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Q6P6C2 (ALKB5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 96. 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:
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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length394 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.12 Ref.15

Cofactor

Binds 1 Fe2+ ion per subunit By similarity.

Subcellular location

Nucleus speckle Ref.12 Ref.15.

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.12 Ref.13

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 processDifferentiation
Spermatogenesis
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

mRNA export from nucleus

Inferred from mutant phenotype Ref.15. Source: UniProtKB

mRNA processing

Inferred from mutant phenotype Ref.15. Source: UniProtKB

oxidative single-stranded RNA demethylation

Inferred from direct assay Ref.15. Source: UniProtKB

response to hypoxia

Inferred from direct assay Ref.12. Source: UniProtKB

spermatogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentnuclear speck

Inferred from direct assay Ref.15. Source: UniProtKB

nucleus

Inferred from direct assay Ref.12. Source: UniProtKB

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

oxidative RNA demethylase activity

Inferred from direct assay Ref.15. 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.12. Source: UniProtKB

poly(A) RNA binding

Inferred from direct assay PubMed 22658674PubMed 22681889. Source: UniProtKB

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 394393RNA demethylase ALKBH5
PRO_0000239283

Regions

Coiled coil67 – 11650 Potential
Compositional bias30 – 4819Ala-rich

Sites

Metal binding2041Iron; catalytic Probable
Metal binding2061Iron; catalytic By similarity
Metal binding2661Iron; catalytic Probable

Amino acid modifications

Modified residue21N-acetylalanine Ref.8 Ref.14
Modified residue641Phosphoserine Ref.7 Ref.9
Modified residue691Phosphoserine Ref.7
Modified residue711Phosphotyrosine Ref.9
Modified residue1321N6-acetyllysine Ref.10
Modified residue3611Phosphoserine Ref.7
Modified residue3711Phosphoserine By similarity
Modified residue3741Phosphoserine Ref.9
Modified residue3841Phosphoserine By similarity

Natural variations

Alternative sequence1 – 3232MAAAS…REAAA → MRRCWRPCPAGRGEGGGGRS P in isoform 3.
VSP_044226
Alternative sequence386 – 3949ARKVKMRRH → GNSGSSLRSGNSGSSLRSCP SFCFEGFVFVHWGVFVFCFL FFLILYIFPWFCCLLGLKNR IGQDLGSHILGIPPGWKGCW HQ in isoform 1.
VSP_019130

Experimental info

Mutagenesis2041H → A: Abolishes catalytic activity. Ref.15
Mutagenesis2661H → A: Impaired catalytic activity. Ref.15
Sequence conflict11M → L in BAA91078. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified October 3, 2012. Version 2.
Checksum: DEB7BF8770BDB3A0

FASTA39444,256
        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 

« Hide

Isoform 1 [UniParc].

Checksum: CAB456568C428C85
Show »

FASTA46752,255
Isoform 3 [UniParc].

Checksum: 45D8A30C0297A361
Show »

FASTA38343,049

References

« Hide '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. 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 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. expand/collapse author list , 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. 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 (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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[9]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"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].
[12]"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.
[13]"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.
[14]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"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. expand/collapse author list , 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.
RefSeqNP_060228.3. NM_017758.3.
UniGeneHs.744130.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4NJ4X-ray2.02A/B66-292[»]
4O61X-ray1.90A/B74-294[»]
ProteinModelPortalQ6P6C2.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120237. 6 interactions.
IntActQ6P6C2. 1 interaction.
STRING9606.ENSP00000382091.

PTM databases

PhosphoSiteQ6P6C2.

Polymorphism databases

DMDM408359959.

Proteomic databases

PaxDbQ6P6C2.
PRIDEQ6P6C2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000399138; ENSP00000382091; ENSG00000091542. [Q6P6C2-2]
GeneID54890.
KEGGhsa:54890.
UCSCuc010cpw.3. human. [Q6P6C2-2]

Organism-specific databases

CTD54890.
GeneCardsGC17P018086.
HGNCHGNC:25996. ALKBH5.
HPAHPA007196.
MIM613303. gene.
neXtProtNX_Q6P6C2.
PharmGKBPA142671230.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG264303.
HOGENOMHOG000007505.
HOVERGENHBG080833.
InParanoidQ6P6C2.
KOK10767.
OMAGAKRKYQ.
TreeFamTF329212.

Gene expression databases

ArrayExpressQ6P6C2.
BgeeQ6P6C2.
CleanExHS_ALKBH5.
GenevestigatorQ6P6C2.

Family and domain databases

Gene3D2.60.120.590. 1 hit.
InterProIPR027450. AlkB-like.
[Graphical view]
PfamPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi54890.
NextBio57883.
PROQ6P6C2.
SOURCESearch...

Entry information

Entry nameALKB5_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 96 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 17

Human chromosome 17: entries, gene names and cross-references to MIM