DDRGK_HUMAN
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 03-AUG-2022, entry version 167.
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:0000250|UniProtKB:Q80WW9};
DE Flags: Precursor;
GN Name=DDRGK1 {ECO:0000303|PubMed:20228063, ECO:0000312|HGNC:HGNC:16110};
GN Synonyms=C20orf116 {ECO:0000312|HGNC:HGNC:16110},
GN UFBP1 {ECO:0000250|UniProtKB:Q80WW9};
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 TRIP4 AND UFL1, REGION, AND MUTAGENESIS OF
RP 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 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 [16]
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).
CC -!- FUNCTION: Substrate adapter for ufmylation, the covalent attachment of
CC the ubiquitin-like modifier UFM1 to substrate proteins, which plays a
CC key role in reticulophagy (also called ER-phagy) (PubMed:32160526). In
CC response to endoplasmic reticulum stress, promotes recruitment of the
CC E3 UFM1-protein ligase UFL1 to the endoplasmic reticulum membrane: in
CC turn, UFL1 mediates ufmylation of proteins such as RPN1 and RPL26/uL24,
CC promoting reticulophagy of endoplasmic reticulum sheets
CC (PubMed:32160526). Ufmylation-dependent reticulophagy inhibits the
CC unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability
CC (PubMed:28128204, PubMed:32160526). Ufmylation in response to
CC endoplasmic reticulum stress is essential for processes such as
CC hematopoiesis or inflammatory response (By similarity). Required for
CC TRIP4 ufmylation, thereby regulating nuclear receptors-mediated.
CC transcription (PubMed:25219498). May play a role in NF-kappa-B-mediated
CC transcription through regulation of the phosphorylation and the
CC degradation of NFKBIA, the inhibitor of NF-kappa-B (PubMed:23675531).
CC Plays a role in cartilage development through SOX9, inhibiting the
CC ubiquitin-mediated proteasomal degradation of this transcriptional
CC regulator (PubMed:28263186). {ECO:0000250|UniProtKB:Q80WW9,
CC ECO:0000269|PubMed:23675531, ECO:0000269|PubMed:25219498,
CC ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:28263186,
CC ECO:0000269|PubMed:32160526}.
CC -!- SUBUNIT: Interacts with TRIP4; the interaction with TRIP4 is direct
CC (PubMed:25219498). Interacts (via PCI domain) with UFL1
CC (PubMed:25219498, PubMed:32160526). Interacts with (unphosphorylated)
CC ERN1/IRE1-alpha; interaction is dependent on UFM1 and takes place in
CC response to endoplasmic reticulum stress, regulating ERN1/IRE1-alpha
CC stability (PubMed:28128204). Interacts with NFKBIA (PubMed:23675531).
CC Interacts with CDK5RAP3 (PubMed:20228063). Interacts with SOX9
CC (PubMed:28263186). {ECO:0000269|PubMed:20228063,
CC ECO:0000269|PubMed:23675531, ECO:0000269|PubMed:25219498,
CC ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:28263186,
CC ECO:0000269|PubMed:32160526}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:32160526}. Endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:32160526}. Note=Localizes to the
CC endoplasmic reticulum membrane in response to endoplasmic reticulum
CC stress. {ECO:0000269|PubMed:32160526}.
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 -!- 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:28128204). The relevance of
CC ufmylation is however unclear: as DDRGK1 acts as substrate adapters for
CC ufmylation, it is uncertain whether ufmylation is a collatoral effect
CC of ufmylation process or is required to regulate its activity
CC (PubMed:32160526). {ECO:0000269|PubMed:20018847,
CC ECO:0000269|PubMed:28128204, 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}.
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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_023935.2. [Q96HY6-1]
DR AlphaFoldDB; Q96HY6; -.
DR SMR; Q96HY6; -.
DR BioGRID; 122441; 1246.
DR IntAct; Q96HY6; 36.
DR MINT; Q96HY6; -.
DR STRING; 9606.ENSP00000346483; -.
DR iPTMnet; Q96HY6; -.
DR PhosphoSitePlus; Q96HY6; -.
DR BioMuta; DDRGK1; -.
DR DMDM; 37077728; -.
DR EPD; Q96HY6; -.
DR jPOST; Q96HY6; -.
DR MassIVE; Q96HY6; -.
DR MaxQB; Q96HY6; -.
DR PaxDb; Q96HY6; -.
DR PeptideAtlas; Q96HY6; -.
DR PRIDE; Q96HY6; -.
DR ProteomicsDB; 76794; -. [Q96HY6-1]
DR ProteomicsDB; 76795; -. [Q96HY6-2]
DR Antibodypedia; 2721; 77 antibodies from 19 providers.
DR DNASU; 65992; -.
DR Ensembl; ENST00000354488.8; ENSP00000346483.3; ENSG00000198171.13. [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 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 neXtProt; NX_Q96HY6; -.
DR OpenTargets; ENSG00000198171; -.
DR Orphanet; 93352; Spondyloepimetaphyseal dysplasia, Shohat type.
DR PharmGKB; PA164718734; -.
DR VEuPathDB; HostDB:ENSG00000198171; -.
DR eggNOG; KOG3054; Eukaryota.
DR GeneTree; ENSGT00390000017193; -.
DR HOGENOM; CLU_059562_0_0_1; -.
DR InParanoid; Q96HY6; -.
DR OMA; QEFIQYI; -.
DR OrthoDB; 1553559at2759; -.
DR PhylomeDB; Q96HY6; -.
DR TreeFam; TF314645; -.
DR PathwayCommons; Q96HY6; -.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR SignaLink; Q96HY6; -.
DR BioGRID-ORCS; 65992; 88 hits in 1086 CRISPR screens.
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 192 other tissues.
DR ExpressionAtlas; Q96HY6; baseline and differential.
DR Genevisible; Q96HY6; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI: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:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
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:1905050; P:positive regulation of metallopeptidase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP: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:1905636; P:positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding; IMP:ParkinsonsUK-UCL.
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:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0061709; P:reticulophagy; IDA:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR019153; DDRGK_dom-contain.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF09756; DDRGK; 1.
DR SMART; SM01128; DDRGK; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Dwarfism; Endoplasmic reticulum; Isopeptide bond;
KW Membrane; Phosphoprotein; Reference proteome; Signal; Ubl conjugation;
KW Ubl conjugation pathway.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..314
FT /note="DDRGK domain-containing protein 1"
FT /id="PRO_0000021033"
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 COMPBIAS 58..75
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:0000305|PubMed:20018847,
FT 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 post-
FT translational modification without affecting interaction
FT with UFL1; when associated with R-146, R-176, R-193, 224-
FT 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 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 R-
FT 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 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 R-
FT 267."
FT /evidence="ECO:0000269|PubMed:20018847,
FT ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:28128204,
FT ECO:0000269|PubMed:32160526"
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
