UniProt functional annotation for Q9HBD1



	UniProt functional annotation for Q9HBD1

UniProt code: Q9HBD1.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H1, possibly leading to feedback loop regulation (By similarity). miRNA- binding protein that regulates microRNA homeostasis. Enhances DICER- mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 and produces polyubiquitin chains (PubMed:26489670). Shows the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (PubMed:26489670). Involved in the ubiquitination of MAP3K5 (PubMed:24448648, PubMed:26489670) (By similarity). Able to interact with double-stranded RNA (dsRNA) (PubMed:26489670). {ECO:0000250|UniProtKB:P0C090, ECO:0000269|PubMed:24448648, ECO:0000269|PubMed:26489670}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269|PubMed:26489670, ECO:0000303|PubMed:24448648};

Activity regulation: Binding to dsRNA, but not CDE RNA, crosstalks with the E3 ubiquitin ligase activity and may inhibit ubiquitination. {ECO:0000269|PubMed:26489670}.

Pathway: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:24448648, ECO:0000269|PubMed:26489670}.

Subunit: Interacts with EDC4. Interacts with CCR4-NOT deadenylase complex (By similarity). Interacts with MAP3K5; the interaction is probably stimulus-dependent (PubMed:24448648). {ECO:0000250|UniProtKB:P0C090, ECO:0000269|PubMed:24448648}.

Subcellular location: Cytoplasm, P-body {ECO:0000250}. Note=During stress, such as that induced by arsenite, localizes to cytosolic stress granules. Localization to stress granules, but not to P-bodies, depends upon the RING-type zinc finger. {ECO:0000269|PubMed:20412057}.

Tissue specificity: Expressed in spleen, testis, ovary and small intestine. {ECO:0000269|PubMed:10938276}.

Domain: The RING-type zinc finger is required for proper localization to stress granules, but not to P-bodies. {ECO:0000250|UniProtKB:Q4VGL6}.

Domain: The ROQ region is required for CDE RNA-binding. Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA (PubMed:26249698). It may also be involved in localization to stress granules (By similarity). {ECO:0000250|UniProtKB:Q4VGL6, ECO:0000269|PubMed:26249698}.

Domain: HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are observed in both N- and C-terminal sides of ROQ domain with 3D structure even if they are poredcted on the basis of sequence. {ECO:0000269|PubMed:26489670}.

Ptm: Proteolytically cleaved after Arg-509 and Arg-585 by MALT1 in activated CD4(+) T cells; cleavage at Arg-509 and Arg-585 is critical for promoting RC3H1 degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling Th17 cell differentiation. {ECO:0000250|UniProtKB:P0C090}.

Sequence caution: Sequence=BAA91340.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15634.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H1, possibly leading to feedback loop regulation (By similarity). miRNA- binding protein that regulates microRNA homeostasis. Enhances DICER- mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 and produces polyubiquitin chains (PubMed:26489670). Shows the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (PubMed:26489670). Involved in the ubiquitination of MAP3K5 (PubMed:24448648, PubMed:26489670) (By similarity). Able to interact with double-stranded RNA (dsRNA) (PubMed:26489670). {ECO:0000250\|UniProtKB:P0C090, ECO:0000269\|PubMed:24448648, ECO:0000269\|PubMed:26489670}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269\|PubMed:26489670, ECO:0000303\|PubMed:24448648};
Activity regulation:		Binding to dsRNA, but not CDE RNA, crosstalks with the E3 ubiquitin ligase activity and may inhibit ubiquitination. {ECO:0000269\|PubMed:26489670}.
Pathway:		Protein modification; protein ubiquitination. {ECO:0000269\|PubMed:24448648, ECO:0000269\|PubMed:26489670}.
Subunit:		Interacts with EDC4. Interacts with CCR4-NOT deadenylase complex (By similarity). Interacts with MAP3K5; the interaction is probably stimulus-dependent (PubMed:24448648). {ECO:0000250\|UniProtKB:P0C090, ECO:0000269\|PubMed:24448648}.
Subcellular location:		Cytoplasm, P-body {ECO:0000250}. Note=During stress, such as that induced by arsenite, localizes to cytosolic stress granules. Localization to stress granules, but not to P-bodies, depends upon the RING-type zinc finger. {ECO:0000269\|PubMed:20412057}.
Tissue specificity:		Expressed in spleen, testis, ovary and small intestine. {ECO:0000269\|PubMed:10938276}.
Domain:		The RING-type zinc finger is required for proper localization to stress granules, but not to P-bodies. {ECO:0000250\|UniProtKB:Q4VGL6}.
Domain:		The ROQ region is required for CDE RNA-binding. Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA (PubMed:26249698). It may also be involved in localization to stress granules (By similarity). {ECO:0000250\|UniProtKB:Q4VGL6, ECO:0000269\|PubMed:26249698}.
Domain:		HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are observed in both N- and C-terminal sides of ROQ domain with 3D structure even if they are poredcted on the basis of sequence. {ECO:0000269\|PubMed:26489670}.
Ptm:		Proteolytically cleaved after Arg-509 and Arg-585 by MALT1 in activated CD4(+) T cells; cleavage at Arg-509 and Arg-585 is critical for promoting RC3H1 degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling Th17 cell differentiation. {ECO:0000250\|UniProtKB:P0C090}.
Sequence caution:		Sequence=BAA91340.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15634.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};