Summary

Name UFL1
Full Name E3 UFM1-protein ligase 1
Synonyms E3 UFM1-protein transferase 1, Multiple alpha-helix protein located at ER, Novel LZAP-binding protein, Regulator of C53/LZAP and DDRGK1 | KIAA0776, MAXER, NLBP, RCAD
Primary ID O94874
Links - -
Type protein
Relations 4
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 (PubMed:20018847, PubMed:20164180, PubMed:20228063, PubMed:25219498, PubMed:32160526). 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 (PubMed:32160526). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) via ERN1/IRE1-alpha (PubMed:23152784, PubMed:32160526). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response (PubMed:32050156). 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 (PubMed:20531390, PubMed:20018847). 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 (PubMed:20531390). Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 (PubMed:30886146). 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). Required for cardiac homeostasis (By similarity).

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ UFL1up-regulates activity img/direct-activation.png ubiquitination H4C1 0.2
Publications: 1 Organism: Homo Sapiens
+ ATMup-regulates activity img/direct-activation.png phosphorylation UFL1 0.2
Publications: 1 Organism: Homo Sapiens
+ MRE11/RAD50/NBS1up-regulates activity img/direct-activation.png relocalization UFL1 0.2
Publications: 1 Organism: Homo Sapiens
+ UFL1up-regulates activity img/direct-activation.png ubiquitination ATM 0.2
Publications: 1 Organism: Homo Sapiens