SZT2_HUMAN
ID SZT2_HUMAN Reviewed; 3432 AA.
AC Q5T011; A0PJK5; A7E2X4; O75055; Q5JUY7; Q5T012; Q5XKC7; Q6ZNI8; Q6ZT24;
AC Q7Z636; Q8NAY9; Q9H5H7; Q9UFQ8;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=KICSTOR complex protein SZT2 {ECO:0000305};
DE AltName: Full=Seizure threshold 2 protein homolog {ECO:0000312|HGNC:HGNC:29040};
GN Name=SZT2 {ECO:0000312|HGNC:HGNC:29040};
GN Synonyms=C1orf84 {ECO:0000312|HGNC:HGNC:29040},
GN KIAA0467 {ECO:0000312|EMBL:BAA32312.2};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 2797-3432 (ISOFORM 1), AND NUCLEOTIDE SEQUENCE [LARGE
RP SCALE MRNA] OF 689-3432 (ISOFORM 3).
RC TISSUE=Lung, Spleen, and Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 142-330 (ISOFORM 1).
RX PubMed=15028280; DOI=10.1016/j.ygeno.2003.07.003;
RA Xie H., Diber A., Pollock S., Nemzer S., Safer H., Meloon B., Olson A.,
RA Hwang J.J., Endress G.A., Savitsky K., Gill-More R.;
RT "Bridging expressed sequence alignments through targeted cDNA sequencing.";
RL Genomics 83:572-576(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 256-369 (ISOFORM 1).
RX PubMed=10737800; DOI=10.1073/pnas.97.7.3491;
RA Dias Neto E., Correa R.G., Verjovski-Almeida S., Briones M.R.S.,
RA Nagai M.A., da Silva W. Jr., Zago M.A., Bordin S., Costa F.F.,
RA Goldman G.H., Carvalho A.F., Matsukuma A., Baia G.S., Simpson D.H.,
RA Brunstein A., de Oliveira P.S.L., Bucher P., Jongeneel C.V., O'Hare M.J.,
RA Soares F., Brentani R.R., Reis L.F.L., de Souza S.J., Simpson A.J.G.;
RT "Shotgun sequencing of the human transcriptome with ORF expressed sequence
RT tags.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:3491-3496(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 424-3432 (ISOFORM 2).
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 689-3432 (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=9455484; DOI=10.1093/dnares/4.5.345;
RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D.,
RA Nomura N., Ohara O.;
RT "Characterization of cDNA clones in size-fractionated cDNA libraries from
RT human brain.";
RL DNA Res. 4:345-349(1997).
RN [7]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2849-3432 (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3099-3432 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=20045724; DOI=10.1016/j.freeradbiomed.2009.12.023;
RA Toutzaris D., Lewerenz J., Albrecht P., Jensen L.T., Letz J., Geerts A.,
RA Golz S., Methner A.;
RT "A novel giant peroxisomal superoxide dismutase motif-containing protein.";
RL Free Radic. Biol. Med. 48:811-820(2010).
RN [11]
RP INVOLVEMENT IN DEE18, VARIANTS DEE18 25-ARG--LEU-3432 DEL; ILE-499 AND
RP 698-GLN--LEU-3432 DEL, AND TISSUE SPECIFICITY.
RX PubMed=23932106; DOI=10.1016/j.ajhg.2013.07.005;
RA Basel-Vanagaite L., Hershkovitz T., Heyman E., Raspall-Chaure M., Kakar N.,
RA Smirin-Yosef P., Vila-Pueyo M., Kornreich L., Thiele H., Bode H.,
RA Lagovsky I., Dahary D., Haviv A., Hubshman M.W., Pasmanik-Chor M.,
RA Nurnberg P., Gothelf D., Kubisch C., Shohat M., Macaya A., Borck G.;
RT "Biallelic SZT2 mutations cause infantile encephalopathy with epilepsy and
RT dysmorphic corpus callosum.";
RL Am. J. Hum. Genet. 93:524-529(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1276 AND SER-1651, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1416 AND THR-1641, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP FUNCTION, IDENTIFICATION IN THE KICSTOR COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=28199306; DOI=10.1038/nature21423;
RA Wolfson R.L., Chantranupong L., Wyant G.A., Gu X., Orozco J.M., Shen K.,
RA Condon K.J., Petri S., Kedir J., Scaria S.M., Abu-Remaileh M.,
RA Frankel W.N., Sabatini D.M.;
RT "KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to
RT regulate mTORC1.";
RL Nature 543:438-442(2017).
RN [15]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND REGION.
RX PubMed=28199315; DOI=10.1038/nature21378;
RA Peng M., Yin N., Li M.O.;
RT "SZT2 dictates GATOR control of mTORC1 signalling.";
RL Nature 543:433-437(2017).
RN [16]
RP VARIANT PHE-1458 DEL.
RX PubMed=24324832; DOI=10.1371/journal.pone.0082810;
RA Falcone M., Yariz K.O., Ross D.B., Foster J. II, Menendez I., Tekin M.;
RT "An amino acid deletion inSZT2 in a family with non-syndromic intellectual
RT disability.";
RL PLoS ONE 8:E82810-E82810(2013).
CC -!- FUNCTION: As part of the KICSTOR complex functions in the amino acid-
CC sensing branch of the TORC1 signaling pathway. Recruits, in an amino
CC acid-independent manner, the GATOR1 complex to the lysosomal membranes
CC and allows its interaction with GATOR2 and the RAG GTPases. Functions
CC upstream of the RAG GTPases and is required to negatively regulate
CC mTORC1 signaling in absence of amino acids. In absence of the KICSTOR
CC complex mTORC1 is constitutively localized to the lysosome and
CC activated. The KICSTOR complex is also probably involved in the
CC regulation of mTORC1 by glucose (PubMed:28199306, PubMed:28199315). May
CC play a role in the cellular response to oxidative stress (By
CC similarity). {ECO:0000250|UniProtKB:A2A9C3,
CC ECO:0000269|PubMed:28199306, ECO:0000269|PubMed:28199315}.
CC -!- SUBUNIT: Part of the KICSTOR complex composed of KPTN, ITFG2, KICS2 and
CC SZT2. SZT2 probably serves as a link between the other three proteins
CC in the KICSTOR complex and mediates the direct interaction with the
CC GATOR1 complex. {ECO:0000269|PubMed:28199306,
CC ECO:0000269|PubMed:28199315}.
CC -!- INTERACTION:
CC Q5T011; Q12980: NPRL3; NbExp=5; IntAct=EBI-10749411, EBI-2650314;
CC Q5T011; Q96S15: WDR24; NbExp=5; IntAct=EBI-10749411, EBI-746424;
CC Q5T011-5; O43186: CRX; NbExp=3; IntAct=EBI-10245139, EBI-748171;
CC Q5T011-5; Q04864: REL; NbExp=3; IntAct=EBI-10245139, EBI-307352;
CC Q5T011-5; P15884: TCF4; NbExp=3; IntAct=EBI-10245139, EBI-533224;
CC Q5T011-5; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-10245139, EBI-11139477;
CC Q5T011-5; Q8N720: ZNF655; NbExp=3; IntAct=EBI-10245139, EBI-625509;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:28199306,
CC ECO:0000269|PubMed:28199315}. Peroxisome
CC {ECO:0000250|UniProtKB:A2A9C3}. Note=Localization to lysosomes is amino
CC acid-independent. {ECO:0000269|PubMed:28199306,
CC ECO:0000269|PubMed:28199315}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q5T011-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5T011-4; Sequence=VSP_034456, VSP_034457;
CC Name=3;
CC IsoId=Q5T011-5; Sequence=VSP_039916;
CC Name=4;
CC IsoId=Q5T011-7; Sequence=VSP_039913, VSP_039914, VSP_039915;
CC -!- TISSUE SPECIFICITY: Expressed in the brain, predominantly in the
CC parietal and frontal cortex, as well as in dorsal root ganglia.
CC Expressed in peripheral white blood cells.
CC {ECO:0000269|PubMed:20045724, ECO:0000269|PubMed:23932106}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 18 (DEE18)
CC [MIM:615476]: A severe autosomal recessive neurologic disorder
CC characterized by lack of psychomotor development apparent from birth,
CC dysmorphic facial features, early onset of refractory seizures, and
CC thick corpus callosum and persistent cavum septum pellucidum on brain
CC imaging. {ECO:0000269|PubMed:23932106}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH52802.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI51233.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15649.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC03755.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=BAC86771.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=BF926328; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BF926328; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC Sequence=BU101724; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AL139289; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL583862; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017576; AAH17576.1; -; mRNA.
DR EMBL; BC041069; AAH41069.1; -; mRNA.
DR EMBL; BC052802; AAH52802.1; ALT_INIT; mRNA.
DR EMBL; BC082968; AAH82968.1; -; mRNA.
DR EMBL; BC151232; AAI51233.1; ALT_INIT; mRNA.
DR EMBL; BU101724; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BF926328; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK131107; BAC85157.1; -; mRNA.
DR EMBL; AB007936; BAA32312.2; -; mRNA.
DR EMBL; AK027078; BAB15649.1; ALT_INIT; mRNA.
DR EMBL; AK091821; BAC03755.1; ALT_SEQ; mRNA.
DR EMBL; AK126972; BAC86771.1; ALT_SEQ; mRNA.
DR EMBL; AL117402; CAB55903.1; -; mRNA.
DR CCDS; CCDS30694.2; -. [Q5T011-5]
DR PIR; T00093; T00093.
DR PIR; T17213; T17213.
DR RefSeq; NP_056099.3; NM_015284.3. [Q5T011-5]
DR RefSeq; XP_006710564.1; XM_006710501.3.
DR BioGRID; 116921; 35.
DR ComplexPortal; CPX-6229; KICSTOR complex.
DR CORUM; Q5T011; -.
DR IntAct; Q5T011; 22.
DR STRING; 9606.ENSP00000457168; -.
DR GlyGen; Q5T011; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5T011; -.
DR PhosphoSitePlus; Q5T011; -.
DR BioMuta; SZT2; -.
DR DMDM; 308153547; -.
DR EPD; Q5T011; -.
DR jPOST; Q5T011; -.
DR MassIVE; Q5T011; -.
DR MaxQB; Q5T011; -.
DR PaxDb; Q5T011; -.
DR PeptideAtlas; Q5T011; -.
DR PRIDE; Q5T011; -.
DR ProteomicsDB; 64109; -. [Q5T011-1]
DR ProteomicsDB; 64110; -. [Q5T011-4]
DR ProteomicsDB; 64111; -. [Q5T011-5]
DR ProteomicsDB; 64112; -. [Q5T011-7]
DR Antibodypedia; 32333; 86 antibodies from 15 providers.
DR Ensembl; ENST00000372450.8; ENSP00000361528.4; ENSG00000198198.17. [Q5T011-7]
DR Ensembl; ENST00000562955.2; ENSP00000457168.1; ENSG00000198198.17. [Q5T011-5]
DR Ensembl; ENST00000634258.3; ENSP00000489255.1; ENSG00000198198.17. [Q5T011-1]
DR GeneID; 23334; -.
DR KEGG; hsa:23334; -.
DR MANE-Select; ENST00000634258.3; ENSP00000489255.1; NM_001365999.1; NP_001352928.1.
DR UCSC; uc001cjh.4; human. [Q5T011-1]
DR CTD; 23334; -.
DR DisGeNET; 23334; -.
DR GeneCards; SZT2; -.
DR HGNC; HGNC:29040; SZT2.
DR HPA; ENSG00000198198; Low tissue specificity.
DR MalaCards; SZT2; -.
DR MIM; 615463; gene.
DR MIM; 615476; phenotype.
DR neXtProt; NX_Q5T011; -.
DR OpenTargets; ENSG00000198198; -.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA142671628; -.
DR VEuPathDB; HostDB:ENSG00000198198; -.
DR eggNOG; ENOG502QPW4; Eukaryota.
DR GeneTree; ENSGT00390000018402; -.
DR HOGENOM; CLU_000250_0_0_1; -.
DR InParanoid; Q5T011; -.
DR OMA; AHPDLHK; -.
DR OrthoDB; 347778at2759; -.
DR PhylomeDB; Q5T011; -.
DR PathwayCommons; Q5T011; -.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q5T011; -.
DR BioGRID-ORCS; 23334; 24 hits in 1078 CRISPR screens.
DR ChiTaRS; SZT2; human.
DR GenomeRNAi; 23334; -.
DR Pharos; Q5T011; Tbio.
DR PRO; PR:Q5T011; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5T011; protein.
DR Bgee; ENSG00000198198; Expressed in colonic epithelium and 156 other tissues.
DR ExpressionAtlas; Q5T011; baseline and differential.
DR Genevisible; Q5T011; HS.
DR GO; GO:0140007; C:KICSTOR complex; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IMP:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB.
DR GO; GO:0021540; P:corpus callosum morphogenesis; IMP:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0043473; P:pigmentation; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; ISS:UniProtKB.
DR GO; GO:0061462; P:protein localization to lysosome; IMP:UniProtKB.
DR GO; GO:1901668; P:regulation of superoxide dismutase activity; ISS:UniProtKB.
DR InterPro; IPR033228; SZT2.
DR PANTHER; PTHR14918; PTHR14918; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Epilepsy; Lysosome; Membrane;
KW Peroxisome; Phosphoprotein; Reference proteome.
FT CHAIN 1..3432
FT /note="KICSTOR complex protein SZT2"
FT /id="PRO_0000275898"
FT REGION 699..731
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1083..1189
FT /note="Mediates interaction with the GATOR1 complex"
FT /evidence="ECO:0000269|PubMed:28199315"
FT REGION 1357..1413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1630..1686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1816..1908
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2124..2144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2399..2513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2737..2757
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2862..2902
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2958..2978
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3212..3236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1634..1658
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1847..1864
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1894..1908
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2399..2420
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2462..2486
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2960..2978
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1276
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1416
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1641
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1651
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 52..53
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039913"
FT VAR_SEQ 167..180
FT /note="VLVQGCLLDPSQRE -> RQGFTMLARLPSNF (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039914"
FT VAR_SEQ 181..3432
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039915"
FT VAR_SEQ 1015..1071
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9455484"
FT /id="VSP_039916"
FT VAR_SEQ 1015..1020
FT /note="EPEGVP -> AAWGRS (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_034456"
FT VAR_SEQ 1021..3432
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_034457"
FT VARIANT 25..3432
FT /note="Missing (in DEE18)"
FT /evidence="ECO:0000269|PubMed:23932106"
FT /id="VAR_078573"
FT VARIANT 499
FT /note="S -> I (in DEE18; alters splice sites and probably
FT alternative splicing; dbSNP:rs886041034)"
FT /evidence="ECO:0000269|PubMed:23932106"
FT /id="VAR_078574"
FT VARIANT 698..3432
FT /note="Missing (in DEE18)"
FT /evidence="ECO:0000269|PubMed:23932106"
FT /id="VAR_078575"
FT VARIANT 1458
FT /note="Missing (found in patients with intellectual
FT disability; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24324832"
FT /id="VAR_078576"
FT CONFLICT 167
FT /note="V -> G (in Ref. 3; BU101724)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="N -> H (in Ref. 3; BU101724)"
FT /evidence="ECO:0000305"
FT CONFLICT 315
FT /note="F -> L (in Ref. 3; BU101724)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="S -> A (in Ref. 3; BU101724)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="P -> S (in Ref. 5; BAC85157)"
FT /evidence="ECO:0000305"
FT CONFLICT 3332
FT /note="S -> P (in Ref. 8; BAB15649)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 3432 AA; 378029 MW; E65E415FA8C55BC1 CRC64;
MASERPEPEV EEAGQVFLLM KKDYRISRNV RLAWFLSHLH QTVQATPQEM LLQSEQELEV
LSVLPPGWQP DEPVVPRPFL LVPSTRVTFL AWQYRFVIEL DLSPSTGIVD DSTGEILFDE
VFHALSRCLG GLLRPFRVPG SCIDFQPEIY VTIQAYSSII GLQSHQVLVQ GCLLDPSQRE
VFLQQIYEQL CLFEDKVATM LQQQYDPQSQ AEDQSPDSGD LLGRKVGVSM VTADLGLVSM
IRQGILALQL LPSNSSAGII VITDGVTSVP DVAVCETLLN QLRSGTVACS FVQVGGVYSY
DCSFGHVPNV ELMKFIAMAT FGSYLSTCPE PEPGNLGLTV YHRAFLLYSF LRSGEALNPE
YYCGSQHRLF NEHLVSASSN PALALRRKKH TEKEVPADLV STVSVRLREG YSVREVTLAK
GGSQLEVKLV LLWKHNMRIE YVAMAPWPLE PEGPRVTRVE VTMEGGYDIL HDVSCALRQP
IRSLYRTHVI RRFWNTLQSI NQTDQMLAHL QSFSSVPEHF TLPDSTKSGV PLFYIPPGST
TPVLSLQPSG SDSSHAQFAA YWKPVLSMDA NSWQRWLHMH RLVLILEHDT PIPKHLHTPG
SNGRYSTIQC RISHSSLTSL LRDWSSFVLV EGYSYVKLLS SAPDQPPNSF YMVRIISKAP
CMVLRLGFPI GTPAPARHKI VSGLREEILR LRFPHRVQSK EPTPKVKRKG LGGAGGGSSP
SKSPPVLGPQ QALSDRPCLV VLHKPLDKLL IRYEKLPLDY RAPFLLTLEP PGPLPLVSGR
SASSSLASLS RYLYHQRWLW SVPSGLAPAL PLSAIAQLLS ILTEVRLSEG FHFACSGEGI
INMVLELPIQ NEPPGQAAAE EKHTCVVQYI LFPPHSTSTK DSFSTDDDND VEVEALEGDS
ELNLVTEVWV EPQYGRVGPG PGIWKHLQDL TYSEIPQALH PRDAACIGSM LSFEYLIQLC
QSKEWGPLPP EPRVSDGLDQ GGDTCVHEIP FHFDLMGLLP QCQQLQMFFL LLAREPEGVP
FAEGSCPAND MVLCLLHSCL GQELSDREIP LTPVDQAAFL SEVLRRTCHV PGAEGPLLGV
HGIPKEQAVG STQATGDSAF TSLSVGLPET LKPLISAQPP QWRCYARLVN PQHVFLTFLP
ATFSDVQRLA ACGLEGPPQE ETKPKFGDWS GAPSLKDLGG TGIKATKSHV PVLSVTLASD
NAQNQGELSP PFRRDLQAYA GRQASQTESA DGPRTRCPVY IYSCSLEALR EQMVGMQPPQ
APRDLIFRTQ FLDHPSPSSA WMEPRYKEAA NHCALLQEHA QRCYVRGLFR SLQQAQSVTS
QDLLTAVDAC EELLQEIDIT PFLLALCGHT WGLPHAPPSP GPLSPGPFSS SMEEGAEPRE
RAILASESSI ETEDLSEPEF QSTRVPGIPD PGPEISLTDV CQLRGEAHGA LHSVIQEKFL
EISRLHFRTV PSNPHYFFYC PPSSRREDEG PRDTVDRKIS DLEFSEAELM GEEGDTSACC
VVTESDPELE VEYRESRESD LGPAGLDSAS LSDVDTVNPD EDSFSILGGD SPTGPESFLH
DLPPLFLHLT CSVRLRGQHS SVPVCSLPTC LGQVLSSLEG PPVGGRVPLR DLSVTLDVFM
LTLPLEVELP TASDPQHHRS TSESSASFPR SPGQPSSLRS DDGLGPPLPP PEEERHPGLS
NLATPHRLAI ETTMNEIRWL LEDEMVGALR RGGIPQSPAL HRAAAHIHSS PGRSTCLRQT
LPLSFVFGPE RSLTQFKEEF RRLHLPGHVL LEDPDSGFFF VAAGQQPGGS HGEPSSAAWA
WHSHEDRAEG IEGETLTASP QAPGSPEDSE GVPLISLPRV PQGGSQPGPS RGLSLMSSQG
SVDSDHLGYD GGSSGSDSEG PNDTLGEKAP FTLRTPPGPA PPQPSLSGLP GPCLPDFWLI
VRVLQDRVEV YAHARSLIRE DGGPGTECRH LQQLLVRRVG EICREVNQRL LLQDLHDSHV
CNSLLVAESE EDLWRSETPF HSRQRAPLPS DDYAADESCA PRGYLAATMQ FVPGHFSCDV
VWGTVIRVHS RLKMGPSMGV SRAIQALRSV LNAFSVVNRK NMFVYQERAT KAVYYLRLLE
TSCSDRPWKG DALPPSLALS RSQEPIYSEE ASGPRSPLDM VSSRSSDAAR PVGQVDRHIQ
LLVHGVGQAG PEITDELVRV LCRRLDEATL DVITVMLVRN CKLTPADVEF IQPPGSLPSE
VLHLALPTSC RPWLPALAWY LRQNLLIFLH SPKYTDSNSR NHFQHPLPPQ GGLPDLDIYL
YNKPGGQGTG GKGVACITLA FVDEGGAPLS LALWPPSSPG PPDPLREEEF EQLTQVIRCP
VVVDSSSAQN GAPRLRLDVW EKGNISIVQL EEKLRGAARQ ALADAIIELQ LLPASLCTED
TPTGSLRNGS LETKSSAGRA STFPPAPVPG EPVTPPSKAG RRSFWDMLSK TECGDLGSPK
TTDDIVLDRP EDTRGRRRHK TESVRTPGGA ERAPGSDSGA QRQKRRTTQL EEGEVGTLHP
VFARVAQRWM EFMVQIGCAS VSRSSAHMVS RFLLPSILSE FTALVTSMAG DTSVRIFEQH
LGSEPEIFGP CSPGQLGPSP RPAAERHLLL LGRNFLQWRR PTQQAAKAMQ RFEPGGDGSS
GRNAPRQRLL LLEVVDKKLQ LLTYNWAPDL GAALGRALVR LVQWQNARAH LIFCLLSQKL
GLFHHYGQLD FPVRDEKEPN PFLLPTMEVE TLIRSASPPL SREQGRLSGS SRGGGPLPLD
TFPFDEALRD ITAARPSSVL GPVPRPPDPV TYHGQQFLEI KMAERRELER QMKMENLFVT
WQQRSTPATM PISAGELETL KQSSRLVHYC ATAMLFDPAA WLHGPPETSG PPDGQRRHRP
ESGSGSREAP TSCESLDVSP PGAREEPWLK ELSLAFLQQY VQYLQSIGFV LVPLRPPSPA
RSTSRPRAMA ILGTEGRGSF SCPKTKTDGS PKSTSSPVTT YHLQRALPGG IILMELAFQG
CYFCVKQFAL ECSRIPMGQA VNSQLSMLFT EECDKVRDLM HVHSFSYDFH LRLVHQHVLG
AHLVLRHGYH LTTFLRHFLA HHPDGPHFGR NHIYQGTLEL PTPLIAAHQL YNYVADHASS
YHMKPLRMAR PGGPEHNEYA LVSAWHSSGS YLDSEGLRHQ DDFDVSLLVC HCAAPFEEQG
EAERHVLRLQ FFVVLTSQRE LFPRLTADMR RFRKPPRLPP EPEAPGSSAG SPGEASGLIL
APGPAPLFPP LAAEVGMARA RLAQLVRLAG GHCRRDTLWK RLFLLEPPGP DRLRLGGRLA
LAELEELLEA VHAKSIGDID PQLDCFLSMT VSWYQSLIKV LLSRFPQSCR HFQSPDLGTQ
YLVVLNQKFT DCFVLVFLDS HLGKTSLTVV FREPFPVQPQ DSESPPAQLV STYHHLESVI
NTACFTLWTR LL
