UniProt functional annotation for Q80WW9



	UniProt functional annotation for Q80WW9

UniProt code: Q80WW9.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Substrate adapter for ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, which plays a key role in reticulophagy (also called ER-phagy) (By similarity). In response to endoplasmic reticulum stress, promotes recruitment of the E3 UFM1-protein ligase UFL1 to the endoplasmic reticulum membrane: in turn, UFL1 mediates ufmylation of proteins such as RPN1 and RPL26/uL24, promoting reticulophagy of endoplasmic reticulum sheets (By similarity). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability (PubMed:28128204). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis or inflammatory response (PubMed:30701081). Required for TRIP4 ufmylation, thereby regulating nuclear receptors-mediated transcription (PubMed:28263186). 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:28263186). Plays a role in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator (PubMed:28263186). {ECO:0000250|UniProtKB:Q96HY6, ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:28263186, ECO:0000269|PubMed:30701081}.

Subunit: Interacts with TRIP4; the interaction with TRIP4 is direct. Interacts (via PCI domain) with UFL1. Interacts with (unphosphorylated) ERN1/IRE1-alpha; interaction is dependent on UFM1 and takes place in response to endoplasmic reticulum stress, regulating ERN1/IRE1-alpha stability. Interacts with NFKBIA. Interacts with CDK5RAP3. Interacts with SOX9. {ECO:0000250|UniProtKB:Q96HY6}.

Subcellular location: Endoplasmic reticulum {ECO:0000269|PubMed:21494687}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q96HY6}. Note=Localizes to the endoplasmic reticulum membrane in response to endoplasmic reticulum stress. {ECO:0000250|UniProtKB:Q96HY6}.

Tissue specificity: Ubiquitously expressed (PubMed:20228063). Higher expression in pancreatic islets, pancreatic acini and testis (at protein level) (PubMed:21494687). Highly expressed in the intestinal exocrine cells (PubMed:30701081). {ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:21494687, ECO:0000269|PubMed:30701081}.

Ptm: Ufmylated; conjugated to ubiquitin-like protein UFM1, probably at Lys-268 by UFL1 (PubMed:21494687). The relevance of ufmylation is however unclear: as DDRGK1 acts as substrate adapters for ufmylation, it is uncertain whether ufmylation is a collateral effect of ufmylation process or is required to regulate its activity (By similarity). {ECO:0000250|UniProtKB:Q96HY6, ECO:0000269|PubMed:21494687}.

Ptm: Ubiquitinated. Ubiquitination probably triggers proteasomal degradation and is negatively regulated by UFL1, the enzyme involved in the ufmylation of DDRGK1. {ECO:0000250|UniProtKB:Q96HY6}.

Disruption phenotype: The knockout of the gene results in embryonic lethality between E11.5 and E12.5 (PubMed:28263186). Chondrogenic mesenchymal condensation is absent in E12.5 embryos (PubMed:28263186). Conditional deletion in intestinal epithelial cells causes a significant loss of both Paneth and goblet cells in intestine, which in turn results in dysbiotic microbiota and increased susceptibility to experimentally induced colitis (PubMed:30701081). {ECO:0000269|PubMed:28263186, ECO:0000269|PubMed:30701081}.

Similarity: Belongs to the DDRGK1 family. {ECO:0000305}.

Sequence caution: Sequence=AAH51541.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Substrate adapter for ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, which plays a key role in reticulophagy (also called ER-phagy) (By similarity). In response to endoplasmic reticulum stress, promotes recruitment of the E3 UFM1-protein ligase UFL1 to the endoplasmic reticulum membrane: in turn, UFL1 mediates ufmylation of proteins such as RPN1 and RPL26/uL24, promoting reticulophagy of endoplasmic reticulum sheets (By similarity). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability (PubMed:28128204). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis or inflammatory response (PubMed:30701081). Required for TRIP4 ufmylation, thereby regulating nuclear receptors-mediated transcription (PubMed:28263186). 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:28263186). Plays a role in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator (PubMed:28263186). {ECO:0000250\|UniProtKB:Q96HY6, ECO:0000269\|PubMed:28128204, ECO:0000269\|PubMed:28263186, ECO:0000269\|PubMed:30701081}.


Subunit:		Interacts with TRIP4; the interaction with TRIP4 is direct. Interacts (via PCI domain) with UFL1. Interacts with (unphosphorylated) ERN1/IRE1-alpha; interaction is dependent on UFM1 and takes place in response to endoplasmic reticulum stress, regulating ERN1/IRE1-alpha stability. Interacts with NFKBIA. Interacts with CDK5RAP3. Interacts with SOX9. {ECO:0000250\|UniProtKB:Q96HY6}.
Subcellular location:		Endoplasmic reticulum {ECO:0000269\|PubMed:21494687}. Endoplasmic reticulum membrane {ECO:0000250\|UniProtKB:Q96HY6}. Note=Localizes to the endoplasmic reticulum membrane in response to endoplasmic reticulum stress. {ECO:0000250\|UniProtKB:Q96HY6}.
Tissue specificity:		Ubiquitously expressed (PubMed:20228063). Higher expression in pancreatic islets, pancreatic acini and testis (at protein level) (PubMed:21494687). Highly expressed in the intestinal exocrine cells (PubMed:30701081). {ECO:0000269\|PubMed:20228063, ECO:0000269\|PubMed:21494687, ECO:0000269\|PubMed:30701081}.
Ptm:		Ufmylated; conjugated to ubiquitin-like protein UFM1, probably at Lys-268 by UFL1 (PubMed:21494687). The relevance of ufmylation is however unclear: as DDRGK1 acts as substrate adapters for ufmylation, it is uncertain whether ufmylation is a collateral effect of ufmylation process or is required to regulate its activity (By similarity). {ECO:0000250\|UniProtKB:Q96HY6, ECO:0000269\|PubMed:21494687}.
Ptm:		Ubiquitinated. Ubiquitination probably triggers proteasomal degradation and is negatively regulated by UFL1, the enzyme involved in the ufmylation of DDRGK1. {ECO:0000250\|UniProtKB:Q96HY6}.
Disruption phenotype:		The knockout of the gene results in embryonic lethality between E11.5 and E12.5 (PubMed:28263186). Chondrogenic mesenchymal condensation is absent in E12.5 embryos (PubMed:28263186). Conditional deletion in intestinal epithelial cells causes a significant loss of both Paneth and goblet cells in intestine, which in turn results in dysbiotic microbiota and increased susceptibility to experimentally induced colitis (PubMed:30701081). {ECO:0000269\|PubMed:28263186, ECO:0000269\|PubMed:30701081}.
Similarity:		Belongs to the DDRGK1 family. {ECO:0000305}.
Sequence caution:		Sequence=AAH51541.1; Type=Erroneous initiation; Evidence={ECO:0000305};