LACTB_HUMAN
ID LACTB_HUMAN Reviewed; 547 AA.
AC P83111; P83096;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Serine beta-lactamase-like protein LACTB, mitochondrial {ECO:0000305};
DE EC=3.4.-.- {ECO:0000269|PubMed:28329758};
DE Flags: Precursor;
GN Name=LACTB {ECO:0000312|HGNC:HGNC:16468};
GN Synonyms=MRPL56 {ECO:0000303|PubMed:11551941};
GN ORFNames=UNQ843/PRO1781 {ECO:0000303|PubMed:12975309};
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 MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
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 [4]
RP IDENTIFICATION, SUBCELLULAR LOCATION, AND CONCEPTUAL TRANSLATION.
RX PubMed=11551941; DOI=10.1074/jbc.m106510200;
RA Koc E.C., Burkhart W., Blackburn K., Moyer M.B., Schlatzer D.M.,
RA Moseley A., Spremulli L.L.;
RT "The large subunit of the mammalian mitochondrial ribosome. Analysis of the
RT complement of ribosomal proteins present.";
RL J. Biol. Chem. 276:43958-43969(2001).
RN [5]
RP IDENTIFICATION, CONCEPTUAL TRANSLATION, AND TISSUE SPECIFICITY.
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=19858488; DOI=10.1073/pnas.0906734106;
RA Polianskyte Z., Peitsaro N., Dapkunas A., Liobikas J., Soliymani R.,
RA Lalowski M., Speer O., Seitsonen J., Butcher S., Cereghetti G.M.,
RA Linder M.D., Merckel M., Thompson J., Eriksson O.;
RT "LACTB is a filament-forming protein localized in mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:18960-18965(2009).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-342, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, VARIANT LYS-469, AND
RP CHARACTERIZATION OF VARIANT LYS-469.
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 (PubMed:28329758). 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 (PubMed:28329758). It
CC is unclear whether it acts directly by mediating proteolysis of PISD or
CC by mediating proteolysis of another lipid metabolism protein
CC (PubMed:28329758). Acts as a tumor suppressor that has the ability to
CC inhibit proliferation of multiple types of breast cancer cells:
CC probably by promoting decreased levels of PISD, thereby affecting
CC mitochondrial lipid metabolism (PubMed:28329758).
CC {ECO:0000269|PubMed:28329758}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:11551941,
CC ECO:0000269|PubMed:19858488, ECO:0000269|PubMed:28329758}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=a;
CC IsoId=P83111-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P83111-2; Sequence=VSP_010011;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in skeletal muscle.
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 -!- CAUTION: Was originally identified as mitochondrial large ribosomal
CC subunit protein mL56 (MRP-L56) (PubMed:11551941), but has since been
CC shown to localize to the mitochondrial intermembrane space where it
CC forms filaments (PubMed:19858488). {ECO:0000305|PubMed:11551941,
CC ECO:0000305|PubMed:19858488}.
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DR EMBL; AK027808; BAB55384.1; -; mRNA.
DR EMBL; AY358709; AAQ89072.1; -; mRNA.
DR EMBL; BC067288; AAH67288.1; -; mRNA.
DR CCDS; CCDS10182.1; -. [P83111-1]
DR CCDS; CCDS45275.1; -. [P83111-2]
DR RefSeq; NP_001275514.1; NM_001288585.1.
DR RefSeq; NP_116246.2; NM_032857.4. [P83111-1]
DR RefSeq; NP_741982.1; NM_171846.3. [P83111-2]
DR PDB; 7V1Y; EM; 2.82 A; A/B/C/D=63-547.
DR PDB; 7V1Z; EM; 2.98 A; A/B/C/D=63-547.
DR PDB; 7V21; EM; 3.08 A; A/B/C/D=63-547.
DR PDBsum; 7V1Y; -.
DR PDBsum; 7V1Z; -.
DR PDBsum; 7V21; -.
DR AlphaFoldDB; P83111; -.
DR SMR; P83111; -.
DR BioGRID; 125311; 303.
DR CORUM; P83111; -.
DR IntAct; P83111; 94.
DR MINT; P83111; -.
DR STRING; 9606.ENSP00000261893; -.
DR DrugCentral; P83111; -.
DR MEROPS; S12.004; -.
DR GlyGen; P83111; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P83111; -.
DR PhosphoSitePlus; P83111; -.
DR BioMuta; LACTB; -.
DR DMDM; 46397478; -.
DR EPD; P83111; -.
DR jPOST; P83111; -.
DR MassIVE; P83111; -.
DR MaxQB; P83111; -.
DR PaxDb; P83111; -.
DR PeptideAtlas; P83111; -.
DR PRIDE; P83111; -.
DR ProteomicsDB; 57733; -. [P83111-1]
DR ProteomicsDB; 57734; -. [P83111-2]
DR Antibodypedia; 13261; 112 antibodies from 26 providers.
DR DNASU; 114294; -.
DR Ensembl; ENST00000261893.9; ENSP00000261893.4; ENSG00000103642.12. [P83111-1]
DR Ensembl; ENST00000413507.3; ENSP00000392956.2; ENSG00000103642.12. [P83111-2]
DR GeneID; 114294; -.
DR KEGG; hsa:114294; -.
DR MANE-Select; ENST00000261893.9; ENSP00000261893.4; NM_032857.5; NP_116246.2.
DR UCSC; uc002alv.5; human. [P83111-1]
DR CTD; 114294; -.
DR DisGeNET; 114294; -.
DR GeneCards; LACTB; -.
DR HGNC; HGNC:16468; LACTB.
DR HPA; ENSG00000103642; Low tissue specificity.
DR MIM; 608440; gene.
DR neXtProt; NX_P83111; -.
DR OpenTargets; ENSG00000103642; -.
DR PharmGKB; PA30262; -.
DR VEuPathDB; HostDB:ENSG00000103642; -.
DR eggNOG; ENOG502QQBX; Eukaryota.
DR GeneTree; ENSGT00390000001062; -.
DR HOGENOM; CLU_020027_6_0_1; -.
DR InParanoid; P83111; -.
DR OMA; LYSYQVG; -.
DR OrthoDB; 1268012at2759; -.
DR PhylomeDB; P83111; -.
DR TreeFam; TF315050; -.
DR PathwayCommons; P83111; -.
DR SignaLink; P83111; -.
DR BioGRID-ORCS; 114294; 16 hits in 1077 CRISPR screens.
DR ChiTaRS; LACTB; human.
DR GeneWiki; LACTB; -.
DR GenomeRNAi; 114294; -.
DR Pharos; P83111; Tbio.
DR PRO; PR:P83111; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P83111; protein.
DR Bgee; ENSG00000103642; Expressed in left ventricle myocardium and 180 other tissues.
DR ExpressionAtlas; P83111; baseline and differential.
DR Genevisible; P83111; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IDA: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 3D-structure; Acetylation; Alternative splicing; Hydrolase;
KW Lipid metabolism; Mitochondrion; Protease; Reference proteome;
KW Transit peptide; Tumor suppressor.
FT TRANSIT 1..115
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 116..547
FT /note="Serine beta-lactamase-like protein LACTB,
FT mitochondrial"
FT /id="PRO_0000195476"
FT REGION 62..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 164
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P15555"
FT MOD_RES 283
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EP89"
FT MOD_RES 284
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EP89"
FT MOD_RES 297
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EP89"
FT MOD_RES 342
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 374..547
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_010011"
FT VARIANT 469
FT /note="R -> K (does not affect serine protease activity;
FT shows reduced tumor suppressor activity; shows reduced
FT ability to down-regulate phosphatidylethanolamine (PtdEtn)
FT levels; dbSNP:rs2729835)"
FT /evidence="ECO:0000269|PubMed:28329758"
FT /id="VAR_018299"
FT CONFLICT 61
FT /note="R -> S (in Ref. 2; BAB55384)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 547 AA; 60694 MW; 4CFAF56D2A390264 CRC64;
MYRLMSAVTA RAAAPGGLAS SCGRRGVHQR AGLPPLGHGW VGGLGLGLGL ALGVKLAGGL
RGAAPAQSPA APDPEASPLA EPPQEQSLAP WSPQTPAPPC SRCFARAIES SRDLLHRIKD
EVGAPGIVVG VSVDGKEVWS EGLGYADVEN RVPCKPETVM RIASISKSLT MVALAKLWEA
GKLDLDIPVQ HYVPEFPEKE YEGEKVSVTT RLLISHLSGI RHYEKDIKKV KEEKAYKALK
MMKENVAFEQ EKEGKSNEKN DFTKFKTEQE NEAKCRNSKP GKKKNDFEQG ELYLREKFEN
SIESLRLFKN DPLFFKPGSQ FLYSTFGYTL LAAIVERASG CKYLDYMQKI FHDLDMLTTV
QEENEPVIYN RARFYVYNKK KRLVNTPYVD NSYKWAGGGF LSTVGDLLKF GNAMLYGYQV
GLFKNSNENL LPGYLKPETM VMMWTPVPNT EMSWDKEGKY AMAWGVVERK QTYGSCRKQR
HYASHTGGAV GASSVLLVLP EELDTETINN KVPPRGIIVS IICNMQSVGL NSTALKIALE
FDKDRSD
