Transportin-1 (or Importin-β 2) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''TNPO1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
This protein is a
karyopherin
Karyopherins are protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme c ...
which interacts with
nuclear localization sequence
A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines ...
to target nuclear proteins to the nucleus. The classical karyopherin receptor complex, such as the complex that uses Importin-β1 (encoded by gene
KPNB1
Importin subunit beta-1 is a protein that in humans is encoded by the ''KPNB1'' gene.
Function
Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. T ...
), is a heterodimer of an alpha subunit which recognizes the nuclear localization signal and a beta subunit which docks the complex at nucleoporins. However, Transportin-1 can directly bind to the cargo proteins and may not need importin alpha subunit to do it.
Transportin-1 is thought to use the same principal mechanism to carry out nuclear transport as other Importins. It mediates docking to the
nuclear pore complex
The nuclear pore complex (NPC), is a large protein complex giving rise to the nuclear pore. A great number of nuclear pores are studded throughout the nuclear envelope that surrounds the eukaryote cell nucleus. The pores enable the nuclear tra ...
through binding to
nucleoporin
Nucleoporins are a family of proteins which are the constituent building blocks of the nuclear pore complex (NPC). The nuclear pore complex is a massive structure embedded in the nuclear envelope at sites where the inner and outer nuclear memb ...
and is subsequently translocated through the pore by an energy requiring mechanism. Then, in the nucleus Ran binds to Transportin-1, it dissociates from cargo, and Transportin-1 is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. Then Transportin-1 is free to bind new cargo.
In addition, Transportin-1 is implicated in helping protein transport into primary
cilium
The cilium (: cilia; ; in Medieval Latin and in anatomy, ''cilium'') is a short hair-like membrane protrusion from many types of eukaryotic cell. (Cilia are absent in bacteria and archaea.) The cilium has the shape of a slender threadlike pr ...
. The function of Transportin-1 in this case is thought to be similar to carrying proteins into the nucleus through a nuclear pore. Transportin-1 binds cargo and then is helping this cargo to pass through a pore at the base of the cilium. Ran and nucleoporins are also implicated in this mechanism.
Alternate splicing of this gene results in two transcript variants encoding different proteins.
Targets
Transportin 1 (TRN1) is part of the non-classical nuclear import pathway. In conjunction with the
RanGTP
Ran (RAs-related Nuclear protein) also known as GTP-binding nuclear protein Ran is a protein that in humans is encoded by the RAN gene. Ran is a small 25 kDa protein that is involved in transport into and out of the cell nucleus during interphase ...
hydrolysis cascade TRN1 acts to import a selection of proteins into the nucleus of cells. These targets typically contain a PY-motif otherwise known as a M9 nuclear localisation signal. Well described examples include
hnRNP A1.
The type of cargo proteins that Transportin 1 can carry into the nucleus include RNA-binding proteins (such as hnRNP A1 and hnRNP F) and also ribosomal proteins.
[Anne-Christine Ström (2001). ''Importin-beta-like nuclear transport receptors''. Genome Biol. 2001; 2(6): reviews3008.1–reviews3008.9.]
Clinical significance
TRN1 has been implicated in the pathogenesis of two neurodegenerative diseases namely
amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
and
frontotemporal dementia
Frontotemporal dementia (FTD), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of the brain's frontal lobe, frontal and tempor ...
.
Interactions
Transportin 1 has been shown to
interact with:
*
RGPD5 and
*
Ran (biology)
Ran (RAs-related Nuclear protein) also known as GTP-binding nuclear protein Ran is a protein that in humans is encoded by the RAN gene. Ran is a small 25 kDa protein that is involved in transport into and out of the cell nucleus during interphase ...
.
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
{{PDB Gallery, geneid=3842