ID DDRGK_HUMAN Reviewed; 314 AA. AC Q96HY6; A6NIU5; C9JSZ5; Q9BW47; DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 26-SEP-2003, sequence version 2. DT 28-JAN-2026, entry version 184. DE RecName: Full=DDRGK domain-containing protein 1 {ECO:0000305}; DE AltName: Full=Dashurin {ECO:0000303|PubMed:20036718}; DE AltName: Full=UFM1-binding and PCI domain-containing protein 1 {ECO:0000303|PubMed:36543799}; GN Name=DDRGK1 {ECO:0000303|PubMed:20228063, GN ECO:0000312|HGNC:HGNC:16110}; GN Synonyms=C20orf116 {ECO:0000312|HGNC:HGNC:16110}, UFBP1 GN {ECO:0000303|PubMed:36543799}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Liver; RX PubMed=20036718; DOI=10.1016/j.bbagen.2009.12.004; RA Neziri D., Ilhan A., Maj M., Majdic O., Baumgartner-Parzer S., Cohen G., RA Base W., Wagner L.; RT "Cloning and molecular characterization of Dashurin encoded by C20orf116, a RT PCI-domain containing protein."; RL Biochim. Biophys. Acta 1800:430-438(2010). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-303. RC TISSUE=Brain, Lymph, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP UFMYLATION AT LYS-267, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP MUTAGENESIS OF LYS-116; LYS-121; LYS-124; LYS-128; LYS-193; LYS-224; RP LYS-227 AND LYS-267. RX PubMed=20018847; DOI=10.1074/jbc.m109.036814; RA Tatsumi K., Sou Y.S., Tada N., Nakamura E., Iemura S., Natsume T., RA Kang S.H., Chung C.H., Kasahara M., Kominami E., Yamamoto M., Tanaka K., RA Komatsu M.; RT "A novel type of E3 ligase for the Ufm1 conjugation system."; RL J. Biol. Chem. 285:5417-5427(2010). RN [7] RP INTERACTION WITH CDK5RAP3, REGION, SUBCELLULAR LOCATION, AND RP UBIQUITINATION. RX PubMed=20228063; DOI=10.1074/jbc.m110.110619; RA Wu J., Lei G., Mei M., Tang Y., Li H.; RT "A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and RT DDRGK domain-containing Protein 1 (DDRGK1) and modulates NF-kappaB RT signaling."; RL J. Biol. Chem. 285:15126-15136(2010). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] RP FUNCTION, AND INTERACTION WITH NFKBIA. RX PubMed=23675531; DOI=10.1371/journal.pone.0064231; RA Xi P., Ding D., Zhou J., Wang M., Cong Y.S.; RT "DDRGK1 regulates NF-kappaB activity by modulating IkappaBalpha RT stability."; RL PLoS ONE 8:E64231-E64231(2013). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] RP FUNCTION, INTERACTION WITH UFL1, REGION, AND MUTAGENESIS OF LYS-267. RX PubMed=25219498; DOI=10.1016/j.molcel.2014.08.007; RA Yoo H.M., Kang S.H., Kim J.Y., Lee J.E., Seong M.W., Lee S.W., Ka S.H., RA Sou Y.S., Komatsu M., Tanaka K., Lee S.T., Noh D.Y., Baek S.H., Jeon Y.J., RA Chung C.H.; RT "Modification of ASC1 by UFM1 is crucial for ERalpha transactivation and RT breast cancer development."; RL Mol. Cell 56:261-274(2014). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [14] RP INVOLVEMENT IN SEMDSH, FUNCTION, AND INTERACTION WITH SOX9. RX PubMed=28263186; DOI=10.1172/jci90193; RA Egunsola A.T., Bae Y., Jiang M.M., Liu D.S., Chen-Evenson Y., Bertin T., RA Chen S., Lu J.T., Nevarez L., Magal N., Raas-Rothschild A., Swindell E.C., RA Cohn D.H., Gibbs R.A., Campeau P.M., Shohat M., Lee B.H.; RT "Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal RT dysplasia."; RL J. Clin. Invest. 127:1475-1484(2017). RN [15] RP UFMYLATION AT LYS-267, AND MUTAGENESIS OF LYS-267. RX PubMed=27926783; DOI=10.1002/1873-3468.12518; RA Ishimura R., Obata M., Kageyama S., Daniel J., Tanaka K., Komatsu M.; RT "A novel approach to assess the ubiquitin-fold modifier 1-system in RT cells."; RL FEBS Lett. 591:196-204(2017). RN [16] RP FUNCTION, INTERACTION WITH ERN1, UFMYLATION AT LYS-267, AND MUTAGENESIS OF RP LYS-267. RX PubMed=28128204; DOI=10.1038/ncomms14186; RA Liu J., Wang Y., Song L., Zeng L., Yi W., Liu T., Chen H., Wang M., Ju Z., RA Cong Y.S.; RT "A critical role of DDRGK1 in endoplasmic reticulum homoeostasis via RT regulation of IRE1alpha stability."; RL Nat. Commun. 8:14186-14186(2017). RN [17] RP FUNCTION. RX PubMed=30626644; DOI=10.1073/pnas.1816202116; RA Walczak C.P., Leto D.E., Zhang L., Riepe C., Muller R.Y., DaRosa P.A., RA Ingolia N.T., Elias J.E., Kopito R.R.; RT "Ribosomal protein RPL26 is the principal target of UFMylation."; RL Proc. Natl. Acad. Sci. U.S.A. 116:1299-1308(2019). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH UFL1, AND MUTAGENESIS OF RP 116-LYS--LYS-128; LYS-146; LYS-176; LYS-193; 224-LYS--LYS-227 AND LYS-267. RX PubMed=32160526; DOI=10.1016/j.cell.2020.02.017; RA Liang J.R., Lingeman E., Luong T., Ahmed S., Muhar M., Nguyen T., RA Olzmann J.A., Corn J.E.; RT "A genome-wide ER-phagy screen highlights key roles of mitochondrial RT metabolism and ER-Resident UFMylation."; RL Cell 180:1160-1177(2020). RN [19] RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE UREL COMPLEX. RX PubMed=36121123; DOI=10.15252/embj.2022111015; RA Peter J.J., Magnussen H.M., DaRosa P.A., Millrine D., Matthews S.P., RA Lamoliatte F., Sundaramoorthy R., Kopito R.R., Kulathu Y.; RT "A non-canonical scaffold-type E3 ligase complex mediates protein RT UFMylation."; RL EMBO J. 41:e111015-e111015(2022). RN [20] RP FUNCTION. RX PubMed=35753586; DOI=10.1016/j.freeradbiomed.2022.06.237; RA Zhu J., Ma X., Jing Y., Zhang G., Zhang D., Mao Z., Ma X., Liu H., Chen F.; RT "P4HB UFMylation regulates mitochondrial function and oxidative stress."; RL Free Radic. Biol. Med. 188:277-286(2022). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE UREL COMPLEX, DOMAIN, RP AND MUTAGENESIS OF 196-PHE--VAL-198 AND LYS-267. RX PubMed=36543799; DOI=10.1038/s41467-022-35501-0; RA Ishimura R., El-Gowily A.H., Noshiro D., Komatsu-Hirota S., Ono Y., RA Shindo M., Hatta T., Abe M., Uemura T., Lee-Okada H.C., Mohamed T.M., RA Yokomizo T., Ueno T., Sakimura K., Natsume T., Sorimachi H., Inada T., RA Waguri S., Noda N.N., Komatsu M.; RT "The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3."; RL Nat. Commun. 13:7857-7857(2022). RN [22] RP FUNCTION. RX PubMed=37795761; DOI=10.1096/fj.202300004rrrr; RA Luo H., Jiao Q.B., Shen C.B., Gong W.Y., Yuan J.H., Liu Y.Y., Chen Z., RA Liu J., Xu X.L., Cong Y.S., Zhang X.W.; RT "UFMylation of HRD1 regulates endoplasmic reticulum homeostasis."; RL FASEB J. 37:e23221-e23221(2023). RN [23] RP FUNCTION, IDENTIFICATION IN THE UREL COMPLEX, DOMAIN, AND MUTAGENESIS OF RP 196-PHE--VAL-198; 271-ILE--LEU-276 AND 302-ILE--TRP-304. RX PubMed=37595036; DOI=10.1126/sciadv.adh3635; RA Ishimura R., Ito S., Mao G., Komatsu-Hirota S., Inada T., Noda N.N., RA Komatsu M.; RT "Mechanistic insights into the roles of the UFM1 E3 ligase complex in RT ufmylation and ribosome-associated protein quality control."; RL Sci. Adv. 9:eadh3635-eadh3635(2023). RN [24] {ECO:0007744|PDB:8B9X} RP X-RAY CRYSTALLOGRAPHY (3.07 ANGSTROMS) OF 207-305 IN COMPLEX WITH UFL1. RX PubMed=37988244; DOI=10.15252/embr.202356920; RA Banerjee S., Varga J.K., Kumar M., Zoltsman G., Rotem-Bamberger S., RA Cohen-Kfir E., Isupov M.N., Rosenzweig R., Schueler-Furman O., Wiener R.; RT "Structural study of UFL1-UFC1 interaction uncovers the role of UFL1 N- RT terminal helix in ufmylation."; RL EMBO Rep. 24:e56920-e56920(2023). RN [25] {ECO:0007744|PDB:8C0D} RP X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) OF 205-314 IN COMPLEX WITH UFL1 AND RP UFC1, FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE UREL COMPLEX, RP DOMAIN, AND MUTAGENESIS OF ARG-265. RX PubMed=38383789; DOI=10.1038/s41586-024-07093-w; RA Makhlouf L., Peter J.J., Magnussen H.M., Thakur R., Millrine D., RA Minshull T.C., Harrison G., Varghese J., Lamoliatte F., Foglizzo M., RA Macartney T., Calabrese A.N., Zeqiraj E., Kulathu Y.; RT "The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER RT translocons."; RL Nature 627:437-444(2024). RN [26] {ECO:0007744|PDB:8OHD, ECO:0007744|PDB:8OJ0, ECO:0007744|PDB:8OJ5} RP STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) OF THE UREL COMPLEX IN RP COMPLEX WITH THE 60S RIBOSOME, FUNCTION, SUBCELLULAR LOCATION, RP IDENTIFICATION IN THE UREL COMPLEX, DOMAIN, AND MUTAGENESIS OF RP 196-PHE--GLU-201. RX PubMed=38383785; DOI=10.1038/s41586-024-07073-0; RA DaRosa P.A., Penchev I., Gumbin S.C., Scavone F., Wachalska M., Paulo J.A., RA Ordureau A., Peter J.J., Kulathu Y., Harper J.W., Becker T., Beckmann R., RA Kopito R.R.; RT "UFM1 E3 ligase promotes recycling of 60S ribosomal subunits from the ER."; RL Nature 627:445-452(2024). CC -!- FUNCTION: Component of the UFM1 ribosome E3 ligase (UREL) complex, a CC multiprotein complex that catalyzes ufmylation of endoplasmic CC reticulum-docked proteins (PubMed:30626644, PubMed:32160526, CC PubMed:35753586, PubMed:36121123, PubMed:36543799, PubMed:37595036, CC PubMed:37795761, PubMed:38383785, PubMed:38383789). The UREL complex CC plays a key role in ribosome recycling by mediating mono-ufmylation of CC the RPL26/uL24 subunit of the 60S ribosome following ribosome CC dissociation: ufmylation weakens the junction between post-termination CC 60S subunits and SEC61 translocons, promoting release and recycling of CC the large ribosomal subunit from the endoplasmic reticulum membrane CC (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 and CC subsequent 60S ribosome recycling either take place after normal CC termination of translation or after ribosome stalling during CC cotranslational translocation at the endoplasmic reticulum CC (PubMed:37595036, PubMed:38383785, PubMed:38383789). Within the UREL CC complex, DDRGK1 tethers the complex to the endoplasmic reticulum CC membrane to restrict its activity to endoplasmic reticulum-docked CC ribosomes and acts as an ufmylation 'reader': following RPL26/uL24 CC ufmylation, DDRGK1 specifically binds to ufmylated RPL26/uL24 via its CC UFIM motif, resulting in stable association between the 60S ribosome CC and the UREL complex, followed by dissociation of the 60S ribosome CC subunit from the endoplasmic reticulum membrane (PubMed:36121123, CC PubMed:37595036, PubMed:38383785, PubMed:38383789). The UREL complex is CC also involved in reticulophagy in response to endoplasmic reticulum CC stress by promoting ufmylation of proteins such as CYB5R3 and RPN1, CC thereby promoting lysosomal degradation of ufmylated proteins CC (PubMed:32160526, PubMed:36543799). Ufmylation-dependent reticulophagy CC inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1- CC alpha stability (PubMed:28128204, PubMed:32160526). Acts as a regulator CC of immunity by promoting differentiation of B-cells into plasma cells: CC acts by promoting expansion of the endoplasmic reticulum and regulating CC the unfolded protein response (UPR) (By similarity). May also be CC required for TRIP4 ufmylation (PubMed:25219498). May play a role in NF- CC kappa-B-mediated transcription through regulation of the CC phosphorylation and the degradation of NFKBIA, the inhibitor of NF- CC kappa-B (PubMed:23675531). Plays a role in cartilage development CC through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation CC of this transcriptional regulator (PubMed:28263186). Required for CC stabilization and ufmylation of ATG9A (By similarity). CC {ECO:0000250|UniProtKB:Q80WW9, ECO:0000269|PubMed:23675531, CC ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:28128204, CC ECO:0000269|PubMed:28263186, ECO:0000269|PubMed:30626644, CC ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:35753586, CC ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:36543799, CC ECO:0000269|PubMed:37595036, ECO:0000269|PubMed:37795761, CC ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}. CC -!- SUBUNIT: Component of the UFM1 ribosome E3 ligase (UREL) complex, CC composed of UFL1, DDRGK1 and CDK5RAP3 (PubMed:20228063, CC PubMed:25219498, PubMed:32160526, PubMed:36121123, PubMed:36543799, CC PubMed:37595036, PubMed:38383785, PubMed:38383789). Interacts with CC (unphosphorylated) ERN1/IRE1-alpha; interaction is dependent on UFM1 CC and takes place in response to endoplasmic reticulum stress, regulating CC ERN1/IRE1-alpha stability (PubMed:28128204). Interacts with NFKBIA CC (PubMed:23675531). Interacts with SOX9 (PubMed:28263186). CC {ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:23675531, CC ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:28128204, CC ECO:0000269|PubMed:28263186, ECO:0000269|PubMed:32160526, CC ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:36543799, CC ECO:0000269|PubMed:37595036, ECO:0000269|PubMed:38383785, CC ECO:0000269|PubMed:38383789}. CC -!- INTERACTION: CC Q96HY6; Q96JB5: CDK5RAP3; NbExp=6; IntAct=EBI-1054024, EBI-718818; CC Q96HY6; P13569: CFTR; NbExp=4; IntAct=EBI-1054024, EBI-349854; CC Q96HY6; O94874: UFL1; NbExp=10; IntAct=EBI-1054024, EBI-1048088; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:32160526, CC ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:38383785, CC ECO:0000269|PubMed:38383789}; Single-pass membrane protein CC {ECO:0000305|PubMed:38383785, ECO:0000305|PubMed:38383789}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96HY6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96HY6-2; Sequence=VSP_008391; CC -!- TISSUE SPECIFICITY: Widely expressed (at protein level). In the brain, CC highest levels in medulla oblongata, followed by cerebral cortex, CC cerebellum and frontal lobe. {ECO:0000269|PubMed:20018847, CC ECO:0000269|PubMed:20036718}. CC -!- DOMAIN: The UFM1-interacting motif (UFIM) specifically recognizes and CC binds ufmylated RPL26/uL24, resulting in stable association between the CC 60S ribosome and the UREL complex. {ECO:0000269|PubMed:36543799, CC ECO:0000269|PubMed:37595036, ECO:0000269|PubMed:38383785, CC ECO:0000269|PubMed:38383789}. CC -!- PTM: Ubiquitinated. Ubiquitination probably triggers proteasomal CC degradation and is negatively regulated by UFL1, the enzyme involved in CC the ufmylation of DDRGK1. {ECO:0000269|PubMed:20228063}. CC -!- PTM: Ufmylated; conjugated to ubiquitin-like protein UFM1, probably at CC Lys-267 by UFL1 (PubMed:20018847, PubMed:27926783, PubMed:28128204). CC The relevance of ufmylation is however unclear: as DDRGK1 acts as a CC substrate adapters for ufmylation, it is uncertain whether ufmylation CC is a collateral effect of ufmylation process or is required to regulate CC its activity (PubMed:32160526). {ECO:0000269|PubMed:20018847, CC ECO:0000269|PubMed:27926783, ECO:0000269|PubMed:28128204, CC ECO:0000269|PubMed:32160526}. CC -!- DISEASE: Spondyloepimetaphyseal dysplasia, Shohat type (SEMDSH) CC [MIM:602557]: An autosomal recessive skeletal dysplasia that affects CC cartilage development. It is characterized by vertebral, epiphyseal, CC and metaphyseal abnormalities, including scoliosis with vertebral CC compression fractures, flattened vertebral bodies, and CC hypomineralization of long bones. Affected individuals may exhibit a CC small trunk, short neck, small limbs, joint laxity, bowlegs, and/or CC abdominal distension with hepatosplenomegaly. CC {ECO:0000269|PubMed:28263186}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the DDRGK1 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL121891; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471133; EAX10544.1; -; Genomic_DNA. DR EMBL; BC000643; AAH00643.1; -; mRNA. DR EMBL; BC007957; AAH07957.1; -; mRNA. DR EMBL; BC011851; AAH11851.1; -; mRNA. DR CCDS; CCDS13050.1; -. [Q96HY6-1] DR RefSeq; NP_076424.1; NM_023935.3. [Q96HY6-1] DR PDB; 7W3N; X-ray; 1.60 A; A=194-202. DR PDB; 8B9X; X-ray; 3.07 A; A/B=207-305. DR PDB; 8C0D; X-ray; 2.56 A; B/E=205-314. DR PDB; 8OHD; EM; 3.10 A; C=1-314. DR PDB; 8OJ0; EM; 3.30 A; C=1-314. DR PDB; 8OJ5; EM; 2.90 A; C=1-314. DR PDB; 8QFC; EM; 3.20 A; D=29-314. DR PDB; 9GY4; EM; 3.00 A; C=1-314. DR PDBsum; 7W3N; -. DR PDBsum; 8B9X; -. DR PDBsum; 8C0D; -. DR PDBsum; 8OHD; -. DR PDBsum; 8OJ0; -. DR PDBsum; 8OJ5; -. DR PDBsum; 8QFC; -. DR PDBsum; 9GY4; -. DR AlphaFoldDB; Q96HY6; -. DR EMDB; EMD-16880; -. DR EMDB; EMD-16902; -. DR EMDB; EMD-16905; -. DR EMDB; EMD-18381; -. DR EMDB; EMD-51681; -. DR SMR; Q96HY6; -. DR BioGRID; 122441; 1289. DR ComplexPortal; CPX-8304; UFM1 ribosome E3 ligase complex. DR FunCoup; Q96HY6; 1151. DR IntAct; Q96HY6; 70. DR MINT; Q96HY6; -. DR STRING; 9606.ENSP00000346483; -. DR iPTMnet; Q96HY6; -. DR PhosphoSitePlus; Q96HY6; -. DR SwissPalm; Q96HY6; -. DR BioMuta; DDRGK1; -. DR DMDM; 37077728; -. DR jPOST; Q96HY6; -. DR MassIVE; Q96HY6; -. DR PaxDb; 9606-ENSP00000346483; -. DR PeptideAtlas; Q96HY6; -. DR ProteomicsDB; 76794; -. [Q96HY6-1] DR ProteomicsDB; 76795; -. [Q96HY6-2] DR Pumba; Q96HY6; -. DR Antibodypedia; 2721; 73 antibodies from 18 providers. DR DNASU; 65992; -. DR Ensembl; ENST00000354488.8; ENSP00000346483.3; ENSG00000198171.14. [Q96HY6-1] DR GeneID; 65992; -. DR KEGG; hsa:65992; -. DR MANE-Select; ENST00000354488.8; ENSP00000346483.3; NM_023935.3; NP_076424.1. DR UCSC; uc002wic.4; human. [Q96HY6-1] DR AGR; HGNC:16110; -. DR ClinPGx; PA164718734; -. DR CTD; 65992; -. DR DisGeNET; 65992; -. DR GeneCards; DDRGK1; -. DR HGNC; HGNC:16110; DDRGK1. DR HPA; ENSG00000198171; Low tissue specificity. DR MalaCards; DDRGK1; -. DR MIM; 602557; phenotype. DR MIM; 616177; gene. DR OpenTargets; ENSG00000198171; -. DR Orphanet; 93352; Spondyloepimetaphyseal dysplasia, Shohat type. DR VEuPathDB; HostDB:ENSG00000198171; -. DR eggNOG; KOG3054; Eukaryota. DR GeneTree; ENSGT00390000017193; -. DR HOGENOM; CLU_059562_0_0_1; -. DR InParanoid; Q96HY6; -. DR OMA; EFTRECN; -. DR OrthoDB; 2285710at2759; -. DR PAN-GO; Q96HY6; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q96HY6; -. DR PathwayCommons; Q96HY6; -. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR SignaLink; Q96HY6; -. DR Agora; ENSG00000198171; -. DR BioGRID-ORCS; 65992; 90 hits in 1164 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; DDRGK1; human. DR GenomeRNAi; 65992; -. DR Pharos; Q96HY6; Tbio. DR PRO; PR:Q96HY6; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q96HY6; protein. DR Bgee; ENSG00000198171; Expressed in tendon of biceps brachii and 194 other cell types or tissues. DR ExpressionAtlas; Q96HY6; baseline and differential. DR GO; GO:0005737; C:cytoplasm; TAS:ParkinsonsUK-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB. DR GO; GO:0141185; F:UFM1-modified protein reader activity; IDA:UniProtKB. DR GO; GO:0051216; P:cartilage development; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:ParkinsonsUK-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ParkinsonsUK-UCL. DR GO; GO:1903895; P:negative regulation of IRE1-mediated unfolded protein response; IDA:UniProtKB. DR GO; GO:1903898; P:negative regulation of PERK-mediated unfolded protein response; ISS:UniProtKB. DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:ParkinsonsUK-UCL. DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; IC:ParkinsonsUK-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:ParkinsonsUK-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:ParkinsonsUK-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ParkinsonsUK-UCL. DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; IMP:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:1900100; P:positive regulation of plasma cell differentiation; ISS:UniProtKB. DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; IMP:UniProtKB. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:1905552; P:positive regulation of protein localization to endoplasmic reticulum; ISS:ParkinsonsUK-UCL. DR GO; GO:1903052; P:positive regulation of proteolysis involved in protein catabolic process; IDA:UniProt. DR GO; GO:0140501; P:positive regulation of reticulophagy; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:ParkinsonsUK-UCL. DR GO; GO:1990592; P:protein K69-linked ufmylation; IDA:UniProtKB. DR GO; GO:0070972; P:protein localization to endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0071569; P:protein ufmylation; IDA:UniProtKB. DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB. DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB. DR GO; GO:0061709; P:reticulophagy; IDA:UniProtKB. DR GO; GO:0032790; P:ribosome disassembly; IDA:UniProtKB. DR FunFam; 1.10.10.10:FF:000143; DDRGK domain-containing protein 1; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR InterPro; IPR019153; DDRGK_dom-contain. DR InterPro; IPR050899; DDRGK_domain-containing. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR48176; DDRGK DOMAIN-CONTAINING PROTEIN 1; 1. DR PANTHER; PTHR48176:SF1; DDRGK DOMAIN-CONTAINING PROTEIN 1; 1. DR Pfam; PF09756; DDRGK; 1. DR SMART; SM01128; DDRGK; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Dwarfism; Endoplasmic reticulum; KW Isopeptide bond; Membrane; Phosphoprotein; Proteomics identification; KW Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation; KW Ubl conjugation pathway. FT CHAIN 1..314 FT /note="DDRGK domain-containing protein 1" FT /id="PRO_0000021033" FT TRANSMEM 1..28 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:38383785" FT TOPO_DOM 29..314 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:38383785" FT DOMAIN 229..273 FT /note="PCI" FT REGION 1..114 FT /note="Mediates interaction with CDK5RAP3" FT /evidence="ECO:0000269|PubMed:20228063" FT REGION 31..75 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 100..186 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 118..216 FT /note="Mediates interaction with TRIP4" FT /evidence="ECO:0000269|PubMed:25219498" FT REGION 216..314 FT /note="Mediates interaction with UFL1" FT /evidence="ECO:0000269|PubMed:25219498" FT MOTIF 195..209 FT /note="UFM1-interacting motif (UFIM)" FT /evidence="ECO:0000269|PubMed:37595036, FT ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789" FT COMPBIAS 124..186 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 72 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 114 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT CROSSLNK 267 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in UFM1)" FT /evidence="ECO:0000269|PubMed:27926783, FT ECO:0000305|PubMed:20018847, ECO:0000305|PubMed:28128204" FT VAR_SEQ 244..299 FT /note="DTINRIQDLLAEGTITGVIDDRGKFIYITPEELAAVANFIRQRGRVSIAELA FT QASN -> VSPGTWPAVCSVARGLWLAERTCPKDRVLMHRLPCPQPRVSSAQKSPGTLG FT ILHF (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_008391" FT VARIANT 303 FT /note="A -> T (in dbSNP:rs11591)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_016923" FT MUTAGEN 116..128 FT /note="KIGAKKLRKLEEK->RIGARRLRRLEER: Impairs some FT post-translational modification without affecting FT interaction with UFL1; when associated with R-146, R-176, FT R-193, 224-R--R-227 and R-267." FT /evidence="ECO:0000269|PubMed:32160526" FT MUTAGEN 116 FT /note="K->R: Weak or no effect on ufmylation." FT /evidence="ECO:0000269|PubMed:20018847" FT MUTAGEN 121 FT /note="K->R: Weak or no effect on ufmylation." FT /evidence="ECO:0000269|PubMed:20018847" FT MUTAGEN 124 FT /note="K->R: Weak or no effect on ufmylation." FT /evidence="ECO:0000269|PubMed:20018847" FT MUTAGEN 128 FT /note="K->R: Weak or no effect on ufmylation." FT /evidence="ECO:0000269|PubMed:20018847" FT MUTAGEN 146 FT /note="K->R: Impairs some post-translational modification FT without affecting interaction with UFL1; when associated FT with 116-R--R-128, R-176, R-193, 224-R--R-227 and R-267." FT /evidence="ECO:0000269|PubMed:32160526" FT MUTAGEN 176 FT /note="K->R: Impairs some post-translational modification FT without affecting interaction with UFL1; when associated FT with 116-R--R-128, R-146, R-193, 224-R--R-227 and R-267." FT /evidence="ECO:0000269|PubMed:32160526" FT MUTAGEN 193 FT /note="K->R: Weak or no effect on ufmylation. Impairs some FT post-translational modification without affecting FT interaction with UFL1; when associated with 116-R--R-128, FT R-146, R-176, 224-R--R-227 and R-267." FT /evidence="ECO:0000269|PubMed:20018847, FT ECO:0000269|PubMed:32160526" FT MUTAGEN 196..201 FT /note="FVVEEE->VVAEEP: Abolished ability to recognize and FT bind ufmylated RPL26/uL24." FT /evidence="ECO:0000269|PubMed:38383785" FT MUTAGEN 196..198 FT /note="FVV->AVA: Abolished ability to recognize and bind FT ufmylated RPL26/uL24." FT /evidence="ECO:0000269|PubMed:36543799, FT ECO:0000269|PubMed:37595036" FT MUTAGEN 224..227 FT /note="KQSK->RQSR: Impairs some post-translational FT modification without affecting interaction with UFL1; when FT associated with 116-R--R-128, R-146, R-176, R-193 and FT R-267." FT /evidence="ECO:0000269|PubMed:32160526" FT MUTAGEN 224 FT /note="K->R: Weak or no effect on ufmylation." FT /evidence="ECO:0000269|PubMed:20018847" FT MUTAGEN 227 FT /note="K->R: Weak or no effect on ufmylation." FT /evidence="ECO:0000269|PubMed:20018847" FT MUTAGEN 265 FT /note="R->A: Decreased ribosome ufmylation." FT /evidence="ECO:0000269|PubMed:38383789" FT MUTAGEN 267 FT /note="K->R: Impairs interaction with UFL1 and ufmylation. FT Impairs interaction with ERN1/IRE1-alpha and ability to FT regulate its stability. Does not affect ability to promote FT reticulophagy. Impairs some post-translational modification FT without affecting interaction with UFL1; when associated FT with 116-R--R-128, R-146, R-176, R-193, 224-R--R-227 and FT R-267." FT /evidence="ECO:0000269|PubMed:20018847, FT ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:27926783, FT ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:32160526, FT ECO:0000269|PubMed:36543799" FT MUTAGEN 271..276 FT /note="ITPEEL->ATPEEA: Abolished interaction with UFL1; FT when associated with 302-A--A-304." FT /evidence="ECO:0000269|PubMed:37595036" FT MUTAGEN 302..304 FT /note="IAW->AAA: Abolished interaction with UFL1; when FT associated with 271-A--A-276." FT /evidence="ECO:0000269|PubMed:37595036" FT HELIX 209..226 FT /evidence="ECO:0007829|PDB:8C0D" FT STRAND 227..230 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 231..238 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 242..254 FT /evidence="ECO:0007829|PDB:8C0D" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:8B9X" FT STRAND 266..269 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 273..286 FT /evidence="ECO:0007829|PDB:8C0D" FT STRAND 287..290 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 291..301 FT /evidence="ECO:0007829|PDB:8C0D" SQ SEQUENCE 314 AA; 35611 MW; 2190D30B0D6D674A CRC64; MVAPVWYLVA AALLVGFILF LTRSRGRAAS AGQEPLHNEE LAGAGRVAQP GPLEPEEPRA GGRPRRRRDL GSRLQAQRRA QRVAWAEADE NEEEAVILAQ EEEGVEKPAE THLSGKIGAK KLRKLEEKQA RKAQREAEEA EREERKRLES QREAEWKKEE ERLRLEEEQK EEEERKAREE QAQREHEEYL KLKEAFVVEE EGVGETMTEE QSQSFLTEFI NYIKQSKVVL LEDLASQVGL RTQDTINRIQ DLLAEGTITG VIDDRGKFIY ITPEELAAVA NFIRQRGRVS IAELAQASNS LIAWGRESPA QAPA //