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Database: UniProt
Entry: IMA6_RAT
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Original site: IMA6_RAT 
ID   IMA6_RAT                Reviewed;         539 AA.
AC   Q56R16; A0A0H2UHW5;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   23-FEB-2022, sequence version 2.
DT   27-MAR-2024, entry version 108.
DE   RecName: Full=Importin subunit alpha-6 {ECO:0000305};
DE   AltName: Full=Karyopherin subunit alpha-5;
GN   Name=Kpna5 {ECO:0000312|RGD:1561324};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND IDENTIFICATION.
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 4-539.
RC   STRAIN=Sprague-Dawley; TISSUE=Testis;
RX   PubMed=16906019; DOI=10.1097/01.fpc.0000220570.82842.4d;
RA   Plant K.E., Everett D.M., Gordon Gibson G., Lyon J., Plant N.J.;
RT   "Transcriptomic and phylogenetic analysis of Kpna genes: a family of
RT   nuclear import factors modulated in xenobiotic-mediated liver growth.";
RL   Pharmacogenet. Genomics 16:647-658(2006).
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. Mediates nuclear import of STAT1 homodimers
CC       and STAT1/STAT2 heterodimers by recognizing non-classical NLSs of STAT1
CC       and STAT2 through ARM repeats 8-9 (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Forms a complex with importin subunit beta-1. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
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 (By similarity).
CC       {ECO:0000250}.
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; AABR07045039; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07045040; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AY779029; AAX07456.1; -; mRNA.
DR   RefSeq; NP_001020284.1; NM_001025113.1.
DR   RefSeq; XP_006256504.1; XM_006256442.2.
DR   AlphaFoldDB; Q56R16; -.
DR   SMR; Q56R16; -.
DR   STRING; 10116.ENSRNOP00000039571; -.
DR   PhosphoSitePlus; Q56R16; -.
DR   jPOST; Q56R16; -.
DR   PaxDb; 10116-ENSRNOP00000039571; -.
DR   Ensembl; ENSRNOT00000097623.1; ENSRNOP00000079511.1; ENSRNOG00000030109.5.
DR   Ensembl; ENSRNOT00055025517; ENSRNOP00055020819; ENSRNOG00055014885.
DR   Ensembl; ENSRNOT00060012882; ENSRNOP00060009759; ENSRNOG00060007724.
DR   GeneID; 294392; -.
DR   KEGG; rno:294392; -.
DR   UCSC; RGD:1561324; rat.
DR   AGR; RGD:1561324; -.
DR   CTD; 3841; -.
DR   RGD; 1561324; Kpna5.
DR   eggNOG; KOG0166; Eukaryota.
DR   GeneTree; ENSGT01050000244950; -.
DR   HOGENOM; CLU_018084_6_0_1; -.
DR   InParanoid; Q56R16; -.
DR   OMA; NWSTISV; -.
DR   OrthoDB; 916229at2759; -.
DR   PhylomeDB; Q56R16; -.
DR   TreeFam; TF354205; -.
DR   PRO; PR:Q56R16; -.
DR   Proteomes; UP000002494; Chromosome 20.
DR   Bgee; ENSRNOG00000030109; Expressed in jejunum and 19 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
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:0006607; P:NLS-bearing protein import into nucleus; IBA:GO_Central.
DR   Gene3D; 1.20.5.690; Importin-alpha, importin-beta-binding domain; 1.
DR   Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 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   PANTHER; PTHR23316; IMPORTIN ALPHA; 1.
DR   PANTHER; PTHR23316:SF10; IMPORTIN SUBUNIT ALPHA-6; 1.
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; ARM repeat; 1.
DR   PROSITE; PS50176; ARM_REPEAT; 2.
DR   PROSITE; PS51214; IBB; 1.
PE   2: Evidence at transcript level;
KW   Cytoplasm; Protein transport; Reference proteome; Repeat; Transport.
FT   CHAIN           1..539
FT                   /note="Importin subunit alpha-6"
FT                   /id="PRO_0000326083"
FT   DOMAIN          1..60
FT                   /note="IBB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00561"
FT   REPEAT          76..118
FT                   /note="ARM 1; truncated"
FT   REPEAT          119..162
FT                   /note="ARM 2"
FT   REPEAT          163..207
FT                   /note="ARM 3"
FT   REPEAT          208..246
FT                   /note="ARM 4"
FT   REPEAT          247..291
FT                   /note="ARM 5"
FT   REPEAT          292..331
FT                   /note="ARM 6"
FT   REPEAT          332..373
FT                   /note="ARM 7"
FT   REPEAT          374..413
FT                   /note="ARM 8"
FT   REPEAT          414..456
FT                   /note="ARM 9"
FT   REPEAT          460..505
FT                   /note="ARM 10; atypical"
FT   REGION          1..38
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          150..242
FT                   /note="NLS binding site (major)"
FT                   /evidence="ECO:0000250"
FT   REGION          319..407
FT                   /note="NLS binding site (minor)"
FT                   /evidence="ECO:0000250"
FT   MOTIF           45..54
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        22..38
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   539 AA;  60632 MW;  E802BED6C320FC2A CRC64;
     MDSMASPGKD NYRMKSYKNK ALNPQEMRRR REEEGIQLRK QKREEQLFKR RNVSLPRNDD
     CMLESPIQDP DVSSTVPIPE EDMITADMIQ MIFSNNAEQQ LTATQKFRKL LSKEPNPPID
     QVIQKPGVVQ RFVKFLERNE NCTLQFEAAW ALTNIASGTF LHTKVVIETG AVPIFIRLLT
     SEHEDVQEQA VWALGNIAGD NAECRDFVLN CEILPPLLEL LTNSNRLTTT RNAVWALSNL
     CRGKNPPPNF SKVSPCLNVL SRLLFSSDPD VLADVCWALS YLSDGPNDKI QVVIDSGVCR
     RLVELLMHND YKVVSPALRA VGNIVTGDDI QTQVILNCSA LPCLLHLLGS PKESVRKEAC
     WTISNITAGN RMQIQAVIDG SIFPVLIEVL QKAEFRTRKE AAWAITNATS GGAPEQIRYL
     VTLGCIKPLC DLLTVMDSKI VQVALNGLEN ILRLGERESK QNGVGINPYC ALIEEAYGLD
     KIEFLQSHEN QEIYQKAFDL IERYFGVEED DPSLVPQVDE QQRQFLFQQC EAPGEGFQL
//
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