J. Hum. Genet. 86:881-891(2010).
CC -!- FUNCTION: Fodrin, which seems to be involved in secretion,
CC interacts with calmodulin in a calcium-dependent manner and is
CC thus candidate for the calcium-dependent movement of the
CC cytoskeleton at the membrane.
CC -!- SUBUNIT: Like erythrocyte spectrin, the spectrin-like proteins are
CC capable of forming dimers which can further associate to
CC tetramers. Interacts with isoform 1 of ACP1. Interacts with CALM
CC and EMD. Interacts (via C-terminal spectrin repeats) with TRPC4.
CC Identified in a complex with ACTN4, CASK, IQGAP1, MAGI2, NPHS1 and
CC SPTBN1 (By similarity).
CC -!- INTERACTION:
CC Q9UI08:EVL; NbExp=4; IntAct=EBI-351450, EBI-346653;
CC O15287:FANCG; NbExp=4; IntAct=EBI-351450, EBI-81610;
CC P40692:MLH1; NbExp=7; IntAct=EBI-351450, EBI-744248;
CC Q01082:SPTBN1; NbExp=7; IntAct=EBI-351450, EBI-351561;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm, cell
CC cortex. Note=Expressed along the cell membrane in podocytes and
CC presumptive tubule cells during glomerulogenesis and is expressed
CC along lateral cell margins in tubule cells (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q13813-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13813-2; Sequence=VSP_012270;
CC Name=3;
CC IsoId=Q13813-3; Sequence=VSP_012271;
CC -!- PTM: Phosphorylation of Tyr-1176 decreases sensitivity to cleavage
CC by calpain in vitro (By similarity).
CC -!- DISEASE: Epileptic encephalopathy, early infantile, 5 (EIEE5)
CC [MIM:613477]: A disorder characterized by seizures associated with
CC hypsarrhythmia, profound mental retardation with lack of visual
CC attention and speech development, as well as spastic quadriplegia.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the spectrin family.
CC -!- SIMILARITY: Contains 3 EF-hand domains.
CC -!- SIMILARITY: Contains 1 SH3 domain.
CC -!- SIMILARITY: Contains 23 spectrin repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93097.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; J05243; AAA51790.1; -; mRNA.
DR EMBL; U83867; AAB41498.1; -; mRNA.
DR EMBL; AB191262; BAD52438.1; -; mRNA.
DR EMBL; AB209860; BAD93097.1; ALT_INIT; mRNA.
DR EMBL; AL356481; CAH71404.1; -; Genomic_DNA.
DR EMBL; AL356481; CAH71405.1; -; Genomic_DNA.
DR EMBL; BC053521; AAH53521.1; -; mRNA.
DR EMBL; M24773; AAA52468.1; -; mRNA.
DR EMBL; M18627; AAA51702.1; -; mRNA.
DR EMBL; U26396; AAB60364.1; -; mRNA.
DR EMBL; AF148808; AAF26672.1; -; Genomic_DNA.
DR EMBL; X86901; CAA60503.1; -; mRNA.
DR PIR; A35715; A35715.
DR RefSeq; NP_001123910.1; NM_001130438.2.
DR RefSeq; NP_001182461.1; NM_001195532.1.
DR RefSeq; NP_003118.2; NM_003127.3.
DR UniGene; Hs.372331; -.
DR PDB; 2FOT; X-ray; 2.45 A; C=1172-1210.
DR PDB; 3F31; X-ray; 2.30 A; A/B=1-147.
DR PDB; 3FB2; X-ray; 2.30 A; A/B=1337-1544.
DR PDBsum; 2FOT; -.
DR PDBsum; 3F31; -.
DR PDBsum; 3FB2; -.
DR ProteinModelPortal; Q13813; -.
DR SMR; Q13813; 8-2470.
DR DIP; DIP-33141N; -.
DR IntAct; Q13813; 44.
DR MINT; MINT-4999298; -.
DR PhosphoSite; Q13813; -.
DR DMDM; 94730425; -.
DR PaxDb; Q13813; -.
DR PRIDE; Q13813; -.
DR Ensembl; ENST00000372731; ENSP00000361816; ENSG00000197694.
DR Ensembl; ENST00000372739; ENSP00000361824; ENSG00000197694.
DR GeneID; 6709; -.
DR KEGG; hsa:6709; -.
DR UCSC; uc004bvl.4; human.
DR CTD; 6709; -.
DR GeneCards; GC09P131314; -.
DR HGNC; HGNC:11273; SPTAN1.
DR HPA; CAB004581; -.
DR HPA; HPA007927; -.
DR MIM; 182810; gene.
DR MIM; 613477; phenotype.
DR neXtProt; NX_Q13813; -.
DR Orphanet; 1934; Early infantile epileptic encephalopathy.
DR PharmGKB; PA36102; -.
DR eggNOG; COG5126; -.
DR HOVERGEN; HBG059266; -.
DR KO; K06114; -.
DR OrthoDB; EOG7GXP9K; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_127416; Developmental Biology.
DR Reactome; REACT_578; Apoptosis.
DR ChiTaRS; SPTAN1; human.
DR EvolutionaryTrace; Q13813; -.
DR GeneWiki; SPTAN1; -.
DR GenomeRNAi; 6709; -.
DR NextBio; 26162; -.
DR PRO; PR:Q13813; -.
DR ArrayExpress; Q13813; -.
DR Bgee; Q13813; -.
DR Genevestigator; Q13813; -.
DR GO; GO:0032437; C:cuticular plate; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005916; C:fascia adherens; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016328; C:lateral plasma membrane; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0008091; C:spectrin; TAS:ProtInc.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; TAS:ProtInc.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0051693; P:actin filament capping; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
DR Gene3D; 1.10.238.10; -; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR014837; EF-hand_Ca_insen.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR013315; Spectrin_alpha_SH3.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF08726; EFhand_Ca_insen; 1.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF00435; Spectrin; 20.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR01887; SPECTRNALPHA.
DR SMART; SM00054; EFh; 2.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00150; SPEC; 20.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin capping; Actin-binding;
KW Alternative splicing; Calcium; Calmodulin-binding; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease mutation;
KW Epilepsy; Mental retardation; Metal-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; SH3 domain.
FT CHAIN 1 2472 Spectrin alpha chain, non-erythrocytic 1.
FT /FTId=PRO_0000073455.
FT REPEAT 10 42 Spectrin 1.
FT REPEAT 44 147 Spectrin 2.
FT REPEAT 149 253 Spectrin 3.
FT REPEAT 255 359 Spectrin 4.
FT REPEAT 361 465 Spectrin 5.
FT REPEAT 467 571 Spectrin 6.
FT REPEAT 573 676 Spectrin 7.
FT REPEAT 678 782 Spectrin 8.
FT REPEAT 784 888 Spectrin 9.
FT REPEAT 890 955 Spectrin 10.
FT DOMAIN 967 1026 SH3.
FT REPEAT 1062 1089 Spectrin 11.
FT REPEAT 1091 1161 Spectrin 12.
FT REPEAT 1208 1231 Spectrin 13.
FT REPEAT 1233 1337 Spectrin 14.
FT REPEAT 1339 1443 Spectrin 15.
FT REPEAT 1445 1549 Spectrin 16.
FT REPEAT 1551 1656 Spectrin 17.
FT REPEAT 1658 1762 Spectrin 18.
FT REPEAT 1764 1868 Spectrin 19.
FT REPEAT 1870 1974 Spectrin 20.
FT REPEAT 1976 2081 Spectrin 21.
FT REPEAT 2091 2195 Spectrin 22.
FT REPEAT 2205 2310 Spectrin 23.
FT DOMAIN 2323 2358 EF-hand 1.
FT DOMAIN 2366 2401 EF-hand 2.
FT DOMAIN 2404 2439 EF-hand 3.
FT CA_BIND 2336 2347 1 (Potential).
FT CA_BIND 2379 2390 2 (Potential).
FT SITE 1176 1177 Cleavage; by mu-calpain.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 637 637 N6-acetyllysine.
FT MOD_RES 982 982 Phosphoserine.
FT MOD_RES 999 999 Phosphoserine.
FT MOD_RES 1041 1041 Phosphoserine.
FT MOD_RES 1176 1176 Phosphotyrosine.
FT MOD_RES 1217 1217 Phosphoserine.
FT MOD_RES 1519 1519 N6-acetyllysine.
FT MOD_RES 1647 1647 Phosphoserine.
FT MOD_RES 2052 2052 N6-acetyllysine.
FT MOD_RES 2421 2421 N6-acetyllysine.
FT VAR_SEQ 1053 1072 Missing (in isoform 3).
FT /FTId=VSP_012271.
FT VAR_SEQ 1586 1586 Q -> QLSKLL (in isoform 2).
FT /FTId=VSP_012270.
FT VARIANT 385 385 N -> S (in dbSNP:rs2227863).
FT /FTId=VAR_038513.
FT VARIANT 904 904 S -> C (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035454.
FT VARIANT 1017 1017 P -> S (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035455.
FT VARIANT 1300 1300 I -> T (in dbSNP:rs1048236).
FT /FTId=VAR_012227.
FT VARIANT 1794 1794 R -> W (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035456.
FT VARIANT 1918 1918 D -> N (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035457.
FT VARIANT 2202 2202 Missing (in EIEE5; could form a
FT heterodimer with SPTBN1 but the
FT heterodimer is thermally unstable;
FT suggests a dominant negative effect).
FT /FTId=VAR_063886.
FT VARIANT 2303 2303 R -> RM (in EIEE5; could form a
FT heterodimer with SPTBN1 but the
FT heterodimer is thermally unstable;
FT suggests a dominant negative effect).
FT /FTId=VAR_063887.
FT CONFLICT 150 150 K -> N (in Ref. 1; AAA51790).
FT CONFLICT 498 498 S -> F (in Ref. 1; AAA51790).
FT CONFLICT 737 737 I -> V (in Ref. 1; AAA51790, 8; AAA52468
FT and 9; AAA51702).
FT CONFLICT 1595 1595 F -> R (in Ref. 8; AAA52468 and 9;
FT AAA51702).
FT CONFLICT 1625 1625 S -> N (in Ref. 1; AAA51790).
FT CONFLICT 1670 1671 FD -> IA (in Ref. 1; AAA51790).
FT CONFLICT 1918 1918 D -> A (in Ref. 1; AAA51790).
FT CONFLICT 1971 1972 KL -> NV (in Ref. 1; AAA51790 and 2;
FT AAB41498).
FT CONFLICT 2163 2163 A -> R (in Ref. 13; CAA60503).
FT CONFLICT 2347 2348 EF -> DG (in Ref. 1; AAA51790).
FT CONFLICT 2448 2448 Y -> I (in Ref. 1; AAA51790).
FT HELIX 14 25
FT HELIX 30 66
FT STRAND 74 76
FT HELIX 78 94
FT HELIX 97 112
FT HELIX 117 146
FT HELIX 1191 1210
FT HELIX 1337 1362
FT STRAND 1369 1371
FT HELIX 1372 1389
FT HELIX 1392 1407
FT HELIX 1413 1466
FT HELIX 1489 1513
FT HELIX 1519 1539
SQ SEQUENCE 2472 AA; 284539 MW; 4433BF74EFCEFC8A CRC64;
MDPSGVKVLE TAEDIQERRQ QVLDRYHRFK ELSTLRRQKL EDSYRFQFFQ RDAEELEKWI
QEKLQIASDE NYKDPTNLQG KLQKHQAFEA EVQANSGAIV KLDETGNLMI SEGHFASETI
RTRLMELHRQ WELLLEKMRE KGIKLLQAQK LVQYLRECED VMDWINDKEA IVTSEELGQD
LEHVEVLQKK FEEFQTDMAA HEERVNEVNQ FAAKLIQEQH PEEELIKTKQ DEVNAAWQRL
KGLALQRQGK LFGAAEVQRF NRDVDETISW IKEKEQLMAS DDFGRDLASV QALLRKHEGL
ERDLAALEDK VKALCAEADR LQQSHPLSAT QIQVKREELI TNWEQIRTLA AERHARLNDS
YRLQRFLADF RDLTSWVTEM KALINADELA SDVAGAEALL DRHQEHKGEI DAHEDSFKSA
DESGQALLAA GHYASDEVRE KLTVLSEERA ALLELWELRR QQYEQCMDLQ LFYRDTEQVD
NWMSKQEAFL LNEDLGDSLD SVEALLKKHE DFEKSLSAQE EKITALDEFA TKLIQNNHYA
MEDVATRRDA LLSRRNALHE RAMRRRAQLA DSFHLQQFFR DSDELKSWVN EKMKTATDEA
YKDPSNLQGK VQKHQAFEAE LSANQSRIDA LEKAGQKLID VNHYAKDEVA ARMNEVISLW
KKLLEATELK GIKLREANQQ QQFNRNVEDI ELWLYEVEGH LASDDYGKDL TNVQNLQKKH
ALLEADVAAH QDRIDGITIQ ARQFQDAGHF DAENIKKKQE ALVARYEALK EPMVARKQKL
ADSLRLQQLF RDVEDEETWI REKEPIAAST NRGKDLIGVQ NLLKKHQALQ AEIAGHEPRI
KAVTQKGNAM VEEGHFAAED VKAKLHELNQ KWEALKAKAS QRRQDLEDSL QAQQYFADAN
EAESWMREKE PIVGSTDYGK DEDSAEALLK KHEALMSDLS AYGSSIQALR EQAQSCRQQV
APTDDETGKE LVLALYDYQE KSPREVTMKK GDILTLLNST NKDWWKVEVN DRQGFVPAAY
VKKLDPAQSA SRENLLEEQG SIALRQEQID NQTRITKEAG SVSLRMKQVE ELYHSLLELG
EKRKGMLEKS CKKFMLFREA NELQQWINEK EAALTSEEVG ADLEQVEVLQ KKFDDFQKDL
KANESRLKDI NKVAEDLESE GLMAEEVQAV QQQEVYGMMP RDETDSKTAS PWKSARLMVH
TVATFNSIKE LNERWRSLQQ LAEERSQLLG SAHEVQRFHR DADETKEWIE EKNQALNTDN
YGHDLASVQA LQRKHEGFER DLAALGDKVN SLGETAERLI QSHPESAEDL QEKCTELNQA
WSSLGKRADQ RKAKLGDSHD LQRFLSDFRD LMSWINGIRG LVSSDELAKD VTGAEALLER
HQEHRTEIDA RAGTFQAFEQ FGQQLLAHGH YASPEIKQKL DILDQERADL EKAWVQRRMM
LDQCLELQLF HRDCEQAENW MAAREAFLNT EDKGDSLDSV EALIKKHEDF DKAINVQEEK
IAALQAFADQ LIAAGHYAKG DISSRRNEVL DRWRRLKAQM IEKRSKLGES QTLQQFSRDV
DEIEAWISEK LQTASDESYK DPTNIQSKHQ KHQAFEAELH ANADRIRGVI DMGNSLIERG
ACAGSEDAVK ARLAALADQW QFLVQKSAEK SQKLKEANKQ QNFNTGIKDF DFWLSEVEAL
LASEDYGKDL ASVNNLLKKH QLLEADISAH EDRLKDLNSQ ADSLMTSSAF DTSQVKDKRD
TINGRFQKIK SMAASRRAKL NESHRLHQFF RDMDDEESWI KEKKLLVGSE DYGRDLTGVQ
NLRKKHKRLE AELAAHEPAI QGVLDTGKKL SDDNTIGKEE IQQRLAQFVE HWKELKQLAA
ARGQRLEESL EYQQFVANVE EEEAWINEKM TLVASEDYGD TLAAIQGLLK KHEAFETDFT
VHKDRVNDVC TNGQDLIKKN NHHEENISSK MKGLNGKVSD LEKAAAQRKA KLDENSAFLQ
FNWKADVVES WIGEKENSLK TDDYGRDLSS VQTLLTKQET FDAGLQAFQQ EGIANITALK
DQLLAAKHVQ SKAIEARHAS LMKRWSQLLA NSAARKKKLL EAQSHFRKVE DLFLTFAKKA
SAFNSWFENA EEDLTDPVRC NSLEEIKALR EAHDAFRSSL SSAQADFNQL AELDRQIKSF
RVASNPYTWF TMEALEETWR NLQKIIKERE LELQKEQRRQ EENDKLRQEF AQHANAFHQW
IQETRTYLLD GSCMVEESGT LESQLEATKR KHQEIRAMRS QLKKIEDLGA AMEEALILDN
KYTEHSTVGL AQQWDQLDQL GMRMQHNLEQ QIQARNTTGV TEEALKEFSM MFKHFDKDKS
GRLNHQEFKS CLRSLGYDLP MVEEGEPDPE FEAILDTVDP NRDGHVSLQE YMAFMISRET
ENVKSSEEIE SAFRALSSEG KPYVTKEELY QNLTREQADY CVSHMKPYVD GKGRELPTAF
DYVEFTRSLF VN
//
ID SPTN1_HUMAN Reviewed; 2472 AA.
AC Q13813; Q13186; Q15324; Q16606; Q59EF1; Q5VXV5; Q5VXV6; Q7Z6M5;
read moreAC Q9P0V0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 3.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=Spectrin alpha chain, non-erythrocytic 1;
DE AltName: Full=Alpha-II spectrin;
DE AltName: Full=Fodrin alpha chain;
DE AltName: Full=Spectrin, non-erythroid alpha subunit;
GN Name=SPTAN1; Synonyms=NEAS, SPTA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-1300.
RX PubMed=2307671;
RA Moon R.T., McMahon A.P.;
RT "Generation of diversity in nonerythroid spectrins. Multiple
RT polypeptides are predicted by sequence analysis of cDNAs encompassing
RT the coding region of human nonerythroid alpha-spectrin.";
RL J. Biol. Chem. 265:4427-4433(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Fetal brain;
RX PubMed=10625438; DOI=10.1021/bi991458k;
RA Cianci C.D., Zhang Z., Pradhan D., Morrow J.S.;
RT "Brain and muscle express a unique alternative transcript of alphaII
RT spectrin.";
RL Biochemistry 38:15721-15730(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Kato S.;
RT "Human full-length cDNA starting with the capped site sequence.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Aorta;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 157-168; 970-981; 990-1002; 1608-1619; 2138-2155
RP AND 2455-2467, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 676-1595 (ISOFORM 1), AND VARIANT
RP THR-1300.
RC TISSUE=Lung;
RX PubMed=3691949;
RA McMahon A.P., Moon R.T.;
RT "Structure and evolution of a non-erythroid spectrin, human alpha-
RT fodrin.";
RL Biochem. Soc. Trans. 15:804-807(1987).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 676-1595 (ISOFORM 1), AND VARIANT
RP THR-1300.
RX PubMed=3038643; DOI=10.1111/j.1432-0436.1987.tb00052.x;
RA McMahon A.P., Giebelhaus D.H., Champion J.E., Bailes J.A., Lacey S.,
RA Carritt B., Henchman S.K., Moon R.T.;
RT "cDNA cloning, sequencing and chromosome mapping of a non-erythroid
RT spectrin, human alpha-fodrin.";
RL Differentiation 34:68-78(1987).
RN [10]
RP ERRATUM.
RA McMahon A.P., Giebelhaus D.H., Champion J.E., Bailes J.A., Lacey S.,
RA Carritt B., Henchman S.K., Moon R.T.;
RL Differentiation 34:241-241(1987).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 811-1529 (ISOFORMS 1/2), AND
RP MUTAGENESIS.
RX PubMed=8993318; DOI=10.1021/bi962034i;
RA Stabach P.R., Cianci C.D., Glantz S.B., Zhang Z., Morrow J.S.;
RT "Site-directed mutagenesis of alpha II spectrin at codon 1175
RT modulates its mu-calpain susceptibility.";
RL Biochemistry 36:57-65(1997).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1073-1349.
RA Murakami N., Speed W.C., Seaman M.I., Zychowski R.L., Wetterberg L.,
RA Pakstis A.J., Kidd J.R., Kidd K.K.;
RT "Association and linkage analyses of the nonerythroid alpha-spectrin
RT (SPTAN1) gene on chromosome 9q34 with a large Swedish kindred.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2059-2433 (ISOFORMS 1/2/3).
RC TISSUE=Fetal liver;
RX PubMed=7607240; DOI=10.1111/j.1432-1033.1995.0658h.x;
RA Lundberg S., Bjoerk J., Loefvenberg L., Backman L.;
RT "Cloning, expression and characterization of two putative calcium-
RT binding sites in human non-erythroid alpha-spectrin.";
RL Eur. J. Biochem. 230:658-665(1995).
RN [14]
RP INTERACTION WITH ACP1.
RX PubMed=11971983; DOI=10.1128/MCB.22.10.3527-3536.2002;
RA Nicolas G., Fournier C.M., Galand C., Malbert-Colas L., Bournier O.,
RA Kroviarski Y., Bourgeois M., Camonis J.H., Dhermy D., Grandchamp B.,
RA Lecomte M.-C.;
RT "Tyrosine phosphorylation regulates alpha II spectrin cleavage by
RT calpain.";
RL Mol. Cell. Biol. 22:3527-3536(2002).
RN [15]
RP INTERACTION WITH EMD.
RX PubMed=15328537; DOI=10.1371/journal.pbio.0020231;
RA Holaska J.M., Kowalski A.K., Wilson K.L.;
RT "Emerin caps the pointed end of actin filaments: evidence for an actin
RT cortical network at the nuclear inner membrane.";
RL PLoS Biol. 2:1354-1362(2004).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1217, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [17]
RP INTERACTION WITH TRPC4.
RX PubMed=18048348; DOI=10.1074/jbc.M709729200;
RA Odell A.F., Van Helden D.F., Scott J.L.;
RT "The spectrin cytoskeleton influences the surface expression and
RT activation of human transient receptor potential channel 4 channels.";
RL J. Biol. Chem. 283:4395-4407(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1041 AND TYR-1176, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-637; LYS-1519; LYS-2052 AND
RP LYS-2421, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-982; SER-999; SER-1217
RP AND SER-1647, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1217, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 1172-1210 IN COMPLEX WITH
RP CALM.
RX PubMed=16945920; DOI=10.1074/jbc.M604613200;
RA Simonovic M., Zhang Z., Cianci C.D., Steitz T.A., Morrow J.S.;
RT "Structure of the calmodulin alphaII-spectrin complex provides insight
RT into the regulation of cell plasticity.";
RL J. Biol. Chem. 281:34333-34340(2006).
RN [27]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-904; SER-1017; TRP-1794 AND
RP ASN-1918.
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.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [28]
RP VARIANTS EIEE5 GLU-2202 DEL AND MET-2303 INS, AND CHARACTERIZATION OF
RP VARIANTS EIEE5 GLU-2202 DEL AND MET-2303 INS.
RX PubMed=20493457; DOI=10.1016/j.ajhg.2010.04.013;
RA Saitsu H., Tohyama J., Kumada T., Egawa K., Hamada K., Okada I.,
RA Mizuguchi T., Osaka H., Miyata R., Furukawa T., Haginoya K.,
RA Hoshino H., Goto T., Hachiya Y., Yamagata T., Saitoh S., Nagai T.,
RA Nishiyama K., Nishimura A., Miyake N., Komada M., Hayashi K.,
RA Hirai S., Ogata K., Kato M., Fukuda A., Matsumoto N.;
RT "Dominant-negative mutations in alpha-II spectrin cause West syndrome
RT with severe cerebral hypomyelination, spastic quadriplegia, and
RT developmental delay.";
RL Am. J. Hum. Genet. 86:881-891(2010).
CC -!- FUNCTION: Fodrin, which seems to be involved in secretion,
CC interacts with calmodulin in a calcium-dependent manner and is
CC thus candidate for the calcium-dependent movement of the
CC cytoskeleton at the membrane.
CC -!- SUBUNIT: Like erythrocyte spectrin, the spectrin-like proteins are
CC capable of forming dimers which can further associate to
CC tetramers. Interacts with isoform 1 of ACP1. Interacts with CALM
CC and EMD. Interacts (via C-terminal spectrin repeats) with TRPC4.
CC Identified in a complex with ACTN4, CASK, IQGAP1, MAGI2, NPHS1 and
CC SPTBN1 (By similarity).
CC -!- INTERACTION:
CC Q9UI08:EVL; NbExp=4; IntAct=EBI-351450, EBI-346653;
CC O15287:FANCG; NbExp=4; IntAct=EBI-351450, EBI-81610;
CC P40692:MLH1; NbExp=7; IntAct=EBI-351450, EBI-744248;
CC Q01082:SPTBN1; NbExp=7; IntAct=EBI-351450, EBI-351561;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm, cell
CC cortex. Note=Expressed along the cell membrane in podocytes and
CC presumptive tubule cells during glomerulogenesis and is expressed
CC along lateral cell margins in tubule cells (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q13813-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13813-2; Sequence=VSP_012270;
CC Name=3;
CC IsoId=Q13813-3; Sequence=VSP_012271;
CC -!- PTM: Phosphorylation of Tyr-1176 decreases sensitivity to cleavage
CC by calpain in vitro (By similarity).
CC -!- DISEASE: Epileptic encephalopathy, early infantile, 5 (EIEE5)
CC [MIM:613477]: A disorder characterized by seizures associated with
CC hypsarrhythmia, profound mental retardation with lack of visual
CC attention and speech development, as well as spastic quadriplegia.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the spectrin family.
CC -!- SIMILARITY: Contains 3 EF-hand domains.
CC -!- SIMILARITY: Contains 1 SH3 domain.
CC -!- SIMILARITY: Contains 23 spectrin repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93097.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
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DR EMBL; J05243; AAA51790.1; -; mRNA.
DR EMBL; U83867; AAB41498.1; -; mRNA.
DR EMBL; AB191262; BAD52438.1; -; mRNA.
DR EMBL; AB209860; BAD93097.1; ALT_INIT; mRNA.
DR EMBL; AL356481; CAH71404.1; -; Genomic_DNA.
DR EMBL; AL356481; CAH71405.1; -; Genomic_DNA.
DR EMBL; BC053521; AAH53521.1; -; mRNA.
DR EMBL; M24773; AAA52468.1; -; mRNA.
DR EMBL; M18627; AAA51702.1; -; mRNA.
DR EMBL; U26396; AAB60364.1; -; mRNA.
DR EMBL; AF148808; AAF26672.1; -; Genomic_DNA.
DR EMBL; X86901; CAA60503.1; -; mRNA.
DR PIR; A35715; A35715.
DR RefSeq; NP_001123910.1; NM_001130438.2.
DR RefSeq; NP_001182461.1; NM_001195532.1.
DR RefSeq; NP_003118.2; NM_003127.3.
DR UniGene; Hs.372331; -.
DR PDB; 2FOT; X-ray; 2.45 A; C=1172-1210.
DR PDB; 3F31; X-ray; 2.30 A; A/B=1-147.
DR PDB; 3FB2; X-ray; 2.30 A; A/B=1337-1544.
DR PDBsum; 2FOT; -.
DR PDBsum; 3F31; -.
DR PDBsum; 3FB2; -.
DR ProteinModelPortal; Q13813; -.
DR SMR; Q13813; 8-2470.
DR DIP; DIP-33141N; -.
DR IntAct; Q13813; 44.
DR MINT; MINT-4999298; -.
DR PhosphoSite; Q13813; -.
DR DMDM; 94730425; -.
DR PaxDb; Q13813; -.
DR PRIDE; Q13813; -.
DR Ensembl; ENST00000372731; ENSP00000361816; ENSG00000197694.
DR Ensembl; ENST00000372739; ENSP00000361824; ENSG00000197694.
DR GeneID; 6709; -.
DR KEGG; hsa:6709; -.
DR UCSC; uc004bvl.4; human.
DR CTD; 6709; -.
DR GeneCards; GC09P131314; -.
DR HGNC; HGNC:11273; SPTAN1.
DR HPA; CAB004581; -.
DR HPA; HPA007927; -.
DR MIM; 182810; gene.
DR MIM; 613477; phenotype.
DR neXtProt; NX_Q13813; -.
DR Orphanet; 1934; Early infantile epileptic encephalopathy.
DR PharmGKB; PA36102; -.
DR eggNOG; COG5126; -.
DR HOVERGEN; HBG059266; -.
DR KO; K06114; -.
DR OrthoDB; EOG7GXP9K; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_127416; Developmental Biology.
DR Reactome; REACT_578; Apoptosis.
DR ChiTaRS; SPTAN1; human.
DR EvolutionaryTrace; Q13813; -.
DR GeneWiki; SPTAN1; -.
DR GenomeRNAi; 6709; -.
DR NextBio; 26162; -.
DR PRO; PR:Q13813; -.
DR ArrayExpress; Q13813; -.
DR Bgee; Q13813; -.
DR Genevestigator; Q13813; -.
DR GO; GO:0032437; C:cuticular plate; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005916; C:fascia adherens; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016328; C:lateral plasma membrane; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0008091; C:spectrin; TAS:ProtInc.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; TAS:ProtInc.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0051693; P:actin filament capping; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
DR Gene3D; 1.10.238.10; -; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR014837; EF-hand_Ca_insen.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR013315; Spectrin_alpha_SH3.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF08726; EFhand_Ca_insen; 1.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF00435; Spectrin; 20.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR01887; SPECTRNALPHA.
DR SMART; SM00054; EFh; 2.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00150; SPEC; 20.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin capping; Actin-binding;
KW Alternative splicing; Calcium; Calmodulin-binding; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease mutation;
KW Epilepsy; Mental retardation; Metal-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; SH3 domain.
FT CHAIN 1 2472 Spectrin alpha chain, non-erythrocytic 1.
FT /FTId=PRO_0000073455.
FT REPEAT 10 42 Spectrin 1.
FT REPEAT 44 147 Spectrin 2.
FT REPEAT 149 253 Spectrin 3.
FT REPEAT 255 359 Spectrin 4.
FT REPEAT 361 465 Spectrin 5.
FT REPEAT 467 571 Spectrin 6.
FT REPEAT 573 676 Spectrin 7.
FT REPEAT 678 782 Spectrin 8.
FT REPEAT 784 888 Spectrin 9.
FT REPEAT 890 955 Spectrin 10.
FT DOMAIN 967 1026 SH3.
FT REPEAT 1062 1089 Spectrin 11.
FT REPEAT 1091 1161 Spectrin 12.
FT REPEAT 1208 1231 Spectrin 13.
FT REPEAT 1233 1337 Spectrin 14.
FT REPEAT 1339 1443 Spectrin 15.
FT REPEAT 1445 1549 Spectrin 16.
FT REPEAT 1551 1656 Spectrin 17.
FT REPEAT 1658 1762 Spectrin 18.
FT REPEAT 1764 1868 Spectrin 19.
FT REPEAT 1870 1974 Spectrin 20.
FT REPEAT 1976 2081 Spectrin 21.
FT REPEAT 2091 2195 Spectrin 22.
FT REPEAT 2205 2310 Spectrin 23.
FT DOMAIN 2323 2358 EF-hand 1.
FT DOMAIN 2366 2401 EF-hand 2.
FT DOMAIN 2404 2439 EF-hand 3.
FT CA_BIND 2336 2347 1 (Potential).
FT CA_BIND 2379 2390 2 (Potential).
FT SITE 1176 1177 Cleavage; by mu-calpain.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 637 637 N6-acetyllysine.
FT MOD_RES 982 982 Phosphoserine.
FT MOD_RES 999 999 Phosphoserine.
FT MOD_RES 1041 1041 Phosphoserine.
FT MOD_RES 1176 1176 Phosphotyrosine.
FT MOD_RES 1217 1217 Phosphoserine.
FT MOD_RES 1519 1519 N6-acetyllysine.
FT MOD_RES 1647 1647 Phosphoserine.
FT MOD_RES 2052 2052 N6-acetyllysine.
FT MOD_RES 2421 2421 N6-acetyllysine.
FT VAR_SEQ 1053 1072 Missing (in isoform 3).
FT /FTId=VSP_012271.
FT VAR_SEQ 1586 1586 Q -> QLSKLL (in isoform 2).
FT /FTId=VSP_012270.
FT VARIANT 385 385 N -> S (in dbSNP:rs2227863).
FT /FTId=VAR_038513.
FT VARIANT 904 904 S -> C (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035454.
FT VARIANT 1017 1017 P -> S (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035455.
FT VARIANT 1300 1300 I -> T (in dbSNP:rs1048236).
FT /FTId=VAR_012227.
FT VARIANT 1794 1794 R -> W (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035456.
FT VARIANT 1918 1918 D -> N (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035457.
FT VARIANT 2202 2202 Missing (in EIEE5; could form a
FT heterodimer with SPTBN1 but the
FT heterodimer is thermally unstable;
FT suggests a dominant negative effect).
FT /FTId=VAR_063886.
FT VARIANT 2303 2303 R -> RM (in EIEE5; could form a
FT heterodimer with SPTBN1 but the
FT heterodimer is thermally unstable;
FT suggests a dominant negative effect).
FT /FTId=VAR_063887.
FT CONFLICT 150 150 K -> N (in Ref. 1; AAA51790).
FT CONFLICT 498 498 S -> F (in Ref. 1; AAA51790).
FT CONFLICT 737 737 I -> V (in Ref. 1; AAA51790, 8; AAA52468
FT and 9; AAA51702).
FT CONFLICT 1595 1595 F -> R (in Ref. 8; AAA52468 and 9;
FT AAA51702).
FT CONFLICT 1625 1625 S -> N (in Ref. 1; AAA51790).
FT CONFLICT 1670 1671 FD -> IA (in Ref. 1; AAA51790).
FT CONFLICT 1918 1918 D -> A (in Ref. 1; AAA51790).
FT CONFLICT 1971 1972 KL -> NV (in Ref. 1; AAA51790 and 2;
FT AAB41498).
FT CONFLICT 2163 2163 A -> R (in Ref. 13; CAA60503).
FT CONFLICT 2347 2348 EF -> DG (in Ref. 1; AAA51790).
FT CONFLICT 2448 2448 Y -> I (in Ref. 1; AAA51790).
FT HELIX 14 25
FT HELIX 30 66
FT STRAND 74 76
FT HELIX 78 94
FT HELIX 97 112
FT HELIX 117 146
FT HELIX 1191 1210
FT HELIX 1337 1362
FT STRAND 1369 1371
FT HELIX 1372 1389
FT HELIX 1392 1407
FT HELIX 1413 1466
FT HELIX 1489 1513
FT HELIX 1519 1539
SQ SEQUENCE 2472 AA; 284539 MW; 4433BF74EFCEFC8A CRC64;
MDPSGVKVLE TAEDIQERRQ QVLDRYHRFK ELSTLRRQKL EDSYRFQFFQ RDAEELEKWI
QEKLQIASDE NYKDPTNLQG KLQKHQAFEA EVQANSGAIV KLDETGNLMI SEGHFASETI
RTRLMELHRQ WELLLEKMRE KGIKLLQAQK LVQYLRECED VMDWINDKEA IVTSEELGQD
LEHVEVLQKK FEEFQTDMAA HEERVNEVNQ FAAKLIQEQH PEEELIKTKQ DEVNAAWQRL
KGLALQRQGK LFGAAEVQRF NRDVDETISW IKEKEQLMAS DDFGRDLASV QALLRKHEGL
ERDLAALEDK VKALCAEADR LQQSHPLSAT QIQVKREELI TNWEQIRTLA AERHARLNDS
YRLQRFLADF RDLTSWVTEM KALINADELA SDVAGAEALL DRHQEHKGEI DAHEDSFKSA
DESGQALLAA GHYASDEVRE KLTVLSEERA ALLELWELRR QQYEQCMDLQ LFYRDTEQVD
NWMSKQEAFL LNEDLGDSLD SVEALLKKHE DFEKSLSAQE EKITALDEFA TKLIQNNHYA
MEDVATRRDA LLSRRNALHE RAMRRRAQLA DSFHLQQFFR DSDELKSWVN EKMKTATDEA
YKDPSNLQGK VQKHQAFEAE LSANQSRIDA LEKAGQKLID VNHYAKDEVA ARMNEVISLW
KKLLEATELK GIKLREANQQ QQFNRNVEDI ELWLYEVEGH LASDDYGKDL TNVQNLQKKH
ALLEADVAAH QDRIDGITIQ ARQFQDAGHF DAENIKKKQE ALVARYEALK EPMVARKQKL
ADSLRLQQLF RDVEDEETWI REKEPIAAST NRGKDLIGVQ NLLKKHQALQ AEIAGHEPRI
KAVTQKGNAM VEEGHFAAED VKAKLHELNQ KWEALKAKAS QRRQDLEDSL QAQQYFADAN
EAESWMREKE PIVGSTDYGK DEDSAEALLK KHEALMSDLS AYGSSIQALR EQAQSCRQQV
APTDDETGKE LVLALYDYQE KSPREVTMKK GDILTLLNST NKDWWKVEVN DRQGFVPAAY
VKKLDPAQSA SRENLLEEQG SIALRQEQID NQTRITKEAG SVSLRMKQVE ELYHSLLELG
EKRKGMLEKS CKKFMLFREA NELQQWINEK EAALTSEEVG ADLEQVEVLQ KKFDDFQKDL
KANESRLKDI NKVAEDLESE GLMAEEVQAV QQQEVYGMMP RDETDSKTAS PWKSARLMVH
TVATFNSIKE LNERWRSLQQ LAEERSQLLG SAHEVQRFHR DADETKEWIE EKNQALNTDN
YGHDLASVQA LQRKHEGFER DLAALGDKVN SLGETAERLI QSHPESAEDL QEKCTELNQA
WSSLGKRADQ RKAKLGDSHD LQRFLSDFRD LMSWINGIRG LVSSDELAKD VTGAEALLER
HQEHRTEIDA RAGTFQAFEQ FGQQLLAHGH YASPEIKQKL DILDQERADL EKAWVQRRMM
LDQCLELQLF HRDCEQAENW MAAREAFLNT EDKGDSLDSV EALIKKHEDF DKAINVQEEK
IAALQAFADQ LIAAGHYAKG DISSRRNEVL DRWRRLKAQM IEKRSKLGES QTLQQFSRDV
DEIEAWISEK LQTASDESYK DPTNIQSKHQ KHQAFEAELH ANADRIRGVI DMGNSLIERG
ACAGSEDAVK ARLAALADQW QFLVQKSAEK SQKLKEANKQ QNFNTGIKDF DFWLSEVEAL
LASEDYGKDL ASVNNLLKKH QLLEADISAH EDRLKDLNSQ ADSLMTSSAF DTSQVKDKRD
TINGRFQKIK SMAASRRAKL NESHRLHQFF RDMDDEESWI KEKKLLVGSE DYGRDLTGVQ
NLRKKHKRLE AELAAHEPAI QGVLDTGKKL SDDNTIGKEE IQQRLAQFVE HWKELKQLAA
ARGQRLEESL EYQQFVANVE EEEAWINEKM TLVASEDYGD TLAAIQGLLK KHEAFETDFT
VHKDRVNDVC TNGQDLIKKN NHHEENISSK MKGLNGKVSD LEKAAAQRKA KLDENSAFLQ
FNWKADVVES WIGEKENSLK TDDYGRDLSS VQTLLTKQET FDAGLQAFQQ EGIANITALK
DQLLAAKHVQ SKAIEARHAS LMKRWSQLLA NSAARKKKLL EAQSHFRKVE DLFLTFAKKA
SAFNSWFENA EEDLTDPVRC NSLEEIKALR EAHDAFRSSL SSAQADFNQL AELDRQIKSF
RVASNPYTWF TMEALEETWR NLQKIIKERE LELQKEQRRQ EENDKLRQEF AQHANAFHQW
IQETRTYLLD GSCMVEESGT LESQLEATKR KHQEIRAMRS QLKKIEDLGA AMEEALILDN
KYTEHSTVGL AQQWDQLDQL GMRMQHNLEQ QIQARNTTGV TEEALKEFSM MFKHFDKDKS
GRLNHQEFKS CLRSLGYDLP MVEEGEPDPE FEAILDTVDP NRDGHVSLQE YMAFMISRET
ENVKSSEEIE SAFRALSSEG KPYVTKEELY QNLTREQADY CVSHMKPYVD GKGRELPTAF
DYVEFTRSLF VN
//
MIM
182810
*RECORD*
*FIELD* NO
182810
*FIELD* TI
*182810 SPECTRIN, ALPHA, NONERYTHROCYTIC 1; SPTAN1
;;SPECTRIN, NONERYTHROID, ALPHA SUBUNIT; NEAS;;
read moreSPECTRIN, ALPHA-II;;
FODRIN, ALPHA
*FIELD* TX
DESCRIPTION
The spectrins, including nonerythrocytic alpha-spectrin-1 (SPTAN1), are
a family of widely-distributed filamentous cytoskeletal proteins with
have a highly conserved 106-amino acid repeat structure. Spectrins are
heterodimers of a constant alpha-chain and variable, tissue-specific
beta-chains. Functions of these proteins include regulation of receptor
binding and actin crosslinking (Leto et al., 1988).
CLONING
McMahon et al. (1987) cloned SPTAN1, which they termed alpha-fodrin,
from a human lung fibroblast cDNA library. From this, they compared the
structure of alpha-spectrin (SPTA1; 182860) and alpha-fodrin with
deductions as to their evolution. The alpha-fodrin protein contains a
106-residue repeating structure, which is homologous with alpha-spectrin
repeats 7 to 15. A 9-kb transcript was identified. A comparison of
nucleic acid and amino acid homologies between alpha-spectrin and
alpha-fodrin of several vertebrate species indicated that human
nonerythroid alpha-fodrin and the common alpha-subunit of erythroid and
nonerythroid cells of nonmammalian vertebrates are closely related (90
to 96% amino acid homology), whereas alpha-fodrin is only distantly
related to the erythroid-specific alpha-spectrin subunit of mammals (55
to 59% amino acid homology). These data suggested that mammalian
erythroid alpha-spectrin evolved by duplication and rapid divergence
from an ancestral alpha-fodrin-like gene.
Leto et al. (1988) used a probe for nonerythroid alpha-spectrin derived
from a rat brain cDNA library to isolate the corresponding gene in man.
They found close similarity of nonerythroid alpha-spectrin sequences in
diverse species.
Cianci et al. (1999) cloned a full-length SPTAN1 cDNA from a human fetal
brain library. The deduced 2,477-residue protein has a predicted
molecular mass of 285 kD. The protein contains 21 spectrin repeat units,
a central SH3 domain, and a C-terminal EF-hand domain. They noted that
the fundamental structural feature of the conserved spectrin repeat unit
is a triple alpha-helical motif. In addition to 11 amino acid
substitutions that differed from the transcript in human lung
fibroblasts and likely represent polymorphisms, the human fetal brain
SPTAN1 also had a 5-residue (15-bp) insertion in repeat unit 15 that
arose from alternative splicing. Examination of several different mouse
tissues demonstrated that the 5-residue insertion was found only in
brain, heart, skeletal muscle, and embryonic tissues, while other
isoforms were more widely distributed. Combined with other insertions,
Cianci et al. (1999) predicted that at least 4, and as many as 8,
different splice forms of the mature protein may be generated.
Zhang et al. (2010) identified 2 novel alternatively spliced Sptan1
transcripts expressed only in the developing rat heart muscle. The
transcripts contained a 21-residue insert in repeat 21 near the C
terminus that was designated alpha-II-cardio+. The unique sequence
occurs within the high affinity nucleation site for binding of
alpha-II-spectrin to beta-spectrin, causing decreased binding, as shown
by functional expression studies. Zhang et al. (2010) noted that 10
Sptan1 transcripts have now been identified in rat heart tissue.
GENE STRUCTURE
Saitsu et al. (2010) stated that the SPTAN1 gene contains 57 exons.
MAPPING
By somatic cell hybrid studies and in situ hybridization, Barton et al.
(1987) and Leto et al. (1988) mapped the SPTAN1 gene to chromosome
9q33-q34.
Birkenmeier et al. (1988) showed that the brain alpha-spectrin gene is
located on the centromeric end of mouse chromosome 2 and is not closely
linked to any known erythroid or neurologic mutation. They symbolized
this gene in the mouse as Spna-2.
GENE FUNCTION
Metral et al. (2009) found that downregulation of SPTAN1 using small
interfering RNA in cultured human melanoma cells resulted in alterations
of the cell shape, with spectrin-depleted cells being much smaller,
rounded, and less spread out. These changes were associated with
disorganization of the actin cytoskeleton and reduction of the basal
stress fibers network. There was also a progressive decrease in cell
adhesion. Spectrin loss inhibited cell proliferation via arrest at cell
cycle phase G1, which was associated with upregulation of the
cyclin-dependent kinase inhibitor p21 (CDKN1A; 116899).
MOLECULAR GENETICS
In 2 unrelated Japanese patients with early infantile epileptic
encephalopathy-5 (EIEE5; 613477), previously reported by Tohyama et al.
(2008), Saitsu et al. (2010) identified 2 different de novo heterozygous
mutations in the SPTAN1 gene (182810.0001 and 182810.0002,
respectively). In vitro functional expression studies suggested a
dominant-negative effect of the mutations on spectrin heterodimer
stability, as well as perturbation of the axon initial segment.
In an 11-year-old French Canadian boy with EIEE5, Hamdan et al. (2012)
identified a de novo heterozygous mutation in the SPTAN1 gene
(182810.0003). In vitro expression of the mutation in primary mouse
cortical neurons caused formation of spectrin aggregates in about 20% of
cells.
ANIMAL MODEL
From a genetic screen of zebrafish mutants, Voas et al. (2007)
identified a homozygous Sptan1-null mutant that had reduced the numbers
of nodal sodium-channel clusters in myelinated axons of the peripheral
and central nervous systems. The defects were apparent at 5 days
post-fertilization, and the zebrafish died by 15 days post-fertilization
due to failure to inflate their swim bladders. Ultrastructural studies
showed that myelin formed in the posterior lateral line nerve and in the
ventral spinal cord in the mutant zebrafish, but that the node was
abnormally long. Sptan1 was found to function autonomously in neurons
and was enriched at nodes and paranodes in wildtype zebrafish. The
results provided functional evidence that Sptan1 in the axonal
cytoskeleton is essential for stabilizing nascent sodium-channel
clusters and assembling the mature node of Ranvier.
*FIELD* AV
.0001
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 5
SPTAN1, 3-BP DEL, 6619GAG
In a Japanese girl with early infantile epileptic encephalopathy-5
(EIEE5; 613477), Saitsu et al. (2010) identified a de novo heterozygous
3-bp in-frame deletion (6619delGAG) in exon 50 of the SPTAN1 gene,
resulting in a deletion of glu2207 in the continuous helix region
between the last 2 spectrin repeats. The deletion was not found in 500
control Japanese alleles. The patient had onset of intractable seizures
at age 3 months and showed profound mental retardation, poor visual
attention, lack of speech development, and spastic quadriplegia. Brain
MRI showed diffuse hypomyelination and widespread brain atrophy affected
the cortex, corpus callosum, brainstem, and cerebellum. In vitro
functional expression studies showed that the mutant protein could form
a heterodimer with spectrin beta-II (SPTBN1; 182790), but that the
heterodimer was thermally instable. Transient expression of the mutant
SPTAN1 protein in mouse cortical neurons showed that the mutant protein
formed aggregates with SPTNB1 and SPTBN2 (604985) in cell bodies and
axons. Further studies showed that the aggregates disturbed the normal
clustering of ankyrin-G (ANK3; 600465) at the axon initiation segment,
and appeared to cause a depolarizing shift in the action potential. The
overall findings suggested a dominant-negative effect.
.0002
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 5
SPTAN1, 6-BP DUP, NT6923
In a Japanese boy with early infantile epileptic encephalopathy-5
(EIEE5; 613477), Saitsu et al. (2010) identified a de novo heterozygous
6-bp in-frame duplication (nucleotides 6923-6928) in exon 53 of the
SPTAN1 gene, resulting in the duplication of arg2308 and met2309 within
the last spectrin repeat. The duplication was not found in 500 control
Japanese alleles. The patient had onset of intractable seizures at age 3
months and showed profound mental retardation, poor visual attention,
lack of speech development, and spastic quadriplegia. Brain MRI showed
diffuse hypomyelination and widespread brain atrophy affected the
cortex, corpus callosum, brainstem, and cerebellum. In vitro functional
expression studies showed that the mutant protein could form a
heterodimer with SPTBN1, but that the heterodimer was thermally
instable. Transient expression of the mutant SPTAN1 protein in mouse
cortical neurons showed that the mutant protein formed aggregates with
SPTNB1 and SPTBN2 in cell bodies and axons. Further studies showed that
the aggregates disturbed the normal clustering of ankyrin-G at the axon
initiation segment, and appeared to cause a depolarizing shift in the
action potential. The findings suggested a dominant-negative effect.
.0003
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 5
SPTAN1, 3-BP DEL, NT6605
In an 11-year-old French Canadian boy with EIEE5 (613477), Hamdan et al.
(2012) identified a de novo heterozygous 3-bp in-frame deletion
(6605_6607) in the SPTAN1 gene, resulting in the deletion of amino acid
gln2202 in the C-terminal domain required for alpha/beta spectrin
subunit heterodimer formation. The patient had severe intellectual
disability. Although he did not present with early infantile spasms, he
had febrile seizures at age 16 months and later developed mild
generalized epilepsy. Brain MRI showed severe atrophy of the cerebellum
and mild atrophy of the brainstem, without any hypomyelination or other
structural defects. Overall, the phenotype in this patient was less
severe than that of the patients reported by Saitsu et al. (2010). In
vitro expression of the mutation in primary mouse cortical neurons
caused formation of spectrin aggregates in about 20% of cells. In
contrast, expression of the mutation in mouse neuroblastoma (N2A) cells
showed localization of the protein at the cell periphery without the
formation of aggregates, similar to wildtype.
.0004
VARIANT OF UNKNOWN SIGNIFICANCE
SPTAN1, ARG566PRO
This variant is classified as a variant of unknown significance because
its contribution to nonsyndromic intellectual disability has not been
confirmed.
In a 9-year-old French Canadian boy with nonsyndromic mild intellectual
disability, Hamdan et al. (2012) identified a de novo heterozygous
1697G-C transversion in the SPTAN1 gene, resulting in an arg566-to-pro
(R566P) substitution in a well-conserved residue in the N-terminal
domain. The mutation was not found in 190 French Canadian controls. The
patient also had attention deficit with hyperactivity, but no dysmorphic
features and no brain abnormalities on CT scan. The patient had a sister
with nonsyndromic intellectual disability who did not carry the R566P
mutation. In vitro expression of the R566P mutation in mouse
neuroblastoma (N2A) cells induced large aggregates in 86% of cells.
These mutant alpha-II spectrin aggregates colocalized with endogenous
beta-II-spectrin subunits, but not with beta-III-spectrin subunits. In
contrast, expression of R566P in primary mouse cortical neurons did not
result in significant aggregate formation. Hamdan et al. (2012)
concluded that the R566P mutation may not be responsible for the
patient's phenotype.
*FIELD* RF
1. Barton, D. E.; Yang-Feng, T. L.; Leto, T.; Marchesi, V.; Francke,
U.: NEAS encoding a non-erythroid alpha-spectrin is on chromosome
9, region q33-q34 and on mouse chromosome 2. (Abstract) Cytogenet.
Cell Genet. 46: 578, 1987.
2. Birkenmeier, C. S.; McFarland-Starr, E. C.; Barker, J. E.: Chromosomal
location of three spectrin genes: relationship to the inherited hemolytic
anemias of mouse and man. Proc. Nat. Acad. Sci. 85: 8121-8125, 1988.
3. Cianci, C. D.; Zhang, Z.; Pradhan, D.; Morrow, J. S.: Brain and
muscle express a unique alternative transcript of alpha-II spectrin. Biochemistry 38:
15721-15730, 1999.
4. Hamdan, F. F.; Saitsu, H.; Nishiyama, K.; Gauthier, J.; Dobrzeniecka,
S.; Spiegelman, D.; Lacaille, J.-C.; Decarie, J.-C.; Matsumoto, N.;
Rouleau, G. A.; Michaud, J. L.: Identification of a novel in-frame
de novo mutation in SPTAN1 in intellectual disability and pontocerebellar
atrophy. Europ. J. Hum. Genet. 20: 796-800, 2012.
5. Leto, T. L.; Fortugno-Erikson, D.; Barton, D.; Yang-Feng, T. L.;
Francke, U.; Harris, A. S.; Morrow, J. S.; Marchesi, V. T.; Benz,
E. J., Jr.: Comparison of nonerythroid alpha-spectrin genes reveals
strict homology among diverse species. Molec. Cell. Biol. 8: 1-9,
1988.
6. McMahon, A. P.; Giebelhaus, D. H.; Champion, J. E.; Bailes, J.
A.; Lacey, S.; Carritt, B.; Henchman, S. K.; Moon, R. T.: cDNA cloning,
sequencing and chromosome mapping of a non-erythroid spectrin, human
alpha-fodrin. Differentiation 34: 68-78, 1987. Note: Erratum: Ibid.
34: 241 only, 1987.
7. Metral, S.; Machnicka, B.; Bigot, S.; Colin, Y.; Dhermy, D.; Lecomte,
M.-C.: Alpha-II-spectrin is critical for cell adhesion and cell cycle. J.
Biol. Chem. 284: 2409-2418, 2009.
8. Saitsu, H.; Tohyama, J.; Kumada, T.; Egawa, K.; Hamada, K.; Okada,
I.; Mizuguchi, T.; Osaka, H.; Miyata, R.; Furukawa, T.; Haginoya,
K.; Hoshino, H.; and 15 others: Dominant-negative mutations in
alpha-II spectrin cause West syndrome with severe cerebral hypomyelination,
spastic quadriplegia, and developmental delay. Am. J. Hum. Genet. 86:
881-891, 2010.
9. Tohyama, J.; Akasaka, N.; Osaka, H.; Maegaki, Y.; Kato, M.; Saito,
N.; Yamashita, S.; Ohno, K.: Early onset West syndrome with cerebral
hypomyelination and reduced cerebral white matter. Brain Dev. 30:
349-355, 2008.
10. Voas, M. G.; Lyons, D. A.; Naylor, S. G.; Arana, N.; Rasband,
M. N.; Talbot, W. S.: Alpha-II-spectrin is essential for assembly
of the nodes of Ranvier in myelinated axons. Curr. Biol. 17: 562-568,
2007.
11. Zhang, Y.; Resneck, W. G.; Lee, P. C.; Randall, W. R.; Bloch,
R. J.; Ursitti, J. A.: Characterization and expression of a heart-selective
alternatively spliced variant of alpha II-spectrin, cardi+, during
development in the rat. J. Molec. Cell Cardiol. 48: 1050-1059, 2010.
*FIELD* CN
Cassandra L. Kniffin - updated: 7/11/2012
Cassandra L. Kniffin - updated: 8/16/2010
Cassandra L. Kniffin - updated: 7/12/2010
*FIELD* CD
Victor A. McKusick: 8/31/1987
*FIELD* ED
carol: 07/12/2012
terry: 7/12/2012
ckniffin: 7/11/2012
wwang: 8/19/2010
ckniffin: 8/16/2010
carol: 7/30/2010
wwang: 7/13/2010
ckniffin: 7/12/2010
mgross: 3/18/2004
carol: 3/22/1999
terry: 5/22/1996
warfield: 3/29/1994
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
root: 12/19/1988
root: 11/21/1988
*RECORD*
*FIELD* NO
182810
*FIELD* TI
*182810 SPECTRIN, ALPHA, NONERYTHROCYTIC 1; SPTAN1
;;SPECTRIN, NONERYTHROID, ALPHA SUBUNIT; NEAS;;
read moreSPECTRIN, ALPHA-II;;
FODRIN, ALPHA
*FIELD* TX
DESCRIPTION
The spectrins, including nonerythrocytic alpha-spectrin-1 (SPTAN1), are
a family of widely-distributed filamentous cytoskeletal proteins with
have a highly conserved 106-amino acid repeat structure. Spectrins are
heterodimers of a constant alpha-chain and variable, tissue-specific
beta-chains. Functions of these proteins include regulation of receptor
binding and actin crosslinking (Leto et al., 1988).
CLONING
McMahon et al. (1987) cloned SPTAN1, which they termed alpha-fodrin,
from a human lung fibroblast cDNA library. From this, they compared the
structure of alpha-spectrin (SPTA1; 182860) and alpha-fodrin with
deductions as to their evolution. The alpha-fodrin protein contains a
106-residue repeating structure, which is homologous with alpha-spectrin
repeats 7 to 15. A 9-kb transcript was identified. A comparison of
nucleic acid and amino acid homologies between alpha-spectrin and
alpha-fodrin of several vertebrate species indicated that human
nonerythroid alpha-fodrin and the common alpha-subunit of erythroid and
nonerythroid cells of nonmammalian vertebrates are closely related (90
to 96% amino acid homology), whereas alpha-fodrin is only distantly
related to the erythroid-specific alpha-spectrin subunit of mammals (55
to 59% amino acid homology). These data suggested that mammalian
erythroid alpha-spectrin evolved by duplication and rapid divergence
from an ancestral alpha-fodrin-like gene.
Leto et al. (1988) used a probe for nonerythroid alpha-spectrin derived
from a rat brain cDNA library to isolate the corresponding gene in man.
They found close similarity of nonerythroid alpha-spectrin sequences in
diverse species.
Cianci et al. (1999) cloned a full-length SPTAN1 cDNA from a human fetal
brain library. The deduced 2,477-residue protein has a predicted
molecular mass of 285 kD. The protein contains 21 spectrin repeat units,
a central SH3 domain, and a C-terminal EF-hand domain. They noted that
the fundamental structural feature of the conserved spectrin repeat unit
is a triple alpha-helical motif. In addition to 11 amino acid
substitutions that differed from the transcript in human lung
fibroblasts and likely represent polymorphisms, the human fetal brain
SPTAN1 also had a 5-residue (15-bp) insertion in repeat unit 15 that
arose from alternative splicing. Examination of several different mouse
tissues demonstrated that the 5-residue insertion was found only in
brain, heart, skeletal muscle, and embryonic tissues, while other
isoforms were more widely distributed. Combined with other insertions,
Cianci et al. (1999) predicted that at least 4, and as many as 8,
different splice forms of the mature protein may be generated.
Zhang et al. (2010) identified 2 novel alternatively spliced Sptan1
transcripts expressed only in the developing rat heart muscle. The
transcripts contained a 21-residue insert in repeat 21 near the C
terminus that was designated alpha-II-cardio+. The unique sequence
occurs within the high affinity nucleation site for binding of
alpha-II-spectrin to beta-spectrin, causing decreased binding, as shown
by functional expression studies. Zhang et al. (2010) noted that 10
Sptan1 transcripts have now been identified in rat heart tissue.
GENE STRUCTURE
Saitsu et al. (2010) stated that the SPTAN1 gene contains 57 exons.
MAPPING
By somatic cell hybrid studies and in situ hybridization, Barton et al.
(1987) and Leto et al. (1988) mapped the SPTAN1 gene to chromosome
9q33-q34.
Birkenmeier et al. (1988) showed that the brain alpha-spectrin gene is
located on the centromeric end of mouse chromosome 2 and is not closely
linked to any known erythroid or neurologic mutation. They symbolized
this gene in the mouse as Spna-2.
GENE FUNCTION
Metral et al. (2009) found that downregulation of SPTAN1 using small
interfering RNA in cultured human melanoma cells resulted in alterations
of the cell shape, with spectrin-depleted cells being much smaller,
rounded, and less spread out. These changes were associated with
disorganization of the actin cytoskeleton and reduction of the basal
stress fibers network. There was also a progressive decrease in cell
adhesion. Spectrin loss inhibited cell proliferation via arrest at cell
cycle phase G1, which was associated with upregulation of the
cyclin-dependent kinase inhibitor p21 (CDKN1A; 116899).
MOLECULAR GENETICS
In 2 unrelated Japanese patients with early infantile epileptic
encephalopathy-5 (EIEE5; 613477), previously reported by Tohyama et al.
(2008), Saitsu et al. (2010) identified 2 different de novo heterozygous
mutations in the SPTAN1 gene (182810.0001 and 182810.0002,
respectively). In vitro functional expression studies suggested a
dominant-negative effect of the mutations on spectrin heterodimer
stability, as well as perturbation of the axon initial segment.
In an 11-year-old French Canadian boy with EIEE5, Hamdan et al. (2012)
identified a de novo heterozygous mutation in the SPTAN1 gene
(182810.0003). In vitro expression of the mutation in primary mouse
cortical neurons caused formation of spectrin aggregates in about 20% of
cells.
ANIMAL MODEL
From a genetic screen of zebrafish mutants, Voas et al. (2007)
identified a homozygous Sptan1-null mutant that had reduced the numbers
of nodal sodium-channel clusters in myelinated axons of the peripheral
and central nervous systems. The defects were apparent at 5 days
post-fertilization, and the zebrafish died by 15 days post-fertilization
due to failure to inflate their swim bladders. Ultrastructural studies
showed that myelin formed in the posterior lateral line nerve and in the
ventral spinal cord in the mutant zebrafish, but that the node was
abnormally long. Sptan1 was found to function autonomously in neurons
and was enriched at nodes and paranodes in wildtype zebrafish. The
results provided functional evidence that Sptan1 in the axonal
cytoskeleton is essential for stabilizing nascent sodium-channel
clusters and assembling the mature node of Ranvier.
*FIELD* AV
.0001
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 5
SPTAN1, 3-BP DEL, 6619GAG
In a Japanese girl with early infantile epileptic encephalopathy-5
(EIEE5; 613477), Saitsu et al. (2010) identified a de novo heterozygous
3-bp in-frame deletion (6619delGAG) in exon 50 of the SPTAN1 gene,
resulting in a deletion of glu2207 in the continuous helix region
between the last 2 spectrin repeats. The deletion was not found in 500
control Japanese alleles. The patient had onset of intractable seizures
at age 3 months and showed profound mental retardation, poor visual
attention, lack of speech development, and spastic quadriplegia. Brain
MRI showed diffuse hypomyelination and widespread brain atrophy affected
the cortex, corpus callosum, brainstem, and cerebellum. In vitro
functional expression studies showed that the mutant protein could form
a heterodimer with spectrin beta-II (SPTBN1; 182790), but that the
heterodimer was thermally instable. Transient expression of the mutant
SPTAN1 protein in mouse cortical neurons showed that the mutant protein
formed aggregates with SPTNB1 and SPTBN2 (604985) in cell bodies and
axons. Further studies showed that the aggregates disturbed the normal
clustering of ankyrin-G (ANK3; 600465) at the axon initiation segment,
and appeared to cause a depolarizing shift in the action potential. The
overall findings suggested a dominant-negative effect.
.0002
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 5
SPTAN1, 6-BP DUP, NT6923
In a Japanese boy with early infantile epileptic encephalopathy-5
(EIEE5; 613477), Saitsu et al. (2010) identified a de novo heterozygous
6-bp in-frame duplication (nucleotides 6923-6928) in exon 53 of the
SPTAN1 gene, resulting in the duplication of arg2308 and met2309 within
the last spectrin repeat. The duplication was not found in 500 control
Japanese alleles. The patient had onset of intractable seizures at age 3
months and showed profound mental retardation, poor visual attention,
lack of speech development, and spastic quadriplegia. Brain MRI showed
diffuse hypomyelination and widespread brain atrophy affected the
cortex, corpus callosum, brainstem, and cerebellum. In vitro functional
expression studies showed that the mutant protein could form a
heterodimer with SPTBN1, but that the heterodimer was thermally
instable. Transient expression of the mutant SPTAN1 protein in mouse
cortical neurons showed that the mutant protein formed aggregates with
SPTNB1 and SPTBN2 in cell bodies and axons. Further studies showed that
the aggregates disturbed the normal clustering of ankyrin-G at the axon
initiation segment, and appeared to cause a depolarizing shift in the
action potential. The findings suggested a dominant-negative effect.
.0003
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 5
SPTAN1, 3-BP DEL, NT6605
In an 11-year-old French Canadian boy with EIEE5 (613477), Hamdan et al.
(2012) identified a de novo heterozygous 3-bp in-frame deletion
(6605_6607) in the SPTAN1 gene, resulting in the deletion of amino acid
gln2202 in the C-terminal domain required for alpha/beta spectrin
subunit heterodimer formation. The patient had severe intellectual
disability. Although he did not present with early infantile spasms, he
had febrile seizures at age 16 months and later developed mild
generalized epilepsy. Brain MRI showed severe atrophy of the cerebellum
and mild atrophy of the brainstem, without any hypomyelination or other
structural defects. Overall, the phenotype in this patient was less
severe than that of the patients reported by Saitsu et al. (2010). In
vitro expression of the mutation in primary mouse cortical neurons
caused formation of spectrin aggregates in about 20% of cells. In
contrast, expression of the mutation in mouse neuroblastoma (N2A) cells
showed localization of the protein at the cell periphery without the
formation of aggregates, similar to wildtype.
.0004
VARIANT OF UNKNOWN SIGNIFICANCE
SPTAN1, ARG566PRO
This variant is classified as a variant of unknown significance because
its contribution to nonsyndromic intellectual disability has not been
confirmed.
In a 9-year-old French Canadian boy with nonsyndromic mild intellectual
disability, Hamdan et al. (2012) identified a de novo heterozygous
1697G-C transversion in the SPTAN1 gene, resulting in an arg566-to-pro
(R566P) substitution in a well-conserved residue in the N-terminal
domain. The mutation was not found in 190 French Canadian controls. The
patient also had attention deficit with hyperactivity, but no dysmorphic
features and no brain abnormalities on CT scan. The patient had a sister
with nonsyndromic intellectual disability who did not carry the R566P
mutation. In vitro expression of the R566P mutation in mouse
neuroblastoma (N2A) cells induced large aggregates in 86% of cells.
These mutant alpha-II spectrin aggregates colocalized with endogenous
beta-II-spectrin subunits, but not with beta-III-spectrin subunits. In
contrast, expression of R566P in primary mouse cortical neurons did not
result in significant aggregate formation. Hamdan et al. (2012)
concluded that the R566P mutation may not be responsible for the
patient's phenotype.
*FIELD* RF
1. Barton, D. E.; Yang-Feng, T. L.; Leto, T.; Marchesi, V.; Francke,
U.: NEAS encoding a non-erythroid alpha-spectrin is on chromosome
9, region q33-q34 and on mouse chromosome 2. (Abstract) Cytogenet.
Cell Genet. 46: 578, 1987.
2. Birkenmeier, C. S.; McFarland-Starr, E. C.; Barker, J. E.: Chromosomal
location of three spectrin genes: relationship to the inherited hemolytic
anemias of mouse and man. Proc. Nat. Acad. Sci. 85: 8121-8125, 1988.
3. Cianci, C. D.; Zhang, Z.; Pradhan, D.; Morrow, J. S.: Brain and
muscle express a unique alternative transcript of alpha-II spectrin. Biochemistry 38:
15721-15730, 1999.
4. Hamdan, F. F.; Saitsu, H.; Nishiyama, K.; Gauthier, J.; Dobrzeniecka,
S.; Spiegelman, D.; Lacaille, J.-C.; Decarie, J.-C.; Matsumoto, N.;
Rouleau, G. A.; Michaud, J. L.: Identification of a novel in-frame
de novo mutation in SPTAN1 in intellectual disability and pontocerebellar
atrophy. Europ. J. Hum. Genet. 20: 796-800, 2012.
5. Leto, T. L.; Fortugno-Erikson, D.; Barton, D.; Yang-Feng, T. L.;
Francke, U.; Harris, A. S.; Morrow, J. S.; Marchesi, V. T.; Benz,
E. J., Jr.: Comparison of nonerythroid alpha-spectrin genes reveals
strict homology among diverse species. Molec. Cell. Biol. 8: 1-9,
1988.
6. McMahon, A. P.; Giebelhaus, D. H.; Champion, J. E.; Bailes, J.
A.; Lacey, S.; Carritt, B.; Henchman, S. K.; Moon, R. T.: cDNA cloning,
sequencing and chromosome mapping of a non-erythroid spectrin, human
alpha-fodrin. Differentiation 34: 68-78, 1987. Note: Erratum: Ibid.
34: 241 only, 1987.
7. Metral, S.; Machnicka, B.; Bigot, S.; Colin, Y.; Dhermy, D.; Lecomte,
M.-C.: Alpha-II-spectrin is critical for cell adhesion and cell cycle. J.
Biol. Chem. 284: 2409-2418, 2009.
8. Saitsu, H.; Tohyama, J.; Kumada, T.; Egawa, K.; Hamada, K.; Okada,
I.; Mizuguchi, T.; Osaka, H.; Miyata, R.; Furukawa, T.; Haginoya,
K.; Hoshino, H.; and 15 others: Dominant-negative mutations in
alpha-II spectrin cause West syndrome with severe cerebral hypomyelination,
spastic quadriplegia, and developmental delay. Am. J. Hum. Genet. 86:
881-891, 2010.
9. Tohyama, J.; Akasaka, N.; Osaka, H.; Maegaki, Y.; Kato, M.; Saito,
N.; Yamashita, S.; Ohno, K.: Early onset West syndrome with cerebral
hypomyelination and reduced cerebral white matter. Brain Dev. 30:
349-355, 2008.
10. Voas, M. G.; Lyons, D. A.; Naylor, S. G.; Arana, N.; Rasband,
M. N.; Talbot, W. S.: Alpha-II-spectrin is essential for assembly
of the nodes of Ranvier in myelinated axons. Curr. Biol. 17: 562-568,
2007.
11. Zhang, Y.; Resneck, W. G.; Lee, P. C.; Randall, W. R.; Bloch,
R. J.; Ursitti, J. A.: Characterization and expression of a heart-selective
alternatively spliced variant of alpha II-spectrin, cardi+, during
development in the rat. J. Molec. Cell Cardiol. 48: 1050-1059, 2010.
*FIELD* CN
Cassandra L. Kniffin - updated: 7/11/2012
Cassandra L. Kniffin - updated: 8/16/2010
Cassandra L. Kniffin - updated: 7/12/2010
*FIELD* CD
Victor A. McKusick: 8/31/1987
*FIELD* ED
carol: 07/12/2012
terry: 7/12/2012
ckniffin: 7/11/2012
wwang: 8/19/2010
ckniffin: 8/16/2010
carol: 7/30/2010
wwang: 7/13/2010
ckniffin: 7/12/2010
mgross: 3/18/2004
carol: 3/22/1999
terry: 5/22/1996
warfield: 3/29/1994
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
root: 12/19/1988
root: 11/21/1988
MIM
613477
*RECORD*
*FIELD* NO
613477
*FIELD* TI
#613477 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 5; EIEE5
*FIELD* TX
A number sign (#) is used with this entry because early infantile
read moreepileptic encephalopathy-5 (EIEE5) is caused by heterozygous mutation in
the SPTAN1 gene (182810) on chromosome 9q33-q34.
For a general phenotypic description and a discussion of genetic
heterogeneity of EIEE, see EIEE1 (308350).
CLINICAL FEATURES
Tohyama et al. (2008) reported 2 unrelated Japanese infants, a girl and
a boy, with early infantile epileptic encephalopathy. Both had onset of
intractable seizures associated with hypsarrhythmia at age 3 months.
Both had profound mental retardation with lack of visual attention and
speech development, as well as spastic quadriplegia. Brain MRI showed
diffuse hypomyelination and widespread brain atrophy affecting the
cortex, corpus callosum, brainstem, and cerebellum. Progressive
microcephaly was also observed.
Hamdan et al. (2012) reported an 11-year-old French Canadian boy with
EIEE5 and severe intellectual disability. Although he did not present
with early infantile spasms, he had febrile seizures at age 16 months
and later developed mild generalized epilepsy. He could not walk or
speak, but did understand a few commands and was able to communicate
with a few signs. He had hypotonia, but no microcephaly or dysmorphic
features. Brain MRI showed severe atrophy of the cerebellum and mild
atrophy of the brainstem, without any hypomyelination or other
structural defects. Overall, the phenotype in this patient was less
severe than that of the patients reported by Saitsu et al. (2010).
MOLECULAR GENETICS
In 2 unrelated Japanese patients with EIEE5, previously reported by
Tohyama et al. (2008), Saitsu et al. (2010) identified different de novo
heterozygous mutations (182810.0001-182810.0002) in the SPTAN1 gene. In
vitro functional expression studies suggested a dominant-negative effect
of the mutations on spectrin heterodimer stability, as well as
perturbation of the axon initial segment. Another unrelated patient with
a similar disorder, previously reported by Tohyama et al. (2008) and
Saitsu et al. (2008), was found to have a 2.25-Mb microdeletion
encompassing both the STXBP1 (602926) and SPTAN1 genes. This patient had
a slightly milder phenotype with well-controlled seizures and only
mildly decreased white matter with no structural brain anomalies.
Although she had hypomyelination at 12 months, she showed progression of
myelination at age 4 years. Saitsu et al. (2010) hypothesized that this
patient's phenotype was due more to haploinsufficiency of STXBP1 (see
EIEE4; 612164), but that haploinsufficiency of SPTAN1 may have had some
effect on myelination.
In an 11-year-old French Canadian boy with EIEE5, Hamdan et al. (2012)
identified a de novo heterozygous mutation in the SPTAN1 gene
(182810.0003). In vitro expression of the mutation in primary mouse
cortical neurons caused formation of spectrin aggregates in about 20% of
cells.
*FIELD* RF
1. Hamdan, F. F.; Saitsu, H.; Nishiyama, K.; Gauthier, J.; Dobrzeniecka,
S.; Spiegelman, D.; Lacaille, J.-C.; Decarie, J.-C.; Matsumoto, N.;
Rouleau, G. A.; Michaud, J. L.: Identification of a novel in-frame
de novo mutation in SPTAN1 in intellectual disability and pontocerebellar
atrophy. Europ. J. Hum. Genet. 20: 796-800, 2012.
2. Saitsu, H.; Kato, M.; Mizuguchi, T.; Hamada, K.; Osaka, H.; Tohyama,
J.; Uruno, K.; Kumada, S.; Nishiyama, K.; Nishimura, A.; Okada, I.;
Yoshimura, Y.; Hirai, S.; Kumada, T.; Hayasaka, K.; Fukuda, A.; Ogata,
K.; Matsumoto, N.: De novo mutations in the gene encoding STXBP1
(MUNC18-1) cause early infantile epileptic encephalopathy. Nature
Genet. 40: 782-788, 2008.
3. Saitsu, H.; Tohyama, J.; Kumada, T.; Egawa, K.; Hamada, K.; Okada,
I.; Mizuguchi, T.; Osaka, H.; Miyata, R.; Furukawa, T.; Haginoya,
K.; Hoshino, H.; and 15 others: Dominant-negative mutations in
alpha-II spectrin cause West syndrome with severe cerebral hypomyelination,
spastic quadriplegia, and developmental delay. Am. J. Hum. Genet. 86:
881-891, 2010.
4. Tohyama, J.; Akasaka, N.; Osaka, H.; Maegaki, Y.; Kato, M.; Saito,
N.; Yamashita, S.; Ohno, K.: Early onset West syndrome with cerebral
hypomyelination and reduced cerebral white matter. Brain Dev. 30:
349-355, 2008.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Head];
Microcephaly, progressive (in 2 of 3 patients);
[Eyes];
No visual attention
NEUROLOGIC:
[Central nervous system];
Seizures, tonic, intractable;
Mental retardation, severe to profound;
Lack of speech development;
Lack of visual attention;
Hypsarrhythmia;
Spastic quadriplegia;
Lack of independent ambulation;
Hypotonia;
Diffuse hypomyelination;
Widespread brain atrophy;
Thin corpus callosum;
Brainstem atrophy;
Cerebellar atrophy
MISCELLANEOUS:
Onset in infancy;
Variable severity;
Three unrelated patients have been reported (last curated July 2012)
MOLECULAR BASIS:
Caused by mutation in the nonerythrocytic alpha-spectrin 1 gene (SPTAN1,
182810.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 7/11/2012
*FIELD* CD
Cassandra L. Kniffin: 7/12/2010
*FIELD* ED
joanna: 11/30/2012
ckniffin: 7/11/2012
joanna: 10/21/2011
ckniffin: 7/12/2010
*FIELD* CN
Cassandra L. Kniffin - updated: 7/11/2012
*FIELD* CD
Cassandra L. Kniffin: 7/12/2010
*FIELD* ED
carol: 07/12/2012
terry: 7/12/2012
ckniffin: 7/11/2012
carol: 2/11/2011
carol: 7/15/2010
wwang: 7/13/2010
ckniffin: 7/12/2010
*RECORD*
*FIELD* NO
613477
*FIELD* TI
#613477 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 5; EIEE5
*FIELD* TX
A number sign (#) is used with this entry because early infantile
read moreepileptic encephalopathy-5 (EIEE5) is caused by heterozygous mutation in
the SPTAN1 gene (182810) on chromosome 9q33-q34.
For a general phenotypic description and a discussion of genetic
heterogeneity of EIEE, see EIEE1 (308350).
CLINICAL FEATURES
Tohyama et al. (2008) reported 2 unrelated Japanese infants, a girl and
a boy, with early infantile epileptic encephalopathy. Both had onset of
intractable seizures associated with hypsarrhythmia at age 3 months.
Both had profound mental retardation with lack of visual attention and
speech development, as well as spastic quadriplegia. Brain MRI showed
diffuse hypomyelination and widespread brain atrophy affecting the
cortex, corpus callosum, brainstem, and cerebellum. Progressive
microcephaly was also observed.
Hamdan et al. (2012) reported an 11-year-old French Canadian boy with
EIEE5 and severe intellectual disability. Although he did not present
with early infantile spasms, he had febrile seizures at age 16 months
and later developed mild generalized epilepsy. He could not walk or
speak, but did understand a few commands and was able to communicate
with a few signs. He had hypotonia, but no microcephaly or dysmorphic
features. Brain MRI showed severe atrophy of the cerebellum and mild
atrophy of the brainstem, without any hypomyelination or other
structural defects. Overall, the phenotype in this patient was less
severe than that of the patients reported by Saitsu et al. (2010).
MOLECULAR GENETICS
In 2 unrelated Japanese patients with EIEE5, previously reported by
Tohyama et al. (2008), Saitsu et al. (2010) identified different de novo
heterozygous mutations (182810.0001-182810.0002) in the SPTAN1 gene. In
vitro functional expression studies suggested a dominant-negative effect
of the mutations on spectrin heterodimer stability, as well as
perturbation of the axon initial segment. Another unrelated patient with
a similar disorder, previously reported by Tohyama et al. (2008) and
Saitsu et al. (2008), was found to have a 2.25-Mb microdeletion
encompassing both the STXBP1 (602926) and SPTAN1 genes. This patient had
a slightly milder phenotype with well-controlled seizures and only
mildly decreased white matter with no structural brain anomalies.
Although she had hypomyelination at 12 months, she showed progression of
myelination at age 4 years. Saitsu et al. (2010) hypothesized that this
patient's phenotype was due more to haploinsufficiency of STXBP1 (see
EIEE4; 612164), but that haploinsufficiency of SPTAN1 may have had some
effect on myelination.
In an 11-year-old French Canadian boy with EIEE5, Hamdan et al. (2012)
identified a de novo heterozygous mutation in the SPTAN1 gene
(182810.0003). In vitro expression of the mutation in primary mouse
cortical neurons caused formation of spectrin aggregates in about 20% of
cells.
*FIELD* RF
1. Hamdan, F. F.; Saitsu, H.; Nishiyama, K.; Gauthier, J.; Dobrzeniecka,
S.; Spiegelman, D.; Lacaille, J.-C.; Decarie, J.-C.; Matsumoto, N.;
Rouleau, G. A.; Michaud, J. L.: Identification of a novel in-frame
de novo mutation in SPTAN1 in intellectual disability and pontocerebellar
atrophy. Europ. J. Hum. Genet. 20: 796-800, 2012.
2. Saitsu, H.; Kato, M.; Mizuguchi, T.; Hamada, K.; Osaka, H.; Tohyama,
J.; Uruno, K.; Kumada, S.; Nishiyama, K.; Nishimura, A.; Okada, I.;
Yoshimura, Y.; Hirai, S.; Kumada, T.; Hayasaka, K.; Fukuda, A.; Ogata,
K.; Matsumoto, N.: De novo mutations in the gene encoding STXBP1
(MUNC18-1) cause early infantile epileptic encephalopathy. Nature
Genet. 40: 782-788, 2008.
3. Saitsu, H.; Tohyama, J.; Kumada, T.; Egawa, K.; Hamada, K.; Okada,
I.; Mizuguchi, T.; Osaka, H.; Miyata, R.; Furukawa, T.; Haginoya,
K.; Hoshino, H.; and 15 others: Dominant-negative mutations in
alpha-II spectrin cause West syndrome with severe cerebral hypomyelination,
spastic quadriplegia, and developmental delay. Am. J. Hum. Genet. 86:
881-891, 2010.
4. Tohyama, J.; Akasaka, N.; Osaka, H.; Maegaki, Y.; Kato, M.; Saito,
N.; Yamashita, S.; Ohno, K.: Early onset West syndrome with cerebral
hypomyelination and reduced cerebral white matter. Brain Dev. 30:
349-355, 2008.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Head];
Microcephaly, progressive (in 2 of 3 patients);
[Eyes];
No visual attention
NEUROLOGIC:
[Central nervous system];
Seizures, tonic, intractable;
Mental retardation, severe to profound;
Lack of speech development;
Lack of visual attention;
Hypsarrhythmia;
Spastic quadriplegia;
Lack of independent ambulation;
Hypotonia;
Diffuse hypomyelination;
Widespread brain atrophy;
Thin corpus callosum;
Brainstem atrophy;
Cerebellar atrophy
MISCELLANEOUS:
Onset in infancy;
Variable severity;
Three unrelated patients have been reported (last curated July 2012)
MOLECULAR BASIS:
Caused by mutation in the nonerythrocytic alpha-spectrin 1 gene (SPTAN1,
182810.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 7/11/2012
*FIELD* CD
Cassandra L. Kniffin: 7/12/2010
*FIELD* ED
joanna: 11/30/2012
ckniffin: 7/11/2012
joanna: 10/21/2011
ckniffin: 7/12/2010
*FIELD* CN
Cassandra L. Kniffin - updated: 7/11/2012
*FIELD* CD
Cassandra L. Kniffin: 7/12/2010
*FIELD* ED
carol: 07/12/2012
terry: 7/12/2012
ckniffin: 7/11/2012
carol: 2/11/2011
carol: 7/15/2010
wwang: 7/13/2010
ckniffin: 7/12/2010