Full text data of KPNA3
KPNA3
(QIP2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Importin subunit alpha-4 (Importin alpha Q2; Qip2; Karyopherin subunit alpha-3; SRP1-gamma)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Importin subunit alpha-4 (Importin alpha Q2; Qip2; Karyopherin subunit alpha-3; SRP1-gamma)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O00505
ID IMA4_HUMAN Reviewed; 521 AA.
AC O00505; O00191; O43195; Q5JVM9; Q96AA7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2002, sequence version 2.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Importin subunit alpha-4;
DE AltName: Full=Importin alpha Q2;
DE Short=Qip2;
DE AltName: Full=Karyopherin subunit alpha-3;
DE AltName: Full=SRP1-gamma;
GN Name=KPNA3; Synonyms=QIP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=9154134;
RA Takeda S., Fujiwara T., Shimizu F., Kawai A., Shinomiya K., Okuno S.,
RA Ozaki K., Katagiri T., Shimada Y., Nagata M., Watanabe T.,
RA Takaichi A., Kuga Y., Suzuki M., Hishigaki H., Takahashi E., Shin S.,
RA Nakamura Y., Hirai Y.;
RT "Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene
RT that is highly homologous to genes encoding Xenopus importin, yeast
RT SRP1 and human RCH1.";
RL Cytogenet. Cell Genet. 76:87-93(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=9395085; DOI=10.1016/S0014-5793(97)01265-9;
RA Koehler M., Ansieau S., Prehn S., Leutz A., Haller H., Hartmann E.;
RT "Cloning of two novel human importin-alpha subunits and analysis of
RT the expression pattern of the importin-alpha protein family.";
RL FEBS Lett. 417:104-108(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9435235; DOI=10.1073/pnas.95.2.582;
RA Nachury M.V., Ryder U.W., Lamond A.I., Weis K.;
RT "Cloning and characterization of hSRP1 gamma, a tissue-specific
RT nuclear transport factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:582-587(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Fischer R.;
RT "Importin alpha-3, a novel variant of the small importin subunit
RT evolutionarily conserved from hydrozoa to man.";
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH INFLUENZA VIRUS NP.
RX PubMed=12740372; DOI=10.1074/jbc.M303571200;
RA Melen K., Fagerlund R., Franke J., Koehler M., Kinnunen L.,
RA Julkunen I.;
RT "Importin alpha nuclear localization signal binding sites for STAT1,
RT STAT2, and influenza A virus nucleoprotein.";
RL J. Biol. Chem. 278:28193-28200(2003).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, AND MASS
RP SPECTROMETRY.
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 [15]
RP INTERACTION WITH HIV-1 INTEGRASE.
RX PubMed=20554775; DOI=10.1128/JVI.00508-10;
RA Ao Z., Danappa Jayappa K., Wang B., Zheng Y., Kung S., Rassart E.,
RA Depping R., Kohler M., Cohen E.A., Yao X.;
RT "Importin alpha3 interacts with HIV-1 integrase and contributes to
RT HIV-1 nuclear import and replication.";
RL J. Virol. 84:8650-8663(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Functions in nuclear protein import as an adapter
CC protein for nuclear receptor KPNB1. Binds specifically and
CC directly to substrates containing either a simple or bipartite NLS
CC motif. Docking of the importin/substrate complex to the nuclear
CC pore complex (NPC) is mediated by KPNB1 through binding to
CC nucleoporin FxFG repeats and the complex is subsequently
CC translocated through the pore by an energy requiring, Ran-
CC dependent mechanism. At the nucleoplasmic side of the NPC, Ran
CC 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
CC between the cytoplasm and nucleus. In vitro, mediates the nuclear
CC import of human cytomegalovirus UL84 by recognizing a non-
CC classical NLS. Recognizes NLSs of influenza A virus nucleoprotein
CC probably through ARM repeats 7-9.
CC -!- SUBUNIT: Forms a complex with importin subunit beta-1. Interacts
CC with HIV-1 integrase; this interaction might play a role in
CC nuclear import of HIV pre-integration complex. Interacts with
CC influenza virus nucleoprotein; this interaction might play a role
CC in nuclear import of viral genome.
CC -!- INTERACTION:
CC P46527:CDKN1B; NbExp=4; IntAct=EBI-358297, EBI-519280;
CC Q8K4J6:Mkl1 (xeno); NbExp=9; IntAct=EBI-358297, EBI-8291665;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity).
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest levels in heart and
CC skeletal muscle.
CC -!- DOMAIN: Consists of an N-terminal hydrophilic region, a
CC hydrophobic central region composed of 10 repeats, and a short
CC hydrophilic C-terminus. The N-terminal hydrophilic region contains
CC the importin beta binding domain (IBB domain), which is sufficient
CC for binding importin beta and essential for nuclear protein
CC import.
CC -!- DOMAIN: The IBB domain is thought to act as an intrasteric
CC autoregulatory sequence by interacting with the internal
CC autoinhibitory NLS. Binding of KPNB1 probably overlaps the
CC internal NLS and contributes to a high affinity for cytoplasmic
CC NLS-containing cargo substrates. After dissociation of the
CC importin/substrate complex in the nucleus the internal
CC autohibitory NLS contributes to a low affinity for nuclear NLS-
CC containing proteins (By similarity).
CC -!- DOMAIN: The major and minor NLS binding sites are mainly involved
CC in recognition of simple or bipartite NLS motifs. Structurally
CC located within in a helical surface groove they contain several
CC conserved Trp and Asn residues of the corresponding third helices
CC (H3) of ARM repeats which mainly contribute to binding (By
CC similarity).
CC -!- SIMILARITY: Belongs to the importin alpha family.
CC -!- SIMILARITY: Contains 10 ARM repeats.
CC -!- SIMILARITY: Contains 1 IBB domain.
CC -!- CAUTION: Was termed (PubMed:9395085) importin alpha-4.
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DR EMBL; D89618; BAA20378.1; -; mRNA.
DR EMBL; Y12394; CAA73026.1; -; mRNA.
DR EMBL; AF034756; AAB87693.1; -; mRNA.
DR EMBL; AF005263; AAQ13404.1; -; mRNA.
DR EMBL; AK290528; BAF83217.1; -; mRNA.
DR EMBL; AK291000; BAF83689.1; -; mRNA.
DR EMBL; AL136301; CAH71145.1; -; Genomic_DNA.
DR EMBL; AL135901; CAH71145.1; JOINED; Genomic_DNA.
DR EMBL; AL135901; CAI40716.1; -; Genomic_DNA.
DR EMBL; AL136301; CAI40716.1; JOINED; Genomic_DNA.
DR EMBL; CH471075; EAX08837.1; -; Genomic_DNA.
DR EMBL; BC017355; AAH17355.1; -; mRNA.
DR EMBL; BC024202; AAH24202.1; -; mRNA.
DR RefSeq; NP_002258.2; NM_002267.3.
DR UniGene; Hs.527919; -.
DR ProteinModelPortal; O00505; -.
DR SMR; O00505; 11-485.
DR DIP; DIP-27586N; -.
DR IntAct; O00505; 31.
DR MINT; MINT-88920; -.
DR STRING; 9606.ENSP00000261667; -.
DR PhosphoSite; O00505; -.
DR PaxDb; O00505; -.
DR PeptideAtlas; O00505; -.
DR PRIDE; O00505; -.
DR DNASU; 3839; -.
DR Ensembl; ENST00000261667; ENSP00000261667; ENSG00000102753.
DR GeneID; 3839; -.
DR KEGG; hsa:3839; -.
DR UCSC; uc001vdj.2; human.
DR CTD; 3839; -.
DR GeneCards; GC13M050273; -.
DR HGNC; HGNC:6396; KPNA3.
DR HPA; HPA046852; -.
DR MIM; 601892; gene.
DR neXtProt; NX_O00505; -.
DR PharmGKB; PA30187; -.
DR eggNOG; COG5064; -.
DR HOGENOM; HOG000167616; -.
DR HOVERGEN; HBG001846; -.
DR InParanoid; O00505; -.
DR OMA; IANITFC; -.
DR OrthoDB; EOG7VHSWV; -.
DR PhylomeDB; O00505; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; O00505; -.
DR ChiTaRS; KPNA3; human.
DR GeneWiki; KPNA3; -.
DR GenomeRNAi; 3839; -.
DR NextBio; 15107; -.
DR PRO; PR:O00505; -.
DR Bgee; O00505; -.
DR CleanEx; HS_KPNA3; -.
DR Genevestigator; O00505; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005643; C:nuclear pore; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0008139; F:nuclear localization sequence binding; TAS:ProtInc.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0006607; P:NLS-bearing protein import into nucleus; TAS:ProtInc.
DR GO; GO:0006461; P:protein complex assembly; TAS:ProtInc.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0075732; P:viral penetration into host nucleus; IEA:UniProtKB-KW.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR002652; Importin-a_IBB.
DR InterPro; IPR024931; Importing_su_alpha.
DR Pfam; PF00514; Arm; 8.
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; Complete proteome; Cytoplasm; Host-virus interaction;
KW Nucleus; Phosphoprotein; Polymorphism; Protein transport;
KW Reference proteome; Repeat; Transport;
KW Viral penetration into host nucleus; Virus entry into host cell.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 521 Importin subunit alpha-4.
FT /FTId=PRO_0000120724.
FT DOMAIN 2 58 IBB.
FT REPEAT 66 106 ARM 1; truncated.
FT REPEAT 107 149 ARM 2.
FT REPEAT 150 194 ARM 3.
FT REPEAT 195 233 ARM 4.
FT REPEAT 234 278 ARM 5.
FT REPEAT 279 318 ARM 6.
FT REPEAT 319 360 ARM 7.
FT REPEAT 361 400 ARM 8.
FT REPEAT 401 443 ARM 9.
FT REPEAT 447 485 ARM 10; atypical.
FT REGION 137 229 NLS binding site (major) (By similarity).
FT REGION 306 394 NLS binding site (minor) (By similarity).
FT MOTIF 43 52 Nuclear localization signal (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 56 56 Phosphoserine.
FT MOD_RES 60 60 Phosphoserine.
FT VARIANT 291 291 P -> S (in dbSNP:rs1043015).
FT /FTId=VAR_014454.
FT CONFLICT 34 34 V -> M (in Ref. 2; CAA73026).
FT CONFLICT 103 103 R -> Q (in Ref. 1; BAA20378).
FT CONFLICT 154 154 V -> G (in Ref. 3; AAB87693).
FT CONFLICT 236 236 P -> T (in Ref. 3; AAB87693).
FT CONFLICT 237 237 M -> L (in Ref. 2; CAA73026).
FT CONFLICT 256 256 I -> V (in Ref. 2; CAA73026).
FT CONFLICT 259 259 L -> V (in Ref. 2; CAA73026).
SQ SEQUENCE 521 AA; 57811 MW; C4FF132C3F346B7F CRC64;
MAENPSLENH RIKSFKNKGR DVETMRRHRN EVTVELRKNK RDEHLLKKRN VPQEESLEDS
DVDADFKAQN VTLEAILQNA TSDNPVVQLS AVQAARKLLS SDRNPPIDDL IKSGILPILV
KCLERDDNPS LQFEAAWALT NIASGTSAQT QAVVQSNAVP LFLRLLRSPH QNVCEQAVWA
LGNIIGDGPQ CRDYVISLGV VKPLLSFISP 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 DEDPCLIPEA TQGGTYNFDP TANLQTKEFN F
//
ID IMA4_HUMAN Reviewed; 521 AA.
AC O00505; O00191; O43195; Q5JVM9; Q96AA7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2002, sequence version 2.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Importin subunit alpha-4;
DE AltName: Full=Importin alpha Q2;
DE Short=Qip2;
DE AltName: Full=Karyopherin subunit alpha-3;
DE AltName: Full=SRP1-gamma;
GN Name=KPNA3; Synonyms=QIP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=9154134;
RA Takeda S., Fujiwara T., Shimizu F., Kawai A., Shinomiya K., Okuno S.,
RA Ozaki K., Katagiri T., Shimada Y., Nagata M., Watanabe T.,
RA Takaichi A., Kuga Y., Suzuki M., Hishigaki H., Takahashi E., Shin S.,
RA Nakamura Y., Hirai Y.;
RT "Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene
RT that is highly homologous to genes encoding Xenopus importin, yeast
RT SRP1 and human RCH1.";
RL Cytogenet. Cell Genet. 76:87-93(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=9395085; DOI=10.1016/S0014-5793(97)01265-9;
RA Koehler M., Ansieau S., Prehn S., Leutz A., Haller H., Hartmann E.;
RT "Cloning of two novel human importin-alpha subunits and analysis of
RT the expression pattern of the importin-alpha protein family.";
RL FEBS Lett. 417:104-108(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9435235; DOI=10.1073/pnas.95.2.582;
RA Nachury M.V., Ryder U.W., Lamond A.I., Weis K.;
RT "Cloning and characterization of hSRP1 gamma, a tissue-specific
RT nuclear transport factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:582-587(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Fischer R.;
RT "Importin alpha-3, a novel variant of the small importin subunit
RT evolutionarily conserved from hydrozoa to man.";
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH INFLUENZA VIRUS NP.
RX PubMed=12740372; DOI=10.1074/jbc.M303571200;
RA Melen K., Fagerlund R., Franke J., Koehler M., Kinnunen L.,
RA Julkunen I.;
RT "Importin alpha nuclear localization signal binding sites for STAT1,
RT STAT2, and influenza A virus nucleoprotein.";
RL J. Biol. Chem. 278:28193-28200(2003).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, AND MASS
RP SPECTROMETRY.
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 [15]
RP INTERACTION WITH HIV-1 INTEGRASE.
RX PubMed=20554775; DOI=10.1128/JVI.00508-10;
RA Ao Z., Danappa Jayappa K., Wang B., Zheng Y., Kung S., Rassart E.,
RA Depping R., Kohler M., Cohen E.A., Yao X.;
RT "Importin alpha3 interacts with HIV-1 integrase and contributes to
RT HIV-1 nuclear import and replication.";
RL J. Virol. 84:8650-8663(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Functions in nuclear protein import as an adapter
CC protein for nuclear receptor KPNB1. Binds specifically and
CC directly to substrates containing either a simple or bipartite NLS
CC motif. Docking of the importin/substrate complex to the nuclear
CC pore complex (NPC) is mediated by KPNB1 through binding to
CC nucleoporin FxFG repeats and the complex is subsequently
CC translocated through the pore by an energy requiring, Ran-
CC dependent mechanism. At the nucleoplasmic side of the NPC, Ran
CC 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
CC between the cytoplasm and nucleus. In vitro, mediates the nuclear
CC import of human cytomegalovirus UL84 by recognizing a non-
CC classical NLS. Recognizes NLSs of influenza A virus nucleoprotein
CC probably through ARM repeats 7-9.
CC -!- SUBUNIT: Forms a complex with importin subunit beta-1. Interacts
CC with HIV-1 integrase; this interaction might play a role in
CC nuclear import of HIV pre-integration complex. Interacts with
CC influenza virus nucleoprotein; this interaction might play a role
CC in nuclear import of viral genome.
CC -!- INTERACTION:
CC P46527:CDKN1B; NbExp=4; IntAct=EBI-358297, EBI-519280;
CC Q8K4J6:Mkl1 (xeno); NbExp=9; IntAct=EBI-358297, EBI-8291665;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity).
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest levels in heart and
CC skeletal muscle.
CC -!- DOMAIN: Consists of an N-terminal hydrophilic region, a
CC hydrophobic central region composed of 10 repeats, and a short
CC hydrophilic C-terminus. The N-terminal hydrophilic region contains
CC the importin beta binding domain (IBB domain), which is sufficient
CC for binding importin beta and essential for nuclear protein
CC import.
CC -!- DOMAIN: The IBB domain is thought to act as an intrasteric
CC autoregulatory sequence by interacting with the internal
CC autoinhibitory NLS. Binding of KPNB1 probably overlaps the
CC internal NLS and contributes to a high affinity for cytoplasmic
CC NLS-containing cargo substrates. After dissociation of the
CC importin/substrate complex in the nucleus the internal
CC autohibitory NLS contributes to a low affinity for nuclear NLS-
CC containing proteins (By similarity).
CC -!- DOMAIN: The major and minor NLS binding sites are mainly involved
CC in recognition of simple or bipartite NLS motifs. Structurally
CC located within in a helical surface groove they contain several
CC conserved Trp and Asn residues of the corresponding third helices
CC (H3) of ARM repeats which mainly contribute to binding (By
CC similarity).
CC -!- SIMILARITY: Belongs to the importin alpha family.
CC -!- SIMILARITY: Contains 10 ARM repeats.
CC -!- SIMILARITY: Contains 1 IBB domain.
CC -!- CAUTION: Was termed (PubMed:9395085) importin alpha-4.
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DR EMBL; D89618; BAA20378.1; -; mRNA.
DR EMBL; Y12394; CAA73026.1; -; mRNA.
DR EMBL; AF034756; AAB87693.1; -; mRNA.
DR EMBL; AF005263; AAQ13404.1; -; mRNA.
DR EMBL; AK290528; BAF83217.1; -; mRNA.
DR EMBL; AK291000; BAF83689.1; -; mRNA.
DR EMBL; AL136301; CAH71145.1; -; Genomic_DNA.
DR EMBL; AL135901; CAH71145.1; JOINED; Genomic_DNA.
DR EMBL; AL135901; CAI40716.1; -; Genomic_DNA.
DR EMBL; AL136301; CAI40716.1; JOINED; Genomic_DNA.
DR EMBL; CH471075; EAX08837.1; -; Genomic_DNA.
DR EMBL; BC017355; AAH17355.1; -; mRNA.
DR EMBL; BC024202; AAH24202.1; -; mRNA.
DR RefSeq; NP_002258.2; NM_002267.3.
DR UniGene; Hs.527919; -.
DR ProteinModelPortal; O00505; -.
DR SMR; O00505; 11-485.
DR DIP; DIP-27586N; -.
DR IntAct; O00505; 31.
DR MINT; MINT-88920; -.
DR STRING; 9606.ENSP00000261667; -.
DR PhosphoSite; O00505; -.
DR PaxDb; O00505; -.
DR PeptideAtlas; O00505; -.
DR PRIDE; O00505; -.
DR DNASU; 3839; -.
DR Ensembl; ENST00000261667; ENSP00000261667; ENSG00000102753.
DR GeneID; 3839; -.
DR KEGG; hsa:3839; -.
DR UCSC; uc001vdj.2; human.
DR CTD; 3839; -.
DR GeneCards; GC13M050273; -.
DR HGNC; HGNC:6396; KPNA3.
DR HPA; HPA046852; -.
DR MIM; 601892; gene.
DR neXtProt; NX_O00505; -.
DR PharmGKB; PA30187; -.
DR eggNOG; COG5064; -.
DR HOGENOM; HOG000167616; -.
DR HOVERGEN; HBG001846; -.
DR InParanoid; O00505; -.
DR OMA; IANITFC; -.
DR OrthoDB; EOG7VHSWV; -.
DR PhylomeDB; O00505; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; O00505; -.
DR ChiTaRS; KPNA3; human.
DR GeneWiki; KPNA3; -.
DR GenomeRNAi; 3839; -.
DR NextBio; 15107; -.
DR PRO; PR:O00505; -.
DR Bgee; O00505; -.
DR CleanEx; HS_KPNA3; -.
DR Genevestigator; O00505; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005643; C:nuclear pore; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0008139; F:nuclear localization sequence binding; TAS:ProtInc.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0006607; P:NLS-bearing protein import into nucleus; TAS:ProtInc.
DR GO; GO:0006461; P:protein complex assembly; TAS:ProtInc.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0075732; P:viral penetration into host nucleus; IEA:UniProtKB-KW.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR002652; Importin-a_IBB.
DR InterPro; IPR024931; Importing_su_alpha.
DR Pfam; PF00514; Arm; 8.
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; Complete proteome; Cytoplasm; Host-virus interaction;
KW Nucleus; Phosphoprotein; Polymorphism; Protein transport;
KW Reference proteome; Repeat; Transport;
KW Viral penetration into host nucleus; Virus entry into host cell.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 521 Importin subunit alpha-4.
FT /FTId=PRO_0000120724.
FT DOMAIN 2 58 IBB.
FT REPEAT 66 106 ARM 1; truncated.
FT REPEAT 107 149 ARM 2.
FT REPEAT 150 194 ARM 3.
FT REPEAT 195 233 ARM 4.
FT REPEAT 234 278 ARM 5.
FT REPEAT 279 318 ARM 6.
FT REPEAT 319 360 ARM 7.
FT REPEAT 361 400 ARM 8.
FT REPEAT 401 443 ARM 9.
FT REPEAT 447 485 ARM 10; atypical.
FT REGION 137 229 NLS binding site (major) (By similarity).
FT REGION 306 394 NLS binding site (minor) (By similarity).
FT MOTIF 43 52 Nuclear localization signal (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 56 56 Phosphoserine.
FT MOD_RES 60 60 Phosphoserine.
FT VARIANT 291 291 P -> S (in dbSNP:rs1043015).
FT /FTId=VAR_014454.
FT CONFLICT 34 34 V -> M (in Ref. 2; CAA73026).
FT CONFLICT 103 103 R -> Q (in Ref. 1; BAA20378).
FT CONFLICT 154 154 V -> G (in Ref. 3; AAB87693).
FT CONFLICT 236 236 P -> T (in Ref. 3; AAB87693).
FT CONFLICT 237 237 M -> L (in Ref. 2; CAA73026).
FT CONFLICT 256 256 I -> V (in Ref. 2; CAA73026).
FT CONFLICT 259 259 L -> V (in Ref. 2; CAA73026).
SQ SEQUENCE 521 AA; 57811 MW; C4FF132C3F346B7F CRC64;
MAENPSLENH RIKSFKNKGR DVETMRRHRN EVTVELRKNK RDEHLLKKRN VPQEESLEDS
DVDADFKAQN VTLEAILQNA TSDNPVVQLS AVQAARKLLS SDRNPPIDDL IKSGILPILV
KCLERDDNPS LQFEAAWALT NIASGTSAQT QAVVQSNAVP LFLRLLRSPH QNVCEQAVWA
LGNIIGDGPQ CRDYVISLGV VKPLLSFISP 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 DEDPCLIPEA TQGGTYNFDP TANLQTKEFN F
//
MIM
601892
*RECORD*
*FIELD* NO
601892
*FIELD* TI
*601892 KARYOPHERIN ALPHA-3; KPNA3
;;IMPORTIN ALPHA-4
*FIELD* TX
CLONING
From a human fetal brain cDNA library, Takeda et al. (1997) isolated and
read morecharacterized a novel gene, designated KPNA3, encoding a protein highly
homologous to certain nuclear transport proteins of Xenopus and human.
The complete cDNA clone contained an open reading frame encoding 521
amino acids. The predicted amino acid sequence shows 48%, 45%, and 48%
identity with Xenopus importin, yeast SRP1, and human RCH1 (KPNA2;
600685), respectively. The similarities among these proteins suggested
that KPNA3 may be involved in the nuclear transport system.
Kohler et al. (1997) isolated a human KPNA3 cDNA. The predicted KPNA3
protein contains an N-terminal importin-beta-binding (IBB) domain, 8
armadillo repeats, and a C-terminal acidic region, all of which are
characteristics of importin-alphas. Of the known human importin-alphas,
KPNA3 shares the highest sequence identity with KPNA4 (602970). Northern
blot analysis detected a 4.6-kb KPNA3 transcript in all tissues tested.
However, expression levels varied considerably among tissues, with the
highest expression in testis and colon and the lowest expression in
liver, kidney, and peripheral blood leukocytes.
GENE FUNCTION
Using an in vitro import assay based on permeabilized HeLa cells to
study the import substrate specificity of all ubiquitously expressed
importins, including KPNA3, Kohler et al. (1999) found that all
importins tested were able to transport HNRNPK (600712) and PCAF
(602303), in addition to the standard test substrates, but only KPNA4
(601892) showed a strong preference for the import of GDP/GTP exchange
factor RCC1 (179710), which is exclusively located inside the nucleus.
When HNRNPK, PCAF, and RCC1 were offered with a competing substrate
nucleoplasmin (164040), they found that substrate binding was diminished
or abolished in some importins and retained in others.
Mammalian spermiogenesis is characterized by a unique
chromatin-remodeling process in which histones are replaced by
transition protein-1 (TNP1; 190231), TNP2 (190232), and TNP4, which are
further replaced by protamines (see 182880). Pradeepa et al. (2008)
showed that importin alpha-4 was upregulated in tetraploid and haploid
germ cells of rat testis and was required for nuclear import of Tnp2. In
contrast, import of Tnp1 occurred by passive diffusion.
MAPPING
By fluorescence in situ hybridization, Takeda et al. (1997) mapped the
KPNA3 gene to chromosome 13q14.3.
*FIELD* RF
1. Kohler, M.; Ansieau, S.; Prehn, S.; Leutz, A.; Haller, H.; Hartmann,
E.: Cloning of two novel human importin-alpha subunits and analysis
of the expression pattern of the importin-alpha protein family. FEBS
Lett. 417: 104-108, 1997.
2. Kohler, M.; Speck, C.; Christiansen, M.; Bischoff, F. R.; Prehn,
S.; Haller, H.; Gorlich, D.; Hartmann, E.: Evidence for distinct
substrate specificities of importin alpha family members in nuclear
protein import. Molec. Cell. Biol. 19: 7782-7791, 1999.
3. Pradeepa, M. M.; Manjunatha, S.; Sathish, V.; Agrawal, S.; Rao,
M. R. S.: Involvement of importin-4 in the transport of transition
protein 2 into the spermatid nucleus. Molec. Cell. Biol. 28: 4331-4341,
2008.
4. Takeda, S.; Fujiwara, T.; Shimizu, F.; Kawai, A.; Shinomiya, K.;
Okuno, S.; Ozaki, K.; Katagiri, T.; Shimada, Y.; Nagata, M.; Watanabe,
T.; Takaichi, A.; Kuga, Y.; Suzuki, M.; Hishigaki, H.; Takahashi,
E.; Shin, S.; Nakamura, Y.; Hirai, Y.: Isolation and mapping of karyopherin
alpha-3 (KPNA3), a human gene that is highly homologous to genes encoding
Xenopus importin, yeast SRP1 and human RCH1. Cytogenet. Cell Genet. 76:
87-93, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 12/8/2009
Patricia A. Hartz - updated: 11/14/2006
Patti M. Sherman - updated: 2/14/2000
*FIELD* CD
Victor A. McKusick: 6/23/1997
*FIELD* ED
mgross: 01/04/2010
terry: 12/8/2009
wwang: 11/14/2006
mgross: 2/15/2000
psherman: 2/14/2000
alopez: 8/25/1998
psherman: 8/17/1998
carol: 5/1/1998
jenny: 6/27/1997
jenny: 6/23/1997
*RECORD*
*FIELD* NO
601892
*FIELD* TI
*601892 KARYOPHERIN ALPHA-3; KPNA3
;;IMPORTIN ALPHA-4
*FIELD* TX
CLONING
From a human fetal brain cDNA library, Takeda et al. (1997) isolated and
read morecharacterized a novel gene, designated KPNA3, encoding a protein highly
homologous to certain nuclear transport proteins of Xenopus and human.
The complete cDNA clone contained an open reading frame encoding 521
amino acids. The predicted amino acid sequence shows 48%, 45%, and 48%
identity with Xenopus importin, yeast SRP1, and human RCH1 (KPNA2;
600685), respectively. The similarities among these proteins suggested
that KPNA3 may be involved in the nuclear transport system.
Kohler et al. (1997) isolated a human KPNA3 cDNA. The predicted KPNA3
protein contains an N-terminal importin-beta-binding (IBB) domain, 8
armadillo repeats, and a C-terminal acidic region, all of which are
characteristics of importin-alphas. Of the known human importin-alphas,
KPNA3 shares the highest sequence identity with KPNA4 (602970). Northern
blot analysis detected a 4.6-kb KPNA3 transcript in all tissues tested.
However, expression levels varied considerably among tissues, with the
highest expression in testis and colon and the lowest expression in
liver, kidney, and peripheral blood leukocytes.
GENE FUNCTION
Using an in vitro import assay based on permeabilized HeLa cells to
study the import substrate specificity of all ubiquitously expressed
importins, including KPNA3, Kohler et al. (1999) found that all
importins tested were able to transport HNRNPK (600712) and PCAF
(602303), in addition to the standard test substrates, but only KPNA4
(601892) showed a strong preference for the import of GDP/GTP exchange
factor RCC1 (179710), which is exclusively located inside the nucleus.
When HNRNPK, PCAF, and RCC1 were offered with a competing substrate
nucleoplasmin (164040), they found that substrate binding was diminished
or abolished in some importins and retained in others.
Mammalian spermiogenesis is characterized by a unique
chromatin-remodeling process in which histones are replaced by
transition protein-1 (TNP1; 190231), TNP2 (190232), and TNP4, which are
further replaced by protamines (see 182880). Pradeepa et al. (2008)
showed that importin alpha-4 was upregulated in tetraploid and haploid
germ cells of rat testis and was required for nuclear import of Tnp2. In
contrast, import of Tnp1 occurred by passive diffusion.
MAPPING
By fluorescence in situ hybridization, Takeda et al. (1997) mapped the
KPNA3 gene to chromosome 13q14.3.
*FIELD* RF
1. Kohler, M.; Ansieau, S.; Prehn, S.; Leutz, A.; Haller, H.; Hartmann,
E.: Cloning of two novel human importin-alpha subunits and analysis
of the expression pattern of the importin-alpha protein family. FEBS
Lett. 417: 104-108, 1997.
2. Kohler, M.; Speck, C.; Christiansen, M.; Bischoff, F. R.; Prehn,
S.; Haller, H.; Gorlich, D.; Hartmann, E.: Evidence for distinct
substrate specificities of importin alpha family members in nuclear
protein import. Molec. Cell. Biol. 19: 7782-7791, 1999.
3. Pradeepa, M. M.; Manjunatha, S.; Sathish, V.; Agrawal, S.; Rao,
M. R. S.: Involvement of importin-4 in the transport of transition
protein 2 into the spermatid nucleus. Molec. Cell. Biol. 28: 4331-4341,
2008.
4. Takeda, S.; Fujiwara, T.; Shimizu, F.; Kawai, A.; Shinomiya, K.;
Okuno, S.; Ozaki, K.; Katagiri, T.; Shimada, Y.; Nagata, M.; Watanabe,
T.; Takaichi, A.; Kuga, Y.; Suzuki, M.; Hishigaki, H.; Takahashi,
E.; Shin, S.; Nakamura, Y.; Hirai, Y.: Isolation and mapping of karyopherin
alpha-3 (KPNA3), a human gene that is highly homologous to genes encoding
Xenopus importin, yeast SRP1 and human RCH1. Cytogenet. Cell Genet. 76:
87-93, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 12/8/2009
Patricia A. Hartz - updated: 11/14/2006
Patti M. Sherman - updated: 2/14/2000
*FIELD* CD
Victor A. McKusick: 6/23/1997
*FIELD* ED
mgross: 01/04/2010
terry: 12/8/2009
wwang: 11/14/2006
mgross: 2/15/2000
psherman: 2/14/2000
alopez: 8/25/1998
psherman: 8/17/1998
carol: 5/1/1998
jenny: 6/27/1997
jenny: 6/23/1997