DDRGK_BOVIN
ID DDRGK_BOVIN Reviewed; 313 AA.
AC Q1LZB0;
DT 02-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=DDRGK domain-containing protein 1 {ECO:0000305};
DE Flags: Precursor;
GN Name=DDRGK1 {ECO:0000250|UniProtKB:Q96HY6};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hippocampus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
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). In response to
CC endoplasmic reticulum stress, promotes recruitment of the E3 UFM1-
CC protein ligase UFL1 to the endoplasmic reticulum membrane: in turn,
CC UFL1 mediates ufmylation of proteins such as RPN1 and RPL26/uL24,
CC promoting reticulophagy of endoplasmic reticulum sheets. Ufmylation-
CC dependent reticulophagy inhibits the unfolded protein response (UPR) by
CC regulating ERN1/IRE1-alpha stability (By similarity). Ufmylation in
CC response to endoplasmic reticulum stress is essential for processes
CC such as hematopoiesis or inflammatory response (By similarity).
CC Required for TRIP4 ufmylation, thereby regulating nuclear receptors-
CC mediated transcription. 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. Plays a role in
CC cartilage development through SOX9, inhibiting the ubiquitin-mediated
CC proteasomal degradation of this transcriptional regulator (By
CC similarity). {ECO:0000250|UniProtKB:Q80WW9,
CC ECO:0000250|UniProtKB:Q96HY6}.
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:0000250|UniProtKB:Q96HY6}. 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 -!- 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 -!- PTM: Ufmylated; conjugated to ubiquitin-like protein UFM1, probably at
CC Lys-266 by UFL1. The relevance of ufmylation is however unclear: as
CC DDRGK1 acts as substrate adapters for ufmylation, it is uncertain
CC whether ufmylation is a collateral effect of ufmylation process or is
CC required to regulate its activity. {ECO:0000250|UniProtKB:Q96HY6}.
CC -!- SIMILARITY: Belongs to the DDRGK1 family. {ECO:0000305}.
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DR EMBL; BC116112; AAI16113.1; -; mRNA.
DR RefSeq; NP_001068966.1; NM_001075498.1.
DR AlphaFoldDB; Q1LZB0; -.
DR SMR; Q1LZB0; -.
DR STRING; 9913.ENSBTAP00000018273; -.
DR PaxDb; Q1LZB0; -.
DR PeptideAtlas; Q1LZB0; -.
DR PRIDE; Q1LZB0; -.
DR GeneID; 511144; -.
DR KEGG; bta:511144; -.
DR CTD; 65992; -.
DR eggNOG; KOG3054; Eukaryota.
DR InParanoid; Q1LZB0; -.
DR OrthoDB; 1553559at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; ISS:UniProtKB.
DR GO; GO:1903895; P:negative regulation of IRE1-mediated unfolded protein response; ISS:UniProtKB.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; ISS:UniProtKB.
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: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; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS: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 2: Evidence at transcript level;
KW Endoplasmic reticulum; Isopeptide bond; Membrane; Phosphoprotein;
KW Reference proteome; Signal; Ubl conjugation; Ubl conjugation pathway.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..313
FT /note="DDRGK domain-containing protein 1"
FT /id="PRO_0000391851"
FT DOMAIN 228..272
FT /note="PCI"
FT REGION 1..113
FT /note="Mediates interaction with CDK5RAP3"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
FT REGION 40..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 117..215
FT /note="Mediates interaction with TRIP4"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
FT REGION 130..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 215..313
FT /note="Mediates interaction with UFL1"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
FT COMPBIAS 53..76
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 MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
FT CROSSLNK 266
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in UFM1)"
FT /evidence="ECO:0000250|UniProtKB:Q96HY6"
SQ SEQUENCE 313 AA; 35667 MW; 6E1AC35F7FA33202 CRC64;
MVSPVVYLVV AALLVGLILF LTRGRGRAAA AAQEPLHNEE VPAAAGRVAR PQPLEPEEQR
AAGRPRRRRD LGSRLQAQRR AQRVAWADEN EEEAIIQAQE EEDIEKPVET HLSGKIGAKK
LRKLEEKQAR KAQREAEEAE REERKRLESQ REAEWKKEEE RLRLEEEQKE EEERKAQEEQ
AQREHEEYLK LKETFVVVEE GVGETMTEEQ SHSFLAEFIN YIKQSKVVLL EDLASQVGLR
TQDTINRIQD LLAEGTLTGV IDDRGKFIYI TPEELAAVAN FIRQRGRVSI TELAQASNSL
IAWGRETPAQ APA
