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Reviewed, UniProtKB/Swiss-Prot O15131 (IMA5_HUMAN)

Last modified July 7, 2009. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

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

Protein attributes

Sequence length536 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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.

Ontologies

Keywords
   Biological processProtein transport
Transport
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DomainRepeat
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processNLS-bearing substrate import into nucleus Ref.1

Traceable author statement. Source: ProtInc

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear pore

Inferred from electronic annotation. Source: InterPro

   Molecular functionprotein binding

Inferred from physical interaction. Source: IntAct

protein transporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

P069141EBI-540602,EBI-1555692From a different organism.
CDKN1BP465273EBI-540602,EBI-519280

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 536536Importin subunit alpha-6
PRO_0000120728

Regions

Domain1 – 5757IBB
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
O15131-1 [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: 9395085] [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: 14702039] [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: 14574404] [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: 15489334] [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: 12740372] [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: 12610148] [Abstract]
Cited for: INTERACTION WITH HCMV UL84.
[8]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 16959974] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-45 AND SER-316.

Cross-references

Sequence databases

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.
IPIIPI00413214.
RefSeqNP_002260.2.
UniGeneHs.182971

3D structure databases

HSSPHSSP built from PDB template 1BK5 based on UniProtKB Q02821.
SMRO15131. Positions 82-507.
ModBaseSearch...

Protein-protein interaction databases

IntActO15131. 4 interactions.

Proteomic databases

PRIDEO15131.

Genome annotation databases

EnsemblENSG00000196911. Homo sapiens. [Contig view]
GeneID3841.
KEGGhsa:3841.

Organism-specific databases

GeneCardsGC06P117109.
HGNCHGNC:6398. KPNA5.
MIM604545. gene.
PharmGKBPA30189.
GenAtlasSearch...

Phylogenomic databases

HOVERGENO15131.

Gene expression databases

ArrayExpressO15131.
BgeeO15131.
CleanExHS_KPNA5.
GermOnlineENSG00000196911. Homo sapiens.

Family and domain databases

InterProIPR011989. ARM-like.
IPR000225. Armadillo.
IPR002652. Importin-a-like_IBB-bd.
[Graphical view]
Gene3DG3DSA:1.25.10.10. ARM-like. 1 hit.
G3DSA:1.20.5.690. Importin-a-like_IBB-bd. 1 hit.
PfamPF00514. Arm. 8 hits.
PF01749. IBB. 1 hit.
[Graphical view]
SMARTSM00185. ARM. 8 hits.
[Graphical view]
PROSITEPS50176. ARM_REPEAT. 2 hits.
PS51214. IBB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio15115.
SOURCESearch...

Entry information

Entry nameIMA5_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: July 7, 2009
This is version 83 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 6

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents