TNPO3 transportin 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TNPO3provided by HGNC
Official Full Name: transportin 3provided by HGNC
Primary source: HGNC:HGNC:17103
See related: Ensembl:ENSG00000064419 MIM:610032; AllianceGenome:HGNC:17103
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. Several protein-coding and non-coding transcript variants have been found for this gene. [provided by RefSeq, Apr 2020]
Expression: Ubiquitous expression in testis (RPKM 16.7), thyroid (RPKM 13.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q32.1

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (128954185..129056193, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (130267070..130368954, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (128594239..128695165, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

IRF5-TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study.
Title: IRF5-TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study.
Transportin-3 Facilitates Uncoating of Influenza A Virus.
Title: Transportin-3 Facilitates Uncoating of Influenza A Virus.
CRISPR/Cas9-Induced Mutagenesis Corroborates the Role of Transportin-SR2 in HIV-1 Nuclear Import.
Title: CRISPR/Cas9-Induced Mutagenesis Corroborates the Role of Transportin-SR2 in HIV-1 Nuclear Import.
TNPO3-Mediated Nuclear Entry of the Rous Sarcoma Virus Gag Protein Is Independent of the Cargo-Binding Domain.
Title: TNPO3-Mediated Nuclear Entry of the Rous Sarcoma Virus Gag Protein Is Independent of the Cargo-Binding Domain.
An Allele-Specific Functional SNP Associated with Two Systemic Autoimmune Diseases Modulates IRF5 Expression by Long-Range Chromatin Loop Formation.
Title: An Allele-Specific Functional SNP Associated with Two Systemic Autoimmune Diseases Modulates IRF5 Expression by Long-Range Chromatin Loop Formation.
our results support a model in which miR-128 is expressed in primary HIV-1 target cells, is a type I IFN response gene, and functions as a novel antiviral defense mechanism during HIV-1 infection, partly by repressing the nuclear import factors TNPO3 and by inhibiting HIV-1 replication and viral spreading
Title: Interferon-Inducible MicroRNA miR-128 Modulates HIV-1 Replication by Targeting TNPO3 mRNA.
TNPO3 mutant protein expressed in limb girdle muscular dystrophy 1F cells is the second genetic defect leading to strong HIV-1 restriction.
Title: The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection.
The crystal structure of the RSLD-TNPO3 complex revealed potential CPSF6 interaction residues, which were confirmed to mediate TNPO3 binding and CPSF6 nuclear import. Both binding and nuclear import were independent of RSLD phosphorylation, though a hyperphosphorylated mimetic mutant failed to bind TNPO3 and mislocalized to the cell cytoplasm
Title: Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6.
A novel pathogenic variant (Arg923AspfsTer17) in TNPO3 segregates with limb-girdle muscular dystrophy 1F in a Hungarian family.
Title: A novel pathogenic variant in TNPO3 in a Hungarian family with limb-girdle muscular dystrophy 1F.
Combining these results with small-angle X-ray scattering data for the complex of TRN-SR2 with truncated integrase, we propose a molecular model of the complex. We speculate that nuclear import of the PIC may proceed concurrently with the normal nuclear transport.
Title: N-terminal half of transportin SR2 interacts with HIV integrase.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal dominant limb-girdle muscular dystrophy type 1F MedGen: C1842062 OMIM: 608423 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH102793 (e-PCR)
- UniSTS:97127

MARC_10379-10380:999106921:1 (e-PCR)
- UniSTS:267124

D7S2941 (e-PCR)
- UniSTS:4265

STS-AA100521 (e-PCR)
- UniSTS:70323

D7S2931 (e-PCR)
- UniSTS:81862

D7S2544 (e-PCR), detects polymorphism
- UniSTS:66514

SHGC-53241 (e-PCR)
- UniSTS:11990

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables nuclear import signal receptor activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables small GTPase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in protein import into nucleus	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein import into nucleus	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in annulate lamellae	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in nuclear envelope	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: transportin-3

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

NCBI Reference Sequences (RefSeq)

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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

NG_023428.1 RefSeqGene

Range

5063..105989

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001191028.3 → NP_001177957.2 transportin-3 isoform 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)

AC018639, AC025594

Consensus CDS

CCDS55162.1

UniProtKB/TrEMBL

B2R6H7

Related

ENSP00000418646.1, ENST00000471234.5

Conserved Domains (2) summary

smart00913
Location:33 → 96

IBN_N; Importin-beta N-terminal domain

pfam08389
Location:120 → 248

Xpo1; Exportin 1-like protein
NM_001382216.1 → NP_001369145.1 transportin-3 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (4) encodes the longest isoform (3).

Source sequence(s)

AC018639, AC025594

Consensus CDS

CCDS94196.1

UniProtKB/TrEMBL

B2R6H7, C9J7E5

Related

ENSP00000487231.1, ENST00000627585.2

Conserved Domains (2) summary

smart00913
Location:33 → 96

IBN_N; Importin-beta N-terminal domain

pfam08389
Location:121 → 248

Xpo1; Exportin 1-like protein
NM_001382217.1 → NP_001369146.1 transportin-3 isoform 4

Status: REVIEWED

Source sequence(s)

AC018639, AC025594

UniProtKB/TrEMBL

B2R6H7

Conserved Domains (2) summary

smart00913
Location:33 → 96

IBN_N; Importin-beta N-terminal domain

pfam08389
Location:161 → 275

Xpo1; Exportin 1-like protein
NM_001382218.1 → NP_001369147.1 transportin-3 isoform 5

Status: REVIEWED

Source sequence(s)

AC018639, AC025594

UniProtKB/TrEMBL

B2R6H7

Conserved Domains (2) summary

smart00913
Location:33 → 96

IBN_N; Importin-beta N-terminal domain

pfam08389
Location:121 → 248

Xpo1; Exportin 1-like protein
NM_001382219.1 → NP_001369148.1 transportin-3 isoform 6

Status: REVIEWED

Source sequence(s)

AC018639, AC025594

UniProtKB/TrEMBL

B2R6H7

Conserved Domains (2) summary

smart00913
Location:33 → 96

IBN_N; Importin-beta N-terminal domain

pfam08389
Location:121 → 248

Xpo1; Exportin 1-like protein
NM_001382220.1 → NP_001369149.1 transportin-3 isoform 7

Status: REVIEWED

Source sequence(s)

AC018639, AC025594

UniProtKB/TrEMBL

B2R6H7

Conserved Domains (2) summary

smart00913
Location:33 → 96

IBN_N; Importin-beta N-terminal domain

pfam08389
Location:121 → 248

Xpo1; Exportin 1-like protein
NM_001382221.1 → NP_001369150.1 transportin-3 isoform 8

Status: REVIEWED

Source sequence(s)

AC018639, AC025594

UniProtKB/TrEMBL

B2R6H7
NM_001382222.1 → NP_001369151.1 transportin-3 isoform 9

Status: REVIEWED

Source sequence(s)

AC018639, AC025594

UniProtKB/TrEMBL

B2R6H7

Conserved Domains (2) summary

smart00913
Location:33 → 96

IBN_N; Importin-beta N-terminal domain

pfam08389
Location:121 → 248

Xpo1; Exportin 1-like protein
NM_001382223.1 → NP_001369152.1 transportin-3 isoform 10

Status: REVIEWED

Source sequence(s)

AC018639, AC025594

UniProtKB/TrEMBL

B2R6H7

Conserved Domains (2) summary

smart00913
Location:33 → 96

IBN_N; Importin-beta N-terminal domain

pfam08389
Location:121 → 248

Xpo1; Exportin 1-like protein
NM_012470.4 → NP_036602.1 transportin-3 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AC018639, AC025594

Consensus CDS

CCDS5809.1

UniProtKB/Swiss-Prot

A4D1K9, C9IZM0, Q6NUM1, Q96G71, Q96GU9, Q9Y3R2, Q9Y5L0

UniProtKB/TrEMBL

B2R6H7

Related

ENSP00000265388.5, ENST00000265388.10

Conserved Domains (2) summary

smart00913
Location:33 → 96

IBN_N; Importin-beta N-terminal domain

pfam08389
Location:121 → 248

Xpo1; Exportin 1-like protein

RNA

NR_034053.3 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)

AC018639, AC025594
NR_167911.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167912.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167913.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167914.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167915.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167916.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167917.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167918.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167919.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167920.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167921.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167922.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167923.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167924.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167925.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167926.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594
NR_167927.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018639, AC025594