Q6P6C2 (ALKB5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RNA demethylase ALKBH5
EC=1.14.11.-

Alternative name(s):
Alkylated DNA repair protein alkB homolog 5
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5

Gene names

Name:	ALKBH5
Synonyms:	ABH5, OFOXD1

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	394 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Requires molecular oxygen, alpha-ketoglutarate and iron. Demethylation of m6A mRNA affects mRNA processing and export and is required for spermatogenesis. Ref.11 Ref.13
Cofactor	Binds 1 Fe2+ ion per subunit By similarity.
Subcellular location	Nucleus speckle Ref.11 Ref.13.
Tissue specificity	Widely expressed, with highest expression in lung, followed by testis, pancreas, spleen and ovary. Ref.6
Induction	By hypoxia, directly activated by HIF1A. Expression is regulated by PRMT7. Ref.11 Ref.12
Sequence similarities	Belongs to the alkB family.
Sequence caution	The sequence BAA91078.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Differentiation Spermatogenesis
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW mRNA export from nucleus Inferred from mutant phenotype Ref.13. Source: UniProtKB mRNA processing Inferred from mutant phenotype Ref.13. Source: UniProtKB oxidative single-stranded RNA demethylation Inferred from direct assay Ref.13. Source: UniProtKB response to hypoxia Inferred from direct assay Ref.11. Source: UniProtKB spermatogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	nuclear speck Inferred from direct assay Ref.13. Source: UniProtKB
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidative RNA demethylase activity Inferred from direct assay Ref.13. Source: UniProtKB 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 direct assay Ref.11. Source: UniProtKB oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: Q6P6C2-2)

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 1 (identifier: Q6P6C2-1)

The sequence of this isoform differs from the canonical sequence as follows:
     386-394: ARKVKMRRH → GNSGSSLRSG...PPGWKGCWHQ

Note: No experimental confirmation available.

Isoform 3 (identifier: Q6P6C2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: MAAASGYTDLREKLKSMTSRDNYKAGSREAAA → MRRCWRPCPAGRGEGGGGRSP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 394	394	RNA demethylase ALKBH5		PRO_0000239283
Regions
	Coiled coil	67 – 116	50	Potential
	Compositional bias	30 – 48	19	Ala-rich
Sites
	Metal binding	204	1	Iron; catalytic Probable
	Metal binding	206	1	Iron; catalytic By similarity
	Metal binding	266	1	Iron; catalytic Probable
Amino acid modifications
	Modified residue	64	1	Phosphoserine Ref.7 Ref.8
	Modified residue	69	1	Phosphoserine Ref.7
	Modified residue	71	1	Phosphotyrosine Ref.8
	Modified residue	132	1	N6-acetyllysine Ref.9
	Modified residue	361	1	Phosphoserine Ref.7
	Modified residue	371	1	Phosphoserine By similarity
	Modified residue	374	1	Phosphoserine Ref.8
	Modified residue	384	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 32	32	MAAAS…REAAA → MRRCWRPCPAGRGEGGGGRS P in isoform 3.		VSP_044226
	Alternative sequence	386 – 394	9	ARKVKMRRH → GNSGSSLRSGNSGSSLRSCP SFCFEGFVFVHWGVFVFCFL FFLILYIFPWFCCLLGLKNR IGQDLGSHILGIPPGWKGCW HQ in isoform 1.		VSP_019130
Experimental info
	Mutagenesis	204	1	H → A: Abolishes catalytic activity. Ref.13
	Mutagenesis	266	1	H → A: Impaired catalytic activity. Ref.13
	Sequence conflict	1	1	M → L in BAA91078. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified October 3, 2012. Version 2. Checksum: DEB7BF8770BDB3A0	FASTA	394	44,256
	10 20 30 40 50 60 MAAASGYTDL REKLKSMTSR DNYKAGSREA AAAAAAAVAA AAAAAAAAEP YPVSGAKRKY 70 80 90 100 110 120 QEDSDPERSD YEEQQLQKEE EARKVKSGIR QMRLFSQDEC AKIEARIDEV VSRAEKGLYN 130 140 150 160 170 180 EHTVDRAPLR NKYFFGEGYT YGAQLQKRGP GQERLYPPGD VDEIPEWVHQ LVIQKLVEHR 190 200 210 220 230 240 VIPEGFVNSA VINDYQPGGC IVSHVDPIHI FERPIVSVSF FSDSALCFGC KFQFKPIRVS 250 260 270 280 290 300 EPVLSLPVRR GSVTVLSGYA ADEITHCIRP QDIKERRAVI ILRKTRLDAP RLETKSLSSS 310 320 330 340 350 360 VLPPSYASDR LSGNNRDPAL KPKRSHRKAD PDAAHRPRIL EMDKEENRRS VLLPTHRRRG 370 380 390 SFSSENYWRK SYESSEDCSE AAGSPARKVK MRRH
	Isoform 1 [UniParc]. Checksum: CAB456568C428C85	FASTA	467	52,255
	10 20 30 40 50 60 MAAASGYTDL REKLKSMTSR DNYKAGSREA AAAAAAAVAA AAAAAAAAEP YPVSGAKRKY 70 80 90 100 110 120 QEDSDPERSD YEEQQLQKEE EARKVKSGIR QMRLFSQDEC AKIEARIDEV VSRAEKGLYN 130 140 150 160 170 180 EHTVDRAPLR NKYFFGEGYT YGAQLQKRGP GQERLYPPGD VDEIPEWVHQ LVIQKLVEHR 190 200 210 220 230 240 VIPEGFVNSA VINDYQPGGC IVSHVDPIHI FERPIVSVSF FSDSALCFGC KFQFKPIRVS 250 260 270 280 290 300 EPVLSLPVRR GSVTVLSGYA ADEITHCIRP QDIKERRAVI ILRKTRLDAP RLETKSLSSS 310 320 330 340 350 360 VLPPSYASDR LSGNNRDPAL KPKRSHRKAD PDAAHRPRIL EMDKEENRRS VLLPTHRRRG 370 380 390 400 410 420 SFSSENYWRK SYESSEDCSE AAGSPGNSGS SLRSGNSGSS LRSCPSFCFE GFVFVHWGVF 430 440 450 460 VFCFLFFLIL YIFPWFCCLL GLKNRIGQDL GSHILGIPPG WKGCWHQ
	Isoform 3 [UniParc]. Checksum: 45D8A30C0297A361	FASTA	383	43,049
	10 20 30 40 50 60 MRRCWRPCPA GRGEGGGGRS PAAAAAVAAA AAAAAAAEPY PVSGAKRKYQ EDSDPERSDY 70 80 90 100 110 120 EEQQLQKEEE ARKVKSGIRQ MRLFSQDECA KIEARIDEVV SRAEKGLYNE HTVDRAPLRN 130 140 150 160 170 180 KYFFGEGYTY GAQLQKRGPG QERLYPPGDV DEIPEWVHQL VIQKLVEHRV IPEGFVNSAV 190 200 210 220 230 240 INDYQPGGCI VSHVDPIHIF ERPIVSVSFF SDSALCFGCK FQFKPIRVSE PVLSLPVRRG 250 260 270 280 290 300 SVTVLSGYAA DEITHCIRPQ DIKERRAVII LRKTRLDAPR LETKSLSSSV LPPSYASDRL 310 320 330 340 350 360 SGNNRDPALK PKRSHRKADP DAAHRPRILE MDKEENRRSV LLPTHRRRGS FSSENYWRKS 370 380 YESSEDCSEA AGSPARKVKM RRH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 2 AND 3). Tissue: Hepatoma and Spleen.
[2]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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 1). Tissue: Brain.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[6]	"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: TISSUE SPECIFICITY.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; SER-69 AND SER-361, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; TYR-71 AND SER-374, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-132, MASS SPECTROMETRY.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and a direct target of hypoxia-inducible factor 1alpha (HIF-1alpha)." Thalhammer A., Bencokova Z., Poole R., Loenarz C., Adam J., O'Flaherty L., Schodel J., Mole D., Giaslakiotis K., Schofield C.J., Hammond E.M., Ratcliffe P.J., Pollard P.J. PLoS ONE 6:E16210-E16210(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
[12]	"Protein arginine methyltransferase 7 regulates cellular response to DNA damage by methylating promoter histones H2A and H4 of the polymerase delta catalytic subunit gene, POLD1." Karkhanis V., Wang L., Tae S., Hu Y.J., Imbalzano A.N., Sif S. J. Biol. Chem. 287:29801-29814(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[13]	"ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility." Zheng G., Dahl J.A., Niu Y., Fedorcsak P., Huang C.M., Li C.J., Vagbo C.B., Shi Y., Wang W.L., Song S.H., Lu Z., Bosmans R.P., Dai Q., Hao Y.J., Yang X., Zhao W.M., Tong W.M., Wang X.J. , Bogdan F., Furu K., Fu Y., Jia G., Zhao X., Liu J., Krokan H.E., Klungland A., Yang Y.G., He C. Mol. Cell 49:18-29(2013) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-204 AND HIS-266.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK000315 mRNA. Translation: BAA91078.1. Different initiation. AK301107 mRNA. Translation: BAG62706.1. AC087164 Genomic DNA. No translation available. AC109515 Genomic DNA. No translation available. CH471196 Genomic DNA. Translation: EAW55661.1. CH471196 Genomic DNA. Translation: EAW55662.1. BC062339 mRNA. Translation: AAH62339.1.
IPI	IPI00413659. IPI00759562.
RefSeq	NP_060228.3. NM_017758.3.
UniGene	Hs.744130.
3D structure databases
ProteinModelPortal	Q6P6C2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6P6C2. 1 interaction.
STRING	9606.ENSP00000382091.
PTM databases
PhosphoSite	Q6P6C2.
Polymorphism databases
DMDM	74749138.
Proteomic databases
PaxDb	Q6P6C2.
PRIDE	Q6P6C2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000399138; ENSP00000382091; ENSG00000091542.
GeneID	54890.
KEGG	hsa:54890.
UCSC	uc010cpw.3. human.
Organism-specific databases
CTD	54890.
GeneCards	GC17P018086.
HGNC	HGNC:25996. ALKBH5.
HPA	HPA007196.
MIM	613303. gene.
neXtProt	NX_Q6P6C2.
PharmGKB	PA142671230.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG264303.
HOGENOM	HOG000007505.
HOVERGEN	HBG080833.
InParanoid	Q6P6C2.
KO	K10767.
Gene expression databases
Bgee	Q6P6C2.
CleanEx	HS_ALKBH5.
Genevestigator	Q6P6C2.
GermOnline	ENSG00000091542. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.590. 1 hit.
InterPro	IPR027450. AlkB-like. [Graphical view]
Pfam	PF13532. 2OG-FeII_Oxy_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	54890.
NextBio	57883.
SOURCE	Search...

Entry information

Entry name

ALKB5_HUMAN

Accession

Primary (citable) accession number: Q6P6C2
Secondary accession number(s): B4DVJ4, D3DXC6, Q9NXD6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	October 3, 2012
Last modified:	May 29, 2013
This is version 88 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.