Search Results

Overview

Uniprot IDO94874
Protein NameE3 UFM1-protein ligase 1
Gene NameUFL1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
289 SYIKKRYKTTQLLFL
351 QVMRAFSKQASTVVF
414 LESVSTSKKDKKDER
424 KKDERRRKATEGSGS
625 ETKVALTKLHNSLNE

Function

E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in various processes, such as ribosome recycling, response to DNA damage, interferon response or reticulophagy (also called ER-phagy) (PubMed:20018847, PubMed:20164180, PubMed:20228063, PubMed:25219498, PubMed:27351204, PubMed:30626644, PubMed:30783677, PubMed:32160526, PubMed:32807901, PubMed:35394863, PubMed:36121123, PubMed:36543799, PubMed:36893266, PubMed:37036982, PubMed:37311461, PubMed:37595036, PubMed:37795761, PubMed:38377992, PubMed:38383785, PubMed:38383789). Catalyzes ufmylation of many protein, such as CD274/PD-L1, CDK5RAP3, CYB5R3, DDRGK1, EIF6, histone H4, MRE11, P4HB, PDCD1/PD-1, TRIP4, RPN1, RPS20/uS10, RPL10/uL16, RPL26/uL24, SYVN1/HRD1 and TP53/p53 (PubMed:20018847, PubMed:20531390, PubMed:25219498, PubMed:30783677, PubMed:30886146, PubMed:32160526, PubMed:35753586, PubMed:36543799, PubMed:36893266, PubMed:37036982, PubMed:37595036, PubMed:37795761, PubMed:38383785, PubMed:38383789). As part of the UREL complex, plays a key role in ribosome recycling by catalyzing mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 occurs on free 60S ribosomes following ribosome dissociation: it weakens the junction between post-termination 60S subunits and SEC61 translocons, promoting release and recycling of the large ribosomal subunit from the endoplasmic reticulum membrane (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 and subsequent 60S ribosome recycling either take place after normal termination of translation or after ribosome stalling during cotranslational translocation at the endoplasmic reticulum (PubMed:37036982, PubMed:37595036, PubMed:38383785, PubMed:38383789). Involved in reticulophagy in response to endoplasmic reticulum stress by mediating ufmylation of proteins such as CYB5R3 and RPN1, thereby promoting lysosomal degradation of ufmylated proteins (PubMed:23152784, PubMed:32160526, PubMed:36543799). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response (PubMed:32050156). Mediates ufmylation of DDRGK1 and CDK5RAP3; the role of these modifications is however unclear: as both DDRGK1 and CDK5RAP3 act as substrate adapters for ufmylation, it is uncertain whether ufmylation of these proteins is, a collateral effect or is required for ufmylation (PubMed:20018847, PubMed:20531390). Acts as a negative regulator of T-cell activation by mediating ufmylation and stabilization of PDCD1/PD-1 (PubMed:38377992). Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 and ufmylation of MRE11 (PubMed:30783677, PubMed:30886146). Mediates ufmylation of TP53/p53, promoting its stability (PubMed:32807901). Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear receptor-mediated transcription (PubMed:25219498). Required for hematopoietic stem cell function and hematopoiesis (By similarity)

Protein Sequence

10 MADAWEEIRR 20 LAADFQRAQF 30 AEATQRLSER 40 NCIEIVNKLI 50 AQKQLEVVHT 60 LDGKEYITPA 70 QISKEMRDEL 80 HVRGGRVNIV 90 DLQQVINVDL 100 IHIENRIGDI 110 IKSEKHVQLV 120 LGQLIDENYL 130 DRLAEEVNDK 140 LQESGQVTIS 150 ELCKTYDLPG 160 NFLTQALTQR 170 LGRIISGHID 180 LDNRGVIFTE 190 AFVARHKARI 200 RGLFSAITRP 210 TAVNSLISKY 220 GFQEQLLYSV 230 LEELVNSGRL 240 RGTVVGGRQD 250 KAVFVPDIYS 260 RTQSTWVDSF 270 FRQNGYLEFD 280 ALSRLGIPDA 290 VSYIKKRYKT 300 TQLLFLKAAC 310 VGQGLVDQVE 320 ASVEEAISSG 330 TWVDIAPLLP 340 TSLSVEDAAI 350 LLQQVMRAFS 360 KQASTVVFSD 370 TVVVSEKFIN 380 DCTELFRELM 390 HQKAEKEMKN 400 NPVHLITEED 410 LKQISTLESV 420 STSKKDKKDE 430 RRRKATEGSG 440 SMRGGGGGNA 450 REYKIKKVKK 460 KGRKDDDSDD 470 ESQSSHTGKK 480 KPEISFMFQD 490 EIEDFLRKHI 500 QDAPEEFISE 510 LAEYLIKPLN 520 KTYLEVVRSV 530 FMSSTTSASG 540 TGRKRTIKDL 550 QEEVSNLYNN 560 IRLFEKGMKF 570 FADDTQAALT 580 KHLLKSVCTD 590 ITNLIFNFLA 600 SDLMMAVDDP 610 AAITSEIRKK 620 ILSKLSEETK 630 VALTKLHNSL 640 NEKSIEDFIS 650 CLDSAAEACD 660 IMVKRGDKKR 670 ERQILFQHRQ 680 ALAEQLKVTE 690 DPALILHLTS 700 VLLFQFSTHS 710 MLHAPGRCVP 720 QIIAFLNSKI 730 PEDQHALLVK 740 YQGLVVKQLV 750 SQSKKTGQGD 760 YPLNNELDKE 770 QEDVASTTRK 780 ELQELSSSIK 790 DLVLKSRKSS VTEE

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0005789 endoplasmic reticulum membrane
Cellular Component GO:0016020 membrane
Cellular Component GO:0005741 mitochondrial outer membrane
Cellular Component GO:0043005 neuron projection
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0035861 site of double-strand break
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0061666 UFM1 ligase activity
Molecular Function GO:0071568 UFM1 transferase activity
Biological Process GO:0000077 DNA damage checkpoint signaling
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006281 DNA repair
Biological Process GO:0030218 erythrocyte differentiation
Biological Process GO:0060218 hematopoietic stem cell differentiation
Biological Process GO:1903895 negative regulation of IRE1-mediated unfolded protein response
Biological Process GO:0031397 negative regulation of protein ubiquitination
Biological Process GO:0050868 negative regulation of T cell activation
Biological Process GO:0002841 negative regulation of T cell mediated immune response to tumor cell
Biological Process GO:0001649 osteoblast differentiation
Biological Process GO:0010508 positive regulation of autophagy
Biological Process GO:0008284 positive regulation of cell population proliferation
Biological Process GO:1903052 positive regulation of proteolysis involved in protein catabolic process
Biological Process GO:0140501 positive regulation of reticulophagy
Biological Process GO:1990592 protein K69-linked ufmylation
Biological Process GO:0050821 protein stabilization
Biological Process GO:0071569 protein ufmylation
Biological Process GO:0043122 regulation of canonical NF-kappaB signal transduction
Biological Process GO:0050727 regulation of inflammatory response
Biological Process GO:0033146 regulation of intracellular estrogen receptor signaling pathway
Biological Process GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Process GO:0032880 regulation of protein localization
Biological Process GO:0072344 rescue of stalled cytosolic ribosome
Biological Process GO:0034976 response to endoplasmic reticulum stress
Biological Process GO:0061709 reticulophagy
Biological Process GO:0032790 ribosome disassembly

Reference

[1] 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.

[2] 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.