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KICSTOR complex protein SZT2 (Seizure threshold 2 protein) (Transcript increased in glutamate resistance) (TIGR)

 SZT2_MOUSE              Reviewed;        3431 AA.
A2A9C3; Q6PB77; Q7TSS6;
05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
20-FEB-2007, sequence version 1.
12-SEP-2018, entry version 77.
RecName: Full=KICSTOR complex protein SZT2 {ECO:0000305};
AltName: Full=Seizure threshold 2 protein {ECO:0000303|PubMed:19624305};
AltName: Full=Transcript increased in glutamate resistance {ECO:0000303|PubMed:20045724};
Short=TIGR {ECO:0000303|PubMed:20045724};
Name=Szt2 {ECO:0000303|PubMed:19624305, ECO:0000312|MGI:MGI:3033336};
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS
SPECTROMETRY, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
STRAIN=C57BL/6J; TISSUE=Brain;
PubMed=19624305; DOI=10.1111/j.1601-183X.2009.00509.x;
Frankel W.N., Yang Y., Mahaffey C.L., Beyer B.J., O'Brien T.P.;
"Szt2, a novel gene for seizure threshold in mice.";
Genes Brain Behav. 8:568-576(2009).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INDUCTION, TISSUE
SPECIFICITY, AND SUBCELLULAR LOCATION.
PubMed=20045724; DOI=10.1016/j.freeradbiomed.2009.12.023;
Toutzaris D., Lewerenz J., Albrecht P., Jensen L.T., Letz J.,
Geerts A., Golz S., Methner A.;
"A novel giant peroxisomal superoxide dismutase motif-containing
protein.";
Free Radic. Biol. Med. 48:811-820(2010).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J;
PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
Lindblad-Toh K., Eichler E.E., Ponting C.P.;
"Lineage-specific biology revealed by a finished genome assembly of
the mouse.";
PLoS Biol. 7:E1000112-E1000112(2009).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2675-3431.
STRAIN=C57BL/6J, and Czech II; TISSUE=Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain, Pancreas, and Spleen;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
[6]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=28199306; DOI=10.1038/nature21423;
Wolfson R.L., Chantranupong L., Wyant G.A., Gu X., Orozco J.M.,
Shen K., Condon K.J., Petri S., Kedir J., Scaria S.M.,
Abu-Remaileh M., Frankel W.N., Sabatini D.M.;
"KICSTOR recruits GATOR1 to the lysosome and is necessary for
nutrients to regulate mTORC1.";
Nature 543:438-442(2017).
[7]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=28199315; DOI=10.1038/nature21378;
Peng M., Yin N., Li M.O.;
"SZT2 dictates GATOR control of mTORC1 signalling.";
Nature 543:433-437(2017).
-!- FUNCTION: As part of the KICSTOR complex functions in the amino
acid-sensing branch of the TORC1 signaling pathway. Recruits, in
an amino acid-independent manner, the GATOR1 complex to the
lysosomal membranes and allows its interaction with GATOR2 and the
RAG GTPases. Functions upstream of the RAG GTPases and is required
to negatively regulate mTORC1 signaling in absence of amino acids
(By similarity). In absence of the KICSTOR complex mTORC1 is
constitutively localized to the lysosome and activated. The
KICSTOR complex is also probably involved in the regulation of
mTORC1 by glucose (PubMed:28199306, PubMed:28199315). May play a
role in the cellular response to oxidative stress
(PubMed:20045724). {ECO:0000250|UniProtKB:Q5T011,
ECO:0000269|PubMed:20045724, ECO:0000269|PubMed:28199306,
ECO:0000269|PubMed:28199315}.
-!- SUBUNIT: Part of the KICSTOR complex composed of KPTN, ITFG2,
C12orf66 and SZT2. SZT2 probably serves as a link between the
other three proteins in the KICSTOR complex and may mediate the
direct interaction with the GATOR complex via GATOR1. The KICSTOR
complex interacts directly with the GATOR1 complex and most
probably indirectly with the GATOR2 complexe in an amino acid-
independent manner. {ECO:0000250|UniProtKB:Q5T011}.
-!- SUBCELLULAR LOCATION: Lysosome membrane
{ECO:0000250|UniProtKB:Q5T011}. Peroxisome
{ECO:0000269|PubMed:20045724}. Note=Localization to lysosomes is
amino acid-independent. {ECO:0000250|UniProtKB:Q5T011}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=A2A9C3-1; Sequence=Displayed;
Name=2;
IsoId=A2A9C3-2; Sequence=VSP_039917;
-!- TISSUE SPECIFICITY: Mostly expressed in brain, spinal cord and
lung. {ECO:0000269|PubMed:19624305, ECO:0000269|PubMed:20045724}.
-!- INDUCTION: Induced in cells resistant to glutamate toxicity.
{ECO:0000269|PubMed:20045724}.
-!- DISRUPTION PHENOTYPE: Knockout mice lacking Szt2 are born at an
expected Mendelian ratio, but they do not survive weaning or any
fasting (PubMed:28199315). They display increased mTORC1 signaling
in several tissues (PubMed:28199306, PubMed:28199315). Mutant mice
with a gene trap-induced truncating mutation display embryonic
lethality and surviving mutants show significantly decreased
threshold to minimal forebrain clonic seizures (PubMed:19624305).
{ECO:0000269|PubMed:19624305, ECO:0000269|PubMed:28199306,
ECO:0000269|PubMed:28199315}.
-!- SEQUENCE CAUTION:
Sequence=AAH52935.1; Type=Frameshift; Positions=Several; Evidence={ECO:0000305};
Sequence=AAH52935.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
Sequence=GU433214; Type=Frameshift; Positions=Several; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; FJ998170; ACS91341.1; -; mRNA.
EMBL; GU433214; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; AL627212; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC059842; AAH59842.2; -; mRNA.
EMBL; BC052935; AAH52935.1; ALT_SEQ; mRNA.
CCDS; CCDS51283.1; -. [A2A9C3-1]
RefSeq; NP_937813.3; NM_198170.4. [A2A9C3-1]
UniGene; Mm.415218; -.
ProteinModelPortal; A2A9C3; -.
BioGrid; 231000; 1.
STRING; 10090.ENSMUSP00000074862; -.
iPTMnet; A2A9C3; -.
PhosphoSitePlus; A2A9C3; -.
EPD; A2A9C3; -.
MaxQB; A2A9C3; -.
PaxDb; A2A9C3; -.
PeptideAtlas; A2A9C3; -.
PRIDE; A2A9C3; -.
Ensembl; ENSMUST00000075406; ENSMUSP00000074862; ENSMUSG00000033253. [A2A9C3-1]
GeneID; 230676; -.
KEGG; mmu:230676; -.
UCSC; uc012djw.2; mouse. [A2A9C3-1]
UCSC; uc012djx.2; mouse. [A2A9C3-2]
CTD; 23334; -.
MGI; MGI:3033336; Szt2.
eggNOG; ENOG410IE3I; Eukaryota.
eggNOG; ENOG410XTCX; LUCA.
GeneTree; ENSGT00390000018402; -.
HOGENOM; HOG000231148; -.
HOVERGEN; HBG080139; -.
InParanoid; A2A9C3; -.
OMA; DYRAPFL; -.
OrthoDB; EOG091G0OT8; -.
PhylomeDB; A2A9C3; -.
TreeFam; TF333377; -.
PRO; PR:A2A9C3; -.
Proteomes; UP000000589; Chromosome 4.
Bgee; ENSMUSG00000033253; Expressed in 235 organ(s), highest expression level in rostral migratory stream.
ExpressionAtlas; A2A9C3; baseline and differential.
Genevisible; A2A9C3; MM.
GO; GO:1990130; C:GATOR1 complex; IEA:Ensembl.
GO; GO:0061700; C:GATOR2 complex; IEA:Ensembl.
GO; GO:0140007; C:KICSTOR complex; ISS:UniProtKB.
GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
GO; GO:0007417; P:central nervous system development; IMP:MGI.
GO; GO:0021540; P:corpus callosum morphogenesis; ISO:MGI.
GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:UniProtKB.
GO; GO:0043473; P:pigmentation; IMP:MGI.
GO; GO:0009791; P:post-embryonic development; IMP:MGI.
GO; GO:0061462; P:protein localization to lysosome; ISS:UniProtKB.
GO; GO:1901668; P:regulation of superoxide dismutase activity; IMP:UniProtKB.
GO; GO:0031667; P:response to nutrient levels; IMP:UniProtKB.
InterPro; IPR033228; SZT2.
PANTHER; PTHR14918; PTHR14918; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Lysosome; Membrane;
Peroxisome; Phosphoprotein; Reference proteome.
CHAIN 1 3431 KICSTOR complex protein SZT2.
/FTId=PRO_0000399821.
REGION 1082 1188 Mediates interaction with the GATOR1
complex. {ECO:0000250|UniProtKB:Q5T011}.
COMPBIAS 3040 3091 His-rich.
MOD_RES 1275 1275 Phosphoserine.
{ECO:0000250|UniProtKB:Q5T011}.
MOD_RES 1415 1415 Phosphoserine.
{ECO:0000250|UniProtKB:Q5T011}.
MOD_RES 1640 1640 Phosphothreonine.
{ECO:0000250|UniProtKB:Q5T011}.
MOD_RES 1650 1650 Phosphoserine.
{ECO:0000250|UniProtKB:Q5T011}.
VAR_SEQ 2131 2131 Missing (in isoform 2).
{ECO:0000303|PubMed:20045724}.
/FTId=VSP_039917.
CONFLICT 275 275 C -> S (in Ref. 1; GU433214).
{ECO:0000305}.
CONFLICT 888 888 N -> K (in Ref. 1; GU433214).
{ECO:0000305}.
CONFLICT 1067 1067 L -> C (in Ref. 1; GU433214).
{ECO:0000305}.
CONFLICT 1192 1192 L -> H (in Ref. 1; GU433214).
{ECO:0000305}.
CONFLICT 1204 1204 S -> T (in Ref. 1; GU433214).
{ECO:0000305}.
CONFLICT 1308 1308 F -> S (in Ref. 1; GU433214).
{ECO:0000305}.
SEQUENCE 3431 AA; 377627 MW; 2DADDD0F72FC38F7 CRC64;
MASERPEPEV EEAGQVFLLM KKDYRISRNV RLAWFLNHLH QTVQATPQEL LLQSEQELEV
LSVLPPGWQP DEPVVPRPFL LVPSTRVTFL AWQYRFVIEL DLSPSTGIVD DSTGEILFDE
VFHALSRCLG GLLRPFRVPG SCINFQPEIY VTIQAYSSII GLQSHQVLVQ GCLLDPSQRE
AFLQQVYEQL CLFEDKVATM LQQQYEPQGQ AEDQSPESGE SLGRKVGVSM VTADLGLVSM
IRQGILALQL LPSNSSAGII VITDGVTSVP DVAVCETLLN QLRSGTVACS FVQVGGVYSY
DCSFGHVPNV ELMKFIAMAT FGSYLSTCPE TEPGNLGLTV YHRAFLLYSF LRSGEALNPE
YYCGSQHRLF NEHLVSASSN PALALRRKKH TEKEVPADLV STVSVRLREG YSVREVTLAK
GGSQLEVKLV LLWKHNMRIE YVAVAPWPLE PEGPRGTRVE VTMEGGYDIL HDVSCALRQP
IRSLYRTHVI RRFWNTLQSI NQTDQMLAHL QSFSSVPEHF TLPDSTKSGV PLFYIPPGSS
TPVLSLQHSG SDSSHAQFAA YWKPVLSMDA NSWQRWLHMH RLVLILEHDT PLPKHLHTPG
SNGRYSTIQC RISHSSLTSL LRDWSSFVLV EGYSYVKLLS SAPDQPPSSF YMVRIISKTP
CMVLRLGFPI GTPAQARHKI VSGLKEEILR LRFPHRVQSK EPTPKVKRKG LGGVGGSSPS
KSPPTLGPQQ ALSDRPCLVV LHKPLDKLLI RYEKLPLDYR APFLLTLEPP GPLPLVSGRS
ASSSLASLSR YLYHRRWLWS VPSGLAPTLP LSATAQLLSV LTEVRLSEGF HFACSGEGII
NMVLELPVQN EPLGQAAAEE KHTCVVQYIL FPPHSTSTKD SFSTDDDNDV EVEALEGDSE
LNLVTEVWVE PQYGRVGPGP ENWKHLQDLT YSEIPQALHP RDAACIGSLL TFEYLIQLCQ
SKEWGPLPPE PRLSDGLDQR GDTCVHEIPF HFDLLGLLPQ CQQLQMFFLL LSREPEGVPL
AEGPCPTNDM VLCLLHSCLG QELSDREIPL TPADQAAFLN EVLRRSLRDP GPEGPPVGGH
AVAKDRAGNS TQASGDSTLP SQSVVIPGVL RSSISAQPPQ WHCYARLLGP QHVFLTFLPA
TFSDVQHLTA YGLESSFQEE TKPKLGDWSG APSLKDPGAT GTKATESQVP TLSVTLASDS
AQDSGEPSTP SCQDLAANSG RQAPQTEGAD GPRTRCPVYI YSCSLEALRE QMVGLQPPQA
PRDLIFRAQD LDHPSSSSAW MEPRCKEAAT HCALLQEHAQ RCFVRGLFRS LQQAQSVTCQ
DLLTAVDACE ELLQEIDITS FLLALCGHTW GLPHAPPSPG PLSPGPFSSS IEEGPEPRER
AILVSESSIE TEDLSEPEFQ SSRVSGNLDP GPEISLTDVC QLRGEAHDAL HSLIQEKFLE
ISRLHFRTVP SNPHYFFYCP PSSRREDEGP RDTVDRKISD LEFSEAELVG EEGDTSACCV
VTESDPELEV EYRESREPDL GPAGLDSASL SDADTVNPDE DSFSILGGDS PTGPDSLMHD
LPPLFLHLTC SVRLRGQHSS VPVCSLPTCL GQVLSSLEGP PIGGRVPLRD LSITLDVFVL
TLPLEVELPP ASDPQHHRST SESSASFPRS PGQPSSLRSD DGLGPPLPPP EEERHPGLSS
LAMPHRLAIE STMNEIRWLL EDEMVGALRR GGIPQSPALH RAAAHIHSSS GRPTCLRQAP
PLSFVFGPER SLTQFKEEFR RLHLPGHVLL EDPDSGFFFV AAGQQPGVLH GEPPSAAWAW
HNHEDRAEDA EGEVLTASPQ VPGSLEDSEG TPLISLPSLS QGGSQPGPSR GLSLMSSQGS
VDSDHLGYDG GSSGSDSEGP GETLGEKALF TLRTPPGPAP PQPSLPVLPG PSLPDFWLIV
RILQDRVEVY AHARSLSRED GGPGAECRHL QQFLVRRVGE ICREVNQRLL LQDLHDSHVC
NSLLVAESEE DLWRSETPFH SRQRAVLPSD DFAADESCAP RGYLAATMQF VPGHFSCDVV
WGTVIRVHSR LKMGPSMGVS RAIQALRSVL NAFSVVNRKN MFVYQERATK AVYYLRLLET
SCSDRPWEGD TLPPSLALSR SQEPISSEDS VAPRSPLDMA SSRSSDAVRP VGQVDRHIQL
LVHGVGQAGP EITDELVRVL RRRLDEATLD IITVMLVRNC KLTPADVEFI QPPGSLPSEV
LHLVLPPSCR PCLPALAWYL RQNLLTFLHS PKYTDSNSRN HFQHPLPAQG GLPDLDIYLY
NKPGGQGTGG KGVACITLAF VEEGGTPISL ASWPPSSPGP PDPLREEEFE QLTQVIRCPN
TLDSCSAQDG SPRLRLDVWE KGNISIVQLE EKLRAAARQA LADAIMELRL LPASLCTEDI
PPGSLKSGPL DTKSPACRAN TFPCTPVSGE PVTPPSKAGR RSFWDMLSKT EAGDLGSPKT
TDDIVLDRPE DTRGRRRHKT ENVRTPGGSE RAPGPDSGAQ RQRRRTTQLE EGEVGTLHPV
FARVIQRWMG FMVQIGCASV SRSSTHMVSR FLLPSILSEF TTLVISMAGD TSVRVFEQHL
GSEPDVFSPC SPGQLGPAPR PAAQRHLLLL GRNFAQWRRP TQQAAKAVQR FESGGDGSPG
RSAPRQRLLL LEVTDKKLQL LTYNWAPDLG AALGRALIRL VQWQNARAHL ISCLLSQKLG
LFHHCGQLDF PMRDGKEPNP FLLPTMEVET LIRNASPPLS REQGRLSGSS RGGGPLSLDT
FPFDEALRDI TAARPSSTGG PAPRPPDPVT YHGQQFLEIK MTERKELERQ MKMENLFVTW
QQRSAPASMP ISAGELETLK QSSRLVHYCA TALLFDPAAW LHGPPETCAP SEGQRRPCPE
SGSGSREVPT SCESLDVPPP GAREEPWLKE LSLAFLQQYV QYLQSIGFVL VPLRPPSPAR
STSRLRAMAI LGTEGRGSFS CPKAKAEGSP KSTSTPVTTY HLQRALPGGI ILMELTFQGC
YFCVKQFALE CSRIPMGQAV NSQLSLLFTE ECDKVRDLMH VHSFSYDFHL RLVHQHVLGA
HLALRHGYHL TTFLQHFLAH HPDGPHFGRN HIYQGTLELP TPLIAAHQLY NYVADHASSY
HMKPLRMARP GGPEHNEYAL VSAWHSSGSY LDSEGLRHQD DFDVSLLVCH SAAPFEEQGE
AERHVLRLQF FVVLTSQREL FPRLTADMRR FRKPSRLPLE PETPGSLVGS PREASGMMLA
PGPAPLFPPL AAEVGMARAR LAQLVRLAGG HCRRDTLWKR LFLLEPPGPD RLRLGGRLAL
AELEELLEAV HAKSIADIDP QLDCFLSMTV SWYQSLIKVL LSRFPQSCRH FQSPDLGTQY
LVVLNQKFTD CFVLVFLDSH LGKTSLTVVF REPFPVQPQD SESPPAQLVS TYHHLESVIN
TACFTLWTRL L


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