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O15131 (IMA6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Importin subunit alpha-6
Alternative name(s):
Karyopherin subunit alpha-5
Gene names
Name:KPNA5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length536 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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 structure

Forms a complex with importin subunit beta-1.

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.

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.

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.

Sequence similarities

Belongs to the importin alpha family.

Contains 10 ARM repeats.

Contains 1 IBB domain.

Sequence caution

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

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

Ontologies

Keywords
   Biological processProtein transport
Transport
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DomainRepeat
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNLS-bearing protein import into nucleus

Traceable author statement Ref.1. Source: ProtInc

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionprotein transporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CDKN1BP465276EBI-540602,EBI-519280

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 536536Importin subunit alpha-6
PRO_0000120728

Regions

Domain2 – 5756IBB
Repeat73 – 11543ARM 1; truncated
Repeat116 – 15944ARM 2
Repeat160 – 20445ARM 3
Repeat205 – 24339ARM 4
Repeat244 – 28845ARM 5
Repeat289 – 32840ARM 6
Repeat329 – 37042ARM 7
Repeat371 – 41040ARM 8
Repeat411 – 45343ARM 9
Repeat457 – 50246ARM 10; atypical
Region147 – 23993NLS binding site (major) By similarity
Region316 – 40489NLS binding site (minor) By similarity
Motif42 – 5110Nuclear localization signal By similarity
Compositional bias25 – 284Poly-Arg

Natural variations

Natural variant451F → L in a breast cancer sample; somatic mutation. Ref.9
VAR_036245
Natural variant3161R → S in a breast cancer sample; somatic mutation. Ref.9
VAR_036246

Experimental info

Sequence conflict671P → S in AAC51868. Ref.1
Sequence conflict791E → G in AAC51868. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O15131 [UniParc].

Last modified June 16, 2009. Version 2.
Checksum: 757D4C56D0E5661F

FASTA53660,349
        10         20         30         40         50         60 
MASPGKDNYR MKSYKNKALN PQEMRRRREE EGIQLRKQKR EEQLFKRRNV YLPRNDESML 

        70         80         90        100        110        120 
ESPIQDPDIS STVPIPEEEV 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 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"The consensus coding sequences of human breast and colorectal cancers."
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. expand/collapse author list , 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.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-45 AND SER-316.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_002260.2. NM_002269.2.
XP_005267021.1. XM_005266964.1.
UniGeneHs.182971.

3D structure databases

ProteinModelPortalO15131.
SMRO15131. Positions 29-506.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110039. 6 interactions.
DIPDIP-33405N.
IntActO15131. 7 interactions.
MINTMINT-2860255.
STRING9606.ENSP00000348704.

PTM databases

PhosphoSiteO15131.

Proteomic databases

PaxDbO15131.
PRIDEO15131.

Protocols and materials databases

DNASU3841.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356348; ENSP00000348704; ENSG00000196911.
ENST00000368564; ENSP00000357552; ENSG00000196911.
GeneID3841.
KEGGhsa:3841.
UCSCuc003pxh.3. human.

Organism-specific databases

CTD3841.
GeneCardsGC06P117048.
HGNCHGNC:6398. KPNA5.
HPACAB026464.
HPA054037.
MIM604545. gene.
neXtProtNX_O15131.
PharmGKBPA30189.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5064.
HOGENOMHOG000167616.
HOVERGENHBG001846.
InParanoidO15131.
TreeFamTF354205.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkO15131.

Gene expression databases

ArrayExpressO15131.
BgeeO15131.
CleanExHS_KPNA5.
GenevestigatorO15131.

Family and domain databases

Gene3D1.25.10.10. 1 hit.
InterProIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000225. Armadillo.
IPR002652. Importin-a_IBB.
IPR024931. Importing_su_alpha.
[Graphical view]
PfamPF00514. Arm. 8 hits.
PF01749. IBB. 1 hit.
[Graphical view]
PIRSFPIRSF005673. Importin_alpha. 1 hit.
SMARTSM00185. ARM. 8 hits.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
PROSITEPS50176. ARM_REPEAT. 2 hits.
PS51214. IBB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSKPNA5. human.
GeneWikiKPNA5.
GenomeRNAi3841.
NextBio15115.
PROO15131.
SOURCESearch...

Entry information

Entry nameIMA6_HUMAN
AccessionPrimary (citable) accession number: O15131
Secondary accession number(s): B2RAI5, Q86X23
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 16, 2009
Last modified: March 19, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM