Protein: Ribosome quality control complex subunit NEMF (O60524)
Organism: Homo sapiens (Human)
Function: Key component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes as well as their ubiquitin-mediated proteasomal degradation. Thereby, frees 60S subunit ribosomes from the stalled translation complex and prevents the accumulation of nascent polypeptide chains that are potentially toxic for the cell. Within the RQC complex, NEMF specifically binds stalled 60S ribosomal subunits by recognizing an exposed, nascent chain-conjugated tRNA moiety and promotes the recruitment of LTN1 to stalled 60S subunits. Following binding to stalled 60S ribosomal subunits, NEMF mediates CAT tailing by recruiting alanine-charged tRNA to the A- site and directing the elongation of stalled nascent chains independently of mRNA or 40S subunits, leading to non-templated C- terminal alanine extensions (CAT tails). Mainly recruits alanine-charged tRNAs, but can also other amino acid-charged tRNAs. CAT tailing is required to promote ubiquitination of stalled nascent chains by different E3 ubiquitin-protein ligases. In the canonical RQC pathway (RQC-L), CAT tailing facilitates LTN1-dependent ubiquitination by exposing lysine residues that would otherwise remain buried in the ribosomal exit tunnel (By similarity). In the alternative RQC pathway (RQC-C) CAT tailing creates an C-degron mainly composed of alanine that is recognized by the CRL2(KLHDC10) and RCHY1/PIRH2 E3 ligases, leading to ubiquitination and degradation of stalled nascent chains. NEMF may also indirectly play a role in nuclear export
Subcellular location: Cytoplasm, cytosol. Nucleus
Sequence: MKSRFSTIDLRAVLAELNASLLGMRVNNVYDVDNKTYLIRLQKPDFKATLLLESGIRIHTTEFEWPKNMMPSSFAMKCRKHLKSRRLVSAKQLGVDRIVDFQFGSDEAAYHLIIELYDRGNIVLTDYEYVILNILRFRTDEADDVKFAVRERYPLDHARAAEPLLTLERLTEIVASAPKGELLKRVLNPLLPYGPALIEHCLLENGFSGNVKVDEKLETKDIEKVLVSLQKAEDYMKTTSNFSGKGYIIQKREIKPSLEADKPVEDILTYEEFHPFLFSQHSQCPYIEFESFDKAVDEFYSKIEGQKIDLKALQQEKQALKKLDNVRKDHENRLEALQQAQEIDKLKGELIEMNLQIVDRAIQVVRSALANQIDWTEIGLIVKEAQAQGDPVASAIKELKLQTNHVTMLLRNPYLLSEEEDDDVDGDVNVEKNETEPPKGKKKKQKNKQLQKPQKNKPLLVDVDLSLSAYANAKKYYDHKRYAAKKTQKTVEAAEKAFKSAEKKTKQTLKEVQTVTSIQKARKVYWFEKFLWFISSENYLIIGGRDQQQNEIIVKRYLTPGDIYVHADLHGATSCVIKNPTGEPIPPRTLTEAGTMALCYSAAWDARVITSAWWVYHHQVSKTAPTGEYLTTGSFMIRGKKNFLPPSYLMMGFSFLFKVDESCVWRHQGERKVRVQDEDMETLASCTSELISEEMEQLDGGDTSSDEDKEEHETPVEVELMTQVDQEDITLQSGRDELNEELIQEESSEDEGEYEEVRKDQDSVGEMKDEGEETLNYPDTTIDLSHLQPQRSIQKLASKEESSNSSDSKSQSRRHLSAKERREMKKKKLPSDSGDLEALEGKDKEKESTVHIETHQNTSKNVAAVQPMKRGQKSKMKKMKEKYKDQDEEDRELIMKLLGSAGSNKEEKGKKGKKGKTKDEPVKKQPQKPRGGQRVSDNIKKETPFLEVITHELQDFAVDDPHDDKEEQDLDQQGNEENLFDSLTGQPHPEDVLLFAIPICAPYTTMTNYKYKVKLTPGVQKKGKAAKTALNSFMHSKEATAREKDLFRSVKDTDLSRNIPGKVKVSAPNLLNVKRK
InterPro domains: - IPR008532: NFACT, RNA-binding domain (domain) [529-639]
- IPR051608: Ribosome Quality Control Complex Subunit NEMF (family) [1-1064]
- IPR021846: NFACT protein, C-terminal (domain) [975-1066]
Interaction partners: - E3 ubiquitin-protein ligase listerin
- Ribosome quality control complex subunit TCF25
- Large ribosomal subunit protein uL5
- Large ribosomal subunit protein uL5
- Large ribosomal subunit protein uL18
- Large ribosomal subunit protein uL14
- Large ribosomal subunit protein uL23
- Large ribosomal subunit protein uL23
- Large ribosomal subunit protein uL23
- Large ribosomal subunit protein uL6
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0003723 (RNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0009987 (cellular process), GO:0051641 (cellular localization), GO:0044237 (cellular metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0044238 (primary metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0044085 (cellular component biogenesis), GO:0046907 (intracellular transport), GO:0044248 (cellular catabolic process), GO:0006810 (transport), GO:0019538 (protein metabolic process), GO:0051649 (establishment of localization in cell), GO:0016043 (cellular component organization), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009057 (macromolecule catabolic process), GO:1901565 (organonitrogen compound catabolic process), GO:0006508 (proteolysis), GO:0044265 (cellular macromolecule catabolic process), GO:0030163 (protein catabolic process), GO:0051169 (nuclear transport), GO:0043933 (protein-containing complex organization), GO:0022607 (cellular component assembly), GO:0006913 (nucleocytoplasmic transport), GO:0065003 (protein-containing complex assembly), GO:0043632 (modification-dependent macromolecule catabolic process), GO:0010498 (proteasomal protein catabolic process), GO:0051603 (proteolysis involved in protein catabolic process), GO:0051168 (nuclear export), GO:0019941 (modification-dependent protein catabolic process), GO:0043161 (proteasome-mediated ubiquitin-dependent protein catabolic process), GO:0006511 (ubiquitin-dependent protein catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure), GO:0005737 (cytoplasm)