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Protein

RNA demethylase ALKBH5

Gene

ALKBH5

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

Functioni

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 (PubMed:23177736, PubMed:24778178, PubMed:24616105, PubMed:24489119). Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (PubMed:24616105). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:21264265, PubMed:23177736, PubMed:24778178, PubMed:24616105, PubMed:24489119). Demethylation of m6A mRNA affects mRNA processing and export (PubMed:23177736). Required for spermatogenesis (By similarity).By similarity5 Publications

Catalytic activityi

N(6)-methyladenosine in mRNA + 2-oxoglutarate + O2 = adenosine in mRNA + formaldehyde + succinate + CO2.1 Publication

Cofactori

Fe2+3 PublicationsNote: Binds 1 Fe2+ ion per subunit.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi204Iron; catalyticCurated1
Metal bindingi206Iron; catalyticCurated1
Metal bindingi266Iron; catalyticCurated1
Binding sitei277Alpha-ketoglutarate1 Publication1

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • mRNA export from nucleus Source: UniProtKB
  • mRNA processing Source: UniProtKB
  • oxidative single-stranded RNA demethylation Source: UniProtKB
  • response to hypoxia Source: UniProtKB
  • spermatogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

Differentiation, Spermatogenesis

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-73943. Reversal of alkylation damage by DNA dioxygenases.

Names & Taxonomyi

Protein namesi
Recommended name:
RNA demethylase ALKBH51 Publication (EC:1.14.11.-1 Publication)
Alternative name(s):
Alkylated DNA repair protein alkB homolog 5
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5
Gene namesi
Name:ALKBH5
Synonyms:ABH5, OFOXD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:25996. ALKBH5.

Subcellular locationi

GO - Cellular componenti

  • nuclear speck Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi130R → A: Abolishes catalytic activity. 2 Publications1
Mutagenesisi132K → A: No effect on catalytic activity with N(6)-methyladenosine in single-stranded DNA. 1 Publication1
Mutagenesisi139Y → A: Abolishes catalytic activity. 2 Publications1
Mutagenesisi141Y → A: Abolishes catalytic activity with N(6)-methyladenosine in single-stranded DNA. 1 Publication1
Mutagenesisi153E → A: No effect on catalytic activity. 1 Publication1
Mutagenesisi195Y → A: Abolishes catalytic activity. 1 Publication1
Mutagenesisi204H → A: Abolishes catalytic activity. 2 Publications1
Mutagenesisi209 – 210HI → AA: Abolishes catalytic activity. 1 Publication2
Mutagenesisi232 – 234FQF → DDE: Impaired catalytic activity. 1 Publication3
Mutagenesisi266H → A: Impaired catalytic activity. 1 Publication1
Mutagenesisi277R → A: Abolishes catalytic activity; when associated with A-283. 1 Publication1
Mutagenesisi283R → A: Abolishes catalytic activity; when associated with A-277. 1 Publication1

Organism-specific databases

DisGeNETi54890.
OpenTargetsiENSG00000091542.
PharmGKBiPA142671230.

Chemistry databases

ChEMBLiCHEMBL3621037.

Polymorphism and mutation databases

BioMutaiALKBH5.
DMDMi408359959.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002392832 – 394RNA demethylase ALKBH5Add BLAST393

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei64PhosphoserineCombined sources1
Modified residuei69PhosphoserineCombined sources1
Modified residuei71PhosphotyrosineCombined sources1
Modified residuei132N6-acetyllysineCombined sources1
Modified residuei359Omega-N-methylarginineCombined sources1
Modified residuei361PhosphoserineCombined sources1
Modified residuei371PhosphoserineBy similarity1
Modified residuei374PhosphoserineCombined sources1
Modified residuei384PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiQ6P6C2.
PaxDbiQ6P6C2.
PeptideAtlasiQ6P6C2.
PRIDEiQ6P6C2.

PTM databases

iPTMnetiQ6P6C2.
PhosphoSitePlusiQ6P6C2.

Expressioni

Tissue specificityi

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

Inductioni

By hypoxia, directly activated by HIF1A. Expression is regulated by PRMT7.2 Publications

Gene expression databases

BgeeiENSG00000091542.
CleanExiHS_ALKBH5.
ExpressionAtlasiQ6P6C2. baseline and differential.
GenevisibleiQ6P6C2. HS.

Organism-specific databases

HPAiHPA007196.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi120237. 4 interactors.
IntActiQ6P6C2. 3 interactors.
STRINGi9606.ENSP00000382091.

Structurei

Secondary structure

1394
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi75 – 86Combined sources12
Beta strandi89 – 93Combined sources5
Helixi97 – 115Combined sources19
Helixi121 – 123Combined sources3
Beta strandi124 – 127Combined sources4
Beta strandi130 – 137Combined sources8
Beta strandi139 – 141Combined sources3
Beta strandi152 – 155Combined sources4
Beta strandi160 – 162Combined sources3
Helixi166 – 171Combined sources6
Helixi173 – 178Combined sources6
Beta strandi189 – 195Combined sources7
Beta strandi201 – 204Combined sources4
Turni208 – 210Combined sources3
Beta strandi215 – 219Combined sources5
Beta strandi224 – 228Combined sources5
Helixi231 – 233Combined sources3
Turni236 – 238Combined sources3
Beta strandi243 – 248Combined sources6
Beta strandi252 – 256Combined sources5
Helixi258 – 262Combined sources5
Beta strandi266 – 268Combined sources3
Helixi270 – 272Combined sources3
Beta strandi277 – 283Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4NJ4X-ray2.02A/B66-292[»]
4NRMX-ray2.17A66-292[»]
4NROX-ray2.30A66-292[»]
4NRPX-ray1.80A66-292[»]
4NRQX-ray2.50A66-292[»]
4O61X-ray1.90A/B74-294[»]
4O7XX-ray1.78A66-292[»]
4OCTX-ray2.28A/B74-294[»]
ProteinModelPortaliQ6P6C2.
SMRiQ6P6C2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni193 – 195Alpha-ketoglutarate binding1 Publication3

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili67 – 116Sequence analysisAdd BLAST50

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi30 – 48Ala-richAdd BLAST19

Sequence similaritiesi

Belongs to the alkB family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410INB3. Eukaryota.
ENOG410Y0IS. LUCA.
GeneTreeiENSGT00390000009298.
HOGENOMiHOG000007505.
HOVERGENiHBG080833.
InParanoidiQ6P6C2.
KOiK10767.
OMAiWVHELVI.
OrthoDBiEOG091G0KLO.
TreeFamiTF329212.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR032860. ALKBH5.
[Graphical view]
PANTHERiPTHR32074. PTHR32074. 1 hit.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: Q6P6C2-2) [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
MAAASGYTDL REKLKSMTSR DNYKAGSREA AAAAAAAVAA AAAAAAAAEP
60 70 80 90 100
YPVSGAKRKY QEDSDPERSD YEEQQLQKEE EARKVKSGIR QMRLFSQDEC
110 120 130 140 150
AKIEARIDEV VSRAEKGLYN EHTVDRAPLR NKYFFGEGYT YGAQLQKRGP
160 170 180 190 200
GQERLYPPGD VDEIPEWVHQ LVIQKLVEHR VIPEGFVNSA VINDYQPGGC
210 220 230 240 250
IVSHVDPIHI FERPIVSVSF FSDSALCFGC KFQFKPIRVS EPVLSLPVRR
260 270 280 290 300
GSVTVLSGYA ADEITHCIRP QDIKERRAVI ILRKTRLDAP RLETKSLSSS
310 320 330 340 350
VLPPSYASDR LSGNNRDPAL KPKRSHRKAD PDAAHRPRIL EMDKEENRRS
360 370 380 390
VLLPTHRRRG SFSSENYWRK SYESSEDCSE AAGSPARKVK MRRH
Length:394
Mass (Da):44,256
Last modified:October 3, 2012 - v2
Checksum:iDEB7BF8770BDB3A0
GO
Isoform 1 (identifier: Q6P6C2-1) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:467
Mass (Da):52,255
Checksum:iCAB456568C428C85
GO
Isoform 3 (identifier: Q6P6C2-3) [UniParc]FASTAAdd to basket

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

Show »
Length:383
Mass (Da):43,049
Checksum:i45D8A30C0297A361
GO

Sequence cautioni

The sequence BAA91078 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1M → L in BAA91078 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0442261 – 32MAAAS…REAAA → MRRCWRPCPAGRGEGGGGRS P in isoform 3. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_019130386 – 394ARKVKMRRH → GNSGSSLRSGNSGSSLRSCP SFCFEGFVFVHWGVFVFCFL FFLILYIFPWFCCLLGLKNR IGQDLGSHILGIPPGWKGCW HQ in isoform 1. 1 Publication9

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS42272.1. [Q6P6C2-2]
RefSeqiNP_060228.3. NM_017758.3. [Q6P6C2-2]
UniGeneiHs.744130.

Genome annotation databases

EnsembliENST00000399138; ENSP00000382091; ENSG00000091542. [Q6P6C2-2]
GeneIDi54890.
KEGGihsa:54890.
UCSCiuc010cpw.4. human. [Q6P6C2-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS42272.1. [Q6P6C2-2]
RefSeqiNP_060228.3. NM_017758.3. [Q6P6C2-2]
UniGeneiHs.744130.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4NJ4X-ray2.02A/B66-292[»]
4NRMX-ray2.17A66-292[»]
4NROX-ray2.30A66-292[»]
4NRPX-ray1.80A66-292[»]
4NRQX-ray2.50A66-292[»]
4O61X-ray1.90A/B74-294[»]
4O7XX-ray1.78A66-292[»]
4OCTX-ray2.28A/B74-294[»]
ProteinModelPortaliQ6P6C2.
SMRiQ6P6C2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120237. 4 interactors.
IntActiQ6P6C2. 3 interactors.
STRINGi9606.ENSP00000382091.

Chemistry databases

ChEMBLiCHEMBL3621037.

PTM databases

iPTMnetiQ6P6C2.
PhosphoSitePlusiQ6P6C2.

Polymorphism and mutation databases

BioMutaiALKBH5.
DMDMi408359959.

Proteomic databases

EPDiQ6P6C2.
PaxDbiQ6P6C2.
PeptideAtlasiQ6P6C2.
PRIDEiQ6P6C2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000399138; ENSP00000382091; ENSG00000091542. [Q6P6C2-2]
GeneIDi54890.
KEGGihsa:54890.
UCSCiuc010cpw.4. human. [Q6P6C2-2]

Organism-specific databases

CTDi54890.
DisGeNETi54890.
GeneCardsiALKBH5.
HGNCiHGNC:25996. ALKBH5.
HPAiHPA007196.
MIMi613303. gene.
neXtProtiNX_Q6P6C2.
OpenTargetsiENSG00000091542.
PharmGKBiPA142671230.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410INB3. Eukaryota.
ENOG410Y0IS. LUCA.
GeneTreeiENSGT00390000009298.
HOGENOMiHOG000007505.
HOVERGENiHBG080833.
InParanoidiQ6P6C2.
KOiK10767.
OMAiWVHELVI.
OrthoDBiEOG091G0KLO.
TreeFamiTF329212.

Enzyme and pathway databases

ReactomeiR-HSA-73943. Reversal of alkylation damage by DNA dioxygenases.

Miscellaneous databases

ChiTaRSiALKBH5. human.
GenomeRNAii54890.
PROiQ6P6C2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000091542.
CleanExiHS_ALKBH5.
ExpressionAtlasiQ6P6C2. baseline and differential.
GenevisibleiQ6P6C2. HS.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR032860. ALKBH5.
[Graphical view]
PANTHERiPTHR32074. PTHR32074. 1 hit.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiALKB5_HUMAN
AccessioniPrimary (citable) accession number: Q6P6C2
Secondary accession number(s): B4DVJ4, D3DXC6, Q9NXD6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: October 3, 2012
Last modified: November 30, 2016
This is version 122 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, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.