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O15131

- IMA6_HUMAN

UniProt

O15131 - IMA6_HUMAN

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Protein

Importin subunit alpha-6

Gene

KPNA5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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 transporter activity Source: InterPro

GO - Biological processi

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

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
Complete GO annotation...

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

BgeeiO15131.
CleanExiHS_KPNA5.
ExpressionAtlasiO15131. baseline and differential.
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. 9 interactions.
DIPiDIP-33405N.
IntActiO15131. 7 interactions.
MINTiMINT-2860255.
STRINGi9606.ENSP00000348704.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4U2XX-ray3.15D/E/F329-503[»]
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.
GeneTreeiENSGT00760000119094.
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 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MASPGKDNYR MKSYKNKALN PQEMRRRREE EGIQLRKQKR EEQLFKRRNV
60 70 80 90 100
YLPRNDESML ESPIQDPDIS STVPIPEEEV VTTDMVQMIF SNNADQQLTA
110 120 130 140 150
TQKFRKLLSK EPNPPIDQVI QKPGVVQRFV KFLERNENCT LQFEAAWALT
160 170 180 190 200
NIASGTFLHT KVVIETGAVP IFIKLLNSEH EDVQEQAVWA LGNIAGDNAE
210 220 230 240 250
CRDFVLNCEI LPPLLELLTN SNRLTTTRNA VWALSNLCRG KNPPPNFSKV
260 270 280 290 300
SPCLNVLSRL LFSSDPDVLA DVCWALSYLS DGPNDKIQAV IDSGVCRRLV
310 320 330 340 350
ELLMHNDYKV VSPALRAVGN IVTGDDIQTQ VILNCSALPC LLHLLSSPKE
360 370 380 390 400
SIRKEACWTV SNITAGNRAQ IQAVIDANIF PVLIEILQKA EFRTRKEAAW
410 420 430 440 450
AITNATSGGT PEQIRYLVAL GCIKPLCDLL TVMDSKIVQV ALNGLENILR
460 470 480 490 500
LGEQESKQNG IGINPYCALI EEAYGLDKIE FLQSHENQEI YQKAFDLIEH
510 520 530
YFGVEEDDPS IVPQVDENQQ QFIFQQQEAP MDGFQL
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

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4U2X X-ray 3.15 D/E/F 329-503 [» ]
ProteinModelPortali O15131.
SMRi O15131. Positions 10-506.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110039. 9 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.
GeneTreei ENSGT00760000119094.
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

Bgeei O15131.
CleanExi HS_KPNA5.
ExpressionAtlasi O15131. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 135 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3