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TNPO3 transportin 3 [ Homo sapiens (human) ]

Gene ID: 23534, updated on 6-Jan-2019

Summary

Official Symbol
TNPO3provided by HGNC
Official Full Name
transportin 3provided by HGNC
Primary source
HGNC:HGNC:17103
See related
Ensembl:ENSG00000064419 MIM:610032
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IPO12; TRNSR; LGMD1F; LGMDD2; MTR10A; TRN-SR; TRN-SR2
Summary
The protein encoded by this gene is a nuclear import receptor for serine/arginine-rich (SR) proteins such as the splicing factors SFRS1 and SFRS2. The encoded protein has also been shown to be involved in HIV-1 infection, apparently through interaction with the HIV-1 capsid protein. Two transcript variants encoding different isoforms as well as a noncoding transcript have been found for this gene.[provided by RefSeq, Jul 2010]
Expression
Ubiquitous expression in testis (RPKM 16.7), thyroid (RPKM 13.7) and 25 other tissues See more
Orthologs

Genomic context

See TNPO3 in Genome Data Viewer
Location:
7q32.1
Exon count:
24
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 7 NC_000007.14 (128954180..129055173, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (128594234..128695227, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene filamin C pseudogene Neighboring gene interferon regulatory factor 5 Neighboring gene RNA, 7SL, cytoplasmic 306, pseudogene Neighboring gene ornithine decarboxylase pseudogene Neighboring gene triosephosphate isomerase 1 pseudogene 2 Neighboring gene zinc finger protein 195-like

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Limb-girdle muscular dystrophy, type 1F
MedGen: C1842062 OMIM: 608423 GeneReviews: Not available
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NHGRI GWAS Catalog

Description
A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.
NHGRI GWA Catalog
Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX.
NHGRI GWA Catalog
Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.
NHGRI GWA Catalog
Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.
NHGRI GWA Catalog
Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.
NHGRI GWA Catalog
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
NHGRI GWA Catalog
Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.
NHGRI GWA Catalog
Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.
NHGRI GWA Catalog
Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis.
NHGRI GWA Catalog
Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis.
NHGRI GWA Catalog
GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog
Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.
NHGRI GWA Catalog
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
NHGRI GWA Catalog
Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 LAI replication requires PSIP1 (LEDGF) and TNPO3 expression as shown through CRISPR/Cas9 genome editing in primary CD4+ T cells PubMed
Knockdown of CPSF6, TNPO3, or NUP153 through siRNA leads to decreased CA and viral DNA nuclear entry PubMed
shRNA knockdown of TNPO3 renders cells less permissive to HIV-1 WT; HIV-1 is enhanced by TNPO3 PubMed
Knockdown of transportin 3 (TNPO3) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed
Knockdown of transportin 3 (TNPO3) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

Protein interactions

Protein Gene Interaction Pubs
Rev rev HIV-1 Rev disrupts both IN-TNPO3 and IN-importin alpha complexes PubMed
rev The interaction of HIV-1 Rev with RAN or NUP98 hypothetically induces the binding of Rev to transportin 3 PubMed
capsid gag TNPO3 is an export factor for both HIV-1 CA and tRNAs from the nucleus of infected cells PubMed
gag HIV-1 inhibition by TNPO3 knockdown and CPSF6-358 is a CA-dependent manner and cytoplasmic localization of CPSF6-358 is required to inhibit HIV-1 PubMed
gag TNPO3 directly interacts with in vitro-assembled HIV-1 CA-NC complexes. However, the other report that TNPO3 does not interact directly with HIV-1 CA tubes in vitro PubMed
gag Cyclophilin A stabilizes the HIV-1 CA and antagonizes TNPO3 acceleration of uncoating in vitro PubMed
gag HIV-1 N74D CA mutant remains partially dependent on TRN-SR2 for efficient infection when carrying the HIV envelope PubMed
gag Residues N57, M66, Q67, K70, N74, and T107 in the N-terminal domain of HIV-1 CA are important for the binding to CPSF6. Mutations on these residues lead to the loss or reduction of dependency on TNPO3 and RanBP2 PubMed
gag HIV-1 replication is dependent on TNPO3 expression and HIV-1 CA is the primary determinant for HIV-1 dependence upon TNPO3 PubMed
gag Replacing HIV-1 CA with the corresponding MLV CA strikingly induce the chimera viruses insensitive to TNPO3 knockdown, suggesting that CA is a dominant viral determinant of TNPO3 dependency during HIV-1 infection PubMed
gag HIV-1 CA and viral tRNAs bind to TNPO3 with greater affinity in the presence of RanGTP. The last 98 residues (amino acids 826-923) are important for CA and tRNA binding PubMed
gag RanGTP inhibits the ability of TNPO3 to stimulate the uncoating of HIV-1 CA cores PubMed
gag HIV-1 CA mutant with five amino acid substitutions (Q67H, K70R, H87P, T107N, and L111I) confers TNPO3-independence PubMed
integrase gag-pol HIV-1 IN mutant R263A/K264A significantly reduces its ability of binding to TRN-SR2 and displays a block in nuclear import and integration PubMed
gag-pol Site specific mutagenesis reveals that residues 185FKRK188 in the catalytic core domain (CCD) and 262RRK264 and K266/R269 in the C-terminal domain (CTD) in HIV-1 IN are important for its binding to TRN-SR2 PubMed
gag-pol HIV-1 IN (amino acids 62-176) interacts with TRN-SR2 (amino acids 62-334) in yeast two-hybrid screen. TRN-SR2 imports the preintegration complex into the nucleus and TRN-SR2 knockdown inhibits early steps of HIV-1 replication PubMed
gag-pol The binding between HIV-1 IN and TNPO3 is inhibited by RanGTP in a dose-dependent manner, leading to a TNPO3-RanGTP complex formation PubMed
gag-pol R400E/R402E and Q761E/R762E substitutions in TNPO3 significantly impair its binding to HIV-1 IN. However, E304R and E391R/E392R have very little effect on the IN-TNPO3 interaction PubMed
gag-pol Peptides (amino acids 170-191, 214-229, and 262-274) derived the C-terminal domain of HIV-1 IN bind to TRN-SR2 PubMed
gag-pol HIV-1 Rev disrupts both IN-TNPO3 and IN-importin alpha complexes PubMed
nucleocapsid gag TNPO3 directly interacts with in vitro-assembled HIV-1 CA-NC complexes PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein transporter activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
signaling receptor activity TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
protein import into nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein import into nucleus IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
 
nucleus IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
transportin-3
Names
imp12
importin 12
limb girdle muscular dystrophy 1F (autosomal dominant)
transportin-SR

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_023428.1 RefSeqGene

    Range
    5001..105994
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001191028.2NP_001177957.2  transportin-3 isoform 2

    See identical proteins and their annotated locations for NP_001177957.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AJ133769, AK022910, AW051835, BQ774864, DA720844
    Consensus CDS
    CCDS55162.1
    UniProtKB/Swiss-Prot
    Q9Y5L0
    UniProtKB/TrEMBL
    B3KMX1
    Related
    ENSP00000418646.1, ENST00000471234.5
    Conserved Domains (2) summary
    smart00913
    Location:3396
    IBN_N; Importin-beta N-terminal domain
    pfam08389
    Location:120248
    Xpo1; Exportin 1-like protein
  2. NM_012470.3NP_036602.1  transportin-3 isoform 1

    See identical proteins and their annotated locations for NP_036602.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AJ133769, AK022910, AW051835, BQ774864, DA720844
    Consensus CDS
    CCDS5809.1
    UniProtKB/Swiss-Prot
    Q9Y5L0
    UniProtKB/TrEMBL
    A0A024R794, B3KMX1
    Related
    ENSP00000265388.5, ENST00000265388.9
    Conserved Domains (2) summary
    smart00913
    Location:3396
    IBN_N; Importin-beta N-terminal domain
    pfam08389
    Location:120248
    Xpo1; Exportin 1-like protein

RNA

  1. NR_034053.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate exon compared to variant 1, that causes a frameshift. An in-frame downstream translational start site is available, but it is probably not used due to an upstream ORF (uORF) with a strong Kozak consensus sequence, as well as two uORFs that overlap the putative downstream start site.
    Source sequence(s)
    AJ133769, AK022910, AW051835, BQ774864, DA188633, DA720844

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p12 Primary Assembly

    Range
    128954180..129055173 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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