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Protein

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 4

Gene

ALKBH4

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

Functioni

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.2 Publications

Cofactori

Fe2+1 PublicationNote: Binds 1 Fe2+ ion per subunit.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi169 – 1691Iron; catalyticCurated
Metal bindingi171 – 1711Iron; catalyticCurated
Metal bindingi254 – 2541Iron; catalyticCurated
Binding sitei265 – 26512-oxoglutarateSequence Analysis

GO - Molecular functioni

GO - Biological processi

  • actomyosin structure organization Source: UniProtKB
  • cleavage furrow ingression Source: UniProtKB
  • protein demethylation Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Actin-binding, Iron, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 4 (EC:1.14.11.-)
Alternative name(s):
Alkylated DNA repair protein alkB homolog 4
Gene namesi
Name:ALKBH4
Synonyms:ABH4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:21900. ALKBH4.

Subcellular locationi

GO - Cellular componenti

  • contractile ring Source: UniProtKB
  • cytoplasm Source: UniProtKB-SubCell
  • midbody Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi169 – 1691H → 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. 1 Publication
Mutagenesisi171 – 1711D → 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. 1 Publication
Mutagenesisi254 – 2541H → 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. 1 Publication

Organism-specific databases

PharmGKBiPA143485294.

Polymorphism and mutation databases

BioMutaiALKBH4.
DMDMi74734701.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 302301Alpha-ketoglutarate-dependent dioxygenase alkB homolog 4PRO_0000239281Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine2 Publications

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ9NXW9.
PaxDbiQ9NXW9.
PRIDEiQ9NXW9.

Expressioni

Tissue specificityi

Widely expressed, with highest expression in pancreas, ovary and spleen.1 Publication

Gene expression databases

BgeeiQ9NXW9.
CleanExiHS_ALKBH4.
GenevestigatoriQ9NXW9.

Organism-specific databases

HPAiHPA051422.

Interactioni

Subunit structurei

Interacts with ZFHX3, MLLT3, MLLT1, HSF4, EP300, TES, EIF3C, MTMR6 and PSMA6.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
DTX2Q4ZH493EBI-8637516,EBI-10192429
DTX2Q86UW94EBI-8637516,EBI-740376
TRAF4Q9BUZ43EBI-8637516,EBI-3650647

Protein-protein interaction databases

BioGridi120148. 3 interactions.
IntActiQ9NXW9. 3 interactions.
STRINGi9606.ENSP00000292566.

Structurei

3D structure databases

ProteinModelPortaliQ9NXW9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the alkB family.Curated

Phylogenomic databases

eggNOGiNOG255556.
GeneTreeiENSGT00390000006344.
HOGENOMiHOG000015835.
HOVERGENiHBG062006.
InParanoidiQ9NXW9.
KOiK10766.
OMAiCKGVRTC.
OrthoDBiEOG73Z2V0.
PhylomeDBiQ9NXW9.
TreeFamiTF314885.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PfamiPF03171. 2OG-FeII_Oxy. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NXW9-1) [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
MAAAAAETPE VLRECGCKGI RTCLICERQR GSDPPWELPP AKTYRFIYCS
60 70 80 90 100
DTGWAVGTEE SDFEGWAFPF PGVMLIEDFV TREEEAELVR LMDRDPWKLS
110 120 130 140 150
QSGRRKQDYG PKVNFRKQKL KTEGFCGLPS FSREVVRRMG LYPGLEGFRP
160 170 180 190 200
VEQCNLDYCP ERGSAIDPHL DDAWLWGERL VSLNLLSPTV LSMCREAPGS
210 220 230 240 250
LLLCSAPSAA PEALVDSVIA PSRSVLCQEV EVAIPLPARS LLVLTGAARH
260 270 280 290 300
QWKHAIHRRH IEARRVCVTF RELSAEFGPG GRQQELGQEL LRIALSFQGR

PV
Length:302
Mass (Da):33,838
Last modified:October 1, 2000 - v1
Checksum:i67C2DFE058962AF4
GO
Isoform 2 (identifier: Q9NXW9-2) [UniParc]FASTAAdd to basket

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.

Show »
Length:42
Mass (Da):4,556
Checksum:iD1438DF90A61CD02
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti210 – 2101A → V in BAD96409 (Ref. 2) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti247 – 2471A → V.
Corresponds to variant rs41275227 [ dbSNP | Ensembl ].
VAR_061004

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei42 – 421K → E in isoform 2. 1 PublicationVSP_019128
Alternative sequencei43 – 302260Missing in isoform 2. 1 PublicationVSP_036841Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5723.1. [Q9NXW9-1]
RefSeqiNP_060091.1. NM_017621.3. [Q9NXW9-1]
XP_005250521.1. XM_005250464.2.
UniGeneiHs.658598.

Genome annotation databases

EnsembliENST00000292566; ENSP00000292566; ENSG00000160993. [Q9NXW9-1]
ENST00000490528; ENSP00000420362; ENSG00000160993. [Q9NXW9-2]
GeneIDi54784.
KEGGihsa:54784.
UCSCiuc003uzl.3. human. [Q9NXW9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5723.1. [Q9NXW9-1]
RefSeqiNP_060091.1. NM_017621.3. [Q9NXW9-1]
XP_005250521.1. XM_005250464.2.
UniGeneiHs.658598.

3D structure databases

ProteinModelPortaliQ9NXW9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120148. 3 interactions.
IntActiQ9NXW9. 3 interactions.
STRINGi9606.ENSP00000292566.

Polymorphism and mutation databases

BioMutaiALKBH4.
DMDMi74734701.

Proteomic databases

MaxQBiQ9NXW9.
PaxDbiQ9NXW9.
PRIDEiQ9NXW9.

Protocols and materials databases

DNASUi54784.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000292566; ENSP00000292566; ENSG00000160993. [Q9NXW9-1]
ENST00000490528; ENSP00000420362; ENSG00000160993. [Q9NXW9-2]
GeneIDi54784.
KEGGihsa:54784.
UCSCiuc003uzl.3. human. [Q9NXW9-1]

Organism-specific databases

CTDi54784.
GeneCardsiGC07M102096.
HGNCiHGNC:21900. ALKBH4.
HPAiHPA051422.
MIMi613302. gene.
neXtProtiNX_Q9NXW9.
PharmGKBiPA143485294.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG255556.
GeneTreeiENSGT00390000006344.
HOGENOMiHOG000015835.
HOVERGENiHBG062006.
InParanoidiQ9NXW9.
KOiK10766.
OMAiCKGVRTC.
OrthoDBiEOG73Z2V0.
PhylomeDBiQ9NXW9.
TreeFamiTF314885.

Miscellaneous databases

GenomeRNAii54784.
NextBioi57445.
PROiQ9NXW9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NXW9.
CleanExiHS_ALKBH4.
GenevestigatoriQ9NXW9.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PfamiPF03171. 2OG-FeII_Oxy. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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 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.
    , 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. Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  6. 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. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  11. Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIN-BINDING, MUTAGENESIS OF HIS-169; ASP-171 AND HIS-254.

Entry informationi

Entry nameiALKB4_HUMAN
AccessioniPrimary (citable) accession number: Q9NXW9
Secondary accession number(s): Q53H92, Q9H6A4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: October 1, 2000
Last modified: April 29, 2015
This is version 101 of the entry and version 1 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

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.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.