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Q9NXW9 (ALKB4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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:
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 4

EC=1.14.11.-
Alternative name(s):
Alkylated DNA repair protein alkB homolog 4
Gene names
Name:ALKBH4
Synonyms:ABH4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length302 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 mediates demethylation of actin monomethylated at 'Lys-84' (K84me1), thereby acting as a regulator of actomyosin-processes. Demethylation of actin K84me1 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration. May be involved in transcription regulation. Ref.7 Ref.11

Cofactor

Binds 1 Fe2+ ion per subunit. Ref.7

Subunit structure

Interacts with ZFHX3, MLLT3, MLLT1, HSF4, EP300, TES, EIF3C, MTMR6 and PSMA6. Ref.9

Subcellular location

Cytoplasm. Nucleus. Midbody. Note: Associates with the contractile ring and midbody. Ref.5 Ref.9 Ref.11

Tissue specificity

Widely expressed, with highest expression in pancreas, ovary and spleen. Ref.5

Miscellaneous

Actin demethylase activity has not been directly confirmed in vitro; however a number of experiments strongly suggest that ALKBH4 acts as a protein demethylase (Ref.11).

Sequence similarities

Belongs to the alkB family.

Sequence caution

The sequence BAB15358.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandActin-binding
Iron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactomyosin structure organization

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cleavage furrow ingression

Inferred from mutant phenotype Ref.11. Source: UniProtKB

protein demethylation

Inferred from direct assay Ref.11. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcontractile ring

Inferred from direct assay Ref.11. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

midbody

Inferred from direct assay Ref.11. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionactin binding

Inferred from direct assay Ref.11. Source: UniProtKB

demethylase activity

Traceable author statement Ref.11. Source: UniProtKB

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 direct assay Ref.7. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NXW9-1)

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: Q9NXW9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     42-42: K → E
     43-302: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 302301Alpha-ketoglutarate-dependent dioxygenase alkB homolog 4
PRO_0000239281

Sites

Metal binding1691Iron; catalytic Probable
Metal binding1711Iron; catalytic Probable
Metal binding2541Iron; catalytic Probable
Binding site26512-oxoglutarate Potential

Amino acid modifications

Modified residue21N-acetylalanine Ref.8 Ref.10

Natural variations

Alternative sequence421K → E in isoform 2.
VSP_019128
Alternative sequence43 – 302260Missing in isoform 2.
VSP_036841
Natural variant2471A → V.
Corresponds to variant rs41275227 [ dbSNP | Ensembl ].
VAR_061004

Experimental info

Mutagenesis1691H → A: Loss of function mutant that acts as a dominant-negative mutant when overexpressed, leading to multinucleation and cleavage furrow disorganization; when associated with A-171 and A-254. Ref.11
Mutagenesis1711D → A: Loss of function mutant that acts as a dominant-negative mutant when overexpressed, leading to multinucleation and cleavage furrow disorganization; when associated with A-169 and A-254. Ref.11
Mutagenesis2541H → A: Loss of function mutant that acts as a dominant-negative mutant when overexpressed, leading to multinucleation and cleavage furrow disorganization; when associated with A-169 and A-171. Ref.11
Sequence conflict2101A → V in BAD96409. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 67C2DFE058962AF4

FASTA30233,838
        10         20         30         40         50         60 
MAAAAAETPE VLRECGCKGI RTCLICERQR GSDPPWELPP AKTYRFIYCS DTGWAVGTEE 

        70         80         90        100        110        120 
SDFEGWAFPF PGVMLIEDFV TREEEAELVR LMDRDPWKLS QSGRRKQDYG PKVNFRKQKL 

       130        140        150        160        170        180 
KTEGFCGLPS FSREVVRRMG LYPGLEGFRP VEQCNLDYCP ERGSAIDPHL DDAWLWGERL 

       190        200        210        220        230        240 
VSLNLLSPTV LSMCREAPGS LLLCSAPSAA PEALVDSVIA PSRSVLCQEV EVAIPLPARS 

       250        260        270        280        290        300 
LLVLTGAARH QWKHAIHRRH IEARRVCVTF RELSAEFGPG GRQQELGQEL LRIALSFQGR 


PV 

« Hide

Isoform 2 [UniParc].

Checksum: D1438DF90A61CD02
Show »

FASTA424,556

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 1 AND 2).
Tissue: Adipose tissue and Epithelium.
[2]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
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: Lung and Placenta.
[5]"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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]"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].
[7]"Spectroscopic and magnetic studies of wild-type and mutant forms of the Fe(II)-and 2-oxoglutarate-dependent decarboxylase ALKBH4."
Bjornstad L.G., Zoppellaro G., Tomter A.B., Falnes P.O., Andersson K.K.
Biochem. J. 434:391-398(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, COFACTOR.
[8]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [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]"Human ALKBH4 interacts with proteins associated with transcription."
Bjornstad L.G., Meza T.J., Otterlei M., Olafsrud S.M., Meza-Zepeda L.A., Falnes P.O.
PLoS ONE 7:E49045-E49045(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZFHX3; MLLT3; MLLT1; HSF4; EP300; TES; EIF3C; MTMR6 AND PSMA6, SUBCELLULAR LOCATION.
[10]"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].
[11]"ALKBH4-dependent demethylation of actin regulates actomyosin dynamics."
Li M.M., Nilsen A., Shi Y., Fusser M., Ding Y.H., Fu Y., Liu B., Niu Y., Wu Y.S., Huang C.M., Olofsson M., Jin K.X., Lv Y., Xu X.Z., He C., Dong M.Q., Rendtlew Danielsen J.M., Klungland A., Yang Y.G.
Nat. Commun. 4:1832-1832(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIN-BINDING, MUTAGENESIS OF HIS-169; ASP-171 AND HIS-254.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK000020 mRNA. Translation: BAA90888.1.
AK026097 mRNA. Translation: BAB15358.1. Sequence problems.
AK222689 mRNA. Translation: BAD96409.1.
AC093668 Genomic DNA. No translation available.
BC002820 mRNA. Translation: AAH02820.1.
BC017096 mRNA. Translation: AAH17096.1.
CCDSCCDS5723.1. [Q9NXW9-1]
RefSeqNP_060091.1. NM_017621.3. [Q9NXW9-1]
XP_005250521.1. XM_005250464.1.
UniGeneHs.658598.

3D structure databases

ProteinModelPortalQ9NXW9.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120148. 1 interaction.
IntActQ9NXW9. 1 interaction.
STRING9606.ENSP00000292566.

Polymorphism databases

DMDM74734701.

Proteomic databases

MaxQBQ9NXW9.
PaxDbQ9NXW9.
PRIDEQ9NXW9.

Protocols and materials databases

DNASU54784.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000292566; ENSP00000292566; ENSG00000160993. [Q9NXW9-1]
ENST00000490528; ENSP00000420362; ENSG00000160993. [Q9NXW9-2]
GeneID54784.
KEGGhsa:54784.
UCSCuc003uzl.3. human. [Q9NXW9-1]

Organism-specific databases

CTD54784.
GeneCardsGC07M102096.
HGNCHGNC:21900. ALKBH4.
HPAHPA051422.
MIM613302. gene.
neXtProtNX_Q9NXW9.
PharmGKBPA143485294.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG255556.
HOGENOMHOG000015835.
HOVERGENHBG062006.
InParanoidQ9NXW9.
KOK10766.
OMADRDPWKL.
OrthoDBEOG73Z2V0.
PhylomeDBQ9NXW9.
TreeFamTF314885.

Gene expression databases

BgeeQ9NXW9.
CleanExHS_ALKBH4.
GenevestigatorQ9NXW9.

Family and domain databases

Gene3D2.60.120.590. 1 hit.
InterProIPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PfamPF03171. 2OG-FeII_Oxy. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi54784.
NextBio57445.
PROQ9NXW9.
SOURCESearch...

Entry information

Entry nameALKB4_HUMAN
AccessionPrimary (citable) accession number: Q9NXW9
Secondary accession number(s): Q53H92, Q9H6A4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 94 of the entry and version 1 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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM