MB211_HUMAN
ID MB211_HUMAN Reviewed; 359 AA.
AC Q13394; Q6I9T5;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Putative nucleotidyltransferase MAB21L1 {ECO:0000305};
DE EC=2.7.7.- {ECO:0000305};
DE AltName: Full=Protein mab-21-like 1 {ECO:0000312|HGNC:HGNC:6757};
GN Name=MAB21L1 {ECO:0000312|HGNC:HGNC:6757};
GN Synonyms=CAGR1 {ECO:0000303|PubMed:8733127};
GN ORFNames=Nbla00126 {ECO:0000303|PubMed:12880961};
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 [MRNA], TISSUE SPECIFICITY, AND POLYMORPHISM.
RX PubMed=8733127; DOI=10.1093/hmg/5.5.607;
RA Margolis R.L., Stine Q.C., Mcinnis M.G., Ranen N.G., Rubinsztein D.C.,
RA Leggo J., Jones Brando L.V., Kidwai A.S., Loev S.J., Breschel T.S.,
RA Callahan C., Simpson S.G., DePaulo J.R., McMahon F.J., Jain S.,
RA Paykel E.S., Walsh C., DeLisi L.E., Crow T.J., Torrey E.F., Ashworth R.G.,
RA Macke J.P., Nathans J., Ross C.A.;
RT "cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-
RT determining gene mab-21: expression, chromosomal localization and analysis
RT of a highly polymorphic (CAG)n trinucleotide repeat.";
RL Hum. Mol. Genet. 5:607-616(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neuroblastoma;
RX PubMed=12880961; DOI=10.1016/s0304-3835(03)00085-5;
RA Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S.,
RA Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S.,
RA Hirato J., Nakagawara A.;
RT "Neuroblastoma oligo-capping cDNA project: toward the understanding of the
RT genesis and biology of neuroblastoma.";
RL Cancer Lett. 197:63-68(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP POLYMORPHISM.
RX PubMed=9152839; DOI=10.1136/jmg.34.5.411;
RA Potter N.T.;
RT "Meiotic instability associated with the CAGR1 trinucleotide repeat at
RT 13q13.";
RL J. Med. Genet. 34:411-413(1997).
RN [8]
RP POLYMORPHISM.
RX PubMed=9950369;
RA Margolis R.L., Stine O.C., Ward C.M., Franz M.L., Rosenblatt A.,
RA Callahan C., Sherr M., Ross C.A., Potter N.T.;
RT "Unstable expansion of the CAG trinucleotide repeat in MAB21L1: report of a
RT second pedigree and effect on protein expression.";
RL J. Med. Genet. 36:62-64(1999).
RN [9]
RP POLYMORPHISM.
RX PubMed=15526290; DOI=10.1002/bdra.20084;
RA Merello E., De Marco P., Moroni A., Raso A., Calevo M.G., Consalez G.G.,
RA Cama A., Capra V.;
RT "Molecular genetic analysis of human homologs of Caenorhabditis elegans
RT mab-21-like 1 gene in patients with neural tube defects.";
RL Birth Defects Res. A Clin. Mol. Teratol. 70:885-888(2004).
RN [10] {ECO:0007744|PDB:5EOG, ECO:0007744|PDB:5EOM}
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 2-359 IN COMPLEX WITH CTP,
RP FUNCTION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ARG-51 AND ARG-247.
RX PubMed=27271801; DOI=10.1038/srep27498;
RA de Oliveira Mann C.C., Kiefersauer R., Witte G., Hopfner K.P.;
RT "Structural and biochemical characterization of the cell fate determining
RT nucleotidyltransferase fold protein MAB21L1.";
RL Sci. Rep. 6:27498-27498(2016).
RN [11]
RP INVOLVEMENT IN COFG, AND FUNCTION.
RX PubMed=27103078; DOI=10.1111/cge.12794;
RA Bruel A.L., Masurel-Paulet A., Riviere J.B., Duffourd Y., Lehalle D.,
RA Bensignor C., Huet F., Borgnon J., Roucher F., Kuentz P., Deleuze J.F.,
RA Thauvin-Robinet C., Faivre L., Thevenon J.;
RT "Autosomal recessive truncating MAB21L1 mutation associated with a
RT syndromic scrotal agenesis.";
RL Clin. Genet. 91:333-338(2017).
RN [12]
RP INVOLVEMENT IN COFG, FUNCTION, AND VARIANTS COFG PRO-233 AND
RP 280-TYR--LEU-359 DEL.
RX PubMed=30487245; DOI=10.1136/jmedgenet-2018-105623;
RA Rad A., Altunoglu U., Miller R., Maroofian R., James K.N., Caglayan A.O.,
RA Najafi M., Stanley V., Boustany R.M., Yesil G., Sahebzamani A.,
RA Ercan-Sencicek G., Saeidi K., Wu K., Bauer P., Bakey Z., Gleeson J.G.,
RA Hauser N., Gunel M., Kayserili H., Schmidts M.;
RT "MAB21L1 loss of function causes a syndromic neurodevelopmental disorder
RT with distinctive cerebellar, ocular, craniofacial and genital features
RT (COFG syndrome).";
RL J. Med. Genet. 56:332-339(2019).
CC -!- FUNCTION: Putative nucleotidyltransferase required for several aspects
CC of embryonic development including normal development of the eye
CC (PubMed:27103078, PubMed:30487245). It is unclear whether it displays
CC nucleotidyltransferase activity in vivo (PubMed:27271801). Binds
CC single-stranded RNA (ssRNA) (PubMed:27271801).
CC {ECO:0000269|PubMed:27103078, ECO:0000269|PubMed:27271801,
CC ECO:0000269|PubMed:30487245}.
CC -!- SUBUNIT: Monomer (PubMed:27271801). Homodecamer; composed of 2 back to
CC back homopentamers (PubMed:27271801). The protein may exist as monomer
CC in solution and oiligomerizes upon ligand binding (PubMed:27271801).
CC {ECO:0000305|PubMed:27271801}.
CC -!- INTERACTION:
CC Q13394; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-10229059, EBI-747107;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O70299}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, cerebellum and skeletal muscle.
CC {ECO:0000269|PubMed:8733127}.
CC -!- DOMAIN: While it shares structure similarities with CGAS, it also
CC features a number of differences. The crystal structure is in inactive
CC conformation and the enzyme would require a conformational change to be
CC active. The nucleotidyltransferase activity is therefore unclear.
CC {ECO:0000269|PubMed:27271801}.
CC -!- POLYMORPHISM: A CAG trinucleotide repeat occurs in the 5'-UTR of this
CC gene. This repeat has been found to be highly polymorphic, although
CC expanded alleles have not yet been definitely linked with any
CC phenotypic abnormality. {ECO:0000269|PubMed:15526290,
CC ECO:0000269|PubMed:8733127, ECO:0000269|PubMed:9152839,
CC ECO:0000269|PubMed:9950369}.
CC -!- DISEASE: Cerebellar, ocular, craniofacial, and genital syndrome (COFG)
CC [MIM:618479]: An autosomal recessive syndrome characterized by moderate
CC to severe developmental delay, intellectual disability, cerebellar
CC hypoplasia with ataxia, variable microcephaly, ophthalmological
CC anomalies, facial dysmorphism, absent or underdeveloped nipples,
CC underdeveloped labioscrotal folds and scrotal agenesis.
CC {ECO:0000269|PubMed:27103078, ECO:0000269|PubMed:30487245}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the mab-21 family. {ECO:0000305}.
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DR EMBL; U38810; AAB47576.1; -; mRNA.
DR EMBL; AB073388; BAE45718.1; -; mRNA.
DR EMBL; CR457420; CAG33701.1; -; mRNA.
DR EMBL; AL390071; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08547.1; -; Genomic_DNA.
DR EMBL; BC028170; AAH28170.1; -; mRNA.
DR CCDS; CCDS9353.1; -.
DR PIR; G02221; G02221.
DR RefSeq; NP_005575.1; NM_005584.4.
DR PDB; 5EOG; X-ray; 3.05 A; A/B/C/D/F=2-359.
DR PDB; 5EOM; X-ray; 2.55 A; A/B/C/D/E/F/G/H/I/J=2-359.
DR PDBsum; 5EOG; -.
DR PDBsum; 5EOM; -.
DR AlphaFoldDB; Q13394; -.
DR SMR; Q13394; -.
DR BioGRID; 110256; 13.
DR IntAct; Q13394; 11.
DR STRING; 9606.ENSP00000369251; -.
DR iPTMnet; Q13394; -.
DR PhosphoSitePlus; Q13394; -.
DR BioMuta; MAB21L1; -.
DR DMDM; 74739786; -.
DR MassIVE; Q13394; -.
DR PaxDb; Q13394; -.
DR PeptideAtlas; Q13394; -.
DR PRIDE; Q13394; -.
DR ProteomicsDB; 59364; -.
DR TopDownProteomics; Q13394; -.
DR Antibodypedia; 23045; 68 antibodies from 16 providers.
DR DNASU; 4081; -.
DR Ensembl; ENST00000379919.6; ENSP00000369251.4; ENSG00000180660.8.
DR GeneID; 4081; -.
DR KEGG; hsa:4081; -.
DR MANE-Select; ENST00000379919.6; ENSP00000369251.4; NM_005584.5; NP_005575.1.
DR UCSC; uc032aca.2; human.
DR CTD; 4081; -.
DR DisGeNET; 4081; -.
DR GeneCards; MAB21L1; -.
DR HGNC; HGNC:6757; MAB21L1.
DR HPA; ENSG00000180660; Group enriched (brain, retina).
DR MalaCards; MAB21L1; -.
DR MIM; 601280; gene.
DR MIM; 618479; phenotype.
DR neXtProt; NX_Q13394; -.
DR OpenTargets; ENSG00000180660; -.
DR PharmGKB; PA30516; -.
DR VEuPathDB; HostDB:ENSG00000180660; -.
DR eggNOG; KOG3963; Eukaryota.
DR GeneTree; ENSGT01050000244827; -.
DR HOGENOM; CLU_045315_0_0_1; -.
DR InParanoid; Q13394; -.
DR OMA; AVDKCKY; -.
DR PhylomeDB; Q13394; -.
DR TreeFam; TF315012; -.
DR PathwayCommons; Q13394; -.
DR SignaLink; Q13394; -.
DR BioGRID-ORCS; 4081; 17 hits in 1077 CRISPR screens.
DR ChiTaRS; MAB21L1; human.
DR GenomeRNAi; 4081; -.
DR Pharos; Q13394; Tbio.
DR PRO; PR:Q13394; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q13394; protein.
DR Bgee; ENSG00000180660; Expressed in pigmented layer of retina and 107 other tissues.
DR ExpressionAtlas; Q13394; baseline and differential.
DR Genevisible; Q13394; HS.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016779; F:nucleotidyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0001654; P:eye development; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR InterPro; IPR024810; Mab-21_dom.
DR Pfam; PF03281; Mab-21; 1.
DR SMART; SM01265; Mab-21; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Developmental protein; Disease variant;
KW GTP-binding; Intellectual disability; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleotidyltransferase; Nucleus; Reference proteome;
KW Transferase.
FT CHAIN 1..359
FT /note="Putative nucleotidyltransferase MAB21L1"
FT /id="PRO_0000312781"
FT BINDING 23..24
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000269|PubMed:27271801,
FT ECO:0007744|PDB:5EOM"
FT BINDING 63..66
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000269|PubMed:27271801,
FT ECO:0007744|PDB:5EOM"
FT BINDING 73
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 75
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 248
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000269|PubMed:27271801,
FT ECO:0007744|PDB:5EOM"
FT BINDING 252..255
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000269|PubMed:27271801,
FT ECO:0007744|PDB:5EOM"
FT VARIANT 70
FT /note="S -> P (in dbSNP:rs1065316)"
FT /id="VAR_037568"
FT VARIANT 233
FT /note="Q -> P (in COFG; unknown pathological significance;
FT dbSNP:rs1566189161)"
FT /evidence="ECO:0000269|PubMed:30487245"
FT /id="VAR_082959"
FT VARIANT 280..359
FT /note="Missing (in COFG)"
FT /evidence="ECO:0000269|PubMed:30487245"
FT /id="VAR_082960"
FT MUTAGEN 51
FT /note="R->C: Decreased protein stability."
FT /evidence="ECO:0000269|PubMed:27271801"
FT MUTAGEN 247
FT /note="R->Q: Decreased protein stability."
FT /evidence="ECO:0000269|PubMed:27271801"
FT CONFLICT 132
FT /note="F -> L (in Ref. 3; CAG33701)"
FT /evidence="ECO:0000305"
FT HELIX 2..48
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 97..106
FT /evidence="ECO:0007829|PDB:5EOM"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 125..142
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 159..162
FT /evidence="ECO:0007829|PDB:5EOM"
FT TURN 163..165
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 166..176
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 197..205
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:5EOM"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 235..241
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 247..261
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 271..284
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 296..312
FT /evidence="ECO:0007829|PDB:5EOM"
FT TURN 326..329
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 332..351
FT /evidence="ECO:0007829|PDB:5EOM"
FT HELIX 353..358
FT /evidence="ECO:0007829|PDB:5EOM"
SQ SEQUENCE 359 AA; 40956 MW; A27C53FBC997A049 CRC64;
MIAAQAKLVY HLNKYYNEKC QARKAAIAKT IREVCKVVSD VLKEVEVQEP RFISSLNEMD
NRYEGLEVIS PTEFEVVLYL NQMGVFNFVD DGSLPGCAVL KLSDGRKRSM SLWVEFITAS
GYLSARKIRS RFQTLVAQAV DKCSYRDVVK MVADTSEVKL RIRDRYVVQI TPAFKCTGIW
PRSAAHWPLP HIPWPGPNRV AEVKAEGFNL LSKECHSLAG KQSSAESDAW VLQFAEAENR
LQMGGCRKKC LSILKTLRDR HLELPGQPLN NYHMKTLVSY ECEKHPRESD WDESCLGDRL
NGILLQLISC LQCRRCPHYF LPNLDLFQGK PHSALENAAK QTWRLAREIL TNPKSLEKL
