Protein: E3 UFM1-protein ligase 1 (EC 2.3.2.-) (E3 UFM1-protein transferase 1) (Multiple alpha-helix protein located at ER) (Regulator of C53/LZAP and DDRGK1) (B2GV24)
Organism: Rattus norvegicus (Rat)
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 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).
Subcellular location: Endoplasmic reticulum membrane {ECO:0000305|PubMed:20531390}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:O94874}. Nucleus {ECO:0000250|UniProtKB:O94874}. Chromosome {ECO:0000250|UniProtKB:O94874}. Note=Recruited to double-strand breaks by the MRE11-RAD50-NBN (MRN) complex following DNA damage. {ECO:0000250|UniProtKB:O94874}.
Sequence: MADAWEEIRRLAADFQRAQFAESTQRLSERNCIEIVNKLISQKQLEVVHTLDGKEYITPAQISKEMRDELHVRGGRVNIVDLQQVINVDLTHIENRVGDIIKSEKHVQMVLGQLVDENYLDRLSEEVNDKLQESGQVTVSELCKTYDLPGDFLTQALTQRLGRIINGHLDLDNRGVIFTEAFVARHKARIRGLFSAITRPTAVNSLVSKYGFQEQLLYSVLEELVSTGRLRGTVVGGRQDKAVFVPDIYSRTQSTWVDSFFRQNGYLEFDALSRLGIPDAVNYIKKRYKNTPLLFLKATCVGQGLVDQVEASVEEAISSGTWVDVSPLLPSSLSVEDAAMLLQQVMRPFGKHASATVFSDTVVVSEKFINDCTKLFSERMHQKAEKEMKNNPVHLITEEDLKQISILESVNTNKKDKKDERRKKATEGSGSVRGGGGGNAREYKIKKVKKKGRKDEDSDDESQSSHAGKKKPDITFMFQDEIEGCLRKHIPDAPEEFISELAEHLIKPLNKMYLEVVRSVFMSSTSASGTGRKRTIKDLQEEVSNLYNNIRLFEKGMKYFADDTQTALTKHLLKTVCTDITNLMFNFLASDLMMAVEDPATITSDMRKKILSKLTEETKVALTKLHNSLNEKSIEDFLSCLDSATEACDIMVKKGDKKRERQILFQHRQALADQLKVTEDPALILHLTSVLLFQFSTHSMLHAPGRCVPQIIAFLHNKIPEDQHTLLVKYQGLVVKQLVSQNKKSGQGEDPSSDDLDKEQHDVTNTTRKELQELSLSIKDLVLKPRKSSVTEE
InterPro domains: - IPR018611: E3 UFM1-protein ligase 1 (family) [1-788]
- IPR056579: E3 UFM1-protein ligase 1-like, N-terminal (domain) [7-284]
- IPR056761: E3 UFM1-protein ligase-like, C-terminal domain (domain) [660-781]
- IPR056580: E3 UFM1-protein ligase 1-like domain (domain) [537-654]
Interaction partners: - DDRGK domain-containing protein 1
- CDK5 regulatory subunit-associated protein 3
- Ubiquitin-fold modifier 1
- Ubiquitin-fold modifier-conjugating enzyme 1
- Ubiquitin-like modifier-activating enzyme 5
- Ufm1-specific protease 2
- UFM1-specific peptidase 1.
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0019899 (enzyme binding), GO:0019900 (kinase binding), GO:0019901 (protein kinase binding)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0006950 (response to stress), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0009894 (regulation of catabolic process), GO:0032101 (regulation of response to external stimulus), GO:0031323 (regulation of cellular metabolic process), GO:0009966 (regulation of signal transduction), GO:0031325 (positive regulation of cellular metabolic process), GO:0010646 (regulation of cell communication), GO:0033554 (cellular response to stress), GO:0080134 (regulation of response to stress), GO:0009896 (positive regulation of catabolic process), GO:0034976 (response to endoplasmic reticulum stress), GO:0010506 (regulation of autophagy), GO:0031347 (regulation of defense response), GO:0031331 (positive regulation of cellular catabolic process), GO:0050727 (regulation of inflammatory response), GO:0010508 (positive regulation of autophagy), GO:0031329 (regulation of cellular catabolic process), GO:1902531 (regulation of intracellular signal transduction), GO:0043122 (regulation of I-kappaB kinase/NF-kappaB signaling)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0005737 (cytoplasm), GO:0042995 (cell projection), GO:0120025 (plasma membrane bounded cell projection), GO:0043005 (neuron projection)