LACB2_HUMAN
ID LACB2_HUMAN Reviewed; 288 AA.
AC Q53H82; A8K2D6; Q9Y392;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Endoribonuclease LACTB2 {ECO:0000303|PubMed:26826708};
DE EC=3.1.27.- {ECO:0000269|PubMed:26826708};
DE AltName: Full=Beta-lactamase-like protein 2;
GN Name=LACTB2; ORFNames=CGI-83;
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].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
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].
RC TISSUE=Brain;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
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 [8]
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 [9] {ECO:0007744|PDB:4AD9}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH ZINC, FUNCTION,
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, SUBSTRATE SPECIFICITY, SUBUNIT,
RP COFACTOR, MUTAGENESIS OF 77-HIS--HIS-82; ASP-81; ARG-110; ASN-116; GLU-118;
RP ASP-164 AND 216-HIS-ARG-217, AND RNA-BINDING.
RX PubMed=26826708; DOI=10.1093/nar/gkw050;
RA Levy S., Allerston C.K., Liveanu V., Habib M.R., Gileadi O., Schuster G.;
RT "Identification of LACTB2, a metallo-beta-lactamase protein, as a human
RT mitochondrial endoribonuclease.";
RL Nucleic Acids Res. 44:1813-1832(2016).
CC -!- FUNCTION: Endoribonuclease; cleaves preferentially 3' to purine-
CC pyrimidine dinucleotide motifs in single-stranded RNA. The cleavage
CC product contains a free 3' -OH group. Has no activity with double-
CC stranded RNA or DNA. Required for normal mitochondrial function and
CC cell viability. {ECO:0000269|PubMed:26826708}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:26826708};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:26826708};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:26826708}.
CC -!- INTERACTION:
CC Q53H82; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-3943430, EBI-747107;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:26826708}.
CC -!- MISCELLANEOUS: RNAi-mediated down-regulation results in rapid cell
CC death. The reason for this is not clear; there are only minor changes
CC in mitochondrial mRNA levels. {ECO:0000269|PubMed:26826708}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC Glyoxalase II family. {ECO:0000305}.
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DR EMBL; AF151841; AAD34078.1; -; mRNA.
DR EMBL; AK290201; BAF82890.1; -; mRNA.
DR EMBL; AK222699; BAD96419.1; -; mRNA.
DR EMBL; CH471068; EAW86969.1; -; Genomic_DNA.
DR EMBL; BC000878; AAH00878.1; -; mRNA.
DR CCDS; CCDS6208.1; -.
DR PIR; T44603; T44603.
DR RefSeq; NP_057111.1; NM_016027.2.
DR PDB; 4AD9; X-ray; 2.60 A; A/B/C/D/E/F=1-288.
DR PDBsum; 4AD9; -.
DR AlphaFoldDB; Q53H82; -.
DR SMR; Q53H82; -.
DR BioGRID; 119299; 64.
DR IntAct; Q53H82; 5.
DR STRING; 9606.ENSP00000276590; -.
DR GlyGen; Q53H82; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q53H82; -.
DR PhosphoSitePlus; Q53H82; -.
DR BioMuta; LACTB2; -.
DR DMDM; 166223244; -.
DR REPRODUCTION-2DPAGE; IPI00006952; -.
DR EPD; Q53H82; -.
DR jPOST; Q53H82; -.
DR MassIVE; Q53H82; -.
DR MaxQB; Q53H82; -.
DR PaxDb; Q53H82; -.
DR PeptideAtlas; Q53H82; -.
DR PRIDE; Q53H82; -.
DR ProteomicsDB; 62501; -.
DR Antibodypedia; 25088; 270 antibodies from 23 providers.
DR DNASU; 51110; -.
DR Ensembl; ENST00000276590.5; ENSP00000276590.4; ENSG00000147592.9.
DR Ensembl; ENST00000522447.5; ENSP00000428801.1; ENSG00000147592.9.
DR GeneID; 51110; -.
DR KEGG; hsa:51110; -.
DR MANE-Select; ENST00000276590.5; ENSP00000276590.4; NM_016027.3; NP_057111.1.
DR UCSC; uc003xyp.4; human.
DR CTD; 51110; -.
DR DisGeNET; 51110; -.
DR GeneCards; LACTB2; -.
DR HGNC; HGNC:18512; LACTB2.
DR HPA; ENSG00000147592; Tissue enhanced (liver).
DR MIM; 618921; gene.
DR neXtProt; NX_Q53H82; -.
DR OpenTargets; ENSG00000147592; -.
DR PharmGKB; PA134952605; -.
DR VEuPathDB; HostDB:ENSG00000147592; -.
DR eggNOG; KOG0813; Eukaryota.
DR GeneTree; ENSGT00390000001710; -.
DR HOGENOM; CLU_048478_1_2_1; -.
DR InParanoid; Q53H82; -.
DR OMA; EFYLAHR; -.
DR OrthoDB; 576967at2759; -.
DR PhylomeDB; Q53H82; -.
DR TreeFam; TF314297; -.
DR PathwayCommons; Q53H82; -.
DR SignaLink; Q53H82; -.
DR BioGRID-ORCS; 51110; 12 hits in 1077 CRISPR screens.
DR ChiTaRS; LACTB2; human.
DR GenomeRNAi; 51110; -.
DR Pharos; Q53H82; Tbio.
DR PRO; PR:Q53H82; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q53H82; protein.
DR Bgee; ENSG00000147592; Expressed in right adrenal gland and 195 other tissues.
DR ExpressionAtlas; Q53H82; baseline and differential.
DR Genevisible; Q53H82; HS.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0090502; P:RNA phosphodiester bond hydrolysis, endonucleolytic; IDA:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR041516; LACTB2_WH.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF17778; BLACT_WH; 1.
DR Pfam; PF00753; Lactamase_B; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Endonuclease; Hydrolase; Metal-binding;
KW Mitochondrion; Nuclease; Phosphoprotein; Reference proteome; RNA-binding;
KW Zinc.
FT CHAIN 1..288
FT /note="Endoribonuclease LACTB2"
FT /id="PRO_0000315743"
FT BINDING 77
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4AD9"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4AD9"
FT BINDING 81
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:4AD9"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:4AD9"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4AD9"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:4AD9"
FT BINDING 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4AD9"
FT BINDING 164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4AD9"
FT BINDING 164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:4AD9"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:4AD9"
FT MOD_RES 102
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR3"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR3"
FT MOD_RES 273
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR3"
FT MOD_RES 282
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR3"
FT MUTAGEN 77..82
FT /note="Missing: Loss of endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:26826708"
FT MUTAGEN 81
FT /note="D->A: Loss of endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:26826708"
FT MUTAGEN 110
FT /note="R->A: Mildly decreases endoribonuclease activity. No
FT effect on RNA-binding."
FT /evidence="ECO:0000269|PubMed:26826708"
FT MUTAGEN 116
FT /note="N->A: Loss of endoribonuclease activity. No effect
FT on RNA-binding."
FT /evidence="ECO:0000269|PubMed:26826708"
FT MUTAGEN 118
FT /note="E->A: Loss of endoribonuclease activity. No effect
FT on RNA-binding."
FT /evidence="ECO:0000269|PubMed:26826708"
FT MUTAGEN 164
FT /note="D->A: Loss of endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:26826708"
FT MUTAGEN 216..217
FT /note="HR->AT: Loss of endoribonuclease activity. Strongly
FT decreases RNA-binding."
FT /evidence="ECO:0000269|PubMed:26826708"
FT MUTAGEN 220
FT /note="R->T: Loss of endoribonuclease activity. Strongly
FT decreases RNA-binding."
FT /evidence="ECO:0000269|PubMed:26826708"
FT CONFLICT 39
FT /note="G -> S (in Ref. 2; BAF82890)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="L -> P (in Ref. 3; BAD96419)"
FT /evidence="ECO:0000305"
FT STRAND 7..10
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 12..19
FT /evidence="ECO:0007829|PDB:4AD9"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 38..45
FT /evidence="ECO:0007829|PDB:4AD9"
FT HELIX 53..65
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:4AD9"
FT HELIX 80..83
FT /evidence="ECO:0007829|PDB:4AD9"
FT HELIX 86..92
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:4AD9"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 135..141
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:4AD9"
FT TURN 155..158
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 159..163
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:4AD9"
FT HELIX 177..190
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 193..201
FT /evidence="ECO:0007829|PDB:4AD9"
FT HELIX 206..230
FT /evidence="ECO:0007829|PDB:4AD9"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:4AD9"
FT HELIX 238..245
FT /evidence="ECO:0007829|PDB:4AD9"
FT TURN 246..248
FT /evidence="ECO:0007829|PDB:4AD9"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:4AD9"
FT HELIX 254..270
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:4AD9"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:4AD9"
SQ SEQUENCE 288 AA; 32806 MW; F569C7DFB070D52C CRC64;
MAAVLQRVER LSNRVVRVLG CNPGPMTLQG TNTYLVGTGP RRILIDTGEP AIPEYISCLK
QALTEFNTAI QEIVVTHWHR DHSGGIGDIC KSINNDTTYC IKKLPRNPQR EEIIGNGEQQ
YVYLKDGDVI KTEGATLRVL YTPGHTDDHM ALLLEEENAI FSGDCILGEG TTVFEDLYDY
MNSLKELLKI KADIIYPGHG PVIHNAEAKI QQYISHRNIR EQQILTLFRE NFEKSFTVME
LVKIIYKNTP ENLHEMAKHN LLLHLKKLEK EGKIFSNTDP DKKWKAHL
