Q96BT7 (ALKB8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ALKBH8
Synonyms:	ABH8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	664 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Iron Metal-binding RNA-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Oxidoreductase Transferase
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	response to DNA damage stimulus Inferred from direct assay Ref.7. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay Ref.7. Source: UniProtKB microtubule cytoskeleton Inferred from direct assay. Source: HPA nucleus Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW 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 Inferred from electronic annotation. Source: InterPro tRNA (uracil) methyltransferase activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 664

664

Alkylated DNA repair protein alkB homolog 8

PRO_0000337125

Regions

Domain

43 – 120

78

RRM

Domain

220 – 337

118

Fe2OG dioxygenase

Region

227 – 229

3

Alpha-ketoglutarate binding By similarity

Region

328 – 334

7

Alpha-ketoglutarate binding By similarity

Region

411 – 664

254

Methyltransferase domain

Sites

Metal binding

238

1

Iron; catalytic By similarity

Metal binding

240

1

Iron; catalytic By similarity

Metal binding

292

1

Iron; catalytic By similarity

Natural variations

Alternative sequence

1

1

M → MFAM in isoform 4.

VSP_039159

Alternative sequence

215 – 224

10

GYIKHKPDQM → AEKNLEVGIH in isoform 3.

VSP_033925

Alternative sequence

225 – 664

440

Missing in isoform 3.

VSP_033926

Alternative sequence

234 – 238

5

GIPAH → DCHGF in isoform 2.

VSP_033927

Alternative sequence

239 – 664

426

Missing in isoform 2.

VSP_033928

Experimental info

Sequence conflict

210

1

K → R in BAC04566. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

664

Helix Strand Turn

Details...

Beta strand

26 – 28

3

Turn

30 – 34

5

Beta strand

38 – 40

3

Beta strand

43 – 48

6

Helix

52 – 54

3

Helix

58 – 66

9

Beta strand

71 – 75

5

Beta strand

81 – 89

9

Helix

90 – 99

10

Turn

100 – 102

3

Beta strand

104 – 106

3

Beta strand

112 – 114

3

Beta strand

116 – 119

4

Beta strand

121 – 129

9

Beta strand

137 – 140

4

Helix

146 – 153

8

Beta strand

175 – 177

3

Helix

202 – 214

13

Beta strand

222 – 229

8

Beta strand

235 – 238

4

Turn

242 – 244

3

Beta strand

249 – 256

8

Beta strand

258 – 263

6

Beta strand

269 – 274

6

Beta strand

278 – 282

5

Helix

285 – 288

4

Beta strand

290 – 294

5

Beta strand

298 – 304

7

Beta strand

307 – 309

3

Beta strand

315 – 318

4

Beta strand

320 – 324

5

Beta strand

328 – 334

7

Turn

346 – 348

3

Turn

350 – 355

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 20, 2008. Version 2. Checksum: 4BE595D6757C2A43	FASTA	664	75,208
	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
	Isoform 2 [UniParc]. Checksum: 24EF6A3A66DCC2F7	FASTA	238	27,440
	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 YEFHYENNNV DKDKPLSGGL PDICESFLEK WLRKGYIKHK PDQMTINQYE PGQDCHGF
	Isoform 3 [UniParc]. Checksum: 6FD66E832509EE87	FASTA	224	25,742
	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 YEFHYENNNV DKDKPLSGGL PDICESFLEK WLRKAEKNLE VGIH
	Isoform 4 [UniParc]. Checksum: BF6DB408A2B1B39C	FASTA	667	75,558
	10 20 30 40 50 60 MFAMDSNHQS NYKLSKTEKK FLRKQIKAKH TLLRHEGIET VSYATQSLVV ANGGLGNGVS 70 80 90 100 110 120 RNQLLPVLEK CGLVDALLMP PNKPYSFARY RTTEESKRAY VTLNGKEVVD DLGQKITLYL 130 140 150 160 170 180 NFVEKVQWKE LRPQALPPGL MVVEEIISSE EEKMLLESVD WTEDTDNQNS QKSLKHRRVK 190 200 210 220 230 240 HFGYEFHYEN NNVDKDKPLS GGLPDICESF LEKWLRKGYI KHKPDQMTIN QYEPGQGIPA 250 260 270 280 290 300 HIDTHSAFED EIVSLSLGSE IVMDFKHPDG IAVPVMLPRR SLLVMTGESR YLWTHGITCR 310 320 330 340 350 360 KFDTVQASES LKSGIITSDV GDLTLSKRGL RTSFTFRKVR QTPCNCSYPL VCDSQRKETP 370 380 390 400 410 420 PSFPESDKEA SRLEQEYVHQ VYEEIAGHFS STRHTPWPHI VEFLKALPSG SIVADIGCGN 430 440 450 460 470 480 GKYLGINKEL YMIGCDRSQN LVDICRERQF QAFVCDALAV PVRSGSCDAC ISIAVIHHFA 490 500 510 520 530 540 TAERRVAALQ EIVRLLRPGG KALIYVWAME QEYNKQKSKY LRGNRNSQGK KEEMNSDTSV 550 560 570 580 590 600 QRSLVEQMRD MGSRDSASSV PRINDSQEGG CNSRQVSNSK LPVHVNRTSF YSQDVLVPWH 610 620 630 640 650 660 LKGNPDKGKP VEPFGPIGSQ DPSPVFHRYY HVFREGELEG ACRTVSDVRI LQSYYDQGNW CVILQKA

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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.

IPI

IPI00026191.
IPI00154533.
IPI00873081.
IPI00966763.

RefSeq

NP_620130.2. NM_138775.2.

UniGene

Hs.503763.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q96BT7.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000374219.

PTM databases

PhosphoSite

Q96BT7.

Polymorphism databases

DMDM

189027650.

Proteomic databases

PaxDb

Q96BT7.

PRIDE

Q96BT7.

Protocols and materials databases

DNASU

91801.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000260318; ENSP00000260318; ENSG00000137760.
ENST00000389568; ENSP00000374219; ENSG00000137760.
ENST00000417449; ENSP00000397673; ENSG00000137760.
ENST00000428149; ENSP00000415885; ENSG00000137760.
ENST00000429370; ENSP00000391225; ENSG00000137760.

GeneID

91801.

KEGG

hsa:91801.

UCSC

uc001pjk.3. human.

Organism-specific databases

CTD

91801.

GeneCards

GC11M107373.

HGNC

HGNC:25189. ALKBH8.

HPA

HPA038725.

MIM

613306. gene.

neXtProt

NX_Q96BT7.

PharmGKB

PA143485296.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0500.

HOGENOM

HOG000007984.

HOVERGEN

HBG067234.

InParanoid

Q96BT7.

KO

K10770.

OMA

PCNCSYP.

OrthoDB

EOG4JM7PC.

Gene expression databases

ArrayExpress

Q96BT7.

Bgee

Q96BT7.

CleanEx

HS_ALKBH8.

Genevestigator

Q96BT7.

Family and domain databases

InterPro

IPR015095. AlkB_hom8_N.
IPR013216. Methyltransf_11.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]

Pfam

PF13532. 2OG-FeII_Oxy_2. 1 hit.
PF09004. DUF1891. 1 hit.
PF08241. Methyltransf_11. 1 hit.
[Graphical view]

PROSITE

PS51471. FE2OG_OXY. 1 hit.
PS50102. RRM. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q96BT7.

GenomeRNAi

91801.

NextBio

77461.

SOURCE

Search...

Entry information

Entry name

ALKB8_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.