UniProtKB - B2GV24 (UFL1_RAT)
E3 UFM1-protein ligase 1
Ufl1
Functioni
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 reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress. In response to endoplasmic reticulum stress, recruited to the endoplasmic reticulum membrane by DDRGK1, and mediates ufmylation of proteins such as RPN1 and RPL26/uL24, thereby promoting reticulophagy of endoplasmic reticulum sheets. Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) via ERN1/IRE1-alpha. Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response (By similarity).
Regulates inflammation in response to endoplasmic reticulum stress by promoting reticulophagy, leading to inhibit the activity of the NF-kappa-B transcription factor (By similarity).
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 (By similarity).
Catalyzes ufmylation of various subunits of the ribosomal complex or associated components, such as RPS3/uS3, RPS20/uS10, RPL10/uL16, RPL26/uL24 and EIF6 (By similarity).
Anchors CDK5RAP3 in the cytoplasm, preventing its translocation to the nucleus which allows expression of the CCND1 cyclin and progression of cells through the G1/S transition. Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4. Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear receptor-mediated transcription (By similarity).
Required for hematopoietic stem cell function and hematopoiesis. Required for cardiac homeostasis (By similarity).
By similarityGO - Molecular functioni
- protein kinase binding Source: RGD
- UFM1 ligase activity Source: UniProtKB
- UFM1 transferase activity Source: GO_Central
GO - Biological processi
- cellular response to DNA damage stimulus Source: UniProtKB
- DNA repair Source: UniProtKB-KW
- erythrocyte differentiation Source: UniProtKB
- hematopoietic stem cell differentiation Source: UniProtKB
- histone modification Source: UniProtKB
- negative regulation of apoptotic process Source: ParkinsonsUK-UCL
- negative regulation of IRE1-mediated unfolded protein response Source: UniProtKB
- negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
- negative regulation of protein ubiquitination Source: UniProtKB
- positive regulation of autophagy Source: UniProtKB
- positive regulation of cell population proliferation Source: RGD
- positive regulation of glial cell proliferation Source: RGD
- protein K69-linked ufmylation Source: UniProtKB
- protein ufmylation Source: UniProtKB
- regulation of gene expression Source: RGD
- regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- regulation of inflammatory response Source: UniProtKB
- regulation of intracellular estrogen receptor signaling pathway Source: UniProtKB
- regulation of proteasomal ubiquitin-dependent protein catabolic process Source: RGD
- regulation of protein localization Source: RGD
- response to endoplasmic reticulum stress Source: UniProtKB
- response to L-glutamate Source: RGD
- reticulophagy Source: UniProtKB
Keywordsi
Molecular function | Transferase |
Biological process | DNA damage, DNA repair, Ubl conjugation pathway |
Enzyme and pathway databases
Reactomei | R-RNO-983168, Antigen processing: Ubiquitination & Proteasome degradation |
Names & Taxonomyi
Protein namesi | Recommended name: E3 UFM1-protein ligase 1Curated (EC:2.3.2.-By similarity)Alternative name(s): E3 UFM1-protein transferase 1Curated Multiple alpha-helix protein located at ER1 Publication Regulator of C53/LZAP and DDRGK11 Publication |
Gene namesi | |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 1309308, Ufl1 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication
Cytoplasm and Cytosol
- cytosol By similarity
Nucleus
- Nucleus By similarity
Other locations
- Chromosome By similarity
Note: Recruited to double-strand breaks by the MRE11-RAD50-NBN (MRN) complex following DNA damage.By similarity
Cytosol
- cytosol Source: UniProtKB-SubCell
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- neuron projection Source: RGD
- protein-containing complex Source: RGD
- site of double-strand break Source: UniProtKB
Keywords - Cellular componenti
Chromosome, Cytoplasm, Endoplasmic reticulum, Membrane, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000391875 | 2 – 793 | E3 UFM1-protein ligase 1Add BLAST | 792 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineBy similarity | 1 | |
Modified residuei | 433 | Omega-N-methylarginineBy similarity | 1 | |
Modified residuei | 458 | PhosphoserineCombined sources | 1 | |
Modified residuei | 462 | PhosphoserineBy similarity | 1 | |
Modified residuei | 752 | PhosphoserineBy similarity | 1 | |
Modified residuei | 753 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | B2GV24 |
PaxDbi | B2GV24 |
PeptideAtlasi | B2GV24 |
PRIDEi | B2GV24 |
PTM databases
iPTMneti | B2GV24 |
PhosphoSitePlusi | B2GV24 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSRNOG00000007831, Expressed in pancreas and 21 other tissues |
ExpressionAtlasi | B2GV24, baseline and differential |
Genevisiblei | B2GV24, RN |
Interactioni
Subunit structurei
Interacts with DDRGK1 (via PCI domain) (By similarity).
Interacts with UFC1 (By similarity).
Interacts with RELA (By similarity).
Interacts with TRIP4 (By similarity).
Interacts with CDK5RAP3; the interaction is direct (PubMed:20531390).
Interacts with NBN; promoting recruitment to double-strand breaks following DNA damage (By similarity).
By similarity1 PublicationGO - Molecular functioni
- protein kinase binding Source: RGD
Protein-protein interaction databases
IntActi | B2GV24, 2 interactors |
MINTi | B2GV24 |
STRINGi | 10116.ENSRNOP00000010421 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 212 | Required for E3 UFM1-protein ligase activityBy similarityAdd BLAST | 211 | |
Regioni | 2 – 200 | Mediates interaction with DDRGK1By similarityAdd BLAST | 199 | |
Regioni | 121 – 250 | Involved in CDK5RAP3-bindingBy similarityAdd BLAST | 130 | |
Regioni | 200 – 400 | Mediates interaction with TRIP4By similarityAdd BLAST | 201 | |
Regioni | 410 – 473 | DisorderedSequence analysisAdd BLAST | 64 | |
Regioni | 490 – 683 | Mediates interaction with CDK5RAP31 PublicationAdd BLAST | 194 | |
Regioni | 742 – 769 | DisorderedSequence analysisAdd BLAST | 28 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 411 – 428 | Basic and acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 449 – 473 | Basic and acidic residuesSequence analysisAdd BLAST | 25 | |
Compositional biasi | 748 – 768 | Basic and acidic residuesSequence analysisAdd BLAST | 21 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2235, Eukaryota |
GeneTreei | ENSGT00390000002112 |
HOGENOMi | CLU_012417_1_0_1 |
InParanoidi | B2GV24 |
OMAi | QTNRRQT |
OrthoDBi | 289380at2759 |
PhylomeDBi | B2GV24 |
TreeFami | TF319116 |
Family and domain databases
InterProi | View protein in InterPro IPR018611, Ufl1 |
PANTHERi | PTHR31057, PTHR31057, 1 hit |
Pfami | View protein in Pfam PF09743, E3_UFM1_ligase, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MADAWEEIRR LAADFQRAQF AESTQRLSER NCIEIVNKLI SQKQLEVVHT
60 70 80 90 100
LDGKEYITPA QISKEMRDEL HVRGGRVNIV DLQQVINVDL THIENRVGDI
110 120 130 140 150
IKSEKHVQMV LGQLVDENYL DRLSEEVNDK LQESGQVTVS ELCKTYDLPG
160 170 180 190 200
DFLTQALTQR LGRIINGHLD LDNRGVIFTE AFVARHKARI RGLFSAITRP
210 220 230 240 250
TAVNSLVSKY GFQEQLLYSV LEELVSTGRL RGTVVGGRQD KAVFVPDIYS
260 270 280 290 300
RTQSTWVDSF FRQNGYLEFD ALSRLGIPDA VNYIKKRYKN TPLLFLKATC
310 320 330 340 350
VGQGLVDQVE ASVEEAISSG TWVDVSPLLP SSLSVEDAAM LLQQVMRPFG
360 370 380 390 400
KHASATVFSD TVVVSEKFIN DCTKLFSERM HQKAEKEMKN NPVHLITEED
410 420 430 440 450
LKQISILESV NTNKKDKKDE RRKKATEGSG SVRGGGGGNA REYKIKKVKK
460 470 480 490 500
KGRKDEDSDD ESQSSHAGKK KPDITFMFQD EIEGCLRKHI PDAPEEFISE
510 520 530 540 550
LAEHLIKPLN KMYLEVVRSV FMSSTSASGT GRKRTIKDLQ EEVSNLYNNI
560 570 580 590 600
RLFEKGMKYF ADDTQTALTK HLLKTVCTDI TNLMFNFLAS DLMMAVEDPA
610 620 630 640 650
TITSDMRKKI LSKLTEETKV ALTKLHNSLN EKSIEDFLSC LDSATEACDI
660 670 680 690 700
MVKKGDKKRE RQILFQHRQA LADQLKVTED PALILHLTSV LLFQFSTHSM
710 720 730 740 750
LHAPGRCVPQ IIAFLHNKIP EDQHTLLVKY QGLVVKQLVS QNKKSGQGED
760 770 780 790
PSSDDLDKEQ HDVTNTTRKE LQELSLSIKD LVLKPRKSSV TEE
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0G2K266 | A0A0G2K266_RAT | E3 UFM1-protein ligase 1 | Ufl1 | 739 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC166498 mRNA Translation: AAI66498.1 |
RefSeqi | NP_001119751.1, NM_001126279.1 |
Genome annotation databases
Ensembli | ENSRNOT00000010421; ENSRNOP00000010421; ENSRNOG00000007831 |
GeneIDi | 313115 |
KEGGi | rno:313115 |
UCSCi | RGD:1309308, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC166498 mRNA Translation: AAI66498.1 |
RefSeqi | NP_001119751.1, NM_001126279.1 |
3D structure databases
SMRi | B2GV24 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | B2GV24, 2 interactors |
MINTi | B2GV24 |
STRINGi | 10116.ENSRNOP00000010421 |
PTM databases
iPTMneti | B2GV24 |
PhosphoSitePlusi | B2GV24 |
Proteomic databases
jPOSTi | B2GV24 |
PaxDbi | B2GV24 |
PeptideAtlasi | B2GV24 |
PRIDEi | B2GV24 |
Genome annotation databases
Ensembli | ENSRNOT00000010421; ENSRNOP00000010421; ENSRNOG00000007831 |
GeneIDi | 313115 |
KEGGi | rno:313115 |
UCSCi | RGD:1309308, rat |
Organism-specific databases
CTDi | 23376 |
RGDi | 1309308, Ufl1 |
Phylogenomic databases
eggNOGi | KOG2235, Eukaryota |
GeneTreei | ENSGT00390000002112 |
HOGENOMi | CLU_012417_1_0_1 |
InParanoidi | B2GV24 |
OMAi | QTNRRQT |
OrthoDBi | 289380at2759 |
PhylomeDBi | B2GV24 |
TreeFami | TF319116 |
Enzyme and pathway databases
Reactomei | R-RNO-983168, Antigen processing: Ubiquitination & Proteasome degradation |
Miscellaneous databases
PROi | PR:B2GV24 |
Gene expression databases
Bgeei | ENSRNOG00000007831, Expressed in pancreas and 21 other tissues |
ExpressionAtlasi | B2GV24, baseline and differential |
Genevisiblei | B2GV24, RN |
Family and domain databases
InterProi | View protein in InterPro IPR018611, Ufl1 |
PANTHERi | PTHR31057, PTHR31057, 1 hit |
Pfami | View protein in Pfam PF09743, E3_UFM1_ligase, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | UFL1_RAT | |
Accessioni | B2GV24Primary (citable) accession number: B2GV24 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 2, 2010 |
Last sequence update: | June 10, 2008 | |
Last modified: | February 23, 2022 | |
This is version 90 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families