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Q96BT7

- ALKB8_HUMAN

UniProt

Q96BT7 - ALKB8_HUMAN

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Protein

Alkylated DNA repair protein alkB homolog 8

Gene

ALKBH8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

S-adenosyl-L-methionine + carboxymethyluridine(34) in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine(34) in tRNA.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi238 – 2381Iron; catalyticPROSITE-ProRule annotation
Metal bindingi240 – 2401Iron; catalyticPROSITE-ProRule annotation
Metal bindingi292 – 2921Iron; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors Source: InterPro
  3. RNA binding Source: UniProtKB-KW
  4. tRNA (uracil) methyltransferase activity Source: UniProtKB

GO - Biological processi

  1. cellular response to DNA damage stimulus Source: UniProtKB
  2. tRNA methylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Oxidoreductase, Transferase

Keywords - Ligandi

Iron, Metal-binding, RNA-binding, S-adenosyl-L-methionine

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:ALKBH8
Synonyms:ABH8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:25189. ALKBH8.

Subcellular locationi

Cytoplasm. Nucleus
Note: Predominantly cytoplasmic.

GO - Cellular componenti

  1. cytosol Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA143485296.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 664664Alkylated DNA repair protein alkB homolog 8PRO_0000337125Add
BLAST

Proteomic databases

MaxQBiQ96BT7.
PaxDbiQ96BT7.
PRIDEiQ96BT7.

PTM databases

PhosphoSiteiQ96BT7.

Expressioni

Tissue specificityi

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

Inductioni

Up-regulated after DNA damage. Induction is mediated via ATM.1 Publication

Gene expression databases

BgeeiQ96BT7.
CleanExiHS_ALKBH8.
ExpressionAtlasiQ96BT7. baseline and differential.
GenevestigatoriQ96BT7.

Organism-specific databases

HPAiHPA038725.

Interactioni

Subunit structurei

Interacts with TRMT112.1 Publication

Protein-protein interaction databases

STRINGi9606.ENSP00000374219.

Structurei

Secondary structure

1
664
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi26 – 283
Turni30 – 345
Beta strandi38 – 403
Beta strandi43 – 486
Helixi52 – 543
Helixi58 – 669
Beta strandi71 – 755
Beta strandi81 – 899
Helixi90 – 9910
Turni100 – 1023
Beta strandi104 – 1063
Beta strandi112 – 1143
Beta strandi116 – 1194
Beta strandi121 – 1299
Beta strandi137 – 1404
Helixi146 – 1538
Beta strandi175 – 1773
Helixi202 – 21413
Beta strandi222 – 2298
Beta strandi235 – 2384
Turni242 – 2443
Beta strandi249 – 2568
Beta strandi258 – 2636
Beta strandi269 – 2746
Beta strandi278 – 2825
Helixi285 – 2884
Beta strandi290 – 2945
Beta strandi298 – 3047
Beta strandi307 – 3093
Beta strandi315 – 3184
Beta strandi320 – 3245
Beta strandi328 – 3347
Turni346 – 3483
Turni350 – 3556

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CQ2NMR-A25-125[»]
3THPX-ray3.20A25-355[»]
3THTX-ray3.01A/B/C/D25-355[»]
ProteinModelPortaliQ96BT7.
SMRiQ96BT7. Positions 25-355, 404-505.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96BT7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini43 – 12078RRMAdd
BLAST
Domaini220 – 337118Fe2OG dioxygenasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni227 – 2293Alpha-ketoglutarate bindingBy similarity
Regioni328 – 3347Alpha-ketoglutarate bindingBy similarity
Regioni411 – 664254Methyltransferase domainAdd
BLAST

Sequence similaritiesi

Belongs to the alkB family.Curated
Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0500.
GeneTreeiENSGT00530000063536.
HOGENOMiHOG000007984.
HOVERGENiHBG067234.
InParanoidiQ96BT7.
KOiK10770.
OMAiPCNCSYP.
OrthoDBiEOG780RMC.
PhylomeDBiQ96BT7.
TreeFamiTF316056.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
3.40.50.150. 2 hits.
InterProiIPR027450. AlkB-like.
IPR015095. AlkB_hom8_N.
IPR013216. Methyltransf_11.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
PF09004. DUF1891. 1 hit.
PF08241. Methyltransf_11. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q96BT7-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MDSNHQSNYK LSKTEKKFLR KQIKAKHTLL RHEGIETVSY ATQSLVVANG
60 70 80 90 100
GLGNGVSRNQ LLPVLEKCGL VDALLMPPNK PYSFARYRTT EESKRAYVTL
110 120 130 140 150
NGKEVVDDLG QKITLYLNFV EKVQWKELRP QALPPGLMVV EEIISSEEEK
160 170 180 190 200
MLLESVDWTE DTDNQNSQKS LKHRRVKHFG YEFHYENNNV DKDKPLSGGL
210 220 230 240 250
PDICESFLEK WLRKGYIKHK PDQMTINQYE PGQGIPAHID THSAFEDEIV
260 270 280 290 300
SLSLGSEIVM DFKHPDGIAV PVMLPRRSLL VMTGESRYLW THGITCRKFD
310 320 330 340 350
TVQASESLKS GIITSDVGDL TLSKRGLRTS FTFRKVRQTP CNCSYPLVCD
360 370 380 390 400
SQRKETPPSF PESDKEASRL EQEYVHQVYE EIAGHFSSTR HTPWPHIVEF
410 420 430 440 450
LKALPSGSIV ADIGCGNGKY LGINKELYMI GCDRSQNLVD ICRERQFQAF
460 470 480 490 500
VCDALAVPVR SGSCDACISI AVIHHFATAE RRVAALQEIV RLLRPGGKAL
510 520 530 540 550
IYVWAMEQEY NKQKSKYLRG NRNSQGKKEE MNSDTSVQRS LVEQMRDMGS
560 570 580 590 600
RDSASSVPRI NDSQEGGCNS RQVSNSKLPV HVNRTSFYSQ DVLVPWHLKG
610 620 630 640 650
NPDKGKPVEP FGPIGSQDPS PVFHRYYHVF REGELEGACR TVSDVRILQS
660
YYDQGNWCVI LQKA
Length:664
Mass (Da):75,208
Last modified:May 20, 2008 - v2
Checksum:i4BE595D6757C2A43
GO
Isoform 2 (identifier: Q96BT7-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:238
Mass (Da):27,440
Checksum:i24EF6A3A66DCC2F7
GO
Isoform 3 (identifier: Q96BT7-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     215-224: GYIKHKPDQM → AEKNLEVGIH
     225-664: Missing.

Note: No experimental confirmation available.

Show »
Length:224
Mass (Da):25,742
Checksum:i6FD66E832509EE87
GO
Isoform 4 (identifier: Q96BT7-4) [UniParc]FASTAAdd to Basket

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.

Show »
Length:667
Mass (Da):75,558
Checksum:iBF6DB408A2B1B39C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti210 – 2101K → R in BAC04566. (PubMed:14702039)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MFAM in isoform 4. 1 PublicationVSP_039159
Alternative sequencei215 – 22410GYIKHKPDQM → AEKNLEVGIH in isoform 3. 1 PublicationVSP_033925
Alternative sequencei225 – 664440Missing in isoform 3. 1 PublicationVSP_033926Add
BLAST
Alternative sequencei234 – 2385GIPAH → DCHGF in isoform 2. 1 PublicationVSP_033927
Alternative sequencei239 – 664426Missing in isoform 2. 1 PublicationVSP_033928Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS73376.1. [Q96BT7-4]
CCDS8337.2. [Q96BT7-1]
RefSeqiNP_620130.2. NM_138775.2. [Q96BT7-1]
UniGeneiHs.503763.

Genome annotation databases

EnsembliENST00000260318; ENSP00000260318; ENSG00000137760. [Q96BT7-2]
ENST00000389568; ENSP00000374219; ENSG00000137760. [Q96BT7-1]
ENST00000417449; ENSP00000397673; ENSG00000137760. [Q96BT7-4]
ENST00000428149; ENSP00000415885; ENSG00000137760. [Q96BT7-1]
ENST00000429370; ENSP00000391225; ENSG00000137760. [Q96BT7-3]
GeneIDi91801.
KEGGihsa:91801.
UCSCiuc001pjk.3. human. [Q96BT7-1]

Polymorphism databases

DMDMi189027650.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS73376.1. [Q96BT7-4 ]
CCDS8337.2. [Q96BT7-1 ]
RefSeqi NP_620130.2. NM_138775.2. [Q96BT7-1 ]
UniGenei Hs.503763.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2CQ2 NMR - A 25-125 [» ]
3THP X-ray 3.20 A 25-355 [» ]
3THT X-ray 3.01 A/B/C/D 25-355 [» ]
ProteinModelPortali Q96BT7.
SMRi Q96BT7. Positions 25-355, 404-505.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000374219.

PTM databases

PhosphoSitei Q96BT7.

Polymorphism databases

DMDMi 189027650.

Proteomic databases

MaxQBi Q96BT7.
PaxDbi Q96BT7.
PRIDEi Q96BT7.

Protocols and materials databases

DNASUi 91801.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000260318 ; ENSP00000260318 ; ENSG00000137760 . [Q96BT7-2 ]
ENST00000389568 ; ENSP00000374219 ; ENSG00000137760 . [Q96BT7-1 ]
ENST00000417449 ; ENSP00000397673 ; ENSG00000137760 . [Q96BT7-4 ]
ENST00000428149 ; ENSP00000415885 ; ENSG00000137760 . [Q96BT7-1 ]
ENST00000429370 ; ENSP00000391225 ; ENSG00000137760 . [Q96BT7-3 ]
GeneIDi 91801.
KEGGi hsa:91801.
UCSCi uc001pjk.3. human. [Q96BT7-1 ]

Organism-specific databases

CTDi 91801.
GeneCardsi GC11M107373.
HGNCi HGNC:25189. ALKBH8.
HPAi HPA038725.
MIMi 613306. gene.
neXtProti NX_Q96BT7.
PharmGKBi PA143485296.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0500.
GeneTreei ENSGT00530000063536.
HOGENOMi HOG000007984.
HOVERGENi HBG067234.
InParanoidi Q96BT7.
KOi K10770.
OMAi PCNCSYP.
OrthoDBi EOG780RMC.
PhylomeDBi Q96BT7.
TreeFami TF316056.

Miscellaneous databases

EvolutionaryTracei Q96BT7.
GenomeRNAii 91801.
NextBioi 77461.
PROi Q96BT7.
SOURCEi Search...

Gene expression databases

Bgeei Q96BT7.
CleanExi HS_ALKBH8.
ExpressionAtlasi Q96BT7. baseline and differential.
Genevestigatori Q96BT7.

Family and domain databases

Gene3Di 2.60.120.590. 1 hit.
3.40.50.150. 2 hits.
InterProi IPR027450. AlkB-like.
IPR015095. AlkB_hom8_N.
IPR013216. Methyltransf_11.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR029063. SAM-dependent_MTases-like.
[Graphical view ]
Pfami PF13532. 2OG-FeII_Oxy_2. 1 hit.
PF09004. DUF1891. 1 hit.
PF08241. Methyltransf_11. 1 hit.
[Graphical view ]
SUPFAMi SSF53335. SSF53335. 1 hit.
PROSITEi PS51471. FE2OG_OXY. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. 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.

Entry informationi

Entry nameiALKB8_HUMAN
AccessioniPrimary (citable) accession number: Q96BT7
Secondary accession number(s): B1Q2M0, B4DEF6, Q8N989
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: October 29, 2014
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3