Overview
| Uniprot ID | O60524 |
| Protein Name | Ribosome quality control complex subunit NEMF |
| Gene Name | NEMF |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 1037 |
LNSFMHSKEATAREK |
| 795 |
QPQRSIQKLASKEES |
| 828 |
RREMKKKKLPSDSGD |
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 (PubMed:25578875, PubMed:32726578, PubMed:33406423, PubMed:33909987). 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 (PubMed:25578875, PubMed:33406423, PubMed:33909987). 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 (PubMed:25578875). 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) (PubMed:33406423, PubMed:33909987). Mainly recruits alanine-charged tRNAs, but can also other amino acid-charged tRNAs (PubMed:33406423, PubMed:33909987). CAT tailing is required to promote ubiquitination of stalled nascent chains by different E3 ubiquitin-protein ligases (PubMed:33909987). 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 (PubMed:33909987). NEMF may also indirectly play a role in nuclear export (PubMed:16103875)
Protein Sequence
10
MKSRFSTIDL
20
RAVLAELNAS
30
LLGMRVNNVY
40
DVDNKTYLIR
50
LQKPDFKATL
60
LLESGIRIHT
70
TEFEWPKNMM
80
PSSFAMKCRK
90
HLKSRRLVSA
100
KQLGVDRIVD
110
FQFGSDEAAY
120
HLIIELYDRG
130
NIVLTDYEYV
140
ILNILRFRTD
150
EADDVKFAVR
160
ERYPLDHARA
170
AEPLLTLERL
180
TEIVASAPKG
190
ELLKRVLNPL
200
LPYGPALIEH
210
CLLENGFSGN
220
VKVDEKLETK
230
DIEKVLVSLQ
240
KAEDYMKTTS
250
NFSGKGYIIQ
260
KREIKPSLEA
270
DKPVEDILTY
280
EEFHPFLFSQ
290
HSQCPYIEFE
300
SFDKAVDEFY
310
SKIEGQKIDL
320
KALQQEKQAL
330
KKLDNVRKDH
340
ENRLEALQQA
350
QEIDKLKGEL
360
IEMNLQIVDR
370
AIQVVRSALA
380
NQIDWTEIGL
390
IVKEAQAQGD
400
PVASAIKELK
410
LQTNHVTMLL
420
RNPYLLSEEE
430
DDDVDGDVNV
440
EKNETEPPKG
450
KKKKQKNKQL
460
QKPQKNKPLL
470
VDVDLSLSAY
480
ANAKKYYDHK
490
RYAAKKTQKT
500
VEAAEKAFKS
510
AEKKTKQTLK
520
EVQTVTSIQK
530
ARKVYWFEKF
540
LWFISSENYL
550
IIGGRDQQQN
560
EIIVKRYLTP
570
GDIYVHADLH
580
GATSCVIKNP
590
TGEPIPPRTL
600
TEAGTMALCY
610
SAAWDARVIT
620
SAWWVYHHQV
630
SKTAPTGEYL
640
TTGSFMIRGK
650
KNFLPPSYLM
660
MGFSFLFKVD
670
ESCVWRHQGE
680
RKVRVQDEDM
690
ETLASCTSEL
700
ISEEMEQLDG
710
GDTSSDEDKE
720
EHETPVEVEL
730
MTQVDQEDIT
740
LQSGRDELNE
750
ELIQEESSED
760
EGEYEEVRKD
770
QDSVGEMKDE
780
GEETLNYPDT
790
TIDLSHLQPQ
800
RSIQKLASKE
810
ESSNSSDSKS
820
QSRRHLSAKE
830
RREMKKKKLP
840
SDSGDLEALE
850
GKDKEKESTV
860
HIETHQNTSK
870
NVAAVQPMKR
880
GQKSKMKKMK
890
EKYKDQDEED
900
RELIMKLLGS
910
AGSNKEEKGK
920
KGKKGKTKDE
930
PVKKQPQKPR
940
GGQRVSDNIK
950
KETPFLEVIT
960
HELQDFAVDD
970
PHDDKEEQDL
980
DQQGNEENLF
990
DSLTGQPHPE
1000
DVLLFAIPIC
1010
APYTTMTNYK
1020
YKVKLTPGVQ
1030
KKGKAAKTAL
1040
NSFMHSKEAT
1050
AREKDLFRSV
1060
KDTDLSRNIP
1070
GKVKVSAPNL
LNVKRK
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0022626 |
cytosolic ribosome |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:1990112 |
RQC complex |
| Molecular Function |
GO:1904678 |
alpha-aminoacyl-tRNA binding |
| Molecular Function |
GO:0043023 |
ribosomal large subunit binding |
| Molecular Function |
GO:0000049 |
tRNA binding |
| Biological Process |
GO:0140708 |
CAT tailing |
| Biological Process |
GO:0051168 |
nuclear export |
| Biological Process |
GO:0065003 |
protein-containing complex assembly |
| Biological Process |
GO:0072344 |
rescue of stalled cytosolic ribosome |
| Biological Process |
GO:1990116 |
ribosome-associated ubiquitin-dependent protein catabolic process |
Reference
[1] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.