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O15131

- IMA6_HUMAN

UniProt

O15131 - IMA6_HUMAN

Protein

Importin subunit alpha-6

Gene

KPNA5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 2 (16 Jun 2009)
      Previous versions | rss
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    Functioni

    Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediates nuclear import of STAT1 homodimers and STAT1/STAT2 heterodimers by recognizing non-classical NLSs of STAT1 and STAT2 through ARM repeats 8-9. Recognizes influenza A virus nucleoprotein through ARM repeat 7-9 In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. protein transporter activity Source: InterPro

    GO - Biological processi

    1. cytokine-mediated signaling pathway Source: Reactome
    2. NLS-bearing protein import into nucleus Source: ProtInc

    Keywords - Biological processi

    Protein transport, Transport

    Enzyme and pathway databases

    ReactomeiREACT_115831. ISG15 antiviral mechanism.
    SignaLinkiO15131.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Importin subunit alpha-6
    Alternative name(s):
    Karyopherin subunit alpha-5
    Gene namesi
    Name:KPNA5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:6398. KPNA5.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. cytosol Source: Reactome
    3. nucleoplasm Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA30189.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 536536Importin subunit alpha-6PRO_0000120728Add
    BLAST

    Proteomic databases

    MaxQBiO15131.
    PaxDbiO15131.
    PRIDEiO15131.

    PTM databases

    PhosphoSiteiO15131.

    Expressioni

    Tissue specificityi

    Testis.

    Gene expression databases

    ArrayExpressiO15131.
    BgeeiO15131.
    CleanExiHS_KPNA5.
    GenevestigatoriO15131.

    Organism-specific databases

    HPAiCAB026464.
    HPA054037.

    Interactioni

    Subunit structurei

    Forms a complex with importin subunit beta-1.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CDKN1BP465276EBI-540602,EBI-519280

    Protein-protein interaction databases

    BioGridi110039. 6 interactions.
    DIPiDIP-33405N.
    IntActiO15131. 7 interactions.
    MINTiMINT-2860255.
    STRINGi9606.ENSP00000348704.

    Structurei

    3D structure databases

    ProteinModelPortaliO15131.
    SMRiO15131. Positions 10-506.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini2 – 5756IBBPROSITE-ProRule annotationAdd
    BLAST
    Repeati73 – 11543ARM 1; truncatedAdd
    BLAST
    Repeati116 – 15944ARM 2Add
    BLAST
    Repeati160 – 20445ARM 3Add
    BLAST
    Repeati205 – 24339ARM 4Add
    BLAST
    Repeati244 – 28845ARM 5Add
    BLAST
    Repeati289 – 32840ARM 6Add
    BLAST
    Repeati329 – 37042ARM 7Add
    BLAST
    Repeati371 – 41040ARM 8Add
    BLAST
    Repeati411 – 45343ARM 9Add
    BLAST
    Repeati457 – 50246ARM 10; atypicalAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni147 – 23993NLS binding site (major)By similarityAdd
    BLAST
    Regioni316 – 40489NLS binding site (minor)By similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi42 – 5110Nuclear localization signalBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi25 – 284Poly-Arg

    Domaini

    Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import.
    The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins By similarity.By similarity
    The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding By similarity.By similarity

    Sequence similaritiesi

    Belongs to the importin alpha family.Curated
    Contains 10 ARM repeats.PROSITE-ProRule annotation
    Contains 1 IBB domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG5064.
    HOGENOMiHOG000167616.
    HOVERGENiHBG001846.
    InParanoidiO15131.
    PhylomeDBiO15131.
    TreeFamiTF354205.

    Family and domain databases

    Gene3Di1.25.10.10. 1 hit.
    InterProiIPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR000225. Armadillo.
    IPR002652. Importin-a_IBB.
    IPR024931. Importing_su_alpha.
    [Graphical view]
    PfamiPF00514. Arm. 8 hits.
    PF01749. IBB. 1 hit.
    [Graphical view]
    PIRSFiPIRSF005673. Importin_alpha. 1 hit.
    SMARTiSM00185. ARM. 8 hits.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 1 hit.
    PROSITEiPS50176. ARM_REPEAT. 2 hits.
    PS51214. IBB. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O15131-1 [UniParc]FASTAAdd to Basket

    « Hide

    MASPGKDNYR MKSYKNKALN PQEMRRRREE EGIQLRKQKR EEQLFKRRNV    50
    YLPRNDESML ESPIQDPDIS STVPIPEEEV VTTDMVQMIF SNNADQQLTA 100
    TQKFRKLLSK EPNPPIDQVI QKPGVVQRFV KFLERNENCT LQFEAAWALT 150
    NIASGTFLHT KVVIETGAVP IFIKLLNSEH EDVQEQAVWA LGNIAGDNAE 200
    CRDFVLNCEI LPPLLELLTN SNRLTTTRNA VWALSNLCRG KNPPPNFSKV 250
    SPCLNVLSRL LFSSDPDVLA DVCWALSYLS DGPNDKIQAV IDSGVCRRLV 300
    ELLMHNDYKV VSPALRAVGN IVTGDDIQTQ VILNCSALPC LLHLLSSPKE 350
    SIRKEACWTV SNITAGNRAQ IQAVIDANIF PVLIEILQKA EFRTRKEAAW 400
    AITNATSGGT PEQIRYLVAL GCIKPLCDLL TVMDSKIVQV ALNGLENILR 450
    LGEQESKQNG IGINPYCALI EEAYGLDKIE FLQSHENQEI YQKAFDLIEH 500
    YFGVEEDDPS IVPQVDENQQ QFIFQQQEAP MDGFQL 536
    Length:536
    Mass (Da):60,349
    Last modified:June 16, 2009 - v2
    Checksum:i757D4C56D0E5661F
    GO

    Sequence cautioni

    The sequence AAH47409.1 differs from that shown. Reason: Erroneous initiation.
    The sequence CAI20500.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti67 – 671P → S in AAC51868. (PubMed:9395085)Curated
    Sequence conflicti79 – 791E → G in AAC51868. (PubMed:9395085)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti45 – 451F → L in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036245
    Natural varianti316 – 3161R → S in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036246

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF005361 mRNA. Translation: AAC51868.1.
    AK314206 mRNA. Translation: BAG36882.1.
    AL132795 Genomic DNA. Translation: CAI20500.1. Different initiation.
    CH471051 Genomic DNA. Translation: EAW48216.1.
    BC047409 mRNA. Translation: AAH47409.1. Different initiation.
    RefSeqiNP_002260.2. NM_002269.2.
    XP_005267021.1. XM_005266964.1.
    XP_006715537.1. XM_006715474.1.
    UniGeneiHs.182971.

    Genome annotation databases

    EnsembliENST00000356348; ENSP00000348704; ENSG00000196911.
    ENST00000368564; ENSP00000357552; ENSG00000196911.
    GeneIDi3841.
    KEGGihsa:3841.
    UCSCiuc003pxh.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF005361 mRNA. Translation: AAC51868.1 .
    AK314206 mRNA. Translation: BAG36882.1 .
    AL132795 Genomic DNA. Translation: CAI20500.1 . Different initiation.
    CH471051 Genomic DNA. Translation: EAW48216.1 .
    BC047409 mRNA. Translation: AAH47409.1 . Different initiation.
    RefSeqi NP_002260.2. NM_002269.2.
    XP_005267021.1. XM_005266964.1.
    XP_006715537.1. XM_006715474.1.
    UniGenei Hs.182971.

    3D structure databases

    ProteinModelPortali O15131.
    SMRi O15131. Positions 10-506.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110039. 6 interactions.
    DIPi DIP-33405N.
    IntActi O15131. 7 interactions.
    MINTi MINT-2860255.
    STRINGi 9606.ENSP00000348704.

    PTM databases

    PhosphoSitei O15131.

    Proteomic databases

    MaxQBi O15131.
    PaxDbi O15131.
    PRIDEi O15131.

    Protocols and materials databases

    DNASUi 3841.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000356348 ; ENSP00000348704 ; ENSG00000196911 .
    ENST00000368564 ; ENSP00000357552 ; ENSG00000196911 .
    GeneIDi 3841.
    KEGGi hsa:3841.
    UCSCi uc003pxh.3. human.

    Organism-specific databases

    CTDi 3841.
    GeneCardsi GC06P117048.
    HGNCi HGNC:6398. KPNA5.
    HPAi CAB026464.
    HPA054037.
    MIMi 604545. gene.
    neXtProti NX_O15131.
    PharmGKBi PA30189.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5064.
    HOGENOMi HOG000167616.
    HOVERGENi HBG001846.
    InParanoidi O15131.
    PhylomeDBi O15131.
    TreeFami TF354205.

    Enzyme and pathway databases

    Reactomei REACT_115831. ISG15 antiviral mechanism.
    SignaLinki O15131.

    Miscellaneous databases

    ChiTaRSi KPNA5. human.
    GeneWikii KPNA5.
    GenomeRNAii 3841.
    NextBioi 15115.
    PROi O15131.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15131.
    Bgeei O15131.
    CleanExi HS_KPNA5.
    Genevestigatori O15131.

    Family and domain databases

    Gene3Di 1.25.10.10. 1 hit.
    InterProi IPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR000225. Armadillo.
    IPR002652. Importin-a_IBB.
    IPR024931. Importing_su_alpha.
    [Graphical view ]
    Pfami PF00514. Arm. 8 hits.
    PF01749. IBB. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF005673. Importin_alpha. 1 hit.
    SMARTi SM00185. ARM. 8 hits.
    [Graphical view ]
    SUPFAMi SSF48371. SSF48371. 1 hit.
    PROSITEi PS50176. ARM_REPEAT. 2 hits.
    PS51214. IBB. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of two novel human importin-alpha subunits and analysis of the expression pattern of the importin-alpha protein family."
      Koehler M., Ansieau S., Prehn S., Leutz A., Haller H., Hartmann E.
      FEBS Lett. 417:104-108(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Testis.
    3. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Testis.
    6. "Importin alpha nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein."
      Melen K., Fagerlund R., Franke J., Koehler M., Kinnunen L., Julkunen I.
      J. Biol. Chem. 278:28193-28200(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH STAT1; STAT2 AND INFLUENZA VIRUS NP.
    7. "A nonconventional nuclear localization signal within the UL84 protein of human cytomegalovirus mediates nuclear import via the importin alpha/beta pathway."
      Lischka P., Sorg G., Kann M., Winkler M., Stamminger T.
      J. Virol. 77:3734-3748(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HCMV UL84.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-45 AND SER-316.

    Entry informationi

    Entry nameiIMA6_HUMAN
    AccessioniPrimary (citable) accession number: O15131
    Secondary accession number(s): B2RAI5, Q86X23
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: June 16, 2009
    Last modified: October 1, 2014
    This is version 134 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 6
      Human chromosome 6: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3