LOCUS       NM_138775               4067 bp    mRNA    linear   PRI 08-DEC-2024
DEFINITION  Homo sapiens alkB homolog 8, tRNA methyltransferase (ALKBH8),
            transcript variant 2, mRNA.
ACCESSION   NM_138775
VERSION     NM_138775.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4067)
  AUTHORS   Yilmaz,M., Kamasak,T., Terali,K., Cebi,A.H. and Turkyilmaz,A.
  TITLE     The first Turkish family with a novel biallelic missense variant of
            the ALKBH8 gene: A study on the clinical and variant spectrum of
            ALKBH8-related intellectual developmental disorders
  JOURNAL   Am J Med Genet A 194 (5), e63535 (2024)
   PUBMED   38189198
  REMARK    GeneRIF: The first Turkish family with a novel biallelic missense
            variant of the ALKBH8 gene: A study on the clinical and variant
            spectrum of ALKBH8-related intellectual developmental disorders.
REFERENCE   2  (bases 1 to 4067)
  AUTHORS   Cavallin,I., Bartosovic,M., Skalicky,T., Rengaraj,P., Demko,M.,
            Schmidt-Dengler,M.C., Drino,A., Helm,M. and Vanacova,S.
  TITLE     HITS-CLIP analysis of human ALKBH8 reveals interactions with fully
            processed substrate tRNAs and with specific noncoding RNAs
  JOURNAL   RNA 28 (12), 1568-1581 (2022)
   PUBMED   36192131
  REMARK    GeneRIF: HITS-CLIP analysis of human ALKBH8 reveals interactions
            with fully processed substrate tRNAs and with specific noncoding
            RNAs.
REFERENCE   3  (bases 1 to 4067)
  AUTHORS   Maddirevula,S., Alameer,S., Ewida,N., de Sousa,M.M.L., Bjoras,M.,
            Vagbo,C.B. and Alkuraya,F.S.
  TITLE     Insight into ALKBH8-related intellectual developmental disability
            based on the first pathogenic missense variant
  JOURNAL   Hum Genet 141 (2), 209-215 (2022)
   PUBMED   34757492
  REMARK    GeneRIF: Insight into ALKBH8-related intellectual developmental
            disability based on the first pathogenic missense variant.
REFERENCE   4  (bases 1 to 4067)
  AUTHORS   Brumele,B., Mutso,M., Telanne,L., Ounap,K., Spunde,K., Abroi,A. and
            Kurg,R.
  TITLE     Human TRMT112-Methyltransferase Network Consists of Seven Partners
            Interacting with a Common Co-Factor
  JOURNAL   Int J Mol Sci 22 (24), 13593 (2021)
   PUBMED   34948388
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 4067)
  AUTHORS   Saad,A.K., Marafi,D., Mitani,T., Du,H., Rafat,K., Fatih,J.M.,
            Jhangiani,S.N., Coban-Akdemir,Z., Gibbs,R.A., Pehlivan,D.,
            Hunter,J.V., Posey,J.E., Zaki,M.S. and Lupski,J.R.
  CONSRTM   Baylor-Hopkins Center for Mendelian Genomics
  TITLE     Neurodevelopmental disorder in an Egyptian family with a biallelic
            ALKBH8 variant
  JOURNAL   Am J Med Genet A 185 (4), 1288-1293 (2021)
   PUBMED   33544954
  REMARK    GeneRIF: Neurodevelopmental disorder in an Egyptian family with a
            biallelic ALKBH8 variant.
REFERENCE   6  (bases 1 to 4067)
  AUTHORS   Pastore,C., Topalidou,I., Forouhar,F., Yan,A.C., Levy,M. and
            Hunt,J.F.
  TITLE     Crystal structure and RNA binding properties of the RNA recognition
            motif (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an
            enzyme catalyzing tRNA hypermodification
  JOURNAL   J Biol Chem 287 (3), 2130-2143 (2012)
   PUBMED   22065580
REFERENCE   7  (bases 1 to 4067)
  AUTHORS   van den Born,E., Vagbo,C.B., Songe-Moller,L., Leihne,V., Lien,G.F.,
            Leszczynska,G., Malkiewicz,A., Krokan,H.E., Kirpekar,F.,
            Klungland,A. and Falnes,P.O.
  TITLE     ALKBH8-mediated formation of a novel diastereomeric pair of wobble
            nucleosides in mammalian tRNA
  JOURNAL   Nat Commun 2, 172 (2011)
   PUBMED   21285950
  REMARK    GeneRIF: Many eukaryotic tRNAs contain the wobble modification
            5-methoxycarbonylmethyl-uridine (mcm5U). It is demonstrated that
            (R)- and (S)-5-methoxycarbonylhydroxymethyluridine (mchm5U),
            hydroxylated forms of mcm(5)U, are present in mammalian
            tRNA-Arg(UCG), and tRNA-Gly(UCC), respectively. It is shown that
            the hydroxylation reaction leading to the formation of (S)-mchm5U
            is catalyzed by the oxygenase (AlkB) domain of ALKBH8.
            Publication Status: Online-Only
REFERENCE   8  (bases 1 to 4067)
  AUTHORS   Fu,D., Brophy,J.A., Chan,C.T., Atmore,K.A., Begley,U., Paules,R.S.,
            Dedon,P.C., Begley,T.J. and Samson,L.D.
  TITLE     Human AlkB homolog ABH8 Is a tRNA methyltransferase required for
            wobble uridine modification and DNA damage survival
  JOURNAL   Mol Cell Biol 30 (10), 2449-2459 (2010)
   PUBMED   20308323
  REMARK    GeneRIF: Data show that human AlkB homolog 8 (ABH8) catalyzes tRNA
            methylation to generate 5-methylcarboxymethyl uridine (mcm(5)U) at
            the wobble position of certain tRNAs, a critical anticodon loop
            modification linked to DNA damage survival.
REFERENCE   9  (bases 1 to 4067)
  AUTHORS   Songe-Moller,L., van den Born,E., Leihne,V., Vagbo,C.B.,
            Kristoffersen,T., Krokan,H.E., Kirpekar,F., Falnes,P.O. and
            Klungland,A.
  TITLE     Mammalian ALKBH8 possesses tRNA methyltransferase activity required
            for the biogenesis of multiple wobble uridine modifications
            implicated in translational decoding
  JOURNAL   Mol Cell Biol 30 (7), 1814-1827 (2010)
   PUBMED   20123966
  REMARK    GeneRIF: The methyltransferase domain of ALKBH8 is demonstrated to
            be a functional homologue of the Saccharomyces cerevisiae Trm9
            protein, mediating the last step in the formation of the wobble
            uridine modification 5-methoxycarbonylmethyl-uridine in tRNA. This
            modification is shown to be important for efficient selenoprotein
            synthesis. ALKBH8 knock-out mice are generated and described.
REFERENCE   10 (bases 1 to 4067)
  AUTHORS   Shimada,K., Nakamura,M., Anai,S., De Velasco,M., Tanaka,M.,
            Tsujikawa,K., Ouji,Y. and Konishi,N.
  TITLE     A novel human AlkB homologue, ALKBH8, contributes to human bladder
            cancer progression
  JOURNAL   Cancer Res 69 (7), 3157-3164 (2009)
   PUBMED   19293182
  REMARK    GeneRIF: Findings indicate a role for ALKBH8 in urothelial
            carcinoma cell survival mediated by NOX-1-dependent ROS signals,
            further suggesting therapeutic strategies in human bladder cancer
            by inducing JNK/p38/gammaH2AX-mediated cell death by silencing of
            ALKBH8.
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AB218768.1, AP001823.5 and BX649085.1.
            
            On Jun 3, 2019 this sequence version replaced NM_138775.2.
            
            Transcript Variant: This variant (2) represents the longest
            transcript and encodes the longer isoform (1). Variants 1 and 2
            both encode the same isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR14038194.678403.1, AB218768.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000428149.7/ ENSP00000415885.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-860               AB218768.1         1-860
            861-861             AP001823.5         139394-139394       c
            862-2138            AB218768.1         862-2138
            2139-3574           AP001823.5         92810-94245         c
            3575-4067           BX649085.1         2682-3174
FEATURES             Location/Qualifiers
     source          1..4067
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q22.3"
     gene            1..4067
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /note="alkB homolog 8, tRNA methyltransferase"
                     /db_xref="GeneID:91801"
                     /db_xref="HGNC:HGNC:25189"
                     /db_xref="MIM:613306"
     exon            1..135
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            136..270
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     CDS             142..2136
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /EC_number="2.1.1.229"
                     /note="isoform 1 is encoded by transcript variant 2;
                     alkylated DNA repair protein alkB homolog 8; AlkB
                     homologue 8; probable alpha-ketoglutarate-dependent
                     dioxygenase ABH8; S-adenosyl-L-methionine-dependent tRNA
                     methyltransferase ABH8; tRNA
                     (carboxymethyluridine(34)-5-O)-methyltransferase ABH8;
                     alkB, alkylation repair homolog 8; tRNA methyltransferase
                     9 homolog; tRNA methyltransferase 9 related;
                     alpha-ketoglutarate-dependent dioxygenase ALKBH8;
                     S-adenosyl-L-methionine-dependent tRNA methyltransferase
                     ALKBH8; tRNA
                     (carboxymethyluridine(34)-5-O)-methyltransferase ALKBH8"
                     /codon_start=1
                     /product="tRNA
                     (carboxymethyluridine(34)-5-O)-methyltransferase ALKBH8
                     isoform 1"
                     /protein_id="NP_620130.2"
                     /db_xref="CCDS:CCDS8337.2"
                     /db_xref="GeneID:91801"
                     /db_xref="HGNC:HGNC:25189"
                     /db_xref="MIM:613306"
                     /translation="MDSNHQSNYKLSKTEKKFLRKQIKAKHTLLRHEGIETVSYATQS
                     LVVANGGLGNGVSRNQLLPVLEKCGLVDALLMPPNKPYSFARYRTTEESKRAYVTLNG
                     KEVVDDLGQKITLYLNFVEKVQWKELRPQALPPGLMVVEEIISSEEEKMLLESVDWTE
                     DTDNQNSQKSLKHRRVKHFGYEFHYENNNVDKDKPLSGGLPDICESFLEKWLRKGYIK
                     HKPDQMTINQYEPGQGIPAHIDTHSAFEDEIVSLSLGSEIVMDFKHPDGIAVPVMLPR
                     RSLLVMTGESRYLWTHGITCRKFDTVQASESLKSGIITSDVGDLTLSKRGLRTSFTFR
                     KVRQTPCNCSYPLVCDSQRKETPPSFPESDKEASRLEQEYVHQVYEEIAGHFSSTRHT
                     PWPHIVEFLKALPSGSIVADIGCGNGKYLGINKELYMIGCDRSQNLVDICRERQFQAF
                     VCDALAVPVRSGSCDACISIAVIHHFATAERRVAALQEIVRLLRPGGKALIYVWAMEQ
                     EYNKQKSKYLRGNRNSQGKKEEMNSDTSVQRSLVEQMRDMGSRDSASSVPRINDSQEG
                     GCNSRQVSNSKLPVHVNRTSFYSQDVLVPWHLKGNPDKGKPVEPFGPIGSQDPSPVFH
                     RYYHVFREGELEGACRTVSDVRILQSYYDQGNWCVILQKA"
     exon            271..508
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            509..640
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            641..736
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            737..841
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            842..912
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            913..1019
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            1020..1171
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            1172..1428
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            1429..1578
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     exon            1579..4067
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4044..4049
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /note="hexamer: AATAAA"
     polyA_site      4067
                     /gene="ALKBH8"
                     /gene_synonym="ABH8; MRT71; TRM9; TRMT9; TRMT9A"
                     /note="major polyA site"
ORIGIN      
        1 agttttctcc aacatggccg cgcccagggg agatggcgtg caagtatccg ctgcggtgtt
       61 ctggtgctag agtggagagg ctggcaaaga agaaggcaca cgcatggtga gaatccggcc
      121 tgagccgaag cggagtttgc tatggacagc aaccatcaaa gtaattacaa actcagtaaa
      181 actgagaaga agttcttaag gaaacagatt aaagccaagc atactttgct gagacatgaa
      241 ggcattgaga cagtatccta tgccactcag agcctggttg ttgccaatgg tggtttgggt
      301 aatggtgtga gtcggaacca gctgctcccg gttttagaga aatgtggact ggtggatgct
      361 ctcttaatgc cacctaacaa gccgtactca tttgcaagat acagaactac agaagaatct
      421 aagagagcct atgttaccct caatggaaaa gaagtagtgg atgatttagg acaaaagatc
      481 actctgtatt tgaattttgt ggaaaaagtg cagtggaagg agttgaggcc tcaagcctta
      541 ccaccaggac tcatggtagt agaagaaata atttcttctg aggaggagaa aatgcttttg
      601 gaaagtgttg attggacaga agatacagac aatcaaaact ctcaaaaatc cttaaaacac
      661 agaagagtaa agcattttgg ttatgagttc cactatgaga acaacaatgt agataaagat
      721 aagccattat ctgggggtct tcctgacatt tgtgaaagct ttttggagaa atggttgagg
      781 aaaggttaca ttaaacataa acctgatcaa atgaccataa atcagtatga acctgggcaa
      841 ggaattcccg ctcatattga tacacattcc gcttttgagg atgagatcgt ttctctcagt
      901 ttggggtcag agattgtcat ggattttaag cacccagatg gcattgcagt gccagttatg
      961 ttgcctcgtc ggagtttgct ggtgatgaca ggagaatcta gatacctttg gacccatgga
     1021 atcacgtgca gaaaatttga tactgttcaa gcatctgaga gtcttaaaag tggaattatc
     1081 accagtgatg ttggagactt aactttaagc aagaggggac tacgaacatc atttacattt
     1141 aggaaagtga ggcaaacacc ttgtaactgt agttacccgt tggtctgtga tagccagagg
     1201 aaagagactc ccccctcatt tccagagagt gataaagaag cctcacggct ggagcaagag
     1261 tacgtccatc aggtttatga agagattgct gggcacttca gcagcacaag acatacccct
     1321 tggccgcaca ttgtggagtt tttgaaggct ttgccaagtg gttcaatagt ggctgatatt
     1381 ggatgtggta atggaaagta tcttggcatc aataaggagt tatatatgat tggttgtgat
     1441 cgtagccaaa accttgtgga catttgtaga gagaggcaat ttcaggcttt tgtctgtgat
     1501 gcattggcag taccagtccg cagtgggtct tgtgatgcct gcatctccat tgctgttatt
     1561 catcattttg caacagcaga gcgtagagtg gcagctctcc aagaaattgt tcgactcctg
     1621 agaccaggtg ggaaggcact catttatgtc tgggcaatgg aacaagaata taataagcag
     1681 aagtccaagt atcttagagg aaacagaaat agccaaggaa agaaagagga gatgaacagt
     1741 gatacctcag tgcagaggtc acttgtggag caaatgcgtg acatgggcag tcgagactcg
     1801 gcatcttctg tcccccgcat taatgactct caggaaggag gatgtaattc aaggcaagtt
     1861 tctaattcca agctgcctgt tcatgttaac aggacttctt tttattctca agatgtactg
     1921 gttccctggc accttaaggg aaatcctgat aaaggcaaac ctgttgagcc atttggtccc
     1981 ataggatccc aggacccaag tcctgtgttt catcgttact accatgtgtt ccgtgaggga
     2041 gaactggaag gtgcctgcag gactgtgagt gatgtcagaa ttctgcaaag ctactacgat
     2101 caaggaaact ggtgtgtgat tcttcaaaag gcctgattat ttacctgaac acatcatata
     2161 taaagaagaa atgctcactt aaaaaaaaag agagaataaa ttaattaccc ttttaattaa
     2221 agagaaaact tgtgggaaag taccaaagga aagctgagaa aaatttggaa gtagggattc
     2281 attaggagac attcaaatgt ctcctgttgg ctgacatcac agatgtggtg ttggctcctc
     2341 ctacttccct aggagaggtg gtttctaaaa gtgattgaag cagtttgtgc agtgtttgta
     2401 attcttgggt aagagcccag gattttgaag ataatagttt tttagtaaag tgctactaaa
     2461 tgtagtaaat catgtaggat tttagggatg taattatatg ttaatacaga aaatagtcct
     2521 ggtcaataga aaattgtctg aagttttacc tatgattttt agctctgtaa aatcatagac
     2581 aataaccatt ctatttccat gcctgactag cccagggctg gacgtatagc gggtgtccaa
     2641 taacgtttag tcaatcagat aatacccaga acttagtagg agtttcattc aaaaactatt
     2701 ttttgaaccc aaccatgtac cagttactat tttaagtact gataatgaag cagtgaataa
     2761 gaaagagcaa agctcttgcc cttatggtgc ttacattcta gacggggaga cagacagcag
     2821 gcaaatcaat aaatagatac tatgtgccag atagtgataa atgccatgaa aaacataaaa
     2881 tgagagacga ttcaccttgg agcaaaagat tacttttaag tgactgaaat aactactaat
     2941 cctgactaat ttattatcaa gagttaattg gtattccaaa ttcattgagc agggtgctaa
     3001 aaacaaccca aatgtgctcc tttaactcct ttgtttaaat gacaaaagtt agaatgtggt
     3061 cactcagacc taactgtgcc cttagagcca aagctgtggt gtcattattg gttatttcta
     3121 gttgattcat agtttgtccc aatccaggtt caatcgggtt atttttaaga tctgtacaat
     3181 attgcataat agtaacccag ttaacttacc acttaggtta gatttcctgg aggaacaaag
     3241 gtagaaattc aaccataggt caaattatca catagaagga aaaggctttt tttcaaagaa
     3301 aaaatttttt gaacacttta ctcccagtat gcattacttt tgtagtagta atgcttaaga
     3361 ctgttttaaa gaaaaattgc tttctgttta attaatgttt actgttatta atgctagtga
     3421 tacttaatct tgaagcatca agttttcaga aacctatagt gatcaataat gggtctcaga
     3481 tgagaggatg attatttttt tcatggaatt tcagtccaac atcctggtgt actggtccct
     3541 ctgggatgaa tttataaggc tcatgatata ggaaaaggaa tatagggcta aaaatagttt
     3601 tatttctgat ataaattctg gtacttgaca ccaaagtttg aagtcaagtc atgccaataa
     3661 attttaacat ccaaatgaaa tagatgattt tctatgaaga tgaaaaatac caaaattgac
     3721 tcaagaaggg agagaaaatg gaagatgttg aaaaatagca taggaattca gaactgggct
     3781 ctagaatcag atttcctgag agttgaattc tagatctgcc atttattagc tgtgggattt
     3841 tgggcaaatt tcttgacttt ctgtgcttca gttttcttag ctgtaaaatt ggaagagttg
     3901 ttatgaaaat tcactgaaag tatatttgta tacatcatag gatagtgtaa gaatatagta
     3961 tggctttgag aaatgttcat tattattact cccagaggag ttttaggtat taagtgatgc
     4021 caaatataat ttgttaattg tataataaaa atctatattc ttactga
//
