DDRGK domain-containing protein 1 (Dashurin) (UFM1-binding and PCI domain-containing protein 1)
1_MVAPV 6_ WYLVA 11_ AALLV 16_ GFILF 21_ LTRSR 26_ GRAAS 31_ AGQEP 36_ LHNEE 41_ LAGAG 46_ RVAQP 51_ GPLEP 56_ EEPRA 61_ GGRPR 66_ RRRDL 71_ GSRLQ 76_ AQRRA 81_ QRVAW 86_ AEADE 91_ NEEEA 96_ VILAQ 101_ EEEGV 106_ EKPAE 111_ THLSG 116_ KIGAK 121_ KLRKL 126_ EEKQA 131_ RKAQR 136_ EAEEA 141_ EREER 146_ KRLES 151_ QREAE 156_ WKKEE 161_ ERLRL 166_ EEEQK 171_ EEEER 176_ KAREE 181_ QAQRE 186_ HEEYL 191_ KLKEA 196_ FVVEE 201_ EGVGE 206_ TMTEE 211_ QSQSF 216_ LTEFI 221_ NYIKQ 226_ SKVVL 231_ LEDLA 236_ SQVGL 241_ RTQDT 246_ INRIQ 251_ DLLAE 256_ GTITG 261_ VIDDR 266_ GKFIY 271_ ITPEE 276_ LAAVA 281_ NFIRQ 286_ RGRVS 291_ IAELA 296_ QASNS 301_ LIAWG 306_RESPA
1: Component of the UFM1 ribosome E3 ligase (UREL) complex, a multiprotein complex that catalyzes ufmylation of endoplasmic reticulum-docked proteins (PubMed:30626644, PubMed:32160526, PubMed:35753586, PubMed:36121123, PubMed:36543799, PubMed:37595036, PubMed:37795761, PubMed:38383785, PubMed:38383789). The UREL complex plays a key role in ribosome recycling by mediating mono-ufmylation of the RPL26/uL24 subunit of the 60S ribosome following ribosome dissociation: ufmylation 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:37595036, PubMed:38383785, PubMed:38383789). Within the UREL complex, DDRGK1 tethers the complex to the endoplasmic reticulum membrane to restrict its activity to endoplasmic reticulum-docked ribosomes and acts as an ufmylation 'reader': following RPL26/uL24 ufmylation, DDRGK1 specifically binds to ufmylated RPL26/uL24 via its UFIM motif, resulting in stable association between the 60S ribosome and the UREL complex, followed by dissociation of the 60S ribosome subunit from the endoplasmic reticulum membrane (PubMed:36121123, PubMed:37595036, PubMed:38383785, PubMed:38383789). The UREL complex is also involved in reticulophagy in response to endoplasmic reticulum stress by promoting ufmylation of proteins such as CYB5R3 and RPN1, thereby promoting lysosomal degradation of ufmylated proteins (PubMed:32160526, PubMed:36543799). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability (PubMed:28128204, PubMed:32160526). Acts as a regulator of immunity by promoting differentiation of B-cells into plasma cells: acts by promoting expansion of the endoplasmic reticulum and regulating the unfolded protein response (UPR) (By similarity). May also be required for TRIP4 ufmylation (PubMed:25219498). May play a role in NF-kappa-B-mediated transcription through regulation of the phosphorylation and the degradation of NFKBIA, the inhibitor of NF-kappa-B (PubMed:23675531). Plays a role in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator (PubMed:28263186). Required for stabilization and ufmylation of ATG9A (By similarity)