MBLC1_HUMAN
ID MBLC1_HUMAN Reviewed; 266 AA.
AC A4D2B0; Q8N5X8;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Metallo-beta-lactamase domain-containing protein 1;
DE EC=3.1.27.- {ECO:0000269|PubMed:30507380};
DE AltName: Full=Endoribonuclease MBLAC1 {ECO:0000305|PubMed:30507380};
GN Name=MBLAC1 {ECO:0000312|HGNC:HGNC:22180};
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=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [2]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-79 AND ASN-114.
RC TISSUE=Brain;
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 BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [5] {ECO:0007744|PDB:4V0H}
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) IN COMPLEX WITH IRON, FUNCTION,
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, SUBUNIT, DOMAIN, MUTAGENESIS OF
RP HIS-169; ASP-192 AND HIS-231, AND COFACTOR.
RX PubMed=30507380; DOI=10.7554/elife.39865;
RA Pettinati I., Grzechnik P., Ribeiro de Almeida C., Brem J., McDonough M.A.,
RA Dhir S., Proudfoot N.J., Schofield C.J.;
RT "Biosynthesis of histone messenger RNA employs a specific 3' end
RT endonuclease.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Endoribonuclease that catalyzes the hydrolysis of histone-
CC coding pre-mRNA 3'-end. Involved in histone pre-mRNA processing during
CC the S-phase of the cell cycle, which is required for
CC entering/progressing through S-phase (PubMed:30507380). Cleaves histone
CC pre-mRNA at a major and a minor cleavage site after the 5'-ACCCA-3' and
CC the 5'-ACCCACA-3' sequence, respectively, and located downstream of the
CC stem-loop (PubMed:30507380). May require the presence of the HDE
CC element located at the histone pre-RNA 3'-end to avoid non-specific
CC cleavage (PubMed:30507380). {ECO:0000269|PubMed:30507380}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleotidyl-ribonucleotide-RNA + H2O = a 3'-end
CC ribonucleotide-RNA + a 5'-end (5'-phospho)-ribonucleoside-RNA + H(+);
CC Xref=Rhea:RHEA:68096, Rhea:RHEA-COMP:15179, Rhea:RHEA-COMP:17355,
CC Rhea:RHEA-COMP:17428, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:74896, ChEBI:CHEBI:138282, ChEBI:CHEBI:173118;
CC Evidence={ECO:0000269|PubMed:30507380};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68097;
CC Evidence={ECO:0000305|PubMed:30507380};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:30507380};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000305|PubMed:30507380};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:30507380}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:30507380}.
CC Nucleus {ECO:0000269|PubMed:30507380}. Note=Localizes in the nucleus
CC during early S-phase of the cell cycle. {ECO:0000269|PubMed:30507380}.
CC -!- DOMAIN: Contains four of the five characteristic MBL-fold metal-binding
CC motifs, with two waters completing metal coordination.
CC {ECO:0000269|PubMed:30507380}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC Glyoxalase II family. {ECO:0000305}.
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DR EMBL; CH236956; EAL23849.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76587.1; -; Genomic_DNA.
DR EMBL; BC031288; AAH31288.1; -; mRNA.
DR CCDS; CCDS43620.1; -.
DR RefSeq; NP_981942.1; NM_203397.2.
DR RefSeq; XP_005250307.1; XM_005250250.3.
DR PDB; 4V0H; X-ray; 1.79 A; A/B/C/D=1-266.
DR PDBsum; 4V0H; -.
DR AlphaFoldDB; A4D2B0; -.
DR SMR; A4D2B0; -.
DR BioGRID; 129099; 78.
DR IntAct; A4D2B0; 3.
DR STRING; 9606.ENSP00000381150; -.
DR iPTMnet; A4D2B0; -.
DR PhosphoSitePlus; A4D2B0; -.
DR BioMuta; MBLAC1; -.
DR EPD; A4D2B0; -.
DR jPOST; A4D2B0; -.
DR MassIVE; A4D2B0; -.
DR MaxQB; A4D2B0; -.
DR PaxDb; A4D2B0; -.
DR PeptideAtlas; A4D2B0; -.
DR PRIDE; A4D2B0; -.
DR ProteomicsDB; 642; -.
DR Antibodypedia; 71061; 16 antibodies from 9 providers.
DR DNASU; 255374; -.
DR Ensembl; ENST00000398075.4; ENSP00000381150.2; ENSG00000214309.5.
DR GeneID; 255374; -.
DR KEGG; hsa:255374; -.
DR MANE-Select; ENST00000398075.4; ENSP00000381150.2; NM_203397.3; NP_981942.1.
DR UCSC; uc003utp.4; human.
DR CTD; 255374; -.
DR DisGeNET; 255374; -.
DR GeneCards; MBLAC1; -.
DR HGNC; HGNC:22180; MBLAC1.
DR HPA; ENSG00000214309; Low tissue specificity.
DR neXtProt; NX_A4D2B0; -.
DR PharmGKB; PA164722227; -.
DR VEuPathDB; HostDB:ENSG00000214309; -.
DR eggNOG; KOG4736; Eukaryota.
DR GeneTree; ENSGT00390000016193; -.
DR HOGENOM; CLU_030571_2_6_1; -.
DR InParanoid; A4D2B0; -.
DR OMA; FPGQPYS; -.
DR OrthoDB; 1139836at2759; -.
DR PhylomeDB; A4D2B0; -.
DR TreeFam; TF316508; -.
DR PathwayCommons; A4D2B0; -.
DR SignaLink; A4D2B0; -.
DR BioGRID-ORCS; 255374; 17 hits in 1067 CRISPR screens.
DR GenomeRNAi; 255374; -.
DR Pharos; A4D2B0; Tdark.
DR PRO; PR:A4D2B0; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; A4D2B0; protein.
DR Bgee; ENSG00000214309; Expressed in prefrontal cortex and 116 other tissues.
DR ExpressionAtlas; A4D2B0; baseline and differential.
DR Genevisible; A4D2B0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IDA:UniProtKB.
DR GO; GO:0008334; P:histone mRNA metabolic process; IMP:UniProtKB.
DR GO; GO:0031124; P:mRNA 3'-end processing; IMP:UniProtKB.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR039344; MBLAC1.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR PANTHER; PTHR23200; PTHR23200; 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; Cytoplasm; Hydrolase; Metal-binding; Nucleus;
KW Reference proteome; Zinc.
FT CHAIN 1..266
FT /note="Metallo-beta-lactamase domain-containing protein 1"
FT /id="PRO_0000337027"
FT REGION 48..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 229..266
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:30507380,
FT ECO:0007744|PDB:4V0H"
FT BINDING 116
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:30507380,
FT ECO:0007744|PDB:4V0H"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30507380,
FT ECO:0007744|PDB:4V0H"
FT BINDING 119
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30507380,
FT ECO:0007744|PDB:4V0H"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:30507380,
FT ECO:0007744|PDB:4V0H"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:30507380,
FT ECO:0007744|PDB:4V0H"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30507380,
FT ECO:0007744|PDB:4V0H"
FT BINDING 231
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30507380,
FT ECO:0007744|PDB:4V0H"
FT VARIANT 79
FT /note="P -> H (in dbSNP:rs17852945)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_043567"
FT VARIANT 114
FT /note="H -> N (in dbSNP:rs17852946)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_043568"
FT MUTAGEN 169
FT /note="H->A: Loss of endoribonuclease activity; when
FT associated with A-192 and A-231."
FT /evidence="ECO:0000269|PubMed:30507380"
FT MUTAGEN 192
FT /note="D->A: Loss of endoribonuclease activity; when
FT associated with A-169 and A-231."
FT /evidence="ECO:0000269|PubMed:30507380"
FT MUTAGEN 231
FT /note="H->A: Loss of endoribonuclease activity; when
FT associated with A-169 and A-192."
FT /evidence="ECO:0000269|PubMed:30507380"
FT CONFLICT 189
FT /note="Missing (in Ref. 3; AAH31288)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="E -> K (in Ref. 3; AAH31288)"
FT /evidence="ECO:0000305"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 16..25
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:4V0H"
FT HELIX 68..75
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:4V0H"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:4V0H"
FT HELIX 90..99
FT /evidence="ECO:0007829|PDB:4V0H"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:4V0H"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:4V0H"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:4V0H"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 161..165
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 175..182
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 185..191
FT /evidence="ECO:0007829|PDB:4V0H"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:4V0H"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:4V0H"
FT HELIX 210..223
FT /evidence="ECO:0007829|PDB:4V0H"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:4V0H"
SQ SEQUENCE 266 AA; 27202 MW; DFAA2E589D06B784 CRC64;
MRTEPLCGAS PLLVPGDPYS VVVLLQGYAE PEGVGDAVRA DGSVTLVLPQ TRGPASSHRE
SPRGSGGAEA ALEEAARGPI LVDTGGPWAR EALLGALAGQ GVAPGDVTLV VGTHGHSDHI
GNLGLFPGAA LLVSHDFCLP GGRYLPHGLG EGQPLRLGPG LEVWATPGHG GQRDVSVVVA
GTALGTVVVA GDVFERDGDE DSWQALSEDP AAQERSRKRV LVVADVVVPG HGPPFRVLRE
ASQPETEGGG NSQQEPVVGD EEPALH
