Full text data of SPTBN4
SPTBN4
(KIAA1642, SPTBN3)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Spectrin beta chain, non-erythrocytic 4 (Beta-IV spectrin; Spectrin, non-erythroid beta chain 3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Spectrin beta chain, non-erythrocytic 4 (Beta-IV spectrin; Spectrin, non-erythroid beta chain 3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00018829
IPI00018829 Splice isoform 1 of Q9H254 Spectrin beta chain, brain 3 Splice isoform 1 of Q9H254 Spectrin beta chain, brain 3 membrane n/a n/a n/a n/a n/a n/a 1 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 cytoskeleton SIITYVVSFYHYFSK (identified at least 3 times) found at its expected molecular weight found at molecular weight
IPI00018829 Splice isoform 1 of Q9H254 Spectrin beta chain, brain 3 Splice isoform 1 of Q9H254 Spectrin beta chain, brain 3 membrane n/a n/a n/a n/a n/a n/a 1 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 cytoskeleton SIITYVVSFYHYFSK (identified at least 3 times) found at its expected molecular weight found at molecular weight
UniProt
Q9H254
ID SPTN4_HUMAN Reviewed; 2564 AA.
AC Q9H254; E9PGQ5; Q9H1K7; Q9H1K8; Q9H1K9; Q9H253; Q9H3G8; Q9HCD0;
read moreDT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2001, sequence version 2.
DT 22-JAN-2014, entry version 122.
DE RecName: Full=Spectrin beta chain, non-erythrocytic 4;
DE AltName: Full=Beta-IV spectrin;
DE AltName: Full=Spectrin, non-erythroid beta chain 3;
GN Name=SPTBN4; Synonyms=KIAA1642, SPTBN3;
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] (ISOFORMS 1 AND 5), AND VARIANT SER-1331.
RX PubMed=11294830; DOI=10.1074/jbc.M009307200;
RA Tse W.T., Tang J., Jin O., Korsgren C., John K.M., Kung A.L.,
RA Gwynn B., Peters L.L., Lux S.E.;
RT "A new spectrin, beta-IV, has a major truncated isoform that
RT associates with promyelocytic leukemia protein nuclear bodies and the
RT nuclear matrix.";
RL J. Biol. Chem. 276:23974-23985(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RX PubMed=11086001; DOI=10.1083/jcb.151.5.985;
RA Berghs S., Aggujaro D., Dirkx R. Jr., Maksimova E., Stabach P.,
RA Hermel J.-M., Zhang J.-P., Philbrick W., Slepnev V., Ort T.,
RA Solimena M.;
RT "BetaIV spectrin, a new spectrin localized at axon initial segments
RT and nodes of Ranvier in the central and peripheral nervous system.";
RL J. Cell Biol. 151:985-1002(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 386-2382 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes.
RT XVIII. The complete sequences of 100 new cDNA clones from brain which
RT code for large proteins in vitro.";
RL DNA Res. 7:273-281(2000).
CC -!- INTERACTION:
CC Q9NRI5:DISC1; NbExp=3; IntAct=EBI-308543, EBI-529989;
CC Q16849:PTPRN; NbExp=2; IntAct=EBI-308543, EBI-728153;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity).
CC Cytoplasm, cell cortex (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9H254-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H254-2; Sequence=VSP_000725, VSP_000726;
CC Name=3;
CC IsoId=Q9H254-3; Sequence=VSP_000723, VSP_000724;
CC Name=4;
CC IsoId=Q9H254-4; Sequence=VSP_000727, VSP_000728;
CC Name=5;
CC IsoId=Q9H254-5; Sequence=VSP_046383, VSP_046384, VSP_046385;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in brain and pancreatic
CC islets.
CC -!- SIMILARITY: Belongs to the spectrin family.
CC -!- SIMILARITY: Contains 2 CH (calponin-homology) domains.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- SIMILARITY: Contains 18 spectrin repeats.
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DR EMBL; AF311855; AAG42473.1; -; mRNA.
DR EMBL; AF311856; AAG42474.1; -; mRNA.
DR EMBL; AF082075; AAG38874.1; -; mRNA.
DR EMBL; AY004226; AAF93171.1; -; mRNA.
DR EMBL; AY004226; AAF93172.1; -; mRNA.
DR EMBL; AY004227; AAF93173.1; -; mRNA.
DR EMBL; AC020929; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB046862; BAB13468.1; -; mRNA.
DR RefSeq; NP_066022.2; NM_020971.2.
DR RefSeq; NP_079489.2; NM_025213.2.
DR UniGene; Hs.32706; -.
DR ProteinModelPortal; Q9H254; -.
DR SMR; Q9H254; 55-287, 309-2114, 2422-2525.
DR IntAct; Q9H254; 12.
DR MINT; MINT-8247405; -.
DR STRING; 9606.ENSP00000263373; -.
DR PhosphoSite; Q9H254; -.
DR DMDM; 17368942; -.
DR PaxDb; Q9H254; -.
DR PRIDE; Q9H254; -.
DR Ensembl; ENST00000338932; ENSP00000340345; ENSG00000160460.
DR Ensembl; ENST00000352632; ENSP00000263373; ENSG00000160460.
DR Ensembl; ENST00000392023; ENSP00000375877; ENSG00000160460.
DR Ensembl; ENST00000598249; ENSP00000469242; ENSG00000160460.
DR GeneID; 57731; -.
DR KEGG; hsa:57731; -.
DR UCSC; uc002ooa.3; human.
DR CTD; 57731; -.
DR GeneCards; GC19P040973; -.
DR H-InvDB; HIX0015138; -.
DR HGNC; HGNC:14896; SPTBN4.
DR HPA; HPA043370; -.
DR MIM; 606214; gene.
DR neXtProt; NX_Q9H254; -.
DR PharmGKB; PA37918; -.
DR eggNOG; COG5069; -.
DR HOGENOM; HOG000007281; -.
DR HOVERGEN; HBG057912; -.
DR InParanoid; Q9H254; -.
DR KO; K06115; -.
DR OMA; RKEEMSA; -.
DR PhylomeDB; Q9H254; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_127416; Developmental Biology.
DR GeneWiki; SPTBN4; -.
DR GenomeRNAi; 57731; -.
DR NextBio; 64688; -.
DR PRO; PR:Q9H254; -.
DR ArrayExpress; Q9H254; -.
DR Bgee; Q9H254; -.
DR CleanEx; HS_SPTBN4; -.
DR Genevestigator; Q9H254; -.
DR GO; GO:0005912; C:adherens junction; ISS:BHF-UCL.
DR GO; GO:0043203; C:axon hillock; ISS:BHF-UCL.
DR GO; GO:0043194; C:axon initial segment; ISS:BHF-UCL.
DR GO; GO:0070852; C:cell body fiber; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0033270; C:paranode region of axon; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0008091; C:spectrin; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; TAS:UniProtKB.
DR GO; GO:0030506; F:ankyrin binding; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0030507; F:spectrin binding; ISS:BHF-UCL.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:UniProtKB.
DR GO; GO:0051693; P:actin filament capping; IEA:UniProtKB-KW.
DR GO; GO:0007628; P:adult walking behavior; ISS:BHF-UCL.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0061337; P:cardiac conduction; ISS:BHF-UCL.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; ISS:BHF-UCL.
DR GO; GO:0045162; P:clustering of voltage-gated sodium channels; ISS:BHF-UCL.
DR GO; GO:0007016; P:cytoskeletal anchoring at plasma membrane; TAS:UniProtKB.
DR GO; GO:0090002; P:establishment of protein localization to plasma membrane; ISS:BHF-UCL.
DR GO; GO:0009566; P:fertilization; IEA:Ensembl.
DR GO; GO:0010459; P:negative regulation of heart rate; ISS:BHF-UCL.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0033135; P:regulation of peptidyl-serine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:BHF-UCL.
DR GO; GO:0007605; P:sensory perception of sound; ISS:BHF-UCL.
DR GO; GO:0019226; P:transmission of nerve impulse; ISS:BHF-UCL.
DR GO; GO:0016192; P:vesicle-mediated transport; TAS:UniProtKB.
DR Gene3D; 1.10.418.10; -; 2.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR001605; PH_dom-spectrin-type.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR016343; Spectrin_bsu.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF00435; Spectrin; 14.
DR PIRSF; PIRSF002297; Spectrin_beta_subunit; 1.
DR PRINTS; PR00683; SPECTRINPH.
DR SMART; SM00033; CH; 2.
DR SMART; SM00233; PH; 1.
DR SMART; SM00150; SPEC; 16.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS00019; ACTININ_1; 1.
DR PROSITE; PS00020; ACTININ_2; 1.
DR PROSITE; PS50021; CH; 2.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Actin capping; Actin-binding; Alternative splicing; Complete proteome;
KW Cytoplasm; Cytoskeleton; Polymorphism; Reference proteome; Repeat.
FT CHAIN 1 2564 Spectrin beta chain, non-erythrocytic 4.
FT /FTId=PRO_0000073465.
FT DOMAIN 1 282 Actin-binding.
FT DOMAIN 61 165 CH 1.
FT DOMAIN 180 282 CH 2.
FT REPEAT 309 354 Spectrin 1.
FT REPEAT 398 419 Spectrin 2.
FT REPEAT 429 533 Spectrin 3.
FT REPEAT 535 642 Spectrin 4.
FT REPEAT 644 771 Spectrin 5.
FT REPEAT 773 879 Spectrin 6.
FT REPEAT 881 985 Spectrin 7.
FT REPEAT 1019 1086 Spectrin 8.
FT REPEAT 1088 1197 Spectrin 9.
FT REPEAT 1199 1303 Spectrin 10.
FT REPEAT 1305 1408 Spectrin 11.
FT REPEAT 1410 1513 Spectrin 12.
FT REPEAT 1515 1619 Spectrin 13.
FT REPEAT 1621 1725 Spectrin 14.
FT REPEAT 1727 1832 Spectrin 15.
FT REPEAT 1834 1940 Spectrin 16.
FT REPEAT 1942 2046 Spectrin 17.
FT REPEAT 2048 2107 Spectrin 18.
FT DOMAIN 2418 2527 PH.
FT VAR_SEQ 1 1324 Missing (in isoform 5).
FT /FTId=VSP_046383.
FT VAR_SEQ 1 1257 Missing (in isoform 3).
FT /FTId=VSP_000723.
FT VAR_SEQ 1258 1286 AVQAAEGLLRQGNIYGEQAQEAVTRLLEK -> MPHYPSCS
FT SAPSLGTPIPPQIQQLEARHR (in isoform 3).
FT /FTId=VSP_000724.
FT VAR_SEQ 1287 1309 NQENQLRAQQWMQKLHDQLELQH -> CLIIHPALLHPPWE
FT PPYLPRSSS (in isoform 2).
FT /FTId=VSP_000725.
FT VAR_SEQ 1310 2564 Missing (in isoform 2).
FT /FTId=VSP_000726.
FT VAR_SEQ 1973 2002 DVSSVEVLMNYHQGLKTELEARVPELTTCQ -> CPSSLLG
FT LPASPWWPTPATPSPLTAPFSME (in isoform 5).
FT /FTId=VSP_046384.
FT VAR_SEQ 2003 2564 Missing (in isoform 5).
FT /FTId=VSP_046385.
FT VAR_SEQ 2113 2154 IEKIKAEQSKQPPTPLLGRKFFGDPTELAAKAAPLLRPGGY
FT E -> PRREDHLNPGVQDQPWQHTEKPSLPKPKANKEKTAR
FT RDGTCL (in isoform 4).
FT /FTId=VSP_000727.
FT VAR_SEQ 2155 2564 Missing (in isoform 4).
FT /FTId=VSP_000728.
FT VARIANT 1331 1331 G -> S (in dbSNP:rs814501).
FT /FTId=VAR_048632.
FT CONFLICT 604 608 Missing (in Ref. 2; AAG38874/AAF93171).
FT CONFLICT 714 714 L -> S (in Ref. 2; AAG38874/AAF93171/
FT AAF93173).
FT CONFLICT 1189 1189 E -> K (in Ref. 2; AAG38874/AAF93171/
FT AAF93173).
FT CONFLICT 1193 1193 E -> K (in Ref. 2; AAG38874/AAF93171/
FT AAF93173).
SQ SEQUENCE 2564 AA; 288985 MW; 52CDE7D11D601ECC CRC64;
MAQVPGEVDN MEGLPAPNNN PAARWESPDR GWEREQPAAS TAAASLFECS RIKALADERE
AVQKKTFTKW VNSHLARVGC HIGDLYVDLR DGFVLTRLLE VLSGEQLPRP TRGRMRIHSL
ENVDKALQFL KEQRVHLENV GSHDIVDGNH RLTLGLVWTI ILRFQIQVIK IETEDNRETR
SAKDALLLWC QMKTAGYPEV NIQNFTTSWR DGLAFNALIH RHRPDLVDFS KLTKSNANYN
LQRAFRTAEQ HLGLARLLDP EDVNMEAPDE KSIITYVVSF YHYFSKMKAL AVEGKRIGKV
LDQVLEVGKI IERYEELAAE LLAWIHRTVG LISNQKFANS LSGVQQQLQA FTAYCTLEKP
VKFQEKGNLE VLLFSIQSKL RACNRRLFVP REGCGIWDID KAWGELEKAE HEREAALRAE
LIRQEKLELL AQRFDHKVAM RESWLNENQR LVSQDNFGYE LPAVEAAMKK HEAIEADIAA
YEERVQGVAE LAQALAAEGY YDIRRVAAQR DSVLRQWALL TGLVGARRTR LEQNLALQKV
FQEMVYMVDW MEEMQAQLLS RECGQHLVEA DDLLQKHGLL EGDIAAQSER VEALNAAALR
FSQLQGYQPC DPQVICNRVN HVHGCLAELQ EQAARRRAEL EASRSLWALL QELEEAESWA
RDKERLLEAA GGGGAAGAAG AAGTAGGAHD LSSTARLLAQ HKILQGELGG RRALLQQALR
CGEELVAAGG AVGPGADTVH LVGLAERAAS ARRRWQRLEE AAARRERRLQ EARALHQFGA
DLDGLLDWLR DAYRLAAAGD FGHDEASSRR LARQHRALTG EVEAHRGPVS GLRRQLATLG
GASGAGPLVV ALQVRVVEAE QLFAEVTEVA ALRRQWLRDA LAVYRMFGEV HACELWIGEK
EQWLLSMRVP DSLDDVEVVQ HRFESLDQEM NSLMGRVLDV NHTVQELVEG GHPSSDEVRS
CQDHLNSRWN RIVELVEQRK EEMSAVLLVE NHVLEVAEVR AQVREKRRAV ESAPRAGGAL
QWRLSGLEAA LQALEPRQAA LLEEAALLAE RFPAQAARLH QGAEELGAEW GALASAAQAC
GEAVAAAGRL QRFLHDLDAF LDWLVRAQEA AGGSEGPLPN SLEEADALLA RHAALKEEVD
QREEDYARIV AASEALLAAD GAELGPGLAL DEWLPHLELG WHKLLGLWEA RREALVQAHI
YQLFLRDLRQ ALVVLRNQEM ALSGAELPGT VESVEEALKQ HRDFLTTMEL SQQKMQVAVQ
AAEGLLRQGN IYGEQAQEAV TRLLEKNQEN QLRAQQWMQK LHDQLELQHF LRDCHELDGW
IHEKMLMARD GTREDNHKLH KRWLRHQAFM AELAQNKEWL EKIEREGQQL MQEKPELAAS
VRKKLGEIRQ CWAELESTTQ AKARQLFEAS KADQLVQSFA ELDKKLLHME SQLQDVDPGG
DLATVNSQLK KLQSMESQVE EWYREVGELQ AQTAALPLEP ASKELVGERQ NAVGERLVRL
LEPLQERRRL LLASKELHQV AHDLDDELAW VQERLPLAMQ TERGNGLQAV QQHIKKNQGL
RREIQAHGPR LEEVLERAGA LASLRSPEAE AVRRGLEQLQ SAWAGLREAA ERRQQVLDAA
FQVEQYYFDV AEVEAWLGEQ ELLMMSEDKG KDEQSTLQLL KKHLQLEQGV ENYEESIAQL
SRQCRALLEM GHPDSEQISR RQSQVDRLYV ALKELGEERR VALEQQYWLY QLSRQVSELE
HWIAEKEVVA GSPELGQDFE HVSVLQEKFS EFASETGMAG RERLAAVNQM VDELIECGHT
AAATMAEWKD GLNEAWAELL ELMGTRAQLL AASRELHKFF SDARELQGQI EEKRRRLPRL
TTPPEPRPSA SSMQRTLRAF EHDLQLLVSQ VRQLQEGAAQ LRTVYAGEHA EAIASREQEV
LQGWKELLSA CEDARLHVSS TADALRFHSQ VRDLLSWMDG IASQIGAADK PRDVSSVEVL
MNYHQGLKTE LEARVPELTT CQELGRSLLL NKSAMADEIQ AQLDKLGTRK EEVSEKWDRH
WEWLQQMLEV HQFAQEAVVA DAWLTAQEPL LQSRELGSSV DEVEQLIRRH EAFRKAAAAW
EERFSSLRRL TTIEKIKAEQ SKQPPTPLLG RKFFGDPTEL AAKAAPLLRP GGYERGLEPL
ARRASDTLSA EVRTRVGYVR QELKPERLQP RIDRLPEIPG RVEPAALPAA PEDAAETPAT
PAAAEQVRPR PERQESADRA EELPRRRRPE RQESVDQSEE AARRRRPERQ ESAEHEAAHS
LTLGRYEQME RRRERRERRL ERQESSEQEM PIRGDLVKGK ATLADIVEQL QEKEAGPGLP
AGPSLPQPRE LPPGRLPNGL ELPERTPRPD RPRARDRPKP RRRPRPREGG EGGGSRRSRS
APAQGGSAPA PPPPPTHTVQ HEGFLLRKRE LDANRKSSNR SWVSLYCVLS KGELGFYKDS
KGPASGSTHG GEPLLSLHKA TSEVASDYKK KKHVFKLQTQ DGSEFLLQAK DEEEMNGWLE
AVASSVAEHA EIARWGQTLP TTSSTDEGNP KREGGDRRAS GRRK
//
ID SPTN4_HUMAN Reviewed; 2564 AA.
AC Q9H254; E9PGQ5; Q9H1K7; Q9H1K8; Q9H1K9; Q9H253; Q9H3G8; Q9HCD0;
read moreDT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2001, sequence version 2.
DT 22-JAN-2014, entry version 122.
DE RecName: Full=Spectrin beta chain, non-erythrocytic 4;
DE AltName: Full=Beta-IV spectrin;
DE AltName: Full=Spectrin, non-erythroid beta chain 3;
GN Name=SPTBN4; Synonyms=KIAA1642, SPTBN3;
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] (ISOFORMS 1 AND 5), AND VARIANT SER-1331.
RX PubMed=11294830; DOI=10.1074/jbc.M009307200;
RA Tse W.T., Tang J., Jin O., Korsgren C., John K.M., Kung A.L.,
RA Gwynn B., Peters L.L., Lux S.E.;
RT "A new spectrin, beta-IV, has a major truncated isoform that
RT associates with promyelocytic leukemia protein nuclear bodies and the
RT nuclear matrix.";
RL J. Biol. Chem. 276:23974-23985(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RX PubMed=11086001; DOI=10.1083/jcb.151.5.985;
RA Berghs S., Aggujaro D., Dirkx R. Jr., Maksimova E., Stabach P.,
RA Hermel J.-M., Zhang J.-P., Philbrick W., Slepnev V., Ort T.,
RA Solimena M.;
RT "BetaIV spectrin, a new spectrin localized at axon initial segments
RT and nodes of Ranvier in the central and peripheral nervous system.";
RL J. Cell Biol. 151:985-1002(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 386-2382 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes.
RT XVIII. The complete sequences of 100 new cDNA clones from brain which
RT code for large proteins in vitro.";
RL DNA Res. 7:273-281(2000).
CC -!- INTERACTION:
CC Q9NRI5:DISC1; NbExp=3; IntAct=EBI-308543, EBI-529989;
CC Q16849:PTPRN; NbExp=2; IntAct=EBI-308543, EBI-728153;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity).
CC Cytoplasm, cell cortex (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9H254-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H254-2; Sequence=VSP_000725, VSP_000726;
CC Name=3;
CC IsoId=Q9H254-3; Sequence=VSP_000723, VSP_000724;
CC Name=4;
CC IsoId=Q9H254-4; Sequence=VSP_000727, VSP_000728;
CC Name=5;
CC IsoId=Q9H254-5; Sequence=VSP_046383, VSP_046384, VSP_046385;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in brain and pancreatic
CC islets.
CC -!- SIMILARITY: Belongs to the spectrin family.
CC -!- SIMILARITY: Contains 2 CH (calponin-homology) domains.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- SIMILARITY: Contains 18 spectrin repeats.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AF311855; AAG42473.1; -; mRNA.
DR EMBL; AF311856; AAG42474.1; -; mRNA.
DR EMBL; AF082075; AAG38874.1; -; mRNA.
DR EMBL; AY004226; AAF93171.1; -; mRNA.
DR EMBL; AY004226; AAF93172.1; -; mRNA.
DR EMBL; AY004227; AAF93173.1; -; mRNA.
DR EMBL; AC020929; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB046862; BAB13468.1; -; mRNA.
DR RefSeq; NP_066022.2; NM_020971.2.
DR RefSeq; NP_079489.2; NM_025213.2.
DR UniGene; Hs.32706; -.
DR ProteinModelPortal; Q9H254; -.
DR SMR; Q9H254; 55-287, 309-2114, 2422-2525.
DR IntAct; Q9H254; 12.
DR MINT; MINT-8247405; -.
DR STRING; 9606.ENSP00000263373; -.
DR PhosphoSite; Q9H254; -.
DR DMDM; 17368942; -.
DR PaxDb; Q9H254; -.
DR PRIDE; Q9H254; -.
DR Ensembl; ENST00000338932; ENSP00000340345; ENSG00000160460.
DR Ensembl; ENST00000352632; ENSP00000263373; ENSG00000160460.
DR Ensembl; ENST00000392023; ENSP00000375877; ENSG00000160460.
DR Ensembl; ENST00000598249; ENSP00000469242; ENSG00000160460.
DR GeneID; 57731; -.
DR KEGG; hsa:57731; -.
DR UCSC; uc002ooa.3; human.
DR CTD; 57731; -.
DR GeneCards; GC19P040973; -.
DR H-InvDB; HIX0015138; -.
DR HGNC; HGNC:14896; SPTBN4.
DR HPA; HPA043370; -.
DR MIM; 606214; gene.
DR neXtProt; NX_Q9H254; -.
DR PharmGKB; PA37918; -.
DR eggNOG; COG5069; -.
DR HOGENOM; HOG000007281; -.
DR HOVERGEN; HBG057912; -.
DR InParanoid; Q9H254; -.
DR KO; K06115; -.
DR OMA; RKEEMSA; -.
DR PhylomeDB; Q9H254; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_127416; Developmental Biology.
DR GeneWiki; SPTBN4; -.
DR GenomeRNAi; 57731; -.
DR NextBio; 64688; -.
DR PRO; PR:Q9H254; -.
DR ArrayExpress; Q9H254; -.
DR Bgee; Q9H254; -.
DR CleanEx; HS_SPTBN4; -.
DR Genevestigator; Q9H254; -.
DR GO; GO:0005912; C:adherens junction; ISS:BHF-UCL.
DR GO; GO:0043203; C:axon hillock; ISS:BHF-UCL.
DR GO; GO:0043194; C:axon initial segment; ISS:BHF-UCL.
DR GO; GO:0070852; C:cell body fiber; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0033270; C:paranode region of axon; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0008091; C:spectrin; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; TAS:UniProtKB.
DR GO; GO:0030506; F:ankyrin binding; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0030507; F:spectrin binding; ISS:BHF-UCL.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:UniProtKB.
DR GO; GO:0051693; P:actin filament capping; IEA:UniProtKB-KW.
DR GO; GO:0007628; P:adult walking behavior; ISS:BHF-UCL.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0061337; P:cardiac conduction; ISS:BHF-UCL.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; ISS:BHF-UCL.
DR GO; GO:0045162; P:clustering of voltage-gated sodium channels; ISS:BHF-UCL.
DR GO; GO:0007016; P:cytoskeletal anchoring at plasma membrane; TAS:UniProtKB.
DR GO; GO:0090002; P:establishment of protein localization to plasma membrane; ISS:BHF-UCL.
DR GO; GO:0009566; P:fertilization; IEA:Ensembl.
DR GO; GO:0010459; P:negative regulation of heart rate; ISS:BHF-UCL.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0033135; P:regulation of peptidyl-serine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:BHF-UCL.
DR GO; GO:0007605; P:sensory perception of sound; ISS:BHF-UCL.
DR GO; GO:0019226; P:transmission of nerve impulse; ISS:BHF-UCL.
DR GO; GO:0016192; P:vesicle-mediated transport; TAS:UniProtKB.
DR Gene3D; 1.10.418.10; -; 2.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR001605; PH_dom-spectrin-type.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR016343; Spectrin_bsu.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF00435; Spectrin; 14.
DR PIRSF; PIRSF002297; Spectrin_beta_subunit; 1.
DR PRINTS; PR00683; SPECTRINPH.
DR SMART; SM00033; CH; 2.
DR SMART; SM00233; PH; 1.
DR SMART; SM00150; SPEC; 16.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS00019; ACTININ_1; 1.
DR PROSITE; PS00020; ACTININ_2; 1.
DR PROSITE; PS50021; CH; 2.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Actin capping; Actin-binding; Alternative splicing; Complete proteome;
KW Cytoplasm; Cytoskeleton; Polymorphism; Reference proteome; Repeat.
FT CHAIN 1 2564 Spectrin beta chain, non-erythrocytic 4.
FT /FTId=PRO_0000073465.
FT DOMAIN 1 282 Actin-binding.
FT DOMAIN 61 165 CH 1.
FT DOMAIN 180 282 CH 2.
FT REPEAT 309 354 Spectrin 1.
FT REPEAT 398 419 Spectrin 2.
FT REPEAT 429 533 Spectrin 3.
FT REPEAT 535 642 Spectrin 4.
FT REPEAT 644 771 Spectrin 5.
FT REPEAT 773 879 Spectrin 6.
FT REPEAT 881 985 Spectrin 7.
FT REPEAT 1019 1086 Spectrin 8.
FT REPEAT 1088 1197 Spectrin 9.
FT REPEAT 1199 1303 Spectrin 10.
FT REPEAT 1305 1408 Spectrin 11.
FT REPEAT 1410 1513 Spectrin 12.
FT REPEAT 1515 1619 Spectrin 13.
FT REPEAT 1621 1725 Spectrin 14.
FT REPEAT 1727 1832 Spectrin 15.
FT REPEAT 1834 1940 Spectrin 16.
FT REPEAT 1942 2046 Spectrin 17.
FT REPEAT 2048 2107 Spectrin 18.
FT DOMAIN 2418 2527 PH.
FT VAR_SEQ 1 1324 Missing (in isoform 5).
FT /FTId=VSP_046383.
FT VAR_SEQ 1 1257 Missing (in isoform 3).
FT /FTId=VSP_000723.
FT VAR_SEQ 1258 1286 AVQAAEGLLRQGNIYGEQAQEAVTRLLEK -> MPHYPSCS
FT SAPSLGTPIPPQIQQLEARHR (in isoform 3).
FT /FTId=VSP_000724.
FT VAR_SEQ 1287 1309 NQENQLRAQQWMQKLHDQLELQH -> CLIIHPALLHPPWE
FT PPYLPRSSS (in isoform 2).
FT /FTId=VSP_000725.
FT VAR_SEQ 1310 2564 Missing (in isoform 2).
FT /FTId=VSP_000726.
FT VAR_SEQ 1973 2002 DVSSVEVLMNYHQGLKTELEARVPELTTCQ -> CPSSLLG
FT LPASPWWPTPATPSPLTAPFSME (in isoform 5).
FT /FTId=VSP_046384.
FT VAR_SEQ 2003 2564 Missing (in isoform 5).
FT /FTId=VSP_046385.
FT VAR_SEQ 2113 2154 IEKIKAEQSKQPPTPLLGRKFFGDPTELAAKAAPLLRPGGY
FT E -> PRREDHLNPGVQDQPWQHTEKPSLPKPKANKEKTAR
FT RDGTCL (in isoform 4).
FT /FTId=VSP_000727.
FT VAR_SEQ 2155 2564 Missing (in isoform 4).
FT /FTId=VSP_000728.
FT VARIANT 1331 1331 G -> S (in dbSNP:rs814501).
FT /FTId=VAR_048632.
FT CONFLICT 604 608 Missing (in Ref. 2; AAG38874/AAF93171).
FT CONFLICT 714 714 L -> S (in Ref. 2; AAG38874/AAF93171/
FT AAF93173).
FT CONFLICT 1189 1189 E -> K (in Ref. 2; AAG38874/AAF93171/
FT AAF93173).
FT CONFLICT 1193 1193 E -> K (in Ref. 2; AAG38874/AAF93171/
FT AAF93173).
SQ SEQUENCE 2564 AA; 288985 MW; 52CDE7D11D601ECC CRC64;
MAQVPGEVDN MEGLPAPNNN PAARWESPDR GWEREQPAAS TAAASLFECS RIKALADERE
AVQKKTFTKW VNSHLARVGC HIGDLYVDLR DGFVLTRLLE VLSGEQLPRP TRGRMRIHSL
ENVDKALQFL KEQRVHLENV GSHDIVDGNH RLTLGLVWTI ILRFQIQVIK IETEDNRETR
SAKDALLLWC QMKTAGYPEV NIQNFTTSWR DGLAFNALIH RHRPDLVDFS KLTKSNANYN
LQRAFRTAEQ HLGLARLLDP EDVNMEAPDE KSIITYVVSF YHYFSKMKAL AVEGKRIGKV
LDQVLEVGKI IERYEELAAE LLAWIHRTVG LISNQKFANS LSGVQQQLQA FTAYCTLEKP
VKFQEKGNLE VLLFSIQSKL RACNRRLFVP REGCGIWDID KAWGELEKAE HEREAALRAE
LIRQEKLELL AQRFDHKVAM RESWLNENQR LVSQDNFGYE LPAVEAAMKK HEAIEADIAA
YEERVQGVAE LAQALAAEGY YDIRRVAAQR DSVLRQWALL TGLVGARRTR LEQNLALQKV
FQEMVYMVDW MEEMQAQLLS RECGQHLVEA DDLLQKHGLL EGDIAAQSER VEALNAAALR
FSQLQGYQPC DPQVICNRVN HVHGCLAELQ EQAARRRAEL EASRSLWALL QELEEAESWA
RDKERLLEAA GGGGAAGAAG AAGTAGGAHD LSSTARLLAQ HKILQGELGG RRALLQQALR
CGEELVAAGG AVGPGADTVH LVGLAERAAS ARRRWQRLEE AAARRERRLQ EARALHQFGA
DLDGLLDWLR DAYRLAAAGD FGHDEASSRR LARQHRALTG EVEAHRGPVS GLRRQLATLG
GASGAGPLVV ALQVRVVEAE QLFAEVTEVA ALRRQWLRDA LAVYRMFGEV HACELWIGEK
EQWLLSMRVP DSLDDVEVVQ HRFESLDQEM NSLMGRVLDV NHTVQELVEG GHPSSDEVRS
CQDHLNSRWN RIVELVEQRK EEMSAVLLVE NHVLEVAEVR AQVREKRRAV ESAPRAGGAL
QWRLSGLEAA LQALEPRQAA LLEEAALLAE RFPAQAARLH QGAEELGAEW GALASAAQAC
GEAVAAAGRL QRFLHDLDAF LDWLVRAQEA AGGSEGPLPN SLEEADALLA RHAALKEEVD
QREEDYARIV AASEALLAAD GAELGPGLAL DEWLPHLELG WHKLLGLWEA RREALVQAHI
YQLFLRDLRQ ALVVLRNQEM ALSGAELPGT VESVEEALKQ HRDFLTTMEL SQQKMQVAVQ
AAEGLLRQGN IYGEQAQEAV TRLLEKNQEN QLRAQQWMQK LHDQLELQHF LRDCHELDGW
IHEKMLMARD GTREDNHKLH KRWLRHQAFM AELAQNKEWL EKIEREGQQL MQEKPELAAS
VRKKLGEIRQ CWAELESTTQ AKARQLFEAS KADQLVQSFA ELDKKLLHME SQLQDVDPGG
DLATVNSQLK KLQSMESQVE EWYREVGELQ AQTAALPLEP ASKELVGERQ NAVGERLVRL
LEPLQERRRL LLASKELHQV AHDLDDELAW VQERLPLAMQ TERGNGLQAV QQHIKKNQGL
RREIQAHGPR LEEVLERAGA LASLRSPEAE AVRRGLEQLQ SAWAGLREAA ERRQQVLDAA
FQVEQYYFDV AEVEAWLGEQ ELLMMSEDKG KDEQSTLQLL KKHLQLEQGV ENYEESIAQL
SRQCRALLEM GHPDSEQISR RQSQVDRLYV ALKELGEERR VALEQQYWLY QLSRQVSELE
HWIAEKEVVA GSPELGQDFE HVSVLQEKFS EFASETGMAG RERLAAVNQM VDELIECGHT
AAATMAEWKD GLNEAWAELL ELMGTRAQLL AASRELHKFF SDARELQGQI EEKRRRLPRL
TTPPEPRPSA SSMQRTLRAF EHDLQLLVSQ VRQLQEGAAQ LRTVYAGEHA EAIASREQEV
LQGWKELLSA CEDARLHVSS TADALRFHSQ VRDLLSWMDG IASQIGAADK PRDVSSVEVL
MNYHQGLKTE LEARVPELTT CQELGRSLLL NKSAMADEIQ AQLDKLGTRK EEVSEKWDRH
WEWLQQMLEV HQFAQEAVVA DAWLTAQEPL LQSRELGSSV DEVEQLIRRH EAFRKAAAAW
EERFSSLRRL TTIEKIKAEQ SKQPPTPLLG RKFFGDPTEL AAKAAPLLRP GGYERGLEPL
ARRASDTLSA EVRTRVGYVR QELKPERLQP RIDRLPEIPG RVEPAALPAA PEDAAETPAT
PAAAEQVRPR PERQESADRA EELPRRRRPE RQESVDQSEE AARRRRPERQ ESAEHEAAHS
LTLGRYEQME RRRERRERRL ERQESSEQEM PIRGDLVKGK ATLADIVEQL QEKEAGPGLP
AGPSLPQPRE LPPGRLPNGL ELPERTPRPD RPRARDRPKP RRRPRPREGG EGGGSRRSRS
APAQGGSAPA PPPPPTHTVQ HEGFLLRKRE LDANRKSSNR SWVSLYCVLS KGELGFYKDS
KGPASGSTHG GEPLLSLHKA TSEVASDYKK KKHVFKLQTQ DGSEFLLQAK DEEEMNGWLE
AVASSVAEHA EIARWGQTLP TTSSTDEGNP KREGGDRRAS GRRK
//
MIM
606214
*RECORD*
*FIELD* NO
606214
*FIELD* TI
*606214 SPECTRIN, BETA, NONERYTHROCYTIC, 4; SPTBN4
;;SPECTRIN, BETA-IV;;
QUIVERING, MOUSE, HOMOLOG OF; QV
read more*FIELD* TX
Spectrins (e.g., SPTA1; 182860) are rod-shaped proteins that are part of
the lattice-like cytoskeleton under the erythrocyte membrane. This
meshwork is critical for the maintenance of plasma membrane shape and
lipid asymmetry, as revealed by mutant spectrins in diseases such as
elliptocytosis (see 182860) and spherocytosis (see 182870). Although
originally identified in erythrocytes, spectrins have also been found in
the membranes of intracellular organelles, such as the Golgi, lysosomes,
and secretory vesicles. The spectrin molecule is a tetramer consisting
of 2 alpha and 2 beta subunits, in which the N terminus of an alpha
subunit is tightly connected with the C terminus of a beta subunit to
form a heterodimer. Spectrin repeats contain approximately 106 amino
acids. Alpha subunits have 20 spectrin repeats, while beta subunits have
17.
CLONING
By screening a size-fractionated adult brain cDNA library for cDNAs with
the potential to encode large proteins, Nagase et al. (2000) isolated a
partial cDNA encoding SPTBN4, which they called KIAA1642. RT-PCR
analysis detected ubiquitous expression of SPTBN4, with relatively high
levels in adult and fetal brain, low levels in lung, liver, pancreas,
and spleen, and intermediate levels in the other tissues tested and in
specific brain regions.
Using a yeast 2-hybrid screen of a brain cDNA library with the
cytoplasmic domain of ICA512 (PTPRN; 601773) as bait, followed by
probing a brain cDNA library, PCR, and genomic sequence analysis, Berghs
et al. (2000) isolated cDNAs encoding SPTBN4 and several splice
variants. Sequence analysis predicted that the full-length 2,559-amino
acid SPTBN4 protein, designated sigma-1, contains 2 N-terminal calponin
homology domains, which mediate interactions with actin; 16 complete
spectrin repeats; 1 partial spectrin repeat; a unique proline-rich,
basic domain containing 4 ERQES repeats; numerous SH3 binding sites; and
a C-terminal pleckstrin homology domain. An insertion in exon 17 termed
exon 17b yields a 1,302-residue splice variant, sigma-2, which
terminates in spectrin repeat 9, and another variant, sigma-3, which
begins at exon 17b to generate a 1,307-amino acid protein. Variant
sigma-4 has an insertion in exon 30 termed exon 30b that introduces 42
amino acids and a stop codon, resulting in a 2,149-amino acid protein
that lacks the ERQES and pleckstrin homology domains. Binding analysis
indicated that the C terminus of SPTBN4 binds to PTPRN and only weakly
to an active tyrosine phosphatase mutant of PTPRN and to PHOGRIN
(601698). Northern blot analysis revealed expression of 9.0-, 5.1-, and
3.1-kb SPTBN4 transcripts that were predominantly expressed in brain.
Western blot analysis showed expression of 250- and 160-kD proteins in
rat brain and human pancreatic islets, as well as a 140-kD protein in
rat brain only. Phosphatase treatment indicated that the 160-kD protein
is phosphorylated, probably in the ERQES domain, which modifies its
interaction with cytoskeletal and membrane proteins. Immunocytochemistry
and confocal microscopy demonstrated coexpression of PTPRN and SPTBN4 in
both insulin-secreting beta cells and glucagon-secreting alpha cells. In
situ hybridization and immunocytochemistry suggested coexpression of
SPTBN4 and ankyrin-G (ANK3; 600465) in rat brain.
Tse et al. (2001) cloned SPTBN4, which they termed SPTBN3, as well as a
splice variant, sigma-5, encoding a 678-amino acid protein. Whole-mount
in situ hybridization analysis revealed Sptbn4 expression that was
restricted to forebrain, hindbrain, and developing eye in postcoital
day-9.5 mice. Western blot analysis with polyclonal antibodies detected
expression of a predominant 72-kD protein, close to the expected size of
the sigma-5 variant. Immunofluorescence microscopy demonstrated
colocalization of SPTBN4 with PML (102578) and with SUMO1 (UBL1; 601912)
in the cytoplasm and nucleus. The authors showed that both the N- and
C-terminal helical coils of sigma-5 are needed to form nuclear dots and
are associated with the nuclear matrix. Tse et al. (2001) proposed that
a spectrin-based skeleton may be important for the structure of the
nucleus.
GENE STRUCTURE
By genomic sequence analysis, Berghs et al. (2000) determined that the
SPTBN4 gene contains 36 exons. Tse et al. (2001) determined that the
SPTBN4 gene spans over 145 kb.
MAPPING
By radiation hybrid analysis, Nagase et al. (2000) mapped the SPTBN4
gene to chromosome 19. Berghs et al. (2000) localized the gene to
19q13.13 by FISH. They identified a highly related gene that resides on
chromosome 16. Tse et al. (2001) mapped the SPTBN4 gene to
19q13.13-q13.2 by radiation hybrid analysis. Berghs et al. (2000) and
Tse et al. (2001) mapped the mouse Spnb4 gene to chromosome 7b2.
ANIMAL MODEL
The autosomal recessive mouse mutation 'quivering' (qv), described by
Yoon and Les (1957), produces progressive ataxia with hindlimb
paralysis, deafness, and tremor. Ear twitch responses (Preyer reflex) to
sound are absent in homozygous qv/qv mice, although cochlear morphology
seems normal and cochlear potentials recorded at the round window are no
different from those of control mice. However, responses from brainstem
auditory nuclei show abnormal transmission of auditory inflammation,
indicating that in contrast to the many mutations causing deafness
originating in the cochlea, deafness in qv is central in origin (Deol et
al., 1983; Bock et al., 1983). Parkinson et al. (2001) reported that qv
mice carry loss-of-function mutations in the Spnb4 gene that cause
alterations in ion channel localization in myelinated nerves. They
concluded that this finding provides a rationale for the auditory and
motor neuropathies of these mice.
*FIELD* RF
1. Berghs, S.; Aggujaro, D.; Dirkx, R., Jr.; Maksimova, E.; Stabach,
P.; Hermel, J.-M.; Zhang, J.-P.; Philbrick, W.; Slepnev, V.; Ort,
T.; Slimena, M.: Beta-IV spectrin, a new spectrin localized at axon
initial segments and nodes of Ranvier in the central and peripheral
nervous system. J. Cell Biol. 151: 985-1001, 2000.
2. Bock, G. R.; Frank, M. P.; Steel, K. P.; Deol, M. S.: The quivering
mutant mouse: hereditary deafness of central origin. Acta Otolaryng. 96:
371-377, 1983.
3. Deol, M. S.; Frank, M. P.; Steel, K. P.; Bock, G. R.: Genetic
deafness of central origin. Brain Res. 258: 177-179, 1983.
4. Nagase, T.; Kikuno, R.; Nakayama, M.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVIII.
The complete sequences of 100 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 273-281, 2000.
5. Parkinson, N. J.; Olsson, C. L.; Hallows, J. L.; McKee-Johnson,
J.; Keogh, B. P.; Noben-Trauth, K.; Kujawa, S. G.; Tempel, B. L.:
Mutant beta-spectrin 4 causes auditory and motor neuropathies in quivering
mice. Nature Genet. 29: 61-65, 2001.
6. Tse, W. T.; Tang, J.; Jin, O.; Korsgren, C.; John, K. M.; Kung,
A. L.; Gwynn, B.; Peters, L. L.; Lux, S. E.: A new spectrin, beta-IV,
has a major truncated isoform that associates with promyelocytic leukemia
protein nuclear bodies and the nuclear matrix. J. Biol. Chem. 276:
23974-23985, 2001.
7. Yoon, C. H.; Les, E. P.: Quivering, a new first chromosome mutation
in mice. J. Hered. 48: 176-180, 1957.
*FIELD* CN
Victor A. McKusick - updated: 8/23/2001
*FIELD* CD
Paul J. Converse: 8/21/2001
*FIELD* ED
terry: 03/03/2005
terry: 6/27/2002
mgross: 8/23/2001
terry: 8/23/2001
mgross: 8/22/2001
mgross: 8/21/2001
*RECORD*
*FIELD* NO
606214
*FIELD* TI
*606214 SPECTRIN, BETA, NONERYTHROCYTIC, 4; SPTBN4
;;SPECTRIN, BETA-IV;;
QUIVERING, MOUSE, HOMOLOG OF; QV
read more*FIELD* TX
Spectrins (e.g., SPTA1; 182860) are rod-shaped proteins that are part of
the lattice-like cytoskeleton under the erythrocyte membrane. This
meshwork is critical for the maintenance of plasma membrane shape and
lipid asymmetry, as revealed by mutant spectrins in diseases such as
elliptocytosis (see 182860) and spherocytosis (see 182870). Although
originally identified in erythrocytes, spectrins have also been found in
the membranes of intracellular organelles, such as the Golgi, lysosomes,
and secretory vesicles. The spectrin molecule is a tetramer consisting
of 2 alpha and 2 beta subunits, in which the N terminus of an alpha
subunit is tightly connected with the C terminus of a beta subunit to
form a heterodimer. Spectrin repeats contain approximately 106 amino
acids. Alpha subunits have 20 spectrin repeats, while beta subunits have
17.
CLONING
By screening a size-fractionated adult brain cDNA library for cDNAs with
the potential to encode large proteins, Nagase et al. (2000) isolated a
partial cDNA encoding SPTBN4, which they called KIAA1642. RT-PCR
analysis detected ubiquitous expression of SPTBN4, with relatively high
levels in adult and fetal brain, low levels in lung, liver, pancreas,
and spleen, and intermediate levels in the other tissues tested and in
specific brain regions.
Using a yeast 2-hybrid screen of a brain cDNA library with the
cytoplasmic domain of ICA512 (PTPRN; 601773) as bait, followed by
probing a brain cDNA library, PCR, and genomic sequence analysis, Berghs
et al. (2000) isolated cDNAs encoding SPTBN4 and several splice
variants. Sequence analysis predicted that the full-length 2,559-amino
acid SPTBN4 protein, designated sigma-1, contains 2 N-terminal calponin
homology domains, which mediate interactions with actin; 16 complete
spectrin repeats; 1 partial spectrin repeat; a unique proline-rich,
basic domain containing 4 ERQES repeats; numerous SH3 binding sites; and
a C-terminal pleckstrin homology domain. An insertion in exon 17 termed
exon 17b yields a 1,302-residue splice variant, sigma-2, which
terminates in spectrin repeat 9, and another variant, sigma-3, which
begins at exon 17b to generate a 1,307-amino acid protein. Variant
sigma-4 has an insertion in exon 30 termed exon 30b that introduces 42
amino acids and a stop codon, resulting in a 2,149-amino acid protein
that lacks the ERQES and pleckstrin homology domains. Binding analysis
indicated that the C terminus of SPTBN4 binds to PTPRN and only weakly
to an active tyrosine phosphatase mutant of PTPRN and to PHOGRIN
(601698). Northern blot analysis revealed expression of 9.0-, 5.1-, and
3.1-kb SPTBN4 transcripts that were predominantly expressed in brain.
Western blot analysis showed expression of 250- and 160-kD proteins in
rat brain and human pancreatic islets, as well as a 140-kD protein in
rat brain only. Phosphatase treatment indicated that the 160-kD protein
is phosphorylated, probably in the ERQES domain, which modifies its
interaction with cytoskeletal and membrane proteins. Immunocytochemistry
and confocal microscopy demonstrated coexpression of PTPRN and SPTBN4 in
both insulin-secreting beta cells and glucagon-secreting alpha cells. In
situ hybridization and immunocytochemistry suggested coexpression of
SPTBN4 and ankyrin-G (ANK3; 600465) in rat brain.
Tse et al. (2001) cloned SPTBN4, which they termed SPTBN3, as well as a
splice variant, sigma-5, encoding a 678-amino acid protein. Whole-mount
in situ hybridization analysis revealed Sptbn4 expression that was
restricted to forebrain, hindbrain, and developing eye in postcoital
day-9.5 mice. Western blot analysis with polyclonal antibodies detected
expression of a predominant 72-kD protein, close to the expected size of
the sigma-5 variant. Immunofluorescence microscopy demonstrated
colocalization of SPTBN4 with PML (102578) and with SUMO1 (UBL1; 601912)
in the cytoplasm and nucleus. The authors showed that both the N- and
C-terminal helical coils of sigma-5 are needed to form nuclear dots and
are associated with the nuclear matrix. Tse et al. (2001) proposed that
a spectrin-based skeleton may be important for the structure of the
nucleus.
GENE STRUCTURE
By genomic sequence analysis, Berghs et al. (2000) determined that the
SPTBN4 gene contains 36 exons. Tse et al. (2001) determined that the
SPTBN4 gene spans over 145 kb.
MAPPING
By radiation hybrid analysis, Nagase et al. (2000) mapped the SPTBN4
gene to chromosome 19. Berghs et al. (2000) localized the gene to
19q13.13 by FISH. They identified a highly related gene that resides on
chromosome 16. Tse et al. (2001) mapped the SPTBN4 gene to
19q13.13-q13.2 by radiation hybrid analysis. Berghs et al. (2000) and
Tse et al. (2001) mapped the mouse Spnb4 gene to chromosome 7b2.
ANIMAL MODEL
The autosomal recessive mouse mutation 'quivering' (qv), described by
Yoon and Les (1957), produces progressive ataxia with hindlimb
paralysis, deafness, and tremor. Ear twitch responses (Preyer reflex) to
sound are absent in homozygous qv/qv mice, although cochlear morphology
seems normal and cochlear potentials recorded at the round window are no
different from those of control mice. However, responses from brainstem
auditory nuclei show abnormal transmission of auditory inflammation,
indicating that in contrast to the many mutations causing deafness
originating in the cochlea, deafness in qv is central in origin (Deol et
al., 1983; Bock et al., 1983). Parkinson et al. (2001) reported that qv
mice carry loss-of-function mutations in the Spnb4 gene that cause
alterations in ion channel localization in myelinated nerves. They
concluded that this finding provides a rationale for the auditory and
motor neuropathies of these mice.
*FIELD* RF
1. Berghs, S.; Aggujaro, D.; Dirkx, R., Jr.; Maksimova, E.; Stabach,
P.; Hermel, J.-M.; Zhang, J.-P.; Philbrick, W.; Slepnev, V.; Ort,
T.; Slimena, M.: Beta-IV spectrin, a new spectrin localized at axon
initial segments and nodes of Ranvier in the central and peripheral
nervous system. J. Cell Biol. 151: 985-1001, 2000.
2. Bock, G. R.; Frank, M. P.; Steel, K. P.; Deol, M. S.: The quivering
mutant mouse: hereditary deafness of central origin. Acta Otolaryng. 96:
371-377, 1983.
3. Deol, M. S.; Frank, M. P.; Steel, K. P.; Bock, G. R.: Genetic
deafness of central origin. Brain Res. 258: 177-179, 1983.
4. Nagase, T.; Kikuno, R.; Nakayama, M.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVIII.
The complete sequences of 100 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 273-281, 2000.
5. Parkinson, N. J.; Olsson, C. L.; Hallows, J. L.; McKee-Johnson,
J.; Keogh, B. P.; Noben-Trauth, K.; Kujawa, S. G.; Tempel, B. L.:
Mutant beta-spectrin 4 causes auditory and motor neuropathies in quivering
mice. Nature Genet. 29: 61-65, 2001.
6. Tse, W. T.; Tang, J.; Jin, O.; Korsgren, C.; John, K. M.; Kung,
A. L.; Gwynn, B.; Peters, L. L.; Lux, S. E.: A new spectrin, beta-IV,
has a major truncated isoform that associates with promyelocytic leukemia
protein nuclear bodies and the nuclear matrix. J. Biol. Chem. 276:
23974-23985, 2001.
7. Yoon, C. H.; Les, E. P.: Quivering, a new first chromosome mutation
in mice. J. Hered. 48: 176-180, 1957.
*FIELD* CN
Victor A. McKusick - updated: 8/23/2001
*FIELD* CD
Paul J. Converse: 8/21/2001
*FIELD* ED
terry: 03/03/2005
terry: 6/27/2002
mgross: 8/23/2001
terry: 8/23/2001
mgross: 8/22/2001
mgross: 8/21/2001