O15131 (IMA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Importin subunit alpha-6

Alternative name(s):
Karyopherin subunit alpha-5

Gene names

Name:

KPNA5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	536 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Protein transport Transport
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NLS-bearing substrate import into nucleus Traceable author statement Ref.1. Source: ProtInc cytokine-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	protein transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDKN1B	P46527	6	EBI-540602,EBI-519280

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 536	536	Importin subunit alpha-6		PRO_0000120728
Regions
	Domain	2 – 57	56	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
	Compositional bias	25 – 28	4	Poly-Arg
Natural variations
	Natural variant	45	1	F → L in a breast cancer sample; somatic mutation. Ref.9		VAR_036245
	Natural variant	316	1	R → S in a breast cancer sample; somatic mutation. Ref.9		VAR_036246
Experimental info
	Sequence conflict	67	1	P → S in AAC51868. Ref.1
	Sequence conflict	79	1	E → G in AAC51868. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O15131 [UniParc]. Last modified June 16, 2009. Version 2. Checksum: 757D4C56D0E5661F	FASTA	536	60,349
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	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. , 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. , 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.
IPI	IPI00413214.
RefSeq	NP_002260.2. NM_002269.2.
UniGene	Hs.182971.
3D structure databases
ProteinModelPortal	O15131.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-33405N.
IntAct	O15131. 7 interactions.
MINT	MINT-2860255.
STRING	9606.ENSP00000348704.
PTM databases
PhosphoSite	O15131.
Proteomic databases
PaxDb	O15131.
PRIDE	O15131.
Protocols and materials databases
DNASU	3841.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000356348; ENSP00000348704; ENSG00000196911. ENST00000368564; ENSP00000357552; ENSG00000196911.
GeneID	3841.
KEGG	hsa:3841.
UCSC	uc003pxh.3. human.
Organism-specific databases
CTD	3841.
GeneCards	GC06P117048.
HGNC	HGNC:6398. KPNA5.
HPA	CAB026464.
MIM	604545. gene.
neXtProt	NX_O15131.
PharmGKB	PA30189.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5064.
HOGENOM	HOG000167616.
HOVERGEN	HBG001846.
InParanoid	O15131.
OrthoDB	EOG4NP739.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	O15131.
Bgee	O15131.
CleanEx	HS_KPNA5.
Genevestigator	O15131.
GermOnline	ENSG00000196911. Homo sapiens.
Family and domain databases
Gene3D	1.25.10.10. 1 hit.
InterPro	IPR011989. ARM-like. IPR016024. ARM-type_fold. IPR000225. Armadillo. IPR002652. Importin-a_IBB. IPR024931. Importing_su_alpha. [Graphical view]
Pfam	PF00514. Arm. 8 hits. PF01749. IBB. 1 hit. [Graphical view]
PIRSF	PIRSF005673. Importin_alpha. 1 hit.
SMART	SM00185. ARM. 8 hits. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit.
PROSITE	PS50176. ARM_REPEAT. 2 hits. PS51214. IBB. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	KPNA5. human.
GenomeRNAi	3841.
NextBio	15115.
SOURCE	Search...

Entry information

Entry name

IMA5_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.