UniProt functional annotation for Q91X58



	UniProt functional annotation for Q91X58

UniProt code: Q91X58.

Organism: Mus musculus (Mouse).

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

Function: Plays a role in protein homeostasis by regulating both the translocation and the ubiquitin-mediated proteasomal degradation of nascent proteins at the endoplasmic reticulum (PubMed:24160817, PubMed:26337389, PubMed:26692333). It is involved in the regulation of signal-mediated translocation of proteins into the endoplasmic reticulum (PubMed:24160817). It also plays a role in the ubiquitin- mediated proteasomal degradation of proteins for which signal-mediated translocation to the endoplasmic reticulum has failed (PubMed:18467495, PubMed:26337389). May therefore function in the endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:24160817, PubMed:26337389). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000269|PubMed:18467495, ECO:0000269|PubMed:24160817, ECO:0000269|PubMed:26337389, ECO:0000269|PubMed:26692333}.

Subunit: Binds 'Lys-48'-linked polyubiquitin chains of ubiquitinated proteins (PubMed:18467495, PubMed:24160817, PubMed:26876100). Associates with the proteasome complex; upon exposure to arsenite (PubMed:18467495, PubMed:26876100). Interacts (via VIM motif) with VCP; the interaction is direct (PubMed:24160817, PubMed:26337389). Interacts with BAG6 (PubMed:24160817, PubMed:26337389, PubMed:26876100). Interacts with IGF1R (nascent precursor form) (PubMed:26692333). Interacts with DERL1, FAF2, NPLOC4 and UFD1; probably through VCP (PubMed:24160817). {ECO:0000269|PubMed:18467495, ECO:0000269|PubMed:24160817, ECO:0000269|PubMed:26337389, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:26876100}.

Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:18467495}; Lipid-anchor {ECO:0000305|PubMed:18467495}.

Domain: The UIM domains specifically bind 'Lys-48'-linked ubiquitin polymers (PubMed:18467495, PubMed:26876100). The UIM domains mediate interaction with polyubiquitinated proteins (PubMed:18467495, PubMed:26337389). {ECO:0000269|PubMed:18467495, ECO:0000269|PubMed:26337389, ECO:0000269|PubMed:26876100}.

Ptm: Phosphorylated by MAPK14 (Probable). Phosphorylation has no effect on association with the proteasome complex (Probable). {ECO:0000305|PubMed:18467495}.

Disruption phenotype: Knockout mice undergo premature death due to the occurrence of myelo-proliferative neoplasms. The absence of Zfand2b plays a driver role in the development of these neoplasms by hyperactivating the insulin-like growth factor receptor signaling pathway. This is due to increased expression, in particular at the cell surface, of the IGF1R receptor. {ECO:0000269|PubMed:26692333}.

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:		Plays a role in protein homeostasis by regulating both the translocation and the ubiquitin-mediated proteasomal degradation of nascent proteins at the endoplasmic reticulum (PubMed:24160817, PubMed:26337389, PubMed:26692333). It is involved in the regulation of signal-mediated translocation of proteins into the endoplasmic reticulum (PubMed:24160817). It also plays a role in the ubiquitin- mediated proteasomal degradation of proteins for which signal-mediated translocation to the endoplasmic reticulum has failed (PubMed:18467495, PubMed:26337389). May therefore function in the endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:24160817, PubMed:26337389). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000269\|PubMed:18467495, ECO:0000269\|PubMed:24160817, ECO:0000269\|PubMed:26337389, ECO:0000269\|PubMed:26692333}.


Subunit:		Binds 'Lys-48'-linked polyubiquitin chains of ubiquitinated proteins (PubMed:18467495, PubMed:24160817, PubMed:26876100). Associates with the proteasome complex; upon exposure to arsenite (PubMed:18467495, PubMed:26876100). Interacts (via VIM motif) with VCP; the interaction is direct (PubMed:24160817, PubMed:26337389). Interacts with BAG6 (PubMed:24160817, PubMed:26337389, PubMed:26876100). Interacts with IGF1R (nascent precursor form) (PubMed:26692333). Interacts with DERL1, FAF2, NPLOC4 and UFD1; probably through VCP (PubMed:24160817). {ECO:0000269\|PubMed:18467495, ECO:0000269\|PubMed:24160817, ECO:0000269\|PubMed:26337389, ECO:0000269\|PubMed:26692333, ECO:0000269\|PubMed:26876100}.
Subcellular location:		Endoplasmic reticulum membrane {ECO:0000269\|PubMed:18467495}; Lipid-anchor {ECO:0000305\|PubMed:18467495}.
Domain:		The UIM domains specifically bind 'Lys-48'-linked ubiquitin polymers (PubMed:18467495, PubMed:26876100). The UIM domains mediate interaction with polyubiquitinated proteins (PubMed:18467495, PubMed:26337389). {ECO:0000269\|PubMed:18467495, ECO:0000269\|PubMed:26337389, ECO:0000269\|PubMed:26876100}.
Ptm:		Phosphorylated by MAPK14 (Probable). Phosphorylation has no effect on association with the proteasome complex (Probable). {ECO:0000305\|PubMed:18467495}.
Disruption phenotype:		Knockout mice undergo premature death due to the occurrence of myelo-proliferative neoplasms. The absence of Zfand2b plays a driver role in the development of these neoplasms by hyperactivating the insulin-like growth factor receptor signaling pathway. This is due to increased expression, in particular at the cell surface, of the IGF1R receptor. {ECO:0000269\|PubMed:26692333}.