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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:P12270
Protein Name:Nucleoprotein TPR
Length:2363
Molecular Weight:267293.00
Species:Homo sapiens (Human) [9606]
Location1 / Topology2 / Orientation3: Nucleus1
Substrate proteins, RNA

Cross database links:

Structure:
5TO5   5TO6   5TO7   5TVB     

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  • 2° Structure (Network Protein Sequence Analysis)

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FASTA formatted sequence
1:	MAAVLQQVLE RTELNKLPKS VQNKLEKFLA DQQSEIDGLK GRHEKFKVES EQQYFEIEKR 
61:	LSHSQERLVN ETRECQSLRL ELEKLNNQLK ALTEKNKELE IAQDRNIAIQ SQFTRTKEEL 
121:	EAEKRDLIRT NERLSQELEY LTEDVKRLNE KLKESNTTKG ELQLKLDELQ ASDVSVKYRE 
181:	KRLEQEKELL HSQNTWLNTE LKTKTDELLA LGREKGNEIL ELKCNLENKK EEVSRLEEQM 
241:	NGLKTSNEHL QKHVEDLLTK LKEAKEQQAS MEEKFHNELN AHIKLSNLYK SAADDSEAKS 
301:	NELTRAVEEL HKLLKEAGEA NKAIQDHLLE VEQSKDQMEK EMLEKIGRLE KELENANDLL 
361:	SATKRKGAIL SEEELAAMSP TAAAVAKIVK PGMKLTELYN AYVETQDQLL LEKLENKRIN 
421:	KYLDEIVKEV EAKAPILKRQ REEYERAQKA VASLSVKLEQ AMKEIQRLQE DTDKANKQSS 
481:	VLERDNRRME IQVKDLSQQI RVLLMELEEA RGNHVIRDEE VSSADISSSS EVISQHLVSY 
541:	RNIEELQQQN QRLLVALREL GETREREEQE TTSSKITELQ LKLESALTEL EQLRKSRQHQ 
601:	MQLVDSIVRQ RDMYRILLSQ TTGVAIPLHA SSLDDVSLAS TPKRPSTSQT VSTPAPVPVI 
661:	ESTEAIEAKA ALKQLQEIFE NYKKEKAENE KIQNEQLEKL QEQVTDLRSQ NTKISTQLDF 
721:	ASKRYEMLQD NVEGYRREIT SLHERNQKLT ATTQKQEQII NTMTQDLRGA NEKLAVAEVR 
781:	AENLKKEKEM LKLSEVRLSQ QRESLLAEQR GQNLLLTNLQ TIQGILERSE TETKQRLSSQ 
841:	IEKLEHEISH LKKKLENEVE QRHTLTRNLD VQLLDTKRQL DTETNLHLNT KELLKNAQKE 
901:	IATLKQHLSN MEVQVASQSS QRTGKGQPSN KEDVDDLVSQ LRQTEEQVND LKERLKTSTS 
961:	NVEQYQAMVT SLEESLNKEK QVTEEVRKNI EVRLKESAEF QTQLEKKLME VEKEKQELQD 
1021:	DKRRAIESME QQLSELKKTL SSVQNEVQEA LQRASTALSN EQQARRDCQE QAKIAVEAQN 
1081:	KYERELMLHA ADVEALQAAK EQVSKMASVR QHLEETTQKA ESQLLECKAS WEERERMLKD 
1141:	EVSKCVCRCE DLEKQNRLLH DQIEKLSDKV VASVKEGVQG PLNVSLSEEG KSQEQILEIL 
1201:	RFIRREKEIA ETRFEVAQVE SLRYRQRVEL LERELQELQD SLNAEREKVQ VTAKTMAQHE 
1261:	ELMKKTETMN VVMETNKMLR EEKERLEQDL QQMQAKVRKL ELDILPLQEA NAELSEKSGM 
1321:	LQAEKKLLEE DVKRWKARNQ HLVSQQKDPD TEEYRKLLSE KEVHTKRIQQ LTEEIGRLKA 
1381:	EIARSNASLT NNQNLIQSLK EDLNKVRTEK ETIQKDLDAK IIDIQEKVKT ITQVKKIGRR 
1441:	YKTQYEELKA QQDKVMETSA QSSGDHQEQH VSVQEMQELK ETLNQAETKS KSLESQVENL 
1501:	QKTLSEKETE ARNLQEQTVQ LQSELSRLRQ DLQDRTTQEE QLRQQITEKE EKTRKAIVAA 
1561:	KSKIAHLAGV KDQLTKENEE LKQRNGALDQ QKDELDVRIT ALKSQYEGRI SRLERELREH 
1621:	QERHLEQRDE PQEPSNKVPE QQRQITLKTT PASGERGIAS TSDPPTANIK PTPVVSTPSK 
1681:	VTAAAMAGNK STPRASIRPM VTPATVTNPT TTPTATVMPT TQVESQEAMQ SEGPVEHVPV 
1741:	FGSTSGSVRS TSPNVQPSIS QPILTVQQQT QATAFVQPTQ QSHPQIEPAN QELSSNIVEV 
1801:	VQSSPVERPS TSTAVFGTVS ATPSSSLPKR TREEEEDSTI EASDQVSDDT VEMPLPKKLK 
1861:	SVTPVGTEEE VMAEESTDGE VETQVYNQDS QDSIGEGVTQ GDYTPMEDSE ETSQSLQIDL 
1921:	GPLQSDQQTT TSSQDGQGKG DDVIVIDSDD EEEDDDENDG EHEDYEEDEE DDDDDEDDTG 
1981:	MGDEGEDSNE GTGSADGNDG YEADDAEGGD GTDPGTETEE SMGGGEGNHR AADSQNSGEG 
2041:	NTGAAESSFS QEVSREQQPS SASERQAPRA PQSPRRPPHP LPPRLTIHAP PQELGPPVQR 
2101:	IQMTRRQSVG RGLQLTPGIG GMQQHFFDDE DRTVPSTPTL VVPHRTDGFA EAIHSPQVAG 
2161:	VPRFRFGPPE DMPQTSSSHS DLGQLASQGG LGMYETPLFL AHEEESGGRS VPTTPLQVAA 
2221:	PVTVFTESTT SDASEHASQS VPMVTTSTGT LSTTNETATG DDGDEVFVEA ESEGISSEAG 
2281:	LEIDSQQEEE PVQASDESDL PSTSQDPPSS SSVDTSSSQP KPFRRVRLQT TLRQGVRGRQ 
2341:	FNRQRGVSHA MGGRGGINRG NIN