AKIR2_HUMAN
ID AKIR2_HUMAN Reviewed; 203 AA.
AC Q53H80; Q9BQB1;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Akirin-2 {ECO:0000305};
GN Name=AKIRIN2 {ECO:0000303|PubMed:18066067, ECO:0000312|HGNC:HGNC:21407};
GN Synonyms=C6orf166 {ECO:0000312|HGNC:HGNC:21407};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung carcinoma;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-21, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-21, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-21, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN COMPLEX WITH 20S
RP PROTEASOME, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH IPO9,
RP AND MUTAGENESIS OF 201-TYR--SER-203.
RX PubMed=34711951; DOI=10.1038/s41586-021-04035-8;
RA de Almeida M., Hinterndorfer M., Brunner H., Grishkovskaya I., Singh K.,
RA Schleiffer A., Jude J., Deswal S., Kalis R., Vunjak M., Lendl T., Imre R.,
RA Roitinger E., Neumann T., Kandolf S., Schutzbier M., Mechtler K.,
RA Versteeg G.A., Haselbach D., Zuber J.;
RT "AKIRIN2 controls the nuclear import of proteasomes in vertebrates.";
RL Nature 599:491-496(2021).
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:34711951). Plays a
CC 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 (PubMed:34711951).
CC Involved in innate immunity by regulating the production of
CC interleukin-6 (IL6) downstream of Toll-like receptor (TLR): acts by
CC bridging the NF-kappa-B inhibitor NFKBIZ and the SWI/SNF complex,
CC leading to promote induction of IL6 (By similarity). Also involved in
CC adaptive immunity by promoting B-cell activation (By similarity).
CC Involved in brain development: required for the survival and
CC proliferation of cerebral cortical progenitor cells (By similarity).
CC Involved in myogenesis: required for skeletal muscle formation and
CC skeletal development, possibly by regulating expression of muscle
CC differentiation factors (By similarity). Also plays a role in
CC facilitating interdigital tissue regression during limb development (By
CC similarity). {ECO:0000250|UniProtKB:B1AXD8,
CC ECO:0000269|PubMed:34711951}.
CC -!- SUBUNIT: Homodimer (PubMed:34711951). Interacts with IPO9; the
CC interaction is direct (PubMed:34711951). Associates (via SYVS motif)
CC with 20S and 26S proteasomes (PubMed:34711951). Interacts with SMARCD1;
CC promoting SWI/SNF complex recruitment (By similarity). Interacts with
CC NFKBIZ (By similarity). Interacts with YWHAB (By similarity).
CC {ECO:0000250|UniProtKB:B1AXD8, ECO:0000250|UniProtKB:Q25C79,
CC ECO:0000269|PubMed:34711951}.
CC -!- INTERACTION:
CC Q53H80; Q53H80: AKIRIN2; NbExp=3; IntAct=EBI-742928, EBI-742928;
CC Q53H80; P52597: HNRNPF; NbExp=3; IntAct=EBI-742928, EBI-352986;
CC Q53H80; Q9BPX1: HSD17B14; NbExp=3; IntAct=EBI-742928, EBI-742664;
CC Q53H80; Q14696: MESD; NbExp=3; IntAct=EBI-742928, EBI-6165891;
CC Q53H80; Q8TDC0: MYOZ3; NbExp=3; IntAct=EBI-742928, EBI-5662487;
CC Q53H80; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-742928, EBI-741158;
CC Q53H80; O60504: SORBS3; NbExp=3; IntAct=EBI-742928, EBI-741237;
CC Q53H80; Q9NZD8: SPG21; NbExp=11; IntAct=EBI-742928, EBI-742688;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18066067,
CC ECO:0000269|PubMed:34711951}. Cytoplasm {ECO:0000250|UniProtKB:B1AXD8}.
CC Membrane {ECO:0000250|UniProtKB:B1AXD8}. Note=Present mainly in the
CC nuclear fraction, and at much lower level in the cytoplasmic and
CC membrane fractions. {ECO:0000250|UniProtKB:B1AXD8}.
CC -!- TISSUE SPECIFICITY: Widely expressed with the highest expression in
CC peripheral blood leukocytes. {ECO:0000269|PubMed:18066067}.
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}.
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DR EMBL; AK222701; BAD96421.1; -; mRNA.
DR EMBL; AL133211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000764; AAH00764.1; -; mRNA.
DR EMBL; BC003042; AAH03042.1; -; mRNA.
DR EMBL; BC005051; AAH05051.1; -; mRNA.
DR CCDS; CCDS5013.1; -.
DR RefSeq; NP_060534.1; NM_018064.3.
DR PDB; 7NHT; EM; 2.80 A; c/d=1-203.
DR PDBsum; 7NHT; -.
DR AlphaFoldDB; Q53H80; -.
DR SMR; Q53H80; -.
DR BioGRID; 120430; 43.
DR IntAct; Q53H80; 24.
DR STRING; 9606.ENSP00000257787; -.
DR GlyGen; Q53H80; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q53H80; -.
DR PhosphoSitePlus; Q53H80; -.
DR BioMuta; AKIRIN2; -.
DR DMDM; 71152385; -.
DR EPD; Q53H80; -.
DR jPOST; Q53H80; -.
DR MassIVE; Q53H80; -.
DR MaxQB; Q53H80; -.
DR PaxDb; Q53H80; -.
DR PeptideAtlas; Q53H80; -.
DR PRIDE; Q53H80; -.
DR ProteomicsDB; 62500; -.
DR Antibodypedia; 31831; 186 antibodies from 25 providers.
DR DNASU; 55122; -.
DR Ensembl; ENST00000257787.6; ENSP00000257787.5; ENSG00000135334.9.
DR GeneID; 55122; -.
DR KEGG; hsa:55122; -.
DR MANE-Select; ENST00000257787.6; ENSP00000257787.5; NM_018064.4; NP_060534.1.
DR UCSC; uc003pmk.4; human.
DR CTD; 55122; -.
DR DisGeNET; 55122; -.
DR GeneCards; AKIRIN2; -.
DR HGNC; HGNC:21407; AKIRIN2.
DR HPA; ENSG00000135334; Low tissue specificity.
DR MIM; 615165; gene.
DR neXtProt; NX_Q53H80; -.
DR OpenTargets; ENSG00000135334; -.
DR PharmGKB; PA162376195; -.
DR VEuPathDB; HostDB:ENSG00000135334; -.
DR eggNOG; KOG4330; Eukaryota.
DR GeneTree; ENSGT00940000156096; -.
DR HOGENOM; CLU_119227_0_0_1; -.
DR InParanoid; Q53H80; -.
DR OMA; RRCAPIM; -.
DR OrthoDB; 1420469at2759; -.
DR PhylomeDB; Q53H80; -.
DR TreeFam; TF317123; -.
DR PathwayCommons; Q53H80; -.
DR SignaLink; Q53H80; -.
DR BioGRID-ORCS; 55122; 698 hits in 1083 CRISPR screens.
DR ChiTaRS; AKIRIN2; human.
DR GeneWiki; C6orf166; -.
DR GenomeRNAi; 55122; -.
DR Pharos; Q53H80; Tbio.
DR PRO; PR:Q53H80; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q53H80; protein.
DR Bgee; ENSG00000135334; Expressed in oocyte and 184 other tissues.
DR Genevisible; Q53H80; HS.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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; ISS:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0071630; P:nuclear protein quality control by the ubiquitin-proteasome system; IDA:UniProtKB.
DR GO; GO:0002821; P:positive regulation of adaptive immune response; ISS:UniProtKB.
DR GO; GO:0050871; P:positive regulation of B cell activation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0010950; P:positive regulation of endopeptidase activity; IEA:Ensembl.
DR GO; GO:0045089; P:positive regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0031144; P:proteasome localization; IDA:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0051147; P:regulation of muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR InterPro; IPR024132; Akirin.
DR PANTHER; PTHR13293; PTHR13293; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cytoplasm; Developmental protein;
KW Immunity; Innate immunity; Membrane; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Transport.
FT CHAIN 1..203
FT /note="Akirin-2"
FT /id="PRO_0000089555"
FT MOTIF 22..27
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000305|PubMed:18066067"
FT MOTIF 200..203
FT /note="SYVS motif"
FT /evidence="ECO:0000305|PubMed:34711951"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B1AXD8"
FT MUTAGEN 201..203
FT /note="Missing: Abolished association with the 20S and 26S
FT proteasomes."
FT /evidence="ECO:0000269|PubMed:34711951"
FT CONFLICT 171
FT /note="L -> S (in Ref. 1; BAD96421)"
FT /evidence="ECO:0000305"
FT HELIX 157..189
FT /evidence="ECO:0007829|PDB:7NHT"
SQ SEQUENCE 203 AA; 22496 MW; 33AA93AF94DE80A1 CRC64;
MACGATLKRT LDFDPLLSPA SPKRRRCAPL SAPTSAAASP LSAAAATAAS FSAAAASPQK
YLRMEPSPFG DVSSRLTTEQ ILYNIKQEYK RMQKRRHLET SFQQTDPCCT SDAQPHAFLL
SGPASPGTSS AASSPLKKEQ PLFTLRQVGM ICERLLKERE EKVREEYEEI LNTKLAEQYD
AFVKFTHDQI MRRYGEQPAS YVS
