SMG1_DANRE
ID SMG1_DANRE Reviewed; 3640 AA.
AC C5J7W8; F1QLT4; F6NHQ0;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Serine/threonine-protein kinase SMG1 {ECO:0000250|UniProtKB:Q96Q15};
DE Short=smg-1;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q96Q15};
DE AltName: Full=Nonsense-mediated mRNA decay-associated PI3K-related kinase SMG1 {ECO:0000312|ZFIN:ZDB-GENE-061013-767};
GN Name=smg1 {ECO:0000312|ZFIN:ZDB-GENE-061013-767};
GN Synonyms=atx {ECO:0000250|UniProtKB:Q96Q15};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|Proteomes:UP000000437};
RN [1] {ECO:0000312|EMBL:CAX18774.1}
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=19414594; DOI=10.1128/mcb.00177-09;
RA Wittkopp N., Huntzinger E., Weiler C., Sauliere J., Schmidt S.,
RA Sonawane M., Izaurralde E.;
RT "Nonsense-mediated mRNA decay effectors are essential for zebrafish
RT embryonic development and survival.";
RL Mol. Cell. Biol. 29:3517-3528(2009).
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Serine/threonine protein kinase involved in both mRNA
CC surveillance and genotoxic stress response pathways. Recognizes the
CC substrate consensus sequence [ST]-Q. Plays a central role in nonsense-
CC mediated decay (NMD) of mRNAs containing premature stop codons by
CC phosphorylating UPF1/RENT1. {ECO:0000250|UniProtKB:Q96Q15}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q96Q15};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q96Q15};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q96Q15};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96Q15}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q96Q15}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=C5J7W8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=C5J7W8-2; Sequence=VSP_061249;
CC -!- DEVELOPMENTAL STAGE: Expressed during early cleavage, gastrulation and
CC at 1 day post-fertilization. {ECO:0000269|PubMed:19414594}.
CC -!- PTM: Autophosphorylated. {ECO:0000250|UniProtKB:Q96Q15}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in reduced slc24a5
CC expression in wild-type embryos however expression is still detectable
CC in the body and retinal pigment epithelium (PubMed:19414594). In 50% of
CC the embryos expression of slc24a5 is restricted to the retina
CC (PubMed:19414594). {ECO:0000269|PubMed:19414594}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family.
CC {ECO:0000250|UniProtKB:Q96Q15}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; FM986821; CAX18774.1; -; mRNA.
DR EMBL; BX004999; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001073513.2; NM_001080044.2.
DR STRING; 7955.ENSDARP00000071267; -.
DR PeptideAtlas; C5J7W8; -.
DR Ensembl; ENSDART00000076796; ENSDARP00000071267; ENSDARG00000054570. [C5J7W8-1]
DR GeneID; 569810; -.
DR KEGG; dre:569810; -.
DR CTD; 23049; -.
DR ZFIN; ZDB-GENE-061013-767; smg1.
DR eggNOG; KOG0891; Eukaryota.
DR GeneTree; ENSGT00940000154776; -.
DR HOGENOM; CLU_000316_0_0_1; -.
DR InParanoid; C5J7W8; -.
DR OrthoDB; 26975at2759; -.
DR PhylomeDB; C5J7W8; -.
DR TreeFam; TF352560; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 3.
DR Bgee; ENSDARG00000054570; Expressed in tail and 21 other tissues.
DR ExpressionAtlas; C5J7W8; baseline.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0031931; C:TORC1 complex; IBA:GO_Central.
DR GO; GO:0031932; C:TORC2 complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IBA:GO_Central.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0031929; P:TOR signaling; IBA:GO_Central.
DR CDD; cd05170; PIKKc_SMG1; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR003152; FATC_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR014009; PIK_FAT.
DR InterPro; IPR031559; SMG1.
DR InterPro; IPR035175; SMG1_N.
DR InterPro; IPR039414; SMG1_PIKKc.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF15785; SMG1; 1.
DR Pfam; PF17229; SMG1_N; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Manganese;
KW Nonsense-mediated mRNA decay; Nucleotide-binding; Nucleus;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..3640
FT /note="Serine/threonine-protein kinase SMG1"
FT /id="PRO_0000454181"
FT DOMAIN 1495..1843
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT REPEAT 1794..1829
FT /note="HEAT"
FT /evidence="ECO:0000250|UniProtKB:Q8BKX6"
FT DOMAIN 2102..2441
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 3608..3640
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 21..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1870..1890
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2108..2114
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2310..2318
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2330..2354
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT COMPBIAS 21..40
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1397..1401
FT /note="Missing (in isoform 2)"
FT /id="VSP_061249"
FT CONFLICT 1221
FT /note="S -> A (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 3640 AA; 405061 MW; 8E069B2DFB7D8465 CRC64;
MSRKALGSRL SSAHKLQRNW NDWQPRSDSL SASQDGVKCS VSRDRGSEVL FEILPSDRPG
TPPLHNDAFT ATDALEEGGG YDADGGLSEN AYGWKSLGQE LRINDVTTDI TTFQHGNRAL
ATKDMRKSQD RPLAHSEESR LANLLRRASR EDDRERRLAT MKQMKEFIVH SENKVVLVKQ
LDSILSTLND ILNESSKLLQ ELRQEAAWCL GLLCAALSYE AERIFKWMFL KFSVSTKDEV
KLLYLVAVHK ALETAGEKKA FSAVMQLVMS NLQSILENLD TPELLCQSVK CILLVARCYP
HIFSTNFRDT VDILVGWHID HTQKHSLTQQ VSGWLQSLEQ FWVADLAFST TLLGQFLEDM
EAYAEDLSHV VSGESGDEDI PPPTVSLPKL AALLRVFSTV VHSIGERFNP IRGPPITEAY
VTDVLNRVLA CVTTAKQVFF SEAVLTAGNE CVCVLLVSID LGGQLIDAVI SYGLDQLNCC
QNCGPEYSLS VLTLLTLVVD QINTKLPASF VEKLLAPKSH LLELRFHRER EVMAAAHGVY
HAVLSLKNIP ILEAAYKLVL GEMGCALNSL LSPLGLPDAC PHIQHPAFSQ LNFSPERAEF
VLIFNLSALT TIGNTKNSLI GMWALSPTVF ALLSQNLVIV HSDLAVHHPA VQYAVLYTLY
SHCTRHDHFI SSSLSSSSPS LFDGAVISTV TTATKRHFST LLNLLGMLLS KDHLNPEARR
LLLTWSLEVA LMMKKSETYA PLFSLPSFLK FCKGLLANSL NEDTTICLQA CNSLQVLSSS
LTMELLQRCV DVCRVQLVHS AVRVRQAFGK LLRSVPMHVA LSAHSHSEIK EISLAIRRHM
SKVPSNTFHP QDFSDLIGFI LYGTVHRGGK EPWLERLYHS CQRLEKKDSA MVPRALLKTE
AVLWQWAVWE AAQFTVLSKL RTPLGRAQDT FQTIEGMIRS LAAHSLNTEQ ELSQWSGGES
DEGHHTNQLR LALLLQFLEN LEKLMYNAYE GCASALTAPP KGIRTFFYTN RQTCQDWLTR
IRLALMRVGL LSGQPAVTVR HGFDLLTEIK NSSTQGPEME VPVTMLVEAL CELRCPEAIQ
GLAAWSLANT GKSMGWLSSV ALQAEGKFEK AALEYQEQLC AVTGMDCSIK VFDRSLLKLT
GTNTSSPKHT SSGEGRKTVL LKSSECSPEV LNFLANKACE CYVALSDWES VQEWQASMMN
LKKNSSSSSV NLKTDFNYIR SMSRFEEGDF TECRAQLELL PGDDYGLLNS TTKDKIDLKR
LLPAVLSPDP SELQKAIEVQ LLRSAVGAIS ATNHEQDQKV ASSDTLVKYL KQTGRICLGP
LRLSTLTLSD SLPTLSTLQL HCANSLENSL CNQHPEDCLI PLFSEALTTC KQQDVQPWLH
ALRYTTFQRE FFQKLKGSSS PVDSHLMELC LTAVKFARKQ GNIALATRLL SLCSKPAMSD
TEGQDLVQSF RQLSLEGTVG EKWGPELEIE KAKVLFAAGQ SVSAMEMLSS CALSYCHSGK
CELAACRSVL TLCKWLLADW KDLTPQLKMV VKKNSGSTSL STLSKNISGL LELPLEDQGM
PHITTETTVS VGVGEPDFVL GQLYQLSTTQ APEVAKSWAA LASWAYRWGR KVVDNASQGE
GVPLLLGEKK EIEELLPAGT SDEDKETIFG ILGQAMCRPA GIQDEDMALQ NEEDDEDDMV
DVIGRQLLGA CPWLSDVEDT VTDGLIGVWR RVVDRIFSLY RVSCRAYFTF LKLNAGQVPI
DEDDPKLLLN NQNSKQSSDD VIVMATLRLL RLLVKHAGEL REGLEHGLAS TPTAPWRGII
PQLFSRLNHP EAYIRQSICS LLCRVAQDSP HLILYPAIVG SISLGGEAQT AGNKLPSSLP
TLLGNMQGEG LCGGESETGS GPTSQESSRG EEMVMYSSED QAMMQDCYSK IVDKLSSANP
TMVLQVQMLV GELRRVTLLW DELWLGVLQQ QHMHVLRRIQ QLEDEVKRVQ NNNTLRKDEK
VAIMREKHSA LMKPVVFALD HVRSITAAPA ETPHEEWFQE TYGDAIHNAL ERLRSPLNPA
NPASSWVPFK QIMLSLQQRA QKRASYLLRL DEISPRLTAM ANTEMALPGE VSATDAVTIQ
SVGNTITILP TKTKPKKLYF LGSDGRNYPY LFKGLEDLHL DERIMQFLSI VNTMFTKVNQ
QESPRFQARH YSVTPLGTRS GLIQWVDGAT PLFGLYKRWQ QREAVVQAQK AQDSFQQPQN
LPMVPRPSEL YYSKISPALK AVGLSLDVSR RDWPLSVMRD VLRELMEATP PNLLAKELWC
SCTTPSEWWS VTQTYARSTA VMSMVGYIIG LGDRHLDNVL IDMTTGEVVH IDYNVCFEKG
KSLRVPEKVP FRMTHNIETA LGVTGVEGIF RLSCEQVVQI MRRGRETLLT LLEAFVYDPL
VDWTAGGEVG FAGAVYGGGG QQAENKQSKR EMERDITRSL FSSRVAEIKV NWFKNRDEMT
GVLPQLEEAV DEYLNLQEQL TQVEKVQGKL LEELEFLEGA DTRADHPIHS LEHRYSEHTQ
LQSRQRTVQD AIQGKLSDLD QWISQYQAAF ASLEATQLAS LLQEISSPID LGPPSYVPAT
SFLQNAGQAH LISQCEALEA EVSALLQQRR SQLRGCLEHL HSYATVALLY PRAVLHRHRA
HTWKQWMEEL VCDMTVDHCQ TIYHQYEMQF APQPPPATCQ FLSSIEMALQ HHAAETNTRL
LRQVERLKAE GASVPVCEEQ LQEIERCIKV FLHEDAELGS FSLAGIIVSA LCSLTRRNLV
MEGAAASAGE QLVELTSRDG AWFLEELCSM SGNITCLVQL LQQCQLLSHD LDIPSPAETS
QVVYLTNGVY TCLQELNTNF RQIIFPEALR CMLKGENTLE TMLAELDALI DQCADGVSLQ
GLGEILMAHI RNASMGLEED PDDHYLDVTR VLRAQYSELI QPRSMESSVQ ETPKMSAGQM
LLVAFDGMFA QLETAFGLLI DKLNSMDVPA AWRKVDVIRE SRATQAHFFD NVQTRQVLEE
IFFLKRLQTI RDFFRLCGSF AQTLSGTCPT PTDDPPPSNG PVPIVKPLYR GSTVVSEDQM
TRPIKAFTAD FVRQMLMGLP TQALGLAICS SLSALGMDLI AQVEAKDFGA EGKVSLDDLC
KKAVEQGVQA GRLSQLLLNR ATVLASSYDT AWKKLDLVRR LEVSIEACKV SLQRNQLHIA
MFQWQHEDIL GARTQPMTVS PPPRSIILSN MKKKLYKLSQ DDASIGSVQE KLASLEGSIE
QRLKWAGGAN PALAPVLQDF EATIAERRAL VIKESQRANQ VTFLCSTILN FEGLRTRTPE
ALNMDAALFE LVKRCQATCS YAAQFNTSVS SLELQLLHRL SPAMDMSIGG PEWLVYAQNH
LTQEMSSQRA MQEEREQQLE SVTETLQLLV DSIKGTLSNH NRQLADVKHL LRAMAKDEEN
ALAEGEEVTY DGSVRQFLSE YKAWQDNVQI VLFTVVQATG QPRSQEQIEL LQEIPATLKE
LKVQSHSIYN GLVGFASPLV TERGSDCISP TSTVQTSFAA AVRCSGVKTQ PDSMSQNARK
ALPRNFGTPA DTPPSTLMIN SKGLAPSPKR AVRDPKTGRA VQERNSYAVS VWKRVKAKLE
GRDVDPNRRM SVTEQVDYVI KEATNVDNLA QLYEGWTAWV
