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Reviewed, UniProtKB/Swiss-Prot O00505 (IMA3_HUMAN)

Last modified November 3, 2009. Version 102. 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-3
Alternative name(s):
    Karyopherin subunit alpha-3
    SRP1-gamma
    Importin alpha Q2
      Short name=Qip2
Gene names
Name: KPNA3
Synonyms: QIP2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length521 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. 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 processProtein transport
Transport
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainRepeat
   PTMPhosphoprotein
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processNLS-bearing substrate import into nucleus Ref.3

Traceable author statement. Source: ProtInc

protein complex assembly Ref.3

Traceable author statement. Source: ProtInc

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear pore Ref.1

Traceable author statement. Source: ProtInc

   Molecular functionnuclear 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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 521521Importin subunit alpha-3
PRO_0000120724

Regions

Domain1 – 5858IBB
Repeat66 – 10641ARM 1; truncated
Repeat107 – 14943ARM 2
Repeat150 – 19445ARM 3
Repeat195 – 23339ARM 4
Repeat234 – 27845ARM 5
Repeat279 – 31840ARM 6
Repeat319 – 36042ARM 7
Repeat361 – 40040ARM 8
Repeat401 – 44343ARM 9
Repeat447 – 48539ARM 10; atypical
Region137 – 22993NLS binding site (major) By similarity
Region306 – 39489NLS binding site (minor) By similarity
Motif43 – 5210Nuclear localization signal By similarity

Amino acid modifications

Modified residue561Phosphoserine Ref.7
Modified residue601Phosphoserine Ref.7 Ref.6 Ref.8

Natural variations

Natural variant2911P → S: dbSNP rs1043015.
VAR_014454

Experimental info

Sequence conflict341V → M in CAA73026. Ref.2
Sequence conflict1031R → Q in BAA20378. Ref.1
Sequence conflict1541V → G in AAB87693. Ref.3
Sequence conflict2361P → T in AAB87693. Ref.3
Sequence conflict2371M → L in CAA73026. Ref.2
Sequence conflict2561I → V in CAA73026. Ref.2
Sequence conflict2591L → V in CAA73026. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O00505-1 [UniParc].

Last modified January 23, 2002. Version 2.
Checksum: C4FF132C3F346B7F

FASTA52157,811
        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 

« Hide

References

« Hide '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

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.
IPIIPI00299033.
RefSeqNP_002258.2.
UniGeneHs.527919

3D structure databases

HSSPHSSP built from PDB template 1QGK based on UniProtKB P52292.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:27586N.
IntActO00505. 9 interactions.
STRINGO00505.

PTM databases

PhosphoSiteO00505.

Proteomic databases

PeptideAtlasO00505.
PRIDEO00505.

Genome annotation databases

EnsemblENST00000261667; ENSP00000261667; ENSG00000102753; Homo sapiens. [Genome view]
ENST00000436760; ENSP00000393869; ENSG00000102753; Homo sapiens. [Genome view]
ENST00000457886; ENSP00000402768; ENSG00000102753; Homo sapiens. [Genome view]
GeneID3839.
KEGGhsa:3839.
UCSCuc001vdj.1. human.

Organism-specific databases

CTD3839.
GeneCardsGC13M049172.
H-InvDBHIX0011319.
HGNCHGNC:6396. KPNA3.
MIM601892. gene.
PharmGKBPA30187.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO00505.
HOVERGENO00505.
OMAPNLLTHP.

Gene expression databases

ArrayExpressO00505.
BgeeO00505.
CleanExHS_KPNA3.
GenevestigatorO00505.
GermOnlineENSG00000102753. 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. 3 hits.
PS51214. IBB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio15107.
SOURCESearch...

Entry information

Entry nameIMA3_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Human chromosome 13: entries, gene names and cross-references to MIM

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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