ALKB4_MOUSE
ID ALKB4_MOUSE Reviewed; 300 AA.
AC Q9D8F1; Q8R1Y9;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Alpha-ketoglutarate-dependent dioxygenase alkB homolog 4 {ECO:0000305};
DE AltName: Full=Alkylated DNA repair protein alkB homolog 4 {ECO:0000303|PubMed:23673617};
DE AltName: Full=DNA N6-methyl adenine demethylase ALKBH4 {ECO:0000305};
DE EC=1.14.11.51 {ECO:0000269|PubMed:30982744};
DE AltName: Full=Lysine-specific demethylase ALKBH4 {ECO:0000305};
DE EC=1.14.11.- {ECO:0000250|UniProtKB:Q9NXW9};
GN Name=Alkbh4 {ECO:0000303|PubMed:23673617, ECO:0000312|MGI:MGI:1919291};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Small intestine;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=23673617; DOI=10.1038/ncomms2863;
RA Li M.M., Nilsen A., Shi Y., Fusser M., Ding Y.H., Fu Y., Liu B., Niu Y.,
RA Wu Y.S., Huang C.M., Olofsson M., Jin K.X., Lv Y., Xu X.Z., He C.,
RA Dong M.Q., Rendtlew Danielsen J.M., Klungland A., Yang Y.G.;
RT "ALKBH4-dependent demethylation of actin regulates actomyosin dynamics.";
RL Nat. Commun. 4:1832-1832(2013).
RN [5]
RP DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=25153837; DOI=10.1371/journal.pone.0105113;
RA Nilsen A., Fusser M., Greggains G., Fedorcsak P., Klungland A.;
RT "ALKBH4 depletion in mice leads to spermatogenic defects.";
RL PLoS ONE 9:E105113-E105113(2014).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30982744; DOI=10.1016/j.molcel.2019.03.018;
RA Kweon S.M., Chen Y., Moon E., Kvederaviciute K., Klimasauskas S.,
RA Feldman D.E.;
RT "An adversarial DNA N6-methyladenine-sensor network preserves Polycomb
RT silencing.";
RL Mol. Cell 74:1138-1147(2019).
CC -!- FUNCTION: Dioxygenase that mediates demethylation of actin
CC monomethylated at 'Lys-84' (K84me1), thereby acting as a regulator of
CC actomyosin-processes (By similarity). Demethylation of actin K84me1 is
CC required for maintaining actomyosin dynamics supporting normal cleavage
CC furrow ingression during cytokinesis and cell migration (By
CC similarity). In addition to proteins, also demethylates DNA:
CC specifically demethylates DNA methylated on the 6th position of adenine
CC (N(6)-methyladenosine) DNA, thereby regulating Polycomb silencing
CC (PubMed:30982744). {ECO:0000250|UniProtKB:Q9NXW9,
CC ECO:0000269|PubMed:30982744}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + an N(6)-methyl-2'-deoxyadenosine in DNA + O2
CC = a 2'-deoxyadenosine in DNA + CO2 + formaldehyde + succinate;
CC Xref=Rhea:RHEA:49524, Rhea:RHEA-COMP:12418, Rhea:RHEA-COMP:12419,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:90615,
CC ChEBI:CHEBI:90616; EC=1.14.11.51;
CC Evidence={ECO:0000269|PubMed:30982744};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49525;
CC Evidence={ECO:0000269|PubMed:30982744};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + N(6)-methyl-L-lysyl-[protein] + O2 = CO2 +
CC formaldehyde + L-lysyl-[protein] + succinate; Xref=Rhea:RHEA:60924,
CC Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842,
CC ChEBI:CHEBI:29969, ChEBI:CHEBI:30031, ChEBI:CHEBI:61929;
CC Evidence={ECO:0000250|UniProtKB:Q9NXW9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60925;
CC Evidence={ECO:0000250|UniProtKB:Q9NXW9};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:30982744};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q9NXW9};
CC -!- SUBUNIT: Interacts with ZFHX3, MLLT3, MLLT1, HSF4, EP300, TES, EIF3C,
CC MTMR6 and PSMA6. {ECO:0000250|UniProtKB:Q9NXW9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9NXW9}. Nucleus
CC {ECO:0000269|PubMed:25153837}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:25153837}. Midbody {ECO:0000250|UniProtKB:Q9NXW9}.
CC Note=Associates with the contractile ring and midbody.
CC {ECO:0000250|UniProtKB:Q9NXW9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9D8F1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9D8F1-2; Sequence=VSP_019129;
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality (PubMed:23673617).
CC Conditional deletion in developing juvenile mice leads to spermatogenic
CC defects (PubMed:25153837). {ECO:0000269|PubMed:23673617,
CC ECO:0000269|PubMed:25153837}.
CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK008083; BAB25449.1; -; mRNA.
DR EMBL; GL456122; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022729; AAH22729.1; -; mRNA.
DR CCDS; CCDS19753.1; -. [Q9D8F1-2]
DR CCDS; CCDS84973.1; -. [Q9D8F1-1]
DR RefSeq; NP_001334421.1; NM_001347492.1. [Q9D8F1-1]
DR RefSeq; NP_082346.1; NM_028070.1. [Q9D8F1-2]
DR RefSeq; XP_006504566.1; XM_006504503.3.
DR RefSeq; XP_006504567.1; XM_006504504.2.
DR RefSeq; XP_006504568.1; XM_006504505.3. [Q9D8F1-2]
DR AlphaFoldDB; Q9D8F1; -.
DR SMR; Q9D8F1; -.
DR STRING; 10090.ENSMUSP00000098134; -.
DR PhosphoSitePlus; Q9D8F1; -.
DR EPD; Q9D8F1; -.
DR MaxQB; Q9D8F1; -.
DR PaxDb; Q9D8F1; -.
DR PRIDE; Q9D8F1; -.
DR ProteomicsDB; 296022; -. [Q9D8F1-1]
DR ProteomicsDB; 296023; -. [Q9D8F1-2]
DR Antibodypedia; 45707; 158 antibodies from 22 providers.
DR DNASU; 72041; -.
DR Ensembl; ENSMUST00000041100; ENSMUSP00000040403; ENSMUSG00000039754. [Q9D8F1-1]
DR Ensembl; ENSMUST00000100568; ENSMUSP00000098134; ENSMUSG00000039754. [Q9D8F1-2]
DR GeneID; 72041; -.
DR KEGG; mmu:72041; -.
DR UCSC; uc009aaa.1; mouse. [Q9D8F1-1]
DR CTD; 54784; -.
DR MGI; MGI:1919291; Alkbh4.
DR VEuPathDB; HostDB:ENSMUSG00000039754; -.
DR eggNOG; KOG3959; Eukaryota.
DR GeneTree; ENSGT00390000006344; -.
DR HOGENOM; CLU_060545_0_0_1; -.
DR InParanoid; Q9D8F1; -.
DR OMA; VHHFLYD; -.
DR OrthoDB; 933314at2759; -.
DR PhylomeDB; Q9D8F1; -.
DR TreeFam; TF314885; -.
DR BioGRID-ORCS; 72041; 2 hits in 71 CRISPR screens.
DR PRO; PR:Q9D8F1; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9D8F1; protein.
DR Bgee; ENSMUSG00000039754; Expressed in lumbar dorsal root ganglion and 191 other tissues.
DR ExpressionAtlas; Q9D8F1; baseline and differential.
DR Genevisible; Q9D8F1; MM.
DR GO; GO:0070938; C:contractile ring; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0032451; F:demethylase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035516; F:oxidative DNA demethylase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0031032; P:actomyosin structure organization; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0036090; P:cleavage furrow ingression; ISS:UniProtKB.
DR GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB.
DR GO; GO:0070989; P:oxidative demethylation; IBA:GO_Central.
DR GO; GO:0006482; P:protein demethylation; ISS:UniProtKB.
DR GO; GO:1902275; P:regulation of chromatin organization; IDA:UniProtKB.
DR Gene3D; 2.60.120.590; -; 1.
DR InterPro; IPR037151; AlkB-like_sf.
DR InterPro; IPR032857; ALKBH4.
DR PANTHER; PTHR12463; PTHR12463; 1.
PE 1: Evidence at protein level;
KW Acetylation; Actin-binding; Alternative splicing; Chromatin regulator;
KW Cytoplasm; Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase;
KW Reference proteome; Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9NXW9"
FT CHAIN 2..300
FT /note="Alpha-ketoglutarate-dependent dioxygenase alkB
FT homolog 4"
FT /id="PRO_0000239282"
FT DOMAIN 148..272
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 167
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 169
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 252
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 263
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9NXW9"
FT VAR_SEQ 1..85
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019129"
SQ SEQUENCE 300 AA; 33394 MW; C19FBBB89095B6ED CRC64;
MAAAAEVSLL QECGCKGIRT CLICERQRHR DPPWQICLQK KCCFLYCPDT GWAAGAEGSD
LEGWAFPFPG VTLIQDFVTP EEEAEMVRLM DCDPWKLSQS GRKKQDYGPK VNFRKQKLKM
AGFQGLPGFS QKVVQRMGLY PGLEDFQPVE QCNLDYSPER GSAIDPHLDD AWLWGERLVS
LNLLSATVVS MSPEAPGSLL LCSAPSVRPD AFEDSLVAPS RSVPCQEVEV AITVPRRSLL
VLTGAARHQW THAIHRRHIK ARRVCATFRE LSSEFLPGGK QQELGQELLQ AALSFQGRPV
