DDRGK_MOUSE
ID DDRGK_MOUSE Reviewed; 315 AA.
AC Q80WW9; Q14BT4; Q9CT52;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2003, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=DDRGK domain-containing protein 1 {ECO:0000305};
DE AltName: Full=UFM1-binding and PCI domain-containing protein 1 {ECO:0000303|PubMed:21494687};
DE Flags: Precursor;
GN Name=Ddrgk1 {ECO:0000303|PubMed:28263186, ECO:0000312|MGI:MGI:1924256};
GN Synonyms=Ufbp1 {ECO:0000303|PubMed:21494687};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Lung;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-171.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP TISSUE SPECIFICITY.
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 [7]
RP UFMYLATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21494687; DOI=10.1371/journal.pone.0018517;
RA Lemaire K., Moura R.F., Granvik M., Igoillo-Esteve M., Hohmeier H.E.,
RA Hendrickx N., Newgard C.B., Waelkens E., Cnop M., Schuit F.;
RT "Ubiquitin fold modifier 1 (UFM1) and its target UFBP1 protect pancreatic
RT beta cells from ER stress-induced apoptosis.";
RL PLoS ONE 6:E18517-E18517(2011).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [9]
RP FUNCTION.
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 [10]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=30701081; DOI=10.1038/s41421-018-0070-x;
RA Cai Y., Zhu G., Liu S., Pan Z., Quintero M., Poole C.J., Lu C., Zhu H.,
RA Islam B., Riggelen J.V., Browning D., Liu K., Blumberg R., Singh N., Li H.;
RT "Indispensable role of the ubiquitin-fold modifier 1-specific E3 ligase in
RT maintaining intestinal homeostasis and controlling gut inflammation.";
RL Cell Discov. 5:7-7(2019).
RN [11]
RP STRUCTURE BY NMR OF 216-274.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PCI domain from mouse hypothetical protein
RT AAH51541.";
RL Submitted (NOV-2004) to the PDB data bank.
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) (By similarity). 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 (By
CC similarity). Ufmylation-dependent reticulophagy inhibits the unfolded
CC protein response (UPR) by regulating ERN1/IRE1-alpha stability
CC (PubMed:28128204). Ufmylation in response to endoplasmic reticulum
CC stress is essential for processes such as hematopoiesis or inflammatory
CC response (PubMed:30701081). Required for TRIP4 ufmylation, thereby
CC regulating nuclear receptors-mediated transcription (PubMed:28263186).
CC May play a role in NF-kappa-B-mediated transcription through regulation
CC of the phosphorylation and the degradation of NFKBIA, the inhibitor of
CC NF-kappa-B (PubMed:28263186). Plays a role in cartilage development
CC through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation
CC of this transcriptional regulator (PubMed:28263186).
CC {ECO:0000250|UniProtKB:Q96HY6, ECO:0000269|PubMed:28128204,
CC ECO:0000269|PubMed:28263186, ECO:0000269|PubMed:30701081}.
CC -!- SUBUNIT: Interacts with TRIP4; the interaction with TRIP4 is direct.
CC Interacts (via PCI domain) with UFL1. 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. Interacts with NFKBIA. Interacts with CDK5RAP3. Interacts
CC with SOX9. {ECO:0000250|UniProtKB:Q96HY6}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:21494687}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q96HY6}. Note=Localizes to the endoplasmic
CC reticulum membrane in response to endoplasmic reticulum stress.
CC {ECO:0000250|UniProtKB:Q96HY6}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:20228063). Higher
CC expression in pancreatic islets, pancreatic acini and testis (at
CC protein level) (PubMed:21494687). Highly expressed in the intestinal
CC exocrine cells (PubMed:30701081). {ECO:0000269|PubMed:20228063,
CC ECO:0000269|PubMed:21494687, ECO:0000269|PubMed:30701081}.
CC -!- PTM: Ufmylated; conjugated to ubiquitin-like protein UFM1, probably at
CC Lys-268 by UFL1 (PubMed:21494687). The relevance of ufmylation is
CC however unclear: as DDRGK1 acts as substrate adapters for ufmylation,
CC it is uncertain whether ufmylation is a collateral effect of ufmylation
CC process or is required to regulate its activity (By similarity).
CC {ECO:0000250|UniProtKB:Q96HY6, ECO:0000269|PubMed:21494687}.
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:0000250|UniProtKB:Q96HY6}.
CC -!- DISRUPTION PHENOTYPE: The knockout of the gene results in embryonic
CC lethality between 11.5 and 12.5 dpc (PubMed:28263186). Chondrogenic
CC mesenchymal condensation is absent in 12.5 dpc embryos
CC (PubMed:28263186). Conditional deletion in intestinal epithelial cells
CC causes a significant loss of both Paneth and goblet cells in intestine,
CC which in turn results in dysbiotic microbiota and increased
CC susceptibility to experimentally induced colitis (PubMed:30701081).
CC {ECO:0000269|PubMed:28263186, ECO:0000269|PubMed:30701081}.
CC -!- SIMILARITY: Belongs to the DDRGK1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH51541.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AL731707; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL772162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466519; EDL28284.1; -; Genomic_DNA.
DR EMBL; BC115616; AAI15617.1; -; mRNA.
DR EMBL; BC115617; AAI15618.1; -; mRNA.
DR EMBL; BC051541; AAH51541.1; ALT_INIT; mRNA.
DR EMBL; AK011170; BAB27444.1; -; mRNA.
DR CCDS; CCDS38243.1; -.
DR RefSeq; NP_084108.1; NM_029832.2.
DR PDB; 1WI9; NMR; -; A=216-274.
DR PDBsum; 1WI9; -.
DR AlphaFoldDB; Q80WW9; -.
DR SMR; Q80WW9; -.
DR BioGRID; 218455; 2.
DR STRING; 10090.ENSMUSP00000086988; -.
DR iPTMnet; Q80WW9; -.
DR PhosphoSitePlus; Q80WW9; -.
DR EPD; Q80WW9; -.
DR jPOST; Q80WW9; -.
DR MaxQB; Q80WW9; -.
DR PaxDb; Q80WW9; -.
DR PeptideAtlas; Q80WW9; -.
DR PRIDE; Q80WW9; -.
DR ProteomicsDB; 279847; -.
DR Antibodypedia; 2721; 77 antibodies from 19 providers.
DR Ensembl; ENSMUST00000089559; ENSMUSP00000086988; ENSMUSG00000068290.
DR GeneID; 77006; -.
DR KEGG; mmu:77006; -.
DR UCSC; uc008mjs.1; mouse.
DR CTD; 65992; -.
DR MGI; MGI:1924256; Ddrgk1.
DR VEuPathDB; HostDB:ENSMUSG00000068290; -.
DR eggNOG; KOG3054; Eukaryota.
DR GeneTree; ENSGT00390000017193; -.
DR HOGENOM; CLU_059562_0_0_1; -.
DR InParanoid; Q80WW9; -.
DR OMA; QEFIQYI; -.
DR OrthoDB; 1553559at2759; -.
DR PhylomeDB; Q80WW9; -.
DR TreeFam; TF314645; -.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR BioGRID-ORCS; 77006; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Ddrgk1; mouse.
DR EvolutionaryTrace; Q80WW9; -.
DR PRO; PR:Q80WW9; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q80WW9; protein.
DR Bgee; ENSMUSG00000068290; Expressed in retinal neural layer and 242 other tissues.
DR ExpressionAtlas; Q80WW9; baseline and differential.
DR Genevisible; Q80WW9; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; ISS:UniProtKB.
DR GO; GO:0051216; P:cartilage development; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:1903895; P:negative regulation of IRE1-mediated unfolded protein response; IMP:UniProtKB.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; ISS:UniProtKB.
DR GO; GO:1905050; P:positive regulation of metallopeptidase activity; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:1905552; P:positive regulation of protein localization to endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:1905636; P:positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:1990592; P:protein K69-linked ufmylation; ISS:UniProtKB.
DR GO; GO:0070972; P:protein localization to endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0071569; P:protein ufmylation; ISS:UniProtKB.
DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISO:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0061709; P:reticulophagy; ISS: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 3D-structure; Endoplasmic reticulum; Isopeptide bond; Membrane;
KW Phosphoprotein; Reference proteome; Signal; Ubl conjugation;
KW Ubl conjugation pathway.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..315
FT /note="DDRGK domain-containing protein 1"
FT /id="PRO_0000021034"
FT DOMAIN 230..274
FT /note="PCI"
FT REGION 1..115
FT /note="Mediates interaction with CDK5RAP3"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
FT REGION 30..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..217
FT /note="Mediates interaction with TRIP4"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
FT REGION 217..315
FT /note="Mediates interaction with UFL1"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
FT COMPBIAS 30..44
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 57..87
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..184
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
FT CROSSLNK 268
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in UFM1)"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
FT HELIX 216..226
FT /evidence="ECO:0007829|PDB:1WI9"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:1WI9"
FT HELIX 232..239
FT /evidence="ECO:0007829|PDB:1WI9"
FT HELIX 243..256
FT /evidence="ECO:0007829|PDB:1WI9"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:1WI9"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:1WI9"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:1WI9"
SQ SEQUENCE 315 AA; 35977 MW; D973B9AFBE265562 CRC64;
MVGPWVYLVA AVLLIGLILF LTRSRGRAAA ADGEPLHNEE ERAGAGQVGR SLPQESEEQR
TGSRPRRRRD LGSRLQAQRR AQRVAWEDGD ENVGQTVIPA QEEEGIEKPA EVHPTGKIGA
KKLRKLEEKQ ARKAQREAEE AEREERKRLE SQREAEWKKE EERLRLKEEQ KEEEERKAQE
EQARREHEEY LKLKEAFVVE EEGVSETMTE EQSHSFLTEF INYIKKSKVV LLEDLAFQMG
LRTQDAINRI QDLLTEGTLT GVIDDRGKFI YITPEELAAV ANFIRQRGRV SITELAQASN
SLISWGQDLP AQASA
