O00505 (IMA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Importin subunit alpha-3

Alternative name(s):
Importin alpha Q2
Short name=Qip2
Karyopherin subunit alpha-3
SRP1-gamma

Gene names

Name:	KPNA3
Synonyms:	QIP2

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	521 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. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. Recognizes NLSs of influenza A virus nucleoprotein probably through ARM repeats 7-9.
Subunit structure	Forms a complex with importin subunit beta-1. Interacts with HIV-1 integrase; this interaction might play a role in nuclear import of HIV pre-integration complex. Interacts with influenza virus nucleoprotein; this interaction might play a role in nuclear import of viral genome. Ref.9 Ref.14
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
Tissue specificity	Ubiquitous. Highest levels in heart and skeletal muscle.
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.
Caution	Was termed (Ref.2) importin alpha-4.

Ontologies

Keywords
Biological process	Host-virus interaction Protein transport Transport Viral penetration into host nucleus Virus entry into host cell
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NLS-bearing substrate import into nucleus Traceable author statement Ref.3. Source: ProtInc cytokine-mediated signaling pathway Traceable author statement. Source: Reactome protein complex assembly Traceable author statement Ref.3. Source: ProtInc viral entry into host cell Inferred from electronic annotation. Source: UniProtKB-KW viral penetration into host nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nuclear pore Traceable author statement Ref.1. Source: ProtInc nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	nuclear localization sequence binding Traceable author statement Ref.3. Source: ProtInc protein transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDKN1B	P46527	4	EBI-358297,EBI-519280

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 521	521	Importin subunit alpha-3		PRO_0000120724
Regions
	Domain	2 – 58	57	IBB
	Repeat	66 – 106	41	ARM 1; truncated
	Repeat	107 – 149	43	ARM 2
	Repeat	150 – 194	45	ARM 3
	Repeat	195 – 233	39	ARM 4
	Repeat	234 – 278	45	ARM 5
	Repeat	279 – 318	40	ARM 6
	Repeat	319 – 360	42	ARM 7
	Repeat	361 – 400	40	ARM 8
	Repeat	401 – 443	43	ARM 9
	Repeat	447 – 485	39	ARM 10; atypical
	Region	137 – 229	93	NLS binding site (major) By similarity
	Region	306 – 394	89	NLS binding site (minor) By similarity
	Motif	43 – 52	10	Nuclear localization signal By similarity
Amino acid modifications
	Modified residue	56	1	Phosphoserine Ref.13 Ref.15
	Modified residue	60	1	Phosphoserine Ref.10 Ref.12 Ref.13 Ref.15 Ref.17
Natural variations
	Natural variant	291	1	P → S. Corresponds to variant rs1043015 [ dbSNP | Ensembl ].		VAR_014454
Experimental info
	Sequence conflict	34	1	V → M in CAA73026. Ref.2
	Sequence conflict	103	1	R → Q in BAA20378. Ref.1
	Sequence conflict	154	1	V → G in AAB87693. Ref.3
	Sequence conflict	236	1	P → T in AAB87693. Ref.3
	Sequence conflict	237	1	M → L in CAA73026. Ref.2
	Sequence conflict	256	1	I → V in CAA73026. Ref.2
	Sequence conflict	259	1	L → V in CAA73026. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O00505 [UniParc]. Last modified January 23, 2002. Version 2. Checksum: C4FF132C3F346B7F	FASTA	521	57,811
	10 20 30 40 50 60 MAENPSLENH RIKSFKNKGR DVETMRRHRN EVTVELRKNK RDEHLLKKRN VPQEESLEDS 70 80 90 100 110 120 DVDADFKAQN VTLEAILQNA TSDNPVVQLS AVQAARKLLS SDRNPPIDDL IKSGILPILV 130 140 150 160 170 180 KCLERDDNPS LQFEAAWALT NIASGTSAQT QAVVQSNAVP LFLRLLRSPH QNVCEQAVWA 190 200 210 220 230 240 LGNIIGDGPQ CRDYVISLGV VKPLLSFISP SIPITFLRNV TWVIVNLCRN KDPPPPMETV 250 260 270 280 290 300 QEILPALCVL IYHTDINILV DTVWALSYLT DGGNEQIQMV IDSGVVPFLV PLLSHQEVKV 310 320 330 340 350 360 QTAALRAVGN IVTGTDEQTQ VVLNCDVLSH FPNLLSHPKE KINKEAVWFL SNITAGNQQQ 370 380 390 400 410 420 VQAVIDAGLI PMIIHQLAKG DFGTQKEAAW AISNLTISGR KDQVEYLVQQ NVIPPFCNLL 430 440 450 460 470 480 SVKDSQVVQV VLDGLKNILI MAGDEASTIA EIIEECGGLE KIEVLQQHEN EDIYKLAFEI 490 500 510 520 IDQYFSGDDI DEDPCLIPEA TQGGTYNFDP TANLQTKEFN F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene that is highly homologous to genes encoding Xenopus importin, yeast SRP1 and human RCH1." Takeda S., Fujiwara T., Shimizu F., Kawai A., Shinomiya K., Okuno S., Ozaki K., Katagiri T., Shimada Y., Nagata M., Watanabe T., Takaichi A., Kuga Y., Suzuki M., Hishigaki H., Takahashi E., Shin S., Nakamura Y., Hirai Y. Cytogenet. Cell Genet. 76:87-93(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	"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]. Tissue: Lung.
[3]	"Cloning and characterization of hSRP1 gamma, a tissue-specific nuclear transport factor." Nachury M.V., Ryder U.W., Lamond A.I., Weis K. Proc. Natl. Acad. Sci. U.S.A. 95:582-587(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Importin alpha-3, a novel variant of the small importin subunit evolutionarily conserved from hydrozoa to man." Fischer R. Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"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: Brain.
[6]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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].
[8]	"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: Muscle.
[9]	"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 INFLUENZA VIRUS NP.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, MASS SPECTROMETRY. Tissue: Liver.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Importin alpha3 interacts with HIV-1 integrase and contributes to HIV-1 nuclear import and replication." Ao Z., Danappa Jayappa K., Wang B., Zheng Y., Kung S., Rassart E., Depping R., Kohler M., Cohen E.A., Yao X. J. Virol. 84:8650-8663(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV-1 INTEGRASE.
[15]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"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].
[17]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D89618 mRNA. Translation: BAA20378.1. Y12394 mRNA. Translation: CAA73026.1. AF034756 mRNA. Translation: AAB87693.1. AF005263 mRNA. Translation: AAQ13404.1. AK290528 mRNA. Translation: BAF83217.1. AK291000 mRNA. Translation: BAF83689.1. AL136301, AL135901 Genomic DNA. Translation: CAH71145.1. AL135901, AL136301 Genomic DNA. Translation: CAI40716.1. CH471075 Genomic DNA. Translation: EAX08837.1. BC017355 mRNA. Translation: AAH17355.1. BC024202 mRNA. Translation: AAH24202.1.
IPI	IPI00299033.
RefSeq	NP_002258.2. NM_002267.3.
UniGene	Hs.527919.
3D structure databases
ProteinModelPortal	O00505.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27586N.
IntAct	O00505. 24 interactions.
MINT	MINT-88920.
STRING	9606.ENSP00000261667.
PTM databases
PhosphoSite	O00505.
Proteomic databases
PaxDb	O00505.
PeptideAtlas	O00505.
PRIDE	O00505.
Protocols and materials databases
DNASU	3839.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261667; ENSP00000261667; ENSG00000102753.
GeneID	3839.
KEGG	hsa:3839.
UCSC	uc001vdj.2. human.
Organism-specific databases
CTD	3839.
GeneCards	GC13M050273.
HGNC	HGNC:6396. KPNA3.
HPA	HPA046852.
MIM	601892. gene.
neXtProt	NX_O00505.
PharmGKB	PA30187.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5064.
HOGENOM	HOG000167616.
HOVERGEN	HBG001846.
InParanoid	O00505.
OMA	TQGGTFN.
OrthoDB	EOG48GW2Z.
PhylomeDB	O00505.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	O00505.
Bgee	O00505.
CleanEx	HS_KPNA3.
Genevestigator	O00505.
GermOnline	ENSG00000102753. 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. 3 hits. PS51214. IBB. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	KPNA3. human.
GenomeRNAi	3839.
NextBio	15107.
SOURCE	Search...

Entry information

Entry name

IMA3_HUMAN

Accession

Primary (citable) accession number: O00505
Secondary accession number(s): O00191 , O43195, Q5JVM9, Q96AA7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2002
Last modified:	May 1, 2013
This is version 137 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.