DDRGK1
entrez
65992
canonical
uniprot
Q96HY6
canonical
ensembl
ENSG00000198171
resolver
ensp
ENSP00000346483
resolver
genesymbol
DDRGK1
resolver
genesymbol_syn
C20orf116
resolver
genesymbol_syn
UFBP1
resolver
hgnc
HGNC:16110
resolver
uniprot
A6NIU5
resolver
uniprot
C9JSZ5
resolver
uniprot
Q9BW47
resolver
uniprot_entry
DDRGK_HUMAN
resolver
uniprot_sec
A6NIU5
resolver
uniprot_sec
C9JSZ5
resolver
uniprot_sec
Q9BW47
resolver
amino_acid_sequence
MVAPVWYLVAAALLVGFILFLTRSRGRAASAGQEPLHNEELAGAGRVAQPGPLEPEEPRAGGRPRRRRDLGSRLQAQRRAQRVAWAEADENEEEAVILAQEEEGVEKPAETHLSGKIGAKKLRKLEEKQARKAQREAEEAEREERKRLESQREAEWKKEEERLRLEEEQKEEEERKAREEQAQREHEEYLKLKEAFVVEEEGVGETMTEEQSQSFLTEFINYIKQSKVVLLEDLASQVGLRTQDTINRIQDLLAEGTITGVIDDRGKFIYITPEELAAVANFIRQRGRVSIAELAQASNSLIAWGRESPAQAPA
uniprot
proteins
disease_involvement
DISEASE: Spondyloepimetaphyseal dysplasia, Shohat type (SEMDSH) [MIM:602557]: An autosomal recessive skeletal dysplasia that affects cartilage development. It is characterized by vertebral, epiphyseal, and metaphyseal abnormalities, including scoliosis with vertebral compression fractures, flattened vertebral bodies, and hypomineralization of long bones. Affected individuals may exhibit a small trunk, short neck, small limbs, joint laxity, bowlegs, and/or abdominal distension with hepatosplenomegaly. {ECO:0000269|PubMed:28263186}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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). {ECO:0000250|UniProtKB:Q80WW9, ECO:0000269|PubMed:23675531, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:28263186, ECO:0000269|PubMed:30626644, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:35753586, ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:37595036, ECO:0000269|PubMed:37795761, ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}.
uniprot
proteins
mass_dalton
35611
uniprot
proteins
mutagenesis
MUTAGEN 116..128; /note="KIGAKKLRKLEEK->RIGARRLRRLEER: Impairs some post-translational modification without affecting interaction with UFL1; when associated with R-146, R-176, R-193, 224-R--R-227 and R-267."; /evidence="ECO:0000269|PubMed:32160526"; MUTAGEN 116; /note="K->R: Weak or no effect on ufmylation."; /evidence="ECO:0000269|PubMed:20018847"; MUTAGEN 121; /note="K->R: Weak or no effect on ufmylation."; /evidence="ECO:0000269|PubMed:20018847"; MUTAGEN 124; /note="K->R: Weak or no effect on ufmylation."; /evidence="ECO:0000269|PubMed:20018847"; MUTAGEN 128; /note="K->R: Weak or no effect on ufmylation."; /evidence="ECO:0000269|PubMed:20018847"; MUTAGEN 146; /note="K->R: Impairs some post-translational modification without affecting interaction with UFL1; when associated with 116-R--R-128, R-176, R-193, 224-R--R-227 and R-267."; /evidence="ECO:0000269|PubMed:32160526"; MUTAGEN 176; /note="K->R: Impairs some post-translational modification without affecting interaction with UFL1; when associated with 116-R--R-128, R-146, R-193, 224-R--R-227 and R-267."; /evidence="ECO:0000269|PubMed:32160526"; MUTAGEN 193; /note="K->R: Weak or no effect on ufmylation. Impairs some post-translational modification without affecting interaction with UFL1; when associated with 116-R--R-128, R-146, R-176, 224-R--R-227 and R-267."; /evidence="ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:32160526"; MUTAGEN 196..201; /note="FVVEEE->VVAEEP: Abolished ability to recognize and bind ufmylated RPL26/uL24."; /evidence="ECO:0000269|PubMed:38383785"; MUTAGEN 196..198; /note="FVV->AVA: Abolished ability to recognize and bind ufmylated RPL26/uL24."; /evidence="ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:37595036"; MUTAGEN 224..227; /note="KQSK->RQSR: Impairs some post-translational modification without affecting interaction with UFL1; when associated with 116-R--R-128, R-146, R-176, R-193 and R-267."; /evidence="ECO:0000269|PubMed:32160526"; MUTAGEN 224; /note="K->R: Weak or no effect on ufmylation."; /evidence="ECO:0000269|PubMed:20018847"; MUTAGEN 227; /note="K->R: Weak or no effect on ufmylation."; /evidence="ECO:0000269|PubMed:20018847"; MUTAGEN 265; /note="R->A: Decreased ribosome ufmylation."; /evidence="ECO:0000269|PubMed:38383789"; MUTAGEN 267; /note="K->R: Impairs interaction with UFL1 and ufmylation. Impairs interaction with ERN1/IRE1-alpha and ability to regulate its stability. Does not affect ability to promote reticulophagy. Impairs some post-translational modification without affecting interaction with UFL1; when associated with 116-R--R-128, R-146, R-176, R-193, 224-R--R-227 and R-267."; /evidence="ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:27926783, ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:36543799"; MUTAGEN 271..276; /note="ITPEEL->ATPEEA: Abolished interaction with UFL1; when associated with 302-A--A-304."; /evidence="ECO:0000269|PubMed:37595036"; MUTAGEN 302..304; /note="IAW->AAA: Abolished interaction with UFL1; when associated with 271-A--A-276."; /evidence="ECO:0000269|PubMed:37595036
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated. Ubiquitination probably triggers proteasomal degradation and is negatively regulated by UFL1, the enzyme involved in the ufmylation of DDRGK1. {ECO:0000269|PubMed:20228063}.; PTM: Ufmylated; conjugated to ubiquitin-like protein UFM1, probably at Lys-267 by UFL1 (PubMed:20018847, PubMed:27926783, PubMed:28128204). The relevance of ufmylation is however unclear: as DDRGK1 acts as a substrate adapters for ufmylation, it is uncertain whether ufmylation is a collateral effect of ufmylation process or is required to regulate its activity (PubMed:32160526). {ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:27926783, ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:32160526}.
uniprot
proteins
protein_family
DDRGK1 family
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
12975309
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
20018847
uniprot
proteins
pubmed
20036718
uniprot
proteins
pubmed
20228063
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23675531
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25219498
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27926783
uniprot
proteins
pubmed
28128204
uniprot
proteins
pubmed
28263186
uniprot
proteins
pubmed
30626644
uniprot
proteins
pubmed
32160526
uniprot
proteins
pubmed
35753586
uniprot
proteins
pubmed
36121123
uniprot
proteins
pubmed
36543799
uniprot
proteins
pubmed
37595036
uniprot
proteins
pubmed
37795761
uniprot
proteins
pubmed
37988244
uniprot
proteins
pubmed
38383785
uniprot
proteins
pubmed
38383789
uniprot
proteins
sequence_length
314
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}; Single-pass membrane protein {ECO:0000305|PubMed:38383785, ECO:0000305|PubMed:38383789}.
uniprot
proteins
transmembrane_region
TRANSMEM 1..28; /note="Helical"; /evidence="ECO:0000269|PubMed:38383785
uniprot
proteins