LZTR1_MOUSE
ID LZTR1_MOUSE Reviewed; 837 AA.
AC Q9CQ33;
DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Leucine-zipper-like transcriptional regulator 1;
DE Short=LZTR-1;
GN Name=Lztr1 {ECO:0000312|MGI:MGI:1914113}; Synonyms=Tcfl2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryo, Liver, Lung, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=16356934; DOI=10.1074/jbc.m509073200;
RA Nacak T.G., Leptien K., Fellner D., Augustin H.G., Kroll J.;
RT "The BTB-kelch protein LZTR-1 is a novel Golgi protein that is degraded
RT upon induction of apoptosis.";
RL J. Biol. Chem. 281:5065-5071(2006).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30442762; DOI=10.1126/science.aap7607;
RA Steklov M., Pandolfi S., Baietti M.F., Batiuk A., Carai P., Najm P.,
RA Zhang M., Jang H., Renzi F., Cai Y., Abbasi Asbagh L., Pastor T.,
RA De Troyer M., Simicek M., Radaelli E., Brems H., Legius E., Tavernier J.,
RA Gevaert K., Impens F., Messiaen L., Nussinov R., Heymans S., Eyckerman S.,
RA Sablina A.A.;
RT "Mutations in LZTR1 drive human disease by dysregulating RAS
RT ubiquitination.";
RL Science 362:1177-1182(2018).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin-protein ligase complex that mediates ubiquitination of Ras
CC (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS) (PubMed:30442762). Is a
CC negative regulator of RAS-MAPK signaling that acts by controlling Ras
CC levels and decreasing Ras association with membranes (PubMed:30442762).
CC {ECO:0000269|PubMed:30442762}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q8N653}.
CC -!- SUBUNIT: Homodimer. Component of the BCR(LZTR1) E3 ubiquitin ligase
CC complex, at least composed of CUL3, LZTR1 and RBX1. Interacts with Ras
CC (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS). Interacts with RAF1. Interacts
CC with SHOC2. Interacts with PPP1CB. {ECO:0000250|UniProtKB:Q8N653}.
CC -!- SUBCELLULAR LOCATION: Endomembrane system
CC {ECO:0000250|UniProtKB:Q8N653}. Recycling endosome
CC {ECO:0000250|UniProtKB:Q8N653}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q8N653}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CQ33-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CQ33-2; Sequence=VSP_007170;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:16356934}.
CC -!- PTM: Phosphorylated on tyrosine upon induction of apoptosis, leading to
CC its degradation by the proteasome. {ECO:0000250|UniProtKB:Q8N653}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality between 17.5 dpc and birth
CC (PubMed:30442762). Impaired ubiquitination of Ras (K-Ras/Kras, N-
CC Ras/Nras and H-Ras/Hras) (PubMed:30442762). Heterozygous mice display
CC heart malformations, including decreased left ventricular systolic
CC function, increased diastolic dimensions, eccentric hypertrophy,
CC increased cardiomyocyte area and reduced longevity; phenotypes that are
CC reminiscent of human Noonan Syndrome (PubMed:30442762).
CC {ECO:0000269|PubMed:30442762}.
CC -!- MISCELLANEOUS: [Isoform 2]: May result from the retention of an intron
CC in the cDNA in position 800. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the LZTR1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC40662.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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; AK004561; BAB23373.2; -; mRNA.
DR EMBL; AK005037; BAB23764.2; -; mRNA.
DR EMBL; AK083411; BAC38905.1; -; mRNA.
DR EMBL; AK088938; BAC40662.1; ALT_INIT; mRNA.
DR EMBL; BC034400; AAH34400.1; -; mRNA.
DR CCDS; CCDS37272.1; -. [Q9CQ33-1]
DR RefSeq; NP_001318155.1; NM_001331226.1.
DR RefSeq; NP_001318156.1; NM_001331227.1.
DR RefSeq; NP_080084.2; NM_025808.4. [Q9CQ33-1]
DR AlphaFoldDB; Q9CQ33; -.
DR SMR; Q9CQ33; -.
DR BioGRID; 211770; 3.
DR MINT; Q9CQ33; -.
DR STRING; 10090.ENSMUSP00000111345; -.
DR iPTMnet; Q9CQ33; -.
DR PhosphoSitePlus; Q9CQ33; -.
DR EPD; Q9CQ33; -.
DR MaxQB; Q9CQ33; -.
DR PaxDb; Q9CQ33; -.
DR PRIDE; Q9CQ33; -.
DR ProteomicsDB; 290208; -. [Q9CQ33-1]
DR ProteomicsDB; 290209; -. [Q9CQ33-2]
DR Antibodypedia; 8368; 138 antibodies from 27 providers.
DR DNASU; 66863; -.
DR Ensembl; ENSMUST00000023444; ENSMUSP00000023444; ENSMUSG00000022761. [Q9CQ33-1]
DR GeneID; 66863; -.
DR KEGG; mmu:66863; -.
DR UCSC; uc007yla.1; mouse. [Q9CQ33-1]
DR UCSC; uc007ylb.1; mouse. [Q9CQ33-2]
DR CTD; 8216; -.
DR MGI; MGI:1914113; Lztr1.
DR VEuPathDB; HostDB:ENSMUSG00000022761; -.
DR eggNOG; KOG4693; Eukaryota.
DR GeneTree; ENSGT00940000158190; -.
DR HOGENOM; CLU_012081_0_0_1; -.
DR InParanoid; Q9CQ33; -.
DR OMA; ILEDHVI; -.
DR OrthoDB; 1263405at2759; -.
DR PhylomeDB; Q9CQ33; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 66863; 9 hits in 75 CRISPR screens.
DR ChiTaRS; Lztr1; mouse.
DR PRO; PR:Q9CQ33; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9CQ33; protein.
DR Bgee; ENSMUSG00000022761; Expressed in external carotid artery and 280 other tissues.
DR ExpressionAtlas; Q9CQ33; baseline and differential.
DR Genevisible; Q9CQ33; MM.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR Gene3D; 2.120.10.80; -; 2.
DR Gene3D; 3.30.710.10; -; 2.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR Pfam; PF00651; BTB; 2.
DR Pfam; PF01344; Kelch_1; 2.
DR SMART; SM00225; BTB; 2.
DR SMART; SM00612; Kelch; 4.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 2.
DR PROSITE; PS50097; BTB; 2.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Endosome; Golgi apparatus; Kelch repeat;
KW Membrane; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8N653"
FT CHAIN 2..837
FT /note="Leucine-zipper-like transcriptional regulator 1"
FT /id="PRO_0000119136"
FT REPEAT 76..125
FT /note="Kelch 1"
FT /evidence="ECO:0000255"
FT REPEAT 127..182
FT /note="Kelch 2"
FT /evidence="ECO:0000255"
FT REPEAT 184..235
FT /note="Kelch 3"
FT /evidence="ECO:0000255"
FT REPEAT 236..282
FT /note="Kelch 4"
FT /evidence="ECO:0000255"
FT REPEAT 292..338
FT /note="Kelch 5"
FT /evidence="ECO:0000255"
FT REPEAT 396..447
FT /note="Kelch 6"
FT /evidence="ECO:0000255"
FT DOMAIN 440..534
FT /note="BTB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 664..733
FT /note="BTB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REGION 324..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q8N653"
FT VAR_SEQ 800..837
FT /note="VSKLPTLRLLSQQLLLDIIDSLASHISDKQCAELGADI -> VRLWPQCSRS
FT QLSPAGLGTSWPLSTILRQPRPEQARPQEDSSAHPGRLVSSSFGHLCRSLSCPRCGC
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_007170"
FT CONFLICT 330
FT /note="Missing (in Ref. 2; AAH34400)"
FT /evidence="ECO:0000305"
FT CONFLICT 375
FT /note="V -> A (in Ref. 2; AAH34400)"
FT /evidence="ECO:0000305"
FT CONFLICT 495
FT /note="G -> S (in Ref. 2; AAH34400)"
FT /evidence="ECO:0000305"
FT CONFLICT 545
FT /note="M -> V (in Ref. 1; BAC38905)"
FT /evidence="ECO:0000305"
FT CONFLICT 707
FT /note="I -> M (in Ref. 1; BAC40662)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 837 AA; 94476 MW; 7E714AE48C4E2D63 CRC64;
MAGSGGPIGS GALTGGVRSK VAPSVDFDHS CSDSVEYLTL NFGPFETVHR WRRLPPCDEF
VGARRSKHTV VAYKDAIYVF GGDNGKTMLN DLLRFDVKDC SWCRAFTTGT PPAPRYHHSA
VVYGSSMFVF GGYTGDIYSN SNLKNKNDLF EYKFATGQWT EWKIEGRLPV ARSAHGATVY
SDKLWIFAGY DGNARLNDMW TIGLQDRELT CWEEVAQSGE IPPSCCNFPV AVCRDKMFVF
SGQSGAKITN NLFQFEFKDK TWTRIPTEHL LRGSPPPPQR RYGHTMVAFD RHLYVFGGAA
DNTLPNELHC YDVDFQTWEV VQPSSDSEVG GAEMPERASS SEDASTLTSE ERSSFKKSRD
VFGLDFGTTS AKQPVHLASE LPSGRLFHAA AVISDAMYIF GGTVDNNIRS GEMYRFQFSC
YPKCTLHEDY GRLWEGRQFC DVEFVLGEKE ECVQGHVAIV TARSRWLRRK IVQAQEWLAQ
KLEEDGALAP KEAPGPAVGR ARPPLLRVAI REAEARPFEV LMQFLYTDKI KYPRKGHVED
VLLIMDVYKL ALSFQLCRLE QLCRQYIEAS VDLQNVLVVC ESAARLQLGQ LKEHCLNFIV
KESHFNQVIM MKEFERLSSP LIVEIVRRKQ QPPPRTPSDQ PVDIGTSLIQ DMKAYLEGAG
SEFCDITLLL DGQPRPAHKA ILAARSSYFE AMFRSFMPED GQVNISIGEM VPSRQAFESM
LRYIYYGEVN MPPEDSLYLF AAPYYYGFYN NRLQAYCKQN LEMNVTVQNV LQILEAADKT
QALDMKRHCL HIIVHQFTKV SKLPTLRLLS QQLLLDIIDS LASHISDKQC AELGADI
