Search Results

Overview

Uniprot IDQ92616
Protein NameStalled ribosome sensor GCN1
Gene NameGCN1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1556 DSHVKVQKAGQQALR
2621 QAIVNLLKMRQGEEV
436 FKKAFSLKTSTSAVR
788 SAQQDSIKKANMKRE
789 AQQDSIKKANMKREN
797 ANMKRENKAYSFKEQ
821 IKKKKGIKEEVQLTS
829 EEVQLTSKQKEMLQA

Function

Ribosome collision sensor that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes (PubMed:32610081, PubMed:36638793, PubMed:37651229, PubMed:37951215, PubMed:37951216). Directly binds to the ribosome and acts as a sentinel for colliding ribosomes: activated following ribosome stalling and promotes recruitment of RNF14, which directly ubiquitinates EEF1A1/eEF1A, leading to its degradation (PubMed:36638793, PubMed:37951215, PubMed:37951216). In addition to EEF1A1/eEF1A, the RNF14-RNF25 translation quality control pathway mediates degradation of ETF1/eRF1 and ubiquitination of ribosomal protein (PubMed:36638793, PubMed:37651229). GCN1 also acts as a positive activator of the integrated stress response (ISR) by mediating activation of EIF2AK4/GCN2 in response to amino acid starvation (By similarity). Interaction with EIF2AK4/GCN2 on translating ribosomes stimulates EIF2AK4/GCN2 kinase activity, leading to phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) (By similarity). EIF2S1/eIF-2-alpha phosphorylation converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (By similarity)

Protein Sequence

10 MAADTQVSET 20 LKRFAGKVTT 30 ASVKERREIL 40 SELGKCVAGK 50 DLPEGAVKGL 60 CKLFCLTLHR 70 YRDAASRRAL 80 QAAIQQLAEA 90 QPEATAKNLL 100 HSLQSSGIGS 110 KAGVPSKSSG 120 SAALLALTWT 130 CLLVRIVFPS 140 RAKRQGDIWN 150 KLVEVQCLLL 160 LEVLGGSHKH 170 AVDGAVKKLT 180 KLWKENPGLV 190 EQYLSAILSL 200 EPNQNYAGML 210 GLLVQFCTSH 220 KEMDVVSQHK 230 SALLDFYMKN 240 ILMSKVKPPK 250 YLLDSCAPLL 260 RYLSHSEFKD 270 LILPTIQKSL 280 LRSPENVIET 290 ISSLLASVTL 300 DLSQYAMDIV 310 KGLAGHLKSN 320 SPRLMDEAVL 330 ALRNLARQCS 340 DSSAMESLTK 350 HLFAILGGSE 360 GKLTVVAQKM 370 SVLSGIGSVS 380 HHVVSGPSSQ 390 VLNGIVAELF 400 IPFLQQEVHE 410 GTLVHAVSVL 420 ALWCNRFTME 430 VPKKLTEWFK 440 KAFSLKTSTS 450 AVRHAYLQCM 460 LASYRGDTLL 470 QALDLLPLLI 480 QTVEKAASQS 490 TQVPTITEGV 500 AAALLLLKLS 510 VADSQAEAKL 520 SSFWQLIVDE 530 KKQVFTSEKF 540 LVMASEDALC 550 TVLHLTERLF 560 LDHPHRLTGN 570 KVQQYHRALV 580 AVLLSRTWHV 590 RRQAQQTVRK 600 LLSSLGGFKL 610 AHGLLEELKT 620 VLSSHKVLPL 630 EALVTDAGEV 640 TEAGKAYVPP 650 RVLQEALCVI 660 SGVPGLKGDV 670 TDTEQLAQEM 680 LIISHHPSLV 690 AVQSGLWPAL 700 LARMKIDPEA 710 FITRHLDQII 720 PRMTTQSPLN 730 QSSMNAMGSL 740 SVLSPDRVLP 750 QLISTITASV 760 QNPALRLVTR 770 EEFAIMQTPA 780 GELYDKSIIQ 790 SAQQDSIKKA 800 NMKRENKAYS 810 FKEQIIELEL 820 KEEIKKKKGI 830 KEEVQLTSKQ 840 KEMLQAQLDR 850 EAQVRRRLQE 860 LDGELEAALG 870 LLDIILAKNP 880 SGLTQYIPVL 890 VDSFLPLLKS 900 PLAAPRIKNP 910 FLSLAACVMP 920 SRLKALGTLV 930 SHVTLRLLKP 940 ECVLDKSWCQ 950 EELSVAVKRA 960 VMLLHTHTIT 970 SRVGKGEPGA 980 APLSAPAFSL 990 VFPFLKMVLT 1000 EMPHHSEEEE 1010 EWMAQILQIL 1020 TVQAQLRASP 1030 NTPPGRVDEN 1040 GPELLPRVAM 1050 LRLLTWVIGT 1060 GSPRLQVLAS 1070 DTLTTLCASS 1080 SGDDGCAFAE 1090 QEEVDVLLCA 1100 LQSPCASVRE 1110 TVLRGLMELH 1120 MVLPAPDTDE 1130 KNGLNLLRRL 1140 WVVKFDKEEE 1150 IRKLAERLWS 1160 MMGLDLQPDL 1170 CSLLIDDVIY 1180 HEAAVRQAGA 1190 EALSQAVARY 1200 QRQAAEVMGR 1210 LMEIYQEKLY 1220 RPPPVLDALG 1230 RVISESPPDQ 1240 WEARCGLALA 1250 LNKLSQYLDS 1260 SQVKPLFQFF 1270 VPDALNDRHP 1280 DVRKCMLDAA 1290 LATLNTHGKE 1300 NVNSLLPVFE 1310 EFLKNAPNDA 1320 SYDAVRQSVV 1330 VLMGSLAKHL 1340 DKSDPKVKPI 1350 VAKLIAALST 1360 PSQQVQESVA 1370 SCLPPLVPAI 1380 KEDAGGMIQR 1390 LMQQLLESDK 1400 YAERKGAAYG 1410 LAGLVKGLGI 1420 LSLKQQEMMA 1430 ALTDAIQDKK 1440 NFRRREGALF 1450 AFEMLCTMLG 1460 KLFEPYVVHV 1470 LPHLLLCFGD 1480 GNQYVREAAD 1490 DCAKAVMSNL 1500 SAHGVKLVLP 1510 SLLAALEEES 1520 WRTKAGSVEL 1530 LGAMAYCAPK 1540 QLSSCLPNIV 1550 PKLTEVLTDS 1560 HVKVQKAGQQ 1570 ALRQIGSVIR 1580 NPEILAIAPV 1590 LLDALTDPSR 1600 KTQKCLQTLL 1610 DTKFVHFIDA 1620 PSLALIMPIV 1630 QRAFQDRSTD 1640 TRKMAAQIIG 1650 NMYSLTDQKD 1660 LAPYLPSVTP 1670 GLKASLLDPV 1680 PEVRTVSAKA 1690 LGAMVKGMGE 1700 SCFEDLLPWL 1710 METLTYEQSS 1720 VDRSGAAQGL 1730 AEVMAGLGVE 1740 KLEKLMPEIV 1750 ATASKVDIAP 1760 HVRDGYIMMF 1770 NYLPITFGDK 1780 FTPYVGPIIP 1790 CILKALADEN 1800 EFVRDTALRA 1810 GQRVISMYAE 1820 TAIALLLPQL 1830 EQGLFDDLWR 1840 IRFSSVQLLG 1850 DLLFHISGVT 1860 GKMTTETASE 1870 DDNFGTAQSN 1880 KAIITALGVE 1890 RRNRVLAGLY 1900 MGRSDTQLVV 1910 RQASLHVWKI 1920 VVSNTPRTLR 1930 EILPTLFGLL 1940 LGFLASTCAD 1950 KRTIAARTLG 1960 DLVRKLGEKI 1970 LPEIIPILEE 1980 GLRSQKSDER 1990 QGVCIGLSEI 2000 MKSTSRDAVL 2010 YFSESLVPTA 2020 RKALCDPLEE 2030 VREAAAKTFE 2040 QLHSTIGHQA 2050 LEDILPFLLK 2060 QLDDEEVSEF 2070 ALDGLKQVMA 2080 IKSRVVLPYL 2090 VPKLTTPPVN 2100 TRVLAFLSSV 2110 AGDALTRHLG 2120 VILPAVMLAL 2130 KEKLGTPDEQ 2140 LEMANCQAVI 2150 LSVEDDTGHR 2160 IIIEDLLEAT 2170 RSPEVGMRQA 2180 AAIILNIYCS 2190 RSKADYTSHL 2200 RSLVSGLIRL 2210 FNDSSPVVLE 2220 ESWDALNAIT 2230 KKLDAGNQLA 2240 LIEELHKEIR 2250 LIGNESKGEH 2260 VPGFCLPKKG 2270 VTSILPVLRE 2280 GVLTGSPEQK 2290 EEAAKALGLV 2300 IRLTSADALR 2310 PSVVSITGPL 2320 IRILGDRFSW 2330 NVKAALLETL 2340 SLLLAKVGIA 2350 LKPFLPQLQT 2360 TFTKALQDSN 2370 RGVRLKAADA 2380 LGKLISIHIK 2390 VDPLFTELLN 2400 GIRAMEDPGV 2410 RDTMLQALRF 2420 VIQGAGAKVD 2430 AVIRKNIVSL 2440 LLSMLGHDED 2450 NTRISSAGCL 2460 GELCAFLTEE 2470 ELSAVLQQCL 2480 LADVSGIDWM 2490 VRHGRSLALS 2500 VAVNVAPGRL 2510 CAGRYSSDVQ 2520 EMILSSATAD 2530 RIPIAVSGVR 2540 GMGFLMRHHI 2550 ETGGGQLPAK 2560 LSSLFVKCLQ 2570 NPSSDIRLVA 2580 EKMIWWANKD 2590 PLPPLDPQAI 2600 KPILKALLDN 2610 TKDKNTVVRA 2620 YSDQAIVNLL 2630 KMRQGEEVFQ 2640 SLSKILDVAS 2650 LEVLNEVNRR 2660 SLKKLASQAD 2670 STEQVDDTIL T

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0022626 cytosolic ribosome
Cellular Component GO:0016020 membrane
Cellular Component GO:0005840 ribosome
Molecular Function GO:0045296 cadherin binding
Molecular Function GO:0060090 molecular adaptor activity
Molecular Function GO:0019887 protein kinase regulator activity
Molecular Function GO:0043539 protein serine/threonine kinase activator activity
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0170011 stalled ribosome sensor activity
Molecular Function GO:0008135 translation factor activity, RNA binding
Biological Process GO:0034198 cellular response to amino acid starvation
Biological Process GO:0140469 GCN2-mediated signaling
Biological Process GO:0160127 protein-RNA covalent cross-linking repair
Biological Process GO:0006417 regulation of translation
Biological Process GO:0072344 rescue of stalled cytosolic ribosome

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[5] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[6] 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.