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Overview

Uniprot IDQ2TAL8
Protein NameTranscriptional regulator QRICH1
Gene NameQRICH1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
246 ASVLQPVKKRKVDMP
247 SVLQPVKKRKVDMPI
672 STSIRYLKALGIHQT
682 GIHQTGQKVTDDMYA

Function

Transcriptional regulator that acts as a mediator of the integrated stress response (ISR) through transcriptional control of protein homeostasis under conditions of ER stress (PubMed:33384352, PubMed:40355839). Controls the outcome of the unfolded protein response (UPR) which is an ER-stress response pathway (PubMed:33384352). ER stress induces QRICH1 translation by a ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced QRICH1 regulates a transcriptional program associated with protein translation, protein secretion-mediated proteotoxicity and cell death during the terminal UPR (PubMed:33384352). May cooperate with ATF4 transcription factor signaling to regulate ER homeostasis which is critical for cell viability (PubMed:33384352). Up-regulates CASP3/caspase-3 activity in epithelial cells under ER stress. Central regulator of proteotoxicity associated with ER stress-mediated inflammatory diseases in the intestines and liver (PubMed:33384352). Core component of the zincore complex, a heterotetramer that acts as a molecular 'grip' to stabilize transcription factors at DNA-binding sites across the genome, thereby controlling gene expression (PubMed:40608935). The zincore complex binds specifically to zinc finger transcription factors, such as ZFP91, ZNF652, ZNF526 and PRDM15, and stabilizes them onto their cognate DNA motif (PubMed:40608935). Involved in chondrocyte hypertrophy, a process required for normal longitudinal bone growth (PubMed:30281152)

Protein Sequence

10 MNNSLENTIS 20 FEEYIRVKAR 30 SVPQHRMKEF 40 LDSLASKGPE 50 ALQEFQQTAT 60 TTMVYQQGGN 70 CIYTDSTEVA 80 GSLLELACPV 90 TTSVQPQTQQ 100 EQQIQVQQPQ 110 QVQVQVQVQQ 120 SPQQVSAQLS 130 PQLTVHQPTE 140 QPIQVQVQIQ 150 GQAPQSAAPS 160 IQTPSLQSPS 170 PSQLQAAQIQ 180 VQHVQAAQQI 190 QAAEIPEEHI 200 PHQQIQAQLV 210 AGQSLAGGQQ 220 IQIQTVGALS 230 PPPSQQGSPR 240 EGERRVGTAS 250 VLQPVKKRKV 260 DMPITVSYAI 270 SGQPVATVLA 280 IPQGQQQSYV 290 SLRPDLLTVD 300 SAHLYSATGT 310 ITSPTGETWT 320 IPVYSAQPRG 330 DPQQQSITHI 340 AIPQEAYNAV 350 HVSGSPTALA 360 AVKLEDDKEK 370 MVGTTSVVKN 380 SHEEVVQTLA 390 NSLFPAQFMN 400 GNIHIPVAVQ 410 AVAGTYQNTA 420 QTVHIWDPQQ 430 QPQQQTPQEQ 440 TPPPQQQQQQ 450 LQVTCSAQTV 460 QVAEVEPQSQ 470 PQPSPELLLP 480 NSLKPEEGLE 490 VWKNWAQTKN 500 AELEKDAQNR 510 LAPIGRRQLL 520 RFQEDLISSA 530 VAELNYGLCL 540 MTREARNGEG 550 EPYDPDVLYY 560 IFLCIQKYLF 570 ENGRVDDIFS 580 DLYYVRFTEW 590 LHEVLKDVQP 600 RVTPLGYVLP 610 SHVTEEMLWE 620 CKQLGAHSPS 630 TLLTTLMFFN 640 TKYFLLKTVD 650 QHMKLAFSKV 660 LRQTKKNPSN 670 PKDKSTSIRY 680 LKALGIHQTG 690 QKVTDDMYAE 700 QTENPENPLR 710 CPIKLYDFYL 720 FKCPQSVKGR 730 NDTFYLTPEP 740 VVAPNSPIWY 750 SVQPISREQM 760 GQMLTRILVI 770 REIQEAIAVA NASTMH

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005694 chromosome
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005886 plasma membrane
Molecular Function GO:0003677 DNA binding
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0030968 endoplasmic reticulum unfolded protein response
Biological Process GO:0140467 integrated stress response signaling
Biological Process GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
Biological Process GO:0036499 PERK-mediated unfolded protein response
Biological Process GO:0043065 positive regulation of apoptotic process
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0034976 response to endoplasmic reticulum stress

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] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] 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.

[5] 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.