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Q96BT7 (ALKB8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alkylated DNA repair protein alkB homolog 8

EC=1.14.11.-
Alternative name(s):
Probable alpha-ketoglutarate-dependent dioxygenase ABH8
S-adenosyl-L-methionine-dependent tRNA methyltransferase ABH8
tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ABH8
EC=2.1.1.229
Gene names
Name:ALKBH8
Synonyms:ABH8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length664 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA. Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA. Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys). Required for normal survival after DNA damage. May inhibit apoptosis and promote cell survival and angiogenesis. Ref.6 Ref.7

Catalytic activity

S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA. Ref.7

Subunit structure

Interacts with TRMT112. Ref.7

Subcellular location

Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Ref.1 Ref.7

Tissue specificity

Widely expressed, with highest expression in spleen, followed by pancreas and lung. Ref.1

Induction

Up-regulated after DNA damage. Induction is mediated via ATM. Ref.7

Sequence similarities

Belongs to the alkB family.

Contains 1 Fe2OG dioxygenase domain.

Contains 1 RRM (RNA recognition motif) domain.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96BT7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96BT7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     234-238: GIPAH → DCHGF
     239-664: Missing.
Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 3 (identifier: Q96BT7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     215-224: GYIKHKPDQM → AEKNLEVGIH
     225-664: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q96BT7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MFAM
Note: May be due to competing donor splice site. No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 664664Alkylated DNA repair protein alkB homolog 8
PRO_0000337125

Regions

Domain43 – 12078RRM
Domain220 – 337118Fe2OG dioxygenase
Region227 – 2293Alpha-ketoglutarate binding By similarity
Region328 – 3347Alpha-ketoglutarate binding By similarity
Region411 – 664254Methyltransferase domain

Sites

Metal binding2381Iron; catalytic By similarity
Metal binding2401Iron; catalytic By similarity
Metal binding2921Iron; catalytic By similarity

Natural variations

Alternative sequence11M → MFAM in isoform 4.
VSP_039159
Alternative sequence215 – 22410GYIKHKPDQM → AEKNLEVGIH in isoform 3.
VSP_033925
Alternative sequence225 – 664440Missing in isoform 3.
VSP_033926
Alternative sequence234 – 2385GIPAH → DCHGF in isoform 2.
VSP_033927
Alternative sequence239 – 664426Missing in isoform 2.
VSP_033928

Experimental info

Sequence conflict2101K → R in BAC04566. Ref.2

Secondary structure

................................................................... 664
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 20, 2008. Version 2.
Checksum: 4BE595D6757C2A43

FASTA66475,208
        10         20         30         40         50         60 
MDSNHQSNYK LSKTEKKFLR KQIKAKHTLL RHEGIETVSY ATQSLVVANG GLGNGVSRNQ 

        70         80         90        100        110        120 
LLPVLEKCGL VDALLMPPNK PYSFARYRTT EESKRAYVTL NGKEVVDDLG QKITLYLNFV 

       130        140        150        160        170        180 
EKVQWKELRP QALPPGLMVV EEIISSEEEK MLLESVDWTE DTDNQNSQKS LKHRRVKHFG 

       190        200        210        220        230        240 
YEFHYENNNV DKDKPLSGGL PDICESFLEK WLRKGYIKHK PDQMTINQYE PGQGIPAHID 

       250        260        270        280        290        300 
THSAFEDEIV SLSLGSEIVM DFKHPDGIAV PVMLPRRSLL VMTGESRYLW THGITCRKFD 

       310        320        330        340        350        360 
TVQASESLKS GIITSDVGDL TLSKRGLRTS FTFRKVRQTP CNCSYPLVCD SQRKETPPSF 

       370        380        390        400        410        420 
PESDKEASRL EQEYVHQVYE EIAGHFSSTR HTPWPHIVEF LKALPSGSIV ADIGCGNGKY 

       430        440        450        460        470        480 
LGINKELYMI GCDRSQNLVD ICRERQFQAF VCDALAVPVR SGSCDACISI AVIHHFATAE 

       490        500        510        520        530        540 
RRVAALQEIV RLLRPGGKAL IYVWAMEQEY NKQKSKYLRG NRNSQGKKEE MNSDTSVQRS 

       550        560        570        580        590        600 
LVEQMRDMGS RDSASSVPRI NDSQEGGCNS RQVSNSKLPV HVNRTSFYSQ DVLVPWHLKG 

       610        620        630        640        650        660 
NPDKGKPVEP FGPIGSQDPS PVFHRYYHVF REGELEGACR TVSDVRILQS YYDQGNWCVI 


LQKA 

« Hide

Isoform 2 [UniParc].

Checksum: 24EF6A3A66DCC2F7
Show »

FASTA23827,440
Isoform 3 [UniParc].

Checksum: 6FD66E832509EE87
Show »

FASTA22425,742
Isoform 4 [UniParc].

Checksum: BF6DB408A2B1B39C
Show »

FASTA66775,558

References

« Hide 'large scale' references
[1]"Expression and sub-cellular localization of human ABH family molecules."
Tsujikawa K., Koike K., Kitae K., Shinkawa A., Arima H., Suzuki T., Tsuchiya M., Makino Y., Furukawa T., Konishi N., Yamamoto H.
J. Cell. Mol. Med. 11:1105-1116(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
Tissue: Brain and Trachea.
[3]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Uterus.
[6]"A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression."
Shimada K., Nakamura M., Anai S., De Velasco M., Tanaka M., Tsujikawa K., Ouji Y., Konishi N.
Cancer Res. 69:3157-3164(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Human AlkB homolog ABH8 is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival."
Fu D., Brophy J.A., Chan C.T., Atmore K.A., Begley U., Paules R.S., Dedon P.C., Begley T.J., Samson L.D.
Mol. Cell. Biol. 30:2449-2459(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH TRMT112, INDUCTION, IDENTIFICATION BY MASS SPECTROMETRY.
[8]"Solution structure of RNA binding domain in hypothetical protein LOC91801."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 25-125.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB218768 mRNA. Translation: BAG16270.1.
AK095523 mRNA. Translation: BAC04566.1.
AK293603 mRNA. Translation: BAG57067.1.
AK304413 mRNA. Translation: BAG65244.1.
AP001823 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67089.1.
CH471065 Genomic DNA. Translation: EAW67090.1.
BC015183 mRNA. Translation: AAH15183.1.
RefSeqNP_620130.2. NM_138775.2.
XP_005271784.1. XM_005271727.1.
UniGeneHs.503763.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CQ2NMR-A25-125[»]
3THPX-ray3.20A25-355[»]
3THTX-ray3.01A/B/C/D25-355[»]
ProteinModelPortalQ96BT7.
SMRQ96BT7. Positions 25-508.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000374219.

PTM databases

PhosphoSiteQ96BT7.

Polymorphism databases

DMDM189027650.

Proteomic databases

PaxDbQ96BT7.
PRIDEQ96BT7.

Protocols and materials databases

DNASU91801.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260318; ENSP00000260318; ENSG00000137760. [Q96BT7-2]
ENST00000389568; ENSP00000374219; ENSG00000137760. [Q96BT7-1]
ENST00000417449; ENSP00000397673; ENSG00000137760. [Q96BT7-4]
ENST00000428149; ENSP00000415885; ENSG00000137760. [Q96BT7-1]
ENST00000429370; ENSP00000391225; ENSG00000137760. [Q96BT7-3]
GeneID91801.
KEGGhsa:91801.
UCSCuc001pjk.3. human. [Q96BT7-1]

Organism-specific databases

CTD91801.
GeneCardsGC11M107373.
HGNCHGNC:25189. ALKBH8.
HPAHPA038725.
MIM613306. gene.
neXtProtNX_Q96BT7.
PharmGKBPA143485296.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0500.
HOGENOMHOG000007984.
HOVERGENHBG067234.
InParanoidQ96BT7.
KOK10770.
OMAPCNCSYP.
OrthoDBEOG780RMC.
PhylomeDBQ96BT7.
TreeFamTF316056.

Gene expression databases

ArrayExpressQ96BT7.
BgeeQ96BT7.
CleanExHS_ALKBH8.
GenevestigatorQ96BT7.

Family and domain databases

Gene3D2.60.120.590. 1 hit.
InterProIPR027450. AlkB-like.
IPR015095. AlkB_hom8_N.
IPR013216. Methyltransf_11.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PfamPF13532. 2OG-FeII_Oxy_2. 1 hit.
PF09004. DUF1891. 1 hit.
PF08241. Methyltransf_11. 1 hit.
[Graphical view]
PROSITEPS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ96BT7.
GenomeRNAi91801.
NextBio77461.
PROQ96BT7.
SOURCESearch...

Entry information

Entry nameALKB8_HUMAN
AccessionPrimary (citable) accession number: Q96BT7
Secondary accession number(s): B1Q2M0, B4DEF6, Q8N989
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: April 16, 2014
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM