IMA4_MOUSE
ID IMA4_MOUSE Reviewed; 521 AA.
AC O35344;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Importin subunit alpha-4;
DE AltName: Full=Importin alpha Q2;
DE Short=Qip2;
DE AltName: Full=Karyopherin subunit alpha-3;
GN Name=Kpna3; Synonyms=Qip2;
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 [MRNA].
RX PubMed=9369227; DOI=10.1016/s0014-5793(97)01092-2;
RA Tsuji L., Takumi T., Imamoto N., Yoneda Y.;
RT "Identification of novel homologues of mouse importin alpha, the alpha
RT subunit of the nuclear pore-targeting complex, and their tissue-specific
RT expression.";
RL FEBS Lett. 416:30-34(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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).
CC -!- FUNCTION: Functions in nuclear protein import as an adapter protein for
CC nuclear receptor KPNB1. Binds specifically and directly to substrates
CC containing either a simple or bipartite NLS motif. Docking of the
CC importin/substrate complex to the nuclear pore complex (NPC) is
CC mediated by KPNB1 through binding to nucleoporin FxFG repeats and the
CC complex is subsequently translocated through the pore by an energy
CC requiring, Ran-dependent mechanism. At the nucleoplasmic side of the
CC NPC, Ran binds to importin-beta and the three components separate and
CC importin-alpha and -beta are re-exported from the nucleus to the
CC cytoplasm where GTP hydrolysis releases Ran from importin. The
CC directionality of nuclear import is thought to be conferred by an
CC asymmetric distribution of the GTP- and GDP-bound forms of Ran between
CC the cytoplasm and nucleus. In vitro, mediates the nuclear import of
CC human cytomegalovirus UL84 by recognizing a non-classical NLS.
CC -!- SUBUNIT: Forms a complex with importin subunit beta-1. Interacts with
CC NCBP2/CBP20 and NCBP3. {ECO:0000250|UniProtKB:O00505}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected more or less in all tissues examined
CC (Ehrlich ascites tumor cells, testis, kidney, spleen, liver, heart,
CC lung, thymus, skeletal muscle, cerebellum and brain (without
CC cerebellum)).
CC -!- DOMAIN: Consists of an N-terminal hydrophilic region, a hydrophobic
CC central region composed of 10 repeats, and a short hydrophilic C-
CC terminus. The N-terminal hydrophilic region contains the importin beta
CC binding domain (IBB domain), which is sufficient for binding importin
CC beta and essential for nuclear protein import.
CC -!- DOMAIN: The IBB domain is thought to act as an intrasteric
CC autoregulatory sequence by interacting with the internal autoinhibitory
CC NLS. Binding of KPNB1 probably overlaps the internal NLS and
CC contributes to a high affinity for cytoplasmic NLS-containing cargo
CC substrates. After dissociation of the importin/substrate complex in the
CC nucleus the internal autohibitory NLS contributes to a low affinity for
CC nuclear NLS-containing proteins (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The major and minor NLS binding sites are mainly involved in
CC recognition of simple or bipartite NLS motifs. Structurally located
CC within in a helical surface groove they contain several conserved Trp
CC and Asn residues of the corresponding third helices (H3) of ARM repeats
CC which mainly contribute to binding (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the importin alpha family. {ECO:0000305}.
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DR EMBL; AF020772; AAC53372.1; -; mRNA.
DR EMBL; BC026885; AAH26885.1; -; mRNA.
DR CCDS; CCDS36942.1; -.
DR RefSeq; NP_032492.1; NM_008466.5.
DR AlphaFoldDB; O35344; -.
DR SMR; O35344; -.
DR BioGRID; 201008; 16.
DR ComplexPortal; CPX-1058; Importin complex, KPNA3 variant.
DR DIP; DIP-62054N; -.
DR IntAct; O35344; 4.
DR MINT; O35344; -.
DR STRING; 10090.ENSMUSP00000022496; -.
DR iPTMnet; O35344; -.
DR PhosphoSitePlus; O35344; -.
DR EPD; O35344; -.
DR jPOST; O35344; -.
DR PaxDb; O35344; -.
DR PeptideAtlas; O35344; -.
DR PRIDE; O35344; -.
DR ProteomicsDB; 266976; -.
DR Antibodypedia; 23966; 203 antibodies from 33 providers.
DR DNASU; 16648; -.
DR Ensembl; ENSMUST00000022496; ENSMUSP00000022496; ENSMUSG00000021929.
DR GeneID; 16648; -.
DR KEGG; mmu:16648; -.
DR UCSC; uc007ufw.2; mouse.
DR CTD; 3839; -.
DR MGI; MGI:1100863; Kpna3.
DR VEuPathDB; HostDB:ENSMUSG00000021929; -.
DR eggNOG; KOG0166; Eukaryota.
DR GeneTree; ENSGT01050000244891; -.
DR HOGENOM; CLU_018084_6_1_1; -.
DR InParanoid; O35344; -.
DR OMA; XEAVWFL; -.
DR OrthoDB; 1111872at2759; -.
DR PhylomeDB; O35344; -.
DR TreeFam; TF101178; -.
DR BioGRID-ORCS; 16648; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Kpna3; mouse.
DR PRO; PR:O35344; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; O35344; protein.
DR Bgee; ENSMUSG00000021929; Expressed in extensor digitorum longus and 260 other tissues.
DR ExpressionAtlas; O35344; baseline and differential.
DR Genevisible; O35344; MM.
DR GO; GO:0005829; C:cytosol; IC:ComplexPortal.
DR GO; GO:0042564; C:NLS-dependent protein nuclear import complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0061608; F:nuclear import signal receptor activity; IBA:GO_Central.
DR GO; GO:0008139; F:nuclear localization sequence binding; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0006607; P:NLS-bearing protein import into nucleus; IBA:GO_Central.
DR GO; GO:0006606; P:protein import into nucleus; IC:ComplexPortal.
DR Gene3D; 1.20.5.690; -; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR032413; Arm_3.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR002652; Importin-a_IBB.
DR InterPro; IPR036975; Importin-a_IBB_sf.
DR InterPro; IPR024931; Importin_alpha.
DR Pfam; PF00514; Arm; 8.
DR Pfam; PF16186; Arm_3; 1.
DR Pfam; PF01749; IBB; 1.
DR PIRSF; PIRSF005673; Importin_alpha; 1.
DR SMART; SM00185; ARM; 8.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50176; ARM_REPEAT; 3.
DR PROSITE; PS51214; IBB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O00505"
FT CHAIN 2..521
FT /note="Importin subunit alpha-4"
FT /id="PRO_0000120725"
FT DOMAIN 2..58
FT /note="IBB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00561"
FT REPEAT 66..106
FT /note="ARM 1; truncated"
FT REPEAT 107..149
FT /note="ARM 2"
FT REPEAT 150..194
FT /note="ARM 3"
FT REPEAT 195..233
FT /note="ARM 4"
FT REPEAT 234..278
FT /note="ARM 5"
FT REPEAT 279..318
FT /note="ARM 6"
FT REPEAT 319..360
FT /note="ARM 7"
FT REPEAT 361..400
FT /note="ARM 8"
FT REPEAT 401..443
FT /note="ARM 9"
FT REPEAT 447..485
FT /note="ARM 10; atypical"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 137..229
FT /note="NLS binding site (major)"
FT /evidence="ECO:0000250"
FT REGION 306..394
FT /note="NLS binding site (minor)"
FT /evidence="ECO:0000250"
FT MOTIF 43..52
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 9..29
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O00505"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 484
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O00505"
SQ SEQUENCE 521 AA; 57773 MW; 78501CE1AAB3A260 CRC64;
MAENPGLENH RIKSFKNKGR DVETMRRHRN EVTVELRKNK RDEHLLKKRN VPQEESLEDS
DVDADFKAQN VTLEAILQNA TSDNPVVQLS AVQAARKLLS SDRNPPIDDL IKSGILPILV
KCLERDDNPS LQFEAAWALT NIASGTSAQT QAVVQSNAVP LFLRLLHSPH QNVCEQAVWA
LGNIIGDGPQ CRDYVISLGV VKPLLSFINP SIPITFLRNV TWVIVNLCRN KDPPPPMETV
QEILPALCVL IYHTDINILV DTVWALSYLT DGGNEQIQMV IDSGVVPFLV PLLSHQEVKV
QTAALRAVGN IVTGTDEQTQ VVLNCDVLSH FPNLLSHPKE KINKEAVWFL SNITAGNQQQ
VQAVIDAGLI PMIIHQLAKG DFGTQKEAAW AISNLTISGR KDQVEYLVQQ NVIPPFCNLL
SVKDSQVVQV VLDGLKNILI MAGDEASTIA EIIEECGGLE KIEVLQQHEN EDIYKLAFEI
IDQYFSGDDI DEDPSLIPEA TQGGTYNFDP TANLQTKEFN F
