AKIR2_MOUSE
ID AKIR2_MOUSE Reviewed; 201 AA.
AC B1AXD8; Q641L8; Q9DAH4;
DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Akirin-2 {ECO:0000305};
GN Name=Akirin2 {ECO:0000303|PubMed:18066067, ECO:0000312|MGI:MGI:1889364};
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].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB24265.1};
RC TISSUE=Testis {ECO:0000312|EMBL:BAB24265.1};
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-21, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18066067; DOI=10.1038/ni1543;
RA Goto A., Matsushita K., Gesellchen V., El Chamy L., Kuttenkeuler D.,
RA Takeuchi O., Hoffmann J.A., Akira S., Boutros M., Reichhart J.-M.;
RT "Akirins are highly conserved nuclear proteins required for NF-kappaB-
RT dependent gene expression in Drosophila and mice.";
RL Nat. Immunol. 9:97-104(2008).
RN [5]
RP ERRATUM OF PUBMED:18066067.
RA Goto A., Matsushita K., Gesellchen V., El Chamy L., Kuttenkeuler D.,
RA Takeuchi O., Hoffmann J.A., Akira S., Boutros M., Reichhart J.-M.;
RL Nat. Immunol. 9:216-216(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-21 AND SER-55, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP NFKBIZ AND SMARCD1.
RX PubMed=25107474; DOI=10.15252/embj.201488447;
RA Tartey S., Matsushita K., Vandenbon A., Ori D., Imamura T., Mino T.,
RA Standley D.M., Hoffmann J.A., Reichhart J.M., Akira S., Takeuchi O.;
RT "Akirin2 is critical for inducing inflammatory genes by bridging IkappaB-
RT zeta and the SWI/SNF complex.";
RL EMBO J. 33:2332-2348(2014).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26041538; DOI=10.4049/jimmunol.1500373;
RA Tartey S., Matsushita K., Imamura T., Wakabayashi A., Ori D., Mino T.,
RA Takeuchi O.;
RT "Essential function for the nuclear protein Akirin2 in B Cell activation
RT and humoral immune responses.";
RL J. Immunol. 195:519-527(2015).
RN [9]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=27871306; DOI=10.1186/s13064-016-0076-8;
RA Bosch P.J., Fuller L.C., Sleeth C.M., Weiner J.A.;
RT "Akirin2 is essential for the formation of the cerebral cortex.";
RL Neural Dev. 11:21-21(2016).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=30116001; DOI=10.1038/s41598-018-30801-2;
RA Bosch P.J., Fuller L.C., Weiner J.A.;
RT "An essential role for the nuclear protein Akirin2 in mouse limb
RT interdigital tissue regression.";
RL Sci. Rep. 8:12240-12240(2018).
RN [11]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=30801883; DOI=10.1002/dvg.23286;
RA Bosch P.J., Fuller L.C., Weiner J.A.;
RT "A critical role for the nuclear protein Akirin2 in the formation of
RT mammalian muscle in vivo.";
RL Genesis 57:e23286-e23286(2019).
CC -!- FUNCTION: Molecular adapter that acts as a bridge between a variety of
CC multiprotein complexes, and which is involved in embryonic development,
CC immunity, myogenesis and brain development (PubMed:25107474,
CC PubMed:26041538, PubMed:27871306, PubMed:30116001, PubMed:30801883).
CC Plays a key role in nuclear protein degradation by promoting import of
CC proteasomes into the nucleus: directly binds to fully assembled 20S
CC proteasomes at one end and to nuclear import receptor IPO9 at the other
CC end, bridging them together and mediating the import of pre-assembled
CC proteasome complexes through the nuclear pore (By similarity). Involved
CC in innate immunity by regulating the production of interleukin-6 (IL6)
CC downstream of Toll-like receptor (TLR): acts by bridging the NF-kappa-B
CC inhibitor NFKBIZ and the SWI/SNF complex, leading to promote induction
CC of IL6 (PubMed:18066067, PubMed:25107474). Also involved in adaptive
CC immunity by promoting B-cell activation (PubMed:26041538). Involved in
CC brain development: required for the survival and proliferation of
CC cerebral cortical progenitor cells (PubMed:27871306). Involved in
CC myogenesis: required for skeletal muscle formation and skeletal
CC development, possibly by regulating expression of muscle
CC differentiation factors (PubMed:30801883). Also plays a role in
CC facilitating interdigital tissue regression during limb development
CC (PubMed:30116001). {ECO:0000250|UniProtKB:Q53H80,
CC ECO:0000269|PubMed:18066067, ECO:0000269|PubMed:25107474,
CC ECO:0000269|PubMed:26041538, ECO:0000269|PubMed:27871306,
CC ECO:0000269|PubMed:30116001, ECO:0000269|PubMed:30801883}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with IPO9; the
CC interaction is direct (By similarity). Associates with 20S and 26S
CC proteasomes (By similarity). Interacts with SMARCD1; promoting SWI/SNF
CC complex recruitment (PubMed:25107474). Interacts with NFKBIZ
CC (PubMed:25107474). Interacts with YWHAB (By similarity).
CC {ECO:0000250|UniProtKB:Q25C79, ECO:0000250|UniProtKB:Q53H80,
CC ECO:0000269|PubMed:25107474}.
CC -!- INTERACTION:
CC B1AXD8; Q9EST8: Nfkbiz; NbExp=3; IntAct=EBI-10107866, EBI-10107924;
CC B1AXD8; Q61466: Smarcd1; NbExp=2; IntAct=EBI-10107866, EBI-371529;
CC B1AXD8; Q9BYH8: NFKBIZ; Xeno; NbExp=3; IntAct=EBI-10107866, EBI-3939694;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25107474,
CC ECO:0000269|PubMed:30116001, ECO:0000269|PubMed:30801883}. Cytoplasm
CC {ECO:0000269|PubMed:30801883}. Membrane {ECO:0000269|PubMed:30801883}.
CC Note=Present mainly in the nuclear fraction, and at much lower level in
CC the cytoplasmic and membrane fractions. {ECO:0000269|PubMed:30801883}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout cortical development: present
CC throughout the cortical wall at all of these ages, with strong
CC expression in the early ventricular zone and the embryonic
CC preplate/cortical plate (PubMed:27871306). Expressed in the developing
CC limb: expressed in the forelimb bud and somites at 10.5 dpc, as well as
CC in the apical ectodermal ridge (AER) (PubMed:30116001). Ubiquitously
CC expressed throughout the embryonic forelimb at 10.5 dpc: expressed in
CC the dermomyotome and sclerotome divisions of the somite (at protein
CC level) (PubMed:30801883). {ECO:0000269|PubMed:27871306,
CC ECO:0000269|PubMed:30116001, ECO:0000269|PubMed:30801883}.
CC -!- DISRUPTION PHENOTYPE: Mice are embryonic lethal (PubMed:18066067). Null
CC mutant embryos could not be detected even on embryonic day 9.5
CC (PubMed:18066067). Conditional deletion in macrophages impairs
CC proinflammatory cytokine production in response to Listeria infection
CC and clearance of infecting bacteria (PubMed:25107474). Conditional
CC deletion in B-cells causes a decrease in the splenic B-cell numbers,
CC leading to severe proliferation and activation defects in B-cells
CC (PubMed:26041538). The B-cell viability is also impaired, leading to
CC decreased immune responses to T-dependent and T-independent antigens
CC (PubMed:26041538). Conditional deletion in the cortex leads to severe
CC microcephaly: mice do not survive past birth and exhibit extreme
CC microcephaly, with little dorsal telencephalic tissue and no
CC recognizable cortex (PubMed:27871306). Defects in the cortex are caused
CC to massive cell death of early cortical progenitors (PubMed:27871306).
CC Conditional deletion in somitic muscle precursor cells results in
CC neonatal lethality: mutant embryos show a complete lack of forelimb,
CC intercostal and diaphragm muscles due to extensive apoptosis and loss
CC of myoblasts (PubMed:30801883). Embryos lacking Akirin2 in somitic
CC muscle precursor cells also display severe skeletal defects, including
CC craniofacial abnormalities, disrupted ossification and rib fusions
CC (PubMed:30801883). Conditional deletion in limb bud epithelium leads to
CC soft-tissue syndactyly, characterized by a loss of interdigital cell
CC death and an increase in cell proliferation, resulting in retention of
CC the interdigital web (PubMed:30116001). {ECO:0000269|PubMed:18066067,
CC ECO:0000269|PubMed:25107474, ECO:0000269|PubMed:26041538,
CC ECO:0000269|PubMed:27871306, ECO:0000269|PubMed:30116001,
CC ECO:0000269|PubMed:30801883}.
CC -!- MISCELLANEOUS: 'Akiraka ni suru' means 'making things clear' in
CC Japanese. The name is given based on the presence of the clear nuclear
CC localization signal. {ECO:0000305|PubMed:18066067}.
CC -!- SIMILARITY: Belongs to the akirin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB24265.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK005836; BAB24265.1; ALT_FRAME; mRNA.
DR EMBL; AL807397; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS18027.1; -.
DR RefSeq; NP_001007590.2; NM_001007589.3.
DR RefSeq; XP_011248362.1; XM_011250060.2.
DR AlphaFoldDB; B1AXD8; -.
DR SMR; B1AXD8; -.
DR BioGRID; 241383; 1.
DR IntAct; B1AXD8; 7.
DR MINT; B1AXD8; -.
DR STRING; 10090.ENSMUSP00000081322; -.
DR iPTMnet; B1AXD8; -.
DR PhosphoSitePlus; B1AXD8; -.
DR EPD; B1AXD8; -.
DR jPOST; B1AXD8; -.
DR MaxQB; B1AXD8; -.
DR PaxDb; B1AXD8; -.
DR PeptideAtlas; B1AXD8; -.
DR PRIDE; B1AXD8; -.
DR ProteomicsDB; 296153; -.
DR Antibodypedia; 31831; 186 antibodies from 25 providers.
DR DNASU; 433693; -.
DR Ensembl; ENSMUST00000084299; ENSMUSP00000081322; ENSMUSG00000028291.
DR GeneID; 433693; -.
DR KEGG; mmu:433693; -.
DR UCSC; uc008sga.1; mouse.
DR CTD; 55122; -.
DR MGI; MGI:1889364; Akirin2.
DR VEuPathDB; HostDB:ENSMUSG00000028291; -.
DR eggNOG; KOG4330; Eukaryota.
DR GeneTree; ENSGT00940000156096; -.
DR HOGENOM; CLU_119227_0_0_1; -.
DR InParanoid; B1AXD8; -.
DR OMA; RRCAPIM; -.
DR OrthoDB; 1420469at2759; -.
DR PhylomeDB; B1AXD8; -.
DR TreeFam; TF317123; -.
DR BioGRID-ORCS; 433693; 17 hits in 73 CRISPR screens.
DR ChiTaRS; Akirin2; mouse.
DR PRO; PR:B1AXD8; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; B1AXD8; protein.
DR Bgee; ENSMUSG00000028291; Expressed in animal zygote and 255 other tissues.
DR Genevisible; B1AXD8; MM.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0021987; P:cerebral cortex development; IMP:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0071630; P:nuclear protein quality control by the ubiquitin-proteasome system; ISS:UniProtKB.
DR GO; GO:0002821; P:positive regulation of adaptive immune response; IMP:UniProtKB.
DR GO; GO:0050871; P:positive regulation of B cell activation; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010950; P:positive regulation of endopeptidase activity; ISO:MGI.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0031144; P:proteasome localization; ISS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0051147; P:regulation of muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:MGI.
DR InterPro; IPR024132; Akirin.
DR PANTHER; PTHR13293; PTHR13293; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Cytoplasm; Developmental protein; Immunity;
KW Innate immunity; Membrane; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Transport.
FT CHAIN 1..201
FT /note="Akirin-2"
FT /id="PRO_0000355121"
FT MOTIF 23..28
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000305|PubMed:18066067"
FT MOTIF 198..201
FT /note="SYVS motif"
FT /evidence="ECO:0000250|UniProtKB:Q53H80"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 48
FT /note="A -> V (in Ref. 1; BAB24265)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="V -> G (in Ref. 1; BAB24265)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 201 AA; 22113 MW; 8DB8235D12246DD1 CRC64;
MACGATLKRT LDFDPLLSPA SPKRRRCAPL SAPASAAASP AAATAAAAAS AAAASPQKYL
RMEPSPFGDV SSRLTTEQIL YNIKQEYKRM QKRRHLEASF QQADPGCTSD SQPHAFLISG
PASPGTSSAT SSPLKKEQPL FTLRQVGMIC ERLLKEREEK VREEYEEILN TKLAEQYDAF
VKFTHDQIMR RYGEQPASYV S
