Reviewed, UniProtKB/Swiss-Prot O00505 (IMA3_HUMAN)

Names and origin

Protein names

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

Gene names

Name:	KPNA3
Synonyms:	QIP2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	521 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
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	Ref.2 termed this protein 'importin alpha-4'.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	NLS-bearing substrate import into nucleus Ref.3 Traceable author statement. Source: ProtInc protein complex assembly Ref.3 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear pore Ref.1 Traceable author statement. Source: ProtInc
Molecular function	nuclear localization sequence binding Ref.3 Traceable author statement. Source: ProtInc protein 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
	P06914	1	EBI-358297,EBI-1555692	From a different organism.
ARRB1	P49407	1	EBI-358297,EBI-743313
ARRB2	P32121	1	EBI-358297,EBI-714559
CDKN1B	P46527	1	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	1 – 58	58	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.7
	Modified residue	60	1	Phosphoserine Ref.7 Ref.6 Ref.8
Natural variations
	Natural variant	291	1	P → S: dbSNP rs1043015.		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)
	O00505-1 [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: 9154134] [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: 9395085] [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: 9435235] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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: Muscle.
[5]	"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 INFLUENZA VIRUS NP.
[6]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, MASS SPECTROMETRY.
[8]	"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: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, MASS SPECTROMETRY. Tissue: Liver.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D89618 mRNA. Translation: BAA20378.1. Y12394 mRNA. Translation: CAA73026.1. AF034756 mRNA. Translation: AAB87693.1. BC017355 mRNA. Translation: AAH17355.1. BC024202 mRNA. Translation: AAH24202.1.
IPI	IPI00299033.
RefSeq	NP_002258.2.
UniGene	Hs.527919
3D structure databases
HSSP	HSSP built from PDB template 1QGK based on UniProtKB P52292.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:27586N.
IntAct	O00505. 9 interactions.
STRING	O00505.
PTM databases
PhosphoSite	O00505.
Proteomic databases
PeptideAtlas	O00505.
PRIDE	O00505.
Genome annotation databases
Ensembl	ENST00000261667; ENSP00000261667; ENSG00000102753; Homo sapiens. [Genome view] ENST00000436760; ENSP00000393869; ENSG00000102753; Homo sapiens. [Genome view] ENST00000457886; ENSP00000402768; ENSG00000102753; Homo sapiens. [Genome view]
GeneID	3839.
KEGG	hsa:3839.
UCSC	uc001vdj.1. human.
Organism-specific databases
CTD	3839.
GeneCards	GC13M049172.
H-InvDB	HIX0011319.
HGNC	HGNC:6396. KPNA3.
MIM	601892. gene.
PharmGKB	PA30187.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O00505.
HOVERGEN	O00505.
OMA	PNLLTHP.
Gene expression databases
ArrayExpress	O00505.
Bgee	O00505.
CleanEx	HS_KPNA3.
Genevestigator	O00505.
GermOnline	ENSG00000102753. Homo sapiens.
Family and domain databases
InterPro	IPR011989. ARM-like. IPR000225. Armadillo. IPR002652. Importin-a-like_IBB-bd. [Graphical view]
Gene3D	G3DSA:1.25.10.10. ARM-like. 1 hit. G3DSA:1.20.5.690. Importin-a-like_IBB-bd. 1 hit.
Pfam	PF00514. Arm. 8 hits. PF01749. IBB. 1 hit. [Graphical view]
SMART	SM00185. ARM. 8 hits. [Graphical view]
PROSITE	PS50176. ARM_REPEAT. 3 hits. PS51214. IBB. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	15107.
SOURCE	Search...

Entry information

Entry name

IMA3_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2002
Last modified:	November 3, 2009
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.