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 24-JUL-2024, entry version 158. 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}. 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; 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 GlyGen; Q13394; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13394; -. DR PhosphoSitePlus; Q13394; -. DR BioMuta; MAB21L1; -. DR DMDM; 74739786; -. DR MassIVE; Q13394; -. DR PaxDb; 9606-ENSP00000369251; -. DR PeptideAtlas; Q13394; -. DR ProteomicsDB; 59364; -. DR TopDownProteomics; Q13394; -. DR Antibodypedia; 23045; 69 antibodies from 17 providers. DR DNASU; 4081; -. DR Ensembl; ENST00000379919.6; ENSP00000369251.4; ENSG00000180660.9. DR Ensembl; ENST00000707125.1; ENSP00000516753.1; ENSG00000180660.9. 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 AGR; HGNC:6757; -. 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 OrthoDB; 5478899at2759; -. DR PhylomeDB; Q13394; -. DR TreeFam; TF315012; -. DR PathwayCommons; Q13394; -. DR SignaLink; Q13394; -. DR BioGRID-ORCS; 4081; 17 hits in 1149 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 cell types or tissues. DR ExpressionAtlas; Q13394; baseline and differential. 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 Gene3D; 1.10.1410.40; -; 1. DR Gene3D; 3.30.460.90; -; 1. DR InterPro; IPR046903; Mab-21-like_nuc_Trfase. DR InterPro; IPR046906; Mab-21_HhH/H2TH-like. DR InterPro; IPR024810; MAB21L/cGLR. DR PANTHER; PTHR10656; CELL FATE DETERMINING PROTEIN MAB21-RELATED; 1. DR PANTHER; PTHR10656:SF38; NUCLEOTIDYLTRANSFERASE MAB21L1-RELATED; 1. DR Pfam; PF03281; Mab-21; 1. DR Pfam; PF20266; Mab-21_C; 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; uncertain 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 //