Etsin kuvan ja artikkelin. http://www.biochim.ro/media/1569599459/EN_Rez_CB.pdf
https://www.researchgate.net/publication/277967949_The_Role_of_Lectin-Carbohydrate_Interactions_in_the_Regulation_of_ER-Associated_Protein_Degradation
Abstract
Proteins
entering the secretory pathway are translocated across the endoplasmic
reticulum (ER) membrane in an unfolded form. In the ER they are
restricted to a quality control system (ERQC) that ensures correct folding or
eventual degradation of improperly folded polypeptides.
Mannose trimming
of N-glycans on newly synthesized proteins plays an important role in
the recognition and sorting of terminally misfolded glycoproteins for
ER-associated protein degradation (ERAD). In this process misfolded
proteins are retrotranslocated into the cytosol, polyubiquitinated, and
eventually degraded by the proteasome.
The mechanism by which misfolded
glycoproteins are recognized and recruited to the degradation machinery
has been extensively studied during last decade.
In this review, we
focus on ER degradation-enhancing α-mannosidase-like protein (EDEM)
family proteins that seem to play a key role in the discrimination
between proteins undergoing a folding process and terminally misfolded
proteins directed for degradation.
We describe interactions of EDEM
proteins with other components of the ERAD machinery, as well as with
various protein substrates. Carbohydrate-dependent interactions together
with N-glycan-independent interactions seem to regulate the complex
process of protein recognition and direction for proteosomal
degradation.
EDEM3, (1q25.3), ER degradation-enhancing alpha-mannosidase-like protein 3.
Quality control in the endoplasmic reticulum
(ER) ensures that only properly folded proteins are retained in the cell
through recognition and degradation of misfolded or unassembled
proteins. EDEM3 belongs to a group of proteins that accelerate
degradation of misfolded glycoproteins in the ER (Hirao et al., 2006
[PubMed 16431915]).[supplied by OMIM, Mar 2008]
EDEM3 (ER Degradation
Enhancing Alpha-Mannosidase Like Protein 3) is a Protein Coding gene.
Among its related pathways
are Metabolism of proteins and Calnexin/calreticulin cycle.
Gene Ontology (GO) annotations related to this gene include calcium ion binding and glycoprotein endo-alpha-1,2-mannosidase activity.
An important paralog of this gene is EDEM1.
Involved in endoplasmic reticulum-associated
degradation (ERAD). Accelerates the glycoprotein ERAD by proteasomes, by
catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 in the
N-glycans. Seems to have alpha 1,2-mannosidase activity (By similarity). EDEM3_HUMAN,Q9BZQ6
Tässä kuvassa näkyy OS-9 (ERLEC2) sijainti ERAD koneistossa.:
Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e
Masatoshi Hagiwara,1Jingjing Ling, et al.
ER-associated degradation (ERAD) is essential for protein quality control in the ER, not only when the ER is stressed, but also at steady state. We report a new layer of homeostatic control, in which ERAD activity itself is regulated posttranscriptionally and independently of the unfolded protein response by adjusting the endogenous levels of EDEM1, OS-9,and SEL1L (ERAD enhancers). Functional UBC6e requires its precise location in the ER to form a supra-molecular complex with Derlin2. This complex targets ERAD enhancers for degradation, a function that depends on UBC6e’s enzymatic activity. Ablation of UBC6e causes upregulation of active ERAD enhancers and so increases clearance not only of terminally misfolded substrates, but also of wild-type glycoproteins that fold comparatively slowlyin vitro and in vivo. The levels of proteins that comprise the ERAD machinery are thus carefully tuned and adjusted to prevailing needs.
OS-9, ERLEC-2 https://www.genecards.org/cgi-bin/carddisp.pl?gene=OS9&keywords=OS-9
This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Eräs toinen lektiini mainitaan myös SARS-2ORF8 interaktioproteiineissa;. ERLEC1,
XTP3-Transactivated Gene B Protein 3 4
https://www.genecards.org/cgi-bin/carddisp.pl?gene=ERLEC1&keywords=OS-9
This gene encodes a resident endoplasmic reticulum (ER) protein that functions in N-glycan recognition. This protein is thought to be involved in ER-associated degradation via its interaction with the membrane-associated ubiquitin ligase complex. It also functions as a regulator of multiple cellular stress-response pathways in a manner that promotes metastatic cell survival. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 21. [provided by RefSeq, Aug 2011]
Probable lectin that binds selectively to improperly folded lumenal proteins. May function in endoplasmic reticulum quality control (ERQC) and endoplasmic reticulum-associated degradation (ERAD) of both non-glycosylated proteins and glycoproteins
Masatoshi Hagiwara,1Jingjing Ling, et al.
ER-associated degradation (ERAD) is essential for protein quality control in the ER, not only when the ER is stressed, but also at steady state. We report a new layer of homeostatic control, in which ERAD activity itself is regulated posttranscriptionally and independently of the unfolded protein response by adjusting the endogenous levels of EDEM1, OS-9,and SEL1L (ERAD enhancers). Functional UBC6e requires its precise location in the ER to form a supra-molecular complex with Derlin2. This complex targets ERAD enhancers for degradation, a function that depends on UBC6e’s enzymatic activity. Ablation of UBC6e causes upregulation of active ERAD enhancers and so increases clearance not only of terminally misfolded substrates, but also of wild-type glycoproteins that fold comparatively slowlyin vitro and in vivo. The levels of proteins that comprise the ERAD machinery are thus carefully tuned and adjusted to prevailing needs.
OS-9, ERLEC-2 https://www.genecards.org/cgi-bin/carddisp.pl?gene=OS9&keywords=OS-9
This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
OS9 (OS9 Endoplasmic Reticulum Lectin) is a Protein Coding gene.
Diseases associated with OS9 include Submucous Uterine Fibroid and Fibrosarcomatous Osteosarcoma.
Among its related pathways are Metabolism of proteins and Calnexin/calreticulin cycle.
Gene Ontology (GO) annotations related to this gene include carbohydrate binding.
An important paralog of this gene is ERLEC1.
OS-9, ERLEC2 , Lectin which functions in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD). May bind terminally misfolded non-glycosylated proteins as well as improperly folded glycoproteins, retain them in the ER, and possibly transfer them to the ubiquitination machinery and promote their degradation. Possible targets include TRPV4. OS9_HUMAN,Q13438
OS-9, ERLEC2 , Lectin which functions in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD). May bind terminally misfolded non-glycosylated proteins as well as improperly folded glycoproteins, retain them in the ER, and possibly transfer them to the ubiquitination machinery and promote their degradation. Possible targets include TRPV4. OS9_HUMAN,Q13438
Eräs toinen lektiini mainitaan myös SARS-2ORF8 interaktioproteiineissa;. ERLEC1,
XTP3-Transactivated Gene B Protein 3 4
https://www.genecards.org/cgi-bin/carddisp.pl?gene=ERLEC1&keywords=OS-9
This gene encodes a resident endoplasmic reticulum (ER) protein that functions in N-glycan recognition. This protein is thought to be involved in ER-associated degradation via its interaction with the membrane-associated ubiquitin ligase complex. It also functions as a regulator of multiple cellular stress-response pathways in a manner that promotes metastatic cell survival. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 21. [provided by RefSeq, Aug 2011]
Probable lectin that binds selectively to improperly folded lumenal proteins. May function in endoplasmic reticulum quality control (ERQC) and endoplasmic reticulum-associated degradation (ERAD) of both non-glycosylated proteins and glycoproteins
ERLEC1 (Endoplasmic Reticulum Lectin 1) is a Protein Coding gene.
Diseases associated with ERLEC1 include Myeloproliferative Syndrome, Transient.
Among its related pathways are Signaling by GPCR and Signaling by Hedgehog.
An important paralog of this gene is OS9.
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