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UniProtKB/Swiss-Prot entry O15131


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name IMA5_HUMAN
Primary accession number O15131
Secondary accession number Q86X23
Integrated into Swiss-Prot on July 15, 1998
Sequence was last modified on January 1, 1998 (Sequence version 1)
Annotations were last modified on    September 2, 2008 (Entry version 76)
Name and origin of the protein
Protein name Importin subunit alpha-6
Synonym Karyopherin subunit alpha-5
Gene name
Name: KPNA5
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1016/S0014-5793(97)01265-9; PubMed=9395085 [NCBI, ExPASy, EBI, Israel, Japan]
Koehler 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]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature02055; PubMed=14574404 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"The DNA sequence and analysis of human chromosome 6.";
Nature 425:805-811(2003).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Testis;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
INTERACTION WITH STAT1; STAT2 AND INFLUENZA VIRUS NP.
DOI=10.1074/jbc.M303571200; PubMed=12740372 [NCBI, ExPASy, EBI, Israel, Japan]
Melen K., Fagerlund R., Franke J., Koehler M., Kinnunen L., Julkunen I.;
"Importin alpha nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein.";
J. Biol. Chem. 278:28193-28200(2003).
[5]
INTERACTION WITH HCMV UL84.
DOI=10.1128/JVI.77.6.3734-3748.2003; PubMed=12610148 [NCBI, ExPASy, EBI, Israel, Japan]
Lischka P., Sorg G., Kann M., Winkler M., Stamminger T.;
"A nonconventional nuclear localization signal within the UL84 protein of human cytomegalovirus mediates nuclear import via the importin alpha/beta pathway.";
J. Virol. 77:3734-3748(2003).
[6]
VARIANTS [LARGE SCALE ANALYSIS] LEU-45 AND SER-316.
DOI=10.1126/science.1133427; PubMed=16959974 [NCBI, ExPASy, EBI, Israel, Japan]
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal cancers.";
Science 314:268-274(2006).
Comments
  • FUNCTION: 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.
  • SUBUNIT: Forms a complex with importin subunit beta-1.
  • INTERACTION:
    P06914:- (xeno); NbExp=1; IntAct=EBI-540602, EBI-1555692;
    P46527:CDKN1B; NbExp=3; IntAct=EBI-540602, EBI-519280;
  • SUBCELLULAR LOCATION: Cytoplasm.
  • TISSUE SPECIFICITY: Testis.
  • DOMAIN: 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.
  • DOMAIN: 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).
  • DOMAIN: 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).
  • SIMILARITY: Belongs to the importin alpha family.
  • SIMILARITY: Contains 10 ARM repeats.
  • SIMILARITY: Contains 1 IBB domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF005361; AAC51868.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL132795; CAI20500.1; ALT_INIT; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC047409; AAH47409.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_002260.2; -.
UniGene Hs.182971
3D structure databases
HSSP Q02821; 1BK5. [HSSP ENTRY / PDB]
SMR O15131; 82-507.
ModBase O15131.
Protein-protein interaction databases
IntAct O15131; -.
Organism-specific databases
HGNC HGNC:6398; KPNA5.
GenAtlas KPNA5.
MIM 604545; gene. [NCBI / EBI]
PharmGKB PA30189; -.
GeneCards O15131.
Gene expression databases
ArrayExpress O15131; -.
CleanEx HS_KPNA5; -.
GermOnline ENSG00000196911; Homo sapiens.
Ontologies
GO
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0006607; Biological process: NLS-bearing substrate import into nucleus (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR011989; ARM-like.
IPR000225; Armadillo.
IPR002652; Importin-a-like_IBB-bd.
Graphical view of domain structure.
Gene3D G3DSA:1.25.10.10; ARM-like; 1.
G3DSA:1.20.5.690; Importin-a-like_IBB-bd; 1.
Pfam PF00514; Arm; 8.
PF01749; IBB; 1.
Pfam graphical view of domain structure.
SMART SM00185; ARM; 8.
SMART graphical view of domain structure.
PROSITE PS50176; ARM_REPEAT; 2.
PS51214; IBB; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS O15131.
Genome annotation databases
Ensembl ENSG00000196911; Homo sapiens. [Contig view]
GeneID 3841; -.
KEGG hsa:3841; -.
Phylogenomic databases
HOVERGEN O15131; -.
Other
SOURCE KPNA5; Homo sapiens.
ProtoNet O15131.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Cytoplasm; Polymorphism; Protein transport; Repeat; Transport.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   536  536     Importin subunit alpha-6. PRO_0000120728
DOMAIN   1    57  57     IBB. 
REPEAT   73   115  43     ARM 1; truncated. 
REPEAT   116   159  44     ARM 2. 
REPEAT   160   204  45     ARM 3. 
REPEAT   205   243  39     ARM 4. 
REPEAT   244   288  45     ARM 5. 
REPEAT   289   328  40     ARM 6. 
REPEAT   329   370  42     ARM 7. 
REPEAT   371   410  40     ARM 8. 
REPEAT   411   453  43     ARM 9. 
REPEAT   457   502  46     ARM 10; atypical. 
REGION   147   239  93     NLS binding site (major) (By similarity). 
REGION   316   404  89     NLS binding site (minor) (By similarity). 
MOTIF   42    51  10     Nuclear localization signal (By similarity). 
COMPBIAS   25    28  4     Poly-Arg. 
VARIANT   45    45  1     F -> L (in a breast cancer sample; somatic mutation). VAR_036245 
VARIANT   316   316  1     R -> S (in a breast cancer sample; somatic mutation). VAR_036246 [3D]
Sequence information
Length: 536 AA [This is the length of the unprocessed precursor] Molecular weight: 60267 Da [This is the MW of the unprocessed precursor] CRC64: 4E880B1FAD2A420E [This is a checksum on the sequence]
        10         20         30         40         50         60 
MASPGKDNYR MKSYKNKALN PQEMRRRREE EGIQLRKQKR EEQLFKRRNV YLPRNDESML 

        70         80         90        100        110        120 
ESPIQDSDIS STVPIPEEGV VTTDMVQMIF SNNADQQLTA TQKFRKLLSK EPNPPIDQVI 

       130        140        150        160        170        180 
QKPGVVQRFV KFLERNENCT LQFEAAWALT NIASGTFLHT KVVIETGAVP IFIKLLNSEH 

       190        200        210        220        230        240 
EDVQEQAVWA LGNIAGDNAE CRDFVLNCEI LPPLLELLTN SNRLTTTRNA VWALSNLCRG 

       250        260        270        280        290        300 
KNPPPNFSKV SPCLNVLSRL LFSSDPDVLA DVCWALSYLS DGPNDKIQAV IDSGVCRRLV 

       310        320        330        340        350        360 
ELLMHNDYKV VSPALRAVGN IVTGDDIQTQ VILNCSALPC LLHLLSSPKE SIRKEACWTV 

       370        380        390        400        410        420 
SNITAGNRAQ IQAVIDANIF PVLIEILQKA EFRTRKEAAW AITNATSGGT PEQIRYLVAL 

       430        440        450        460        470        480 
GCIKPLCDLL TVMDSKIVQV ALNGLENILR LGEQESKQNG IGINPYCALI EEAYGLDKIE 

       490        500        510        520        530 
FLQSHENQEI YQKAFDLIEH YFGVEEDDPS IVPQVDENQQ QFIFQQQEAP MDGFQL 

O15131 in FASTA format

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