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1.I.1.1.3
Nuclear Pore Complex, NPC, with 86 protein components.  NPCs mediate nucleocytoplasmic transport and gain transport selectivity through nucleoporin FG domains. Chug et al. 2015 reported a structural analysis of the frog FG Nup62•58•54 complex. It comprises a ≈13 nanometer-long trimerization interface with an unusual 2W3F coil, a canonical heterotrimeric coiled coil, and a kink that enforces a compact six-helix bundle. Nup54 also contains a ferredoxin-like domain. Chug et al. 2015 further identified a heterotrimeric Nup93-binding module for NPC anchorage. The quaternary structure alternations in the Nup62 complex, which were previously proposed to trigger a general gating of the NPC, are incompatible with the trimer structure. Chug et al. 2015 suggested that the highly elongated Nup62 complex projects barrier-forming FG repeats far into the central NPC channel, supporting a barrier that guards the entire cross section. The Sun1/UNC84A protein and Sun2/UNC84B may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis (Schaller et al. 2017).  The integral transmembrane nucleoporin Pom121 functionally links nuclear pore complex assembly to nuclear envelope formation (Antonin et al. 2005) and ensures efficient HIV-1 pre-integration complex nuclear import (Guo et al. 2018). Mechanosensing at the nuclear envelope by nuclear pore complex stretch activation involves cell membrane integrins (TC# 8.A.54) and SUN proteins, SUN1 and SUN2, in the nuclear membrane (Donnaloja et al. 2019). TMX2 is a thioredoxin-like protein that facilitates the transport of proteins across the nuclear membrane (Oguro and Imaoka 2019). Torsin ATPase deficiency leads to defects in nuclear pore biogenesis and sequestration of the myelokd leukemia factor 2, MLF2 (Rampello et al. 2020).    G4C2 repeat RNA initiates a POM121-mediated reduction in specific nucleoporins (Coyne et al. 2020) (Pom121: acc# A8CG34). Defects in nucleocytoplasmic transport and accumulation of specific nuclear-pore-complex-associated proteins play roles in multiple neurodegenerative diseases, including C9orf72 Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS/FTD). Using super-resolution structured illumination microscopy, Coyne et al. 2020 have explored the mechanism by which nucleoporins are altered in nuclei isolated from C9orf72 induced pluripotent stem-cell-derived neurons (iPSNs). Of the 23 nucleoporins evaluated, they observed a reduction in a subset of 8, including key components of the nuclear pore complex scaffold and the transmembrane nucleoporin POM121. Reduction in POM121 appeared to initiate a decrease in the expression of seven additional nucleoporins, ultimately affecting the localization of the Ran GTPase and subsequent cellular toxicity in C9orf72 iPSNs. Thus, the expression of expanded C9orf72 ALS/FTD repeat RNA affects nuclear POM121 expression in the initiation of a pathological cascade affecting nucleoporin levels within neuronal nuclei and ultimately downstream neuronal survival (Coyne et al. 2020).  

Accession Number:Q8TEX9
Protein Name:Importin-4
Length:1081
Molecular Weight:118715.00
Species:Homo sapiens (Human) [9606]
Location1 / Topology2 / Orientation3: Cytoplasm1
Substrate proteins, RNA

Cross database links:

Structure:
5XAH   5XBK     

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  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MESAGLEQLL RELLLPDTER IRRATEQLQI VLRAPAALPA LCDLLASAAD PQIRQFAAVL 
61:	TRRRLNTRWR RLAAEQRESL KSLILTALQR ETEHCVSLSL AQLSATIFRK EGLEAWPQLL 
121:	QLLQHSTHSP HSPEREMGLL LLSVVVTSRP EAFQPHHREL LRLLNETLGE VGSPGLLFYS 
181:	LRTLTTMAPY LSTEDVPLAR MLVPKLIMAM QTLIPIDEAK ACEALEALDE LLESEVPVIT 
241:	PYLSEVLTFC LEVARNVALG NAIRIRILCC LTFLVKVKSK ALLKNRLLPP LLHTLFPIVA 
301:	AEPPPGQLDP EDQDSEEEEL EIELMGETPK HFAVQVVDML ALHLPPEKLC PQLMPMLEEA 
361:	LRSESPYQRK AGLLVLAVLS DGAGDHIRQR LLPPLLQIVC KGLEDPSQVV RNAALFALGQ 
421:	FSENLQPHIS SYSREVMPLL LAYLKSVPLG HTHHLAKACY ALENFVENLG PKVQPYLPEL 
481:	MECMLQLLRN PSSPRAKELA VSALGAIATA AQASLLPYFP AIMEHLREFL LTGREDLQPV 
541:	QIQSLETLGV LARAVGEPMR PLAEECCQLG LGLCDQVDDP DLRRCTYSLF AALSGLMGEG 
601:	LAPHLEQITT LMLLSLRSTE GIVPQYDGSS SFLLFDDESD GEEEEELMDE DVEEEDDSEI 
661:	SGYSVENAFF DEKEDTCAAV GEISVNTSVA FLPYMESVFE EVFKLLECPH LNVRKAAHEA 
721:	LGQFCCALHK ACQSCPSEPN TAALQAALAR VVPSYMQAVN RERERQVVMA VLEALTGVLR 
781:	SCGTLTLKPP GRLAELCGVL KAVLQRKTAC QDTDEEEEEE DDDQAEYDAM LLEHAGEAIP 
841:	ALAAAAGGDS FAPFFAGFLP LLVCKTKQGC TVAEKSFAVG TLAETIQGLG AASAQFVSRL 
901:	LPVLLSTAQE ADPEVRSNAI FGMGVLAEHG GHPAQEHFPK LLGLLFPLLA RERHDRVRDN 
961:	ICGALARLLM ASPTRKPEPQ VLAALLHALP LKEDLEEWVT IGRLFSFLYQ SSPDQVIDVA 
1021:	PELLRICSLI LADNKIPPDT KAALLLLLTF LAKQHTDSFQ AALGSLPVDK AQELQAVLGL 
1081:	S