LACTB_MOUSE
ID LACTB_MOUSE Reviewed; 551 AA.
AC Q9EP89;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Serine beta-lactamase-like protein LACTB, mitochondrial {ECO:0000305};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:P83111};
DE Flags: Precursor;
GN Name=Lactb {ECO:0000312|MGI:MGI:1933395}; Synonyms=Lact1;
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 [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=129/Sv, and BALB/cJ;
RX PubMed=11707067; DOI=10.1006/geno.2001.6643;
RA Smith T.S., Southan C., Ellington K., Campbell D., Tew D.G., Debouck C.;
RT "Identification, genomic organization, and mRNA expression of LACTB,
RT encoding a serine beta-lactamase-like protein with an amino-terminal
RT transmembrane domain.";
RL Genomics 78:12-14(2001).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, and Testis;
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 [3]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-287 AND LYS-288, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast, and Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-301, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=28329758; DOI=10.1038/nature21408;
RA Keckesova Z., Donaher J.L., De Cock J., Freinkman E., Lingrell S.,
RA Bachovchin D.A., Bierie B., Tischler V., Noske A., Okondo M.C.,
RA Reinhardt F., Thiru P., Golub T.R., Vance J.E., Weinberg R.A.;
RT "LACTB is a tumour suppressor that modulates lipid metabolism and cell
RT state.";
RL Nature 543:681-686(2017).
CC -!- FUNCTION: Mitochondrial serine protease that acts as a regulator of
CC mitochondrial lipid metabolism (By similarity). Acts by decreasing
CC protein levels of PISD, a mitochondrial enzyme that converts
CC phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn),
CC thereby affecting mitochondrial lipid metabolism (By similarity). It is
CC unclear whether it acts directly by mediating proteolysis of PISD or by
CC mediating proteolysis of another lipid metabolism protein (By
CC similarity). Acts as a tumor suppressor that has the ability to inhibit
CC proliferation of multiple types of cancer cells: probably by promoting
CC decreased levels of PISD, thereby affecting mitochondrial lipid
CC metabolism (PubMed:28329758). {ECO:0000250|UniProtKB:P83111,
CC ECO:0000269|PubMed:28329758}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P83111}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in liver.
CC {ECO:0000269|PubMed:11707067}.
CC -!- INDUCTION: Down-regulated in a number of cancer cells.
CC {ECO:0000269|PubMed:28329758}.
CC -!- SIMILARITY: Belongs to the peptidase S12 family. {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; AF317900; AAG37910.1; -; mRNA.
DR EMBL; AF317901; AAG37911.1; -; Genomic_DNA.
DR CCDS; CCDS40674.1; -.
DR RefSeq; NP_109642.1; NM_030717.1.
DR AlphaFoldDB; Q9EP89; -.
DR SMR; Q9EP89; -.
DR BioGRID; 219844; 5.
DR IntAct; Q9EP89; 1.
DR STRING; 10090.ENSMUSP00000034929; -.
DR ChEMBL; CHEMBL3259498; -.
DR MEROPS; S12.004; -.
DR iPTMnet; Q9EP89; -.
DR PhosphoSitePlus; Q9EP89; -.
DR EPD; Q9EP89; -.
DR jPOST; Q9EP89; -.
DR MaxQB; Q9EP89; -.
DR PaxDb; Q9EP89; -.
DR PRIDE; Q9EP89; -.
DR ProteomicsDB; 252453; -.
DR Antibodypedia; 13261; 112 antibodies from 26 providers.
DR DNASU; 80907; -.
DR Ensembl; ENSMUST00000034929; ENSMUSP00000034929; ENSMUSG00000032370.
DR GeneID; 80907; -.
DR KEGG; mmu:80907; -.
DR UCSC; uc009qfn.1; mouse.
DR CTD; 114294; -.
DR MGI; MGI:1933395; Lactb.
DR VEuPathDB; HostDB:ENSMUSG00000032370; -.
DR eggNOG; ENOG502QQBX; Eukaryota.
DR GeneTree; ENSGT00390000001062; -.
DR HOGENOM; CLU_020027_6_0_1; -.
DR InParanoid; Q9EP89; -.
DR OMA; LYSYQVG; -.
DR OrthoDB; 1268012at2759; -.
DR PhylomeDB; Q9EP89; -.
DR TreeFam; TF315050; -.
DR BioGRID-ORCS; 80907; 2 hits in 71 CRISPR screens.
DR PRO; PR:Q9EP89; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9EP89; protein.
DR Bgee; ENSMUSG00000032370; Expressed in metanephric cortical collecting duct and 244 other tissues.
DR ExpressionAtlas; Q9EP89; baseline and differential.
DR Genevisible; Q9EP89; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.710.10; -; 2.
DR InterPro; IPR001466; Beta-lactam-related.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR Pfam; PF00144; Beta-lactamase; 2.
DR SUPFAM; SSF56601; SSF56601; 1.
PE 1: Evidence at protein level;
KW Acetylation; Hydrolase; Lipid metabolism; Mitochondrion; Protease;
KW Reference proteome; Transit peptide; Tumor suppressor.
FT TRANSIT 1..113
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 114..551
FT /note="Serine beta-lactamase-like protein LACTB,
FT mitochondrial"
FT /id="PRO_0000195477"
FT REGION 69..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 71..88
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..287
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 162
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P15555"
FT MOD_RES 287
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 288
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 301
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 346
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P83111"
SQ SEQUENCE 551 AA; 60705 MW; 816C1EE94B1D6009 CRC64;
MYRLLSSVTA RAAATAGPAW DGGRRGAHRR PGLPVLGLGW AGGLGLGLGL ALGAKLVVGL
RGAVPIQSPA DPEASGTTEL SHEQALSPGS PHTPAPPAAR GFSRAIESSR DLLHRIKDEV
GAPGIVVGVS VDGKEVWSEG LGYADVENRV PCKPETVMRI ASISKSLTMV ALAKLWEAGK
LDLDLPVQHY VPEFPEKEYE GEKVSVTTRL LISHLSGIRH YEKDIKKVKE EKAYKALKMV
KGTPPPSDQE KELKEKGGKN NEKSDAPKAK VEQDSEARCR SAKPGKKKND FEQGELYLKE
KFENSIESLR LFKNDPLFFK PGSQFLYSTF GYTLLAAIVE RASGYKYLDY MQKIFHDLDM
LTTVQEENEP VIYNRARFYV YNKKKRLVNT PYVDNSYKWA GGGFLSTVGD LLKFGNAMLY
GYQVGQFKNS NENLLPGYLK PETMVMMWTP VPNTEMSWDK EGKYAMAWGV VEKKQTYGSC
RKQRHYASHT GGAVGASSVL LVLPEELDSE AVNNKVPPRG IIVSIICNMQ SVGLNSTALK
IALEFDKDRA D
