UniProt functional annotation for Q7Z6Z7



	UniProt functional annotation for Q7Z6Z7

UniProt code: Q7Z6Z7.

Organism: Homo sapiens (Human).

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

Function: E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15989957, PubMed:19713937, PubMed:15567145, PubMed:15767685, PubMed:18488021, PubMed:17567951, PubMed:19037095, PubMed:20534529). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). {ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738}.

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=2.3.2.26;

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with isoform p14ARF of CDKN2A which strongly inhibits HUWE1 ubiquitin ligase activity. Interacts with MYCN, POLB and CDC6. Interacts with isoform 2 of PA2G4. Interacts with NR1D1 (PubMed:20534529). {ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:19713937}. Nucleus {ECO:0000269|PubMed:19713937}. Note=Mainly expressed in the cytoplasm of most tissues, except in the nucleus of spermatogonia, primary spermatocytes and neuronal cells (By similarity). Predominantly cytosolic or perinuclear in some colorectal carcinoma cells. {ECO:0000250|UniProtKB:Q7TMY8}.

Tissue specificity: Weakly expressed in heart, brain and placenta but not in other tissues. Expressed in a number of cell lines, predominantly in those from colorectal carcinomas. {ECO:0000269|PubMed:15567145}.

Domain: The HECT domain mediates inhibition of the transcriptional activity of p53.

Ptm: Phosphorylated on tyrosine; phosphorylation is probably required for its ability to inhibit TP53 transactivation. {ECO:0000250|UniProtKB:Q7TMY8}.

Disease: Mental retardation, X-linked, syndromic, Turner type (MRXST) [MIM:309590]: An X-linked neurodevelopmental disorder with highly variable clinical manifestations. Common features consist of moderate to profound intellectual disability, delayed or absent speech, short stature with small hands and feet, and non-specific but recurrent dysmorphic facial features such as macrocephaly, microcephaly, a broad nasal tip, deep set eyes, epicanthic folds, short palpebral fissures and a short philtrum. Patients may manifest other features, such as hypotonia, seizures and delayed bone age. {ECO:0000269|PubMed:18252223, ECO:0000269|PubMed:25985138, ECO:0000269|PubMed:27130160, ECO:0000269|PubMed:27884935, ECO:0000269|PubMed:29180823}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the UPL family. TOM1/PTR1 subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAC62492.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAF28950.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAF28950.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAB13404.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA, contains the C-terminal part of ATP5ME.; Evidence={ECO:0000305}; Sequence=BAC06833.1; Type=Frameshift; 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:		E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15989957, PubMed:19713937, PubMed:15567145, PubMed:15767685, PubMed:18488021, PubMed:17567951, PubMed:19037095, PubMed:20534529). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). {ECO:0000269\|PubMed:15567145, ECO:0000269\|PubMed:15767685, ECO:0000269\|PubMed:15989956, ECO:0000269\|PubMed:15989957, ECO:0000269\|PubMed:17567951, ECO:0000269\|PubMed:18488021, ECO:0000269\|PubMed:19037095, ECO:0000269\|PubMed:19713937, ECO:0000269\|PubMed:20534529, ECO:0000269\|PubMed:26214738}.


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=2.3.2.26;
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with isoform p14ARF of CDKN2A which strongly inhibits HUWE1 ubiquitin ligase activity. Interacts with MYCN, POLB and CDC6. Interacts with isoform 2 of PA2G4. Interacts with NR1D1 (PubMed:20534529). {ECO:0000269\|PubMed:15989956, ECO:0000269\|PubMed:17567951, ECO:0000269\|PubMed:18488021, ECO:0000269\|PubMed:19037095, ECO:0000269\|PubMed:19713937, ECO:0000269\|PubMed:20534529}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:19713937}. Nucleus {ECO:0000269\|PubMed:19713937}. Note=Mainly expressed in the cytoplasm of most tissues, except in the nucleus of spermatogonia, primary spermatocytes and neuronal cells (By similarity). Predominantly cytosolic or perinuclear in some colorectal carcinoma cells. {ECO:0000250\|UniProtKB:Q7TMY8}.
Tissue specificity:		Weakly expressed in heart, brain and placenta but not in other tissues. Expressed in a number of cell lines, predominantly in those from colorectal carcinomas. {ECO:0000269\|PubMed:15567145}.
Domain:		The HECT domain mediates inhibition of the transcriptional activity of p53.
Ptm:		Phosphorylated on tyrosine; phosphorylation is probably required for its ability to inhibit TP53 transactivation. {ECO:0000250\|UniProtKB:Q7TMY8}.
Disease:		Mental retardation, X-linked, syndromic, Turner type (MRXST) [MIM:309590]: An X-linked neurodevelopmental disorder with highly variable clinical manifestations. Common features consist of moderate to profound intellectual disability, delayed or absent speech, short stature with small hands and feet, and non-specific but recurrent dysmorphic facial features such as macrocephaly, microcephaly, a broad nasal tip, deep set eyes, epicanthic folds, short palpebral fissures and a short philtrum. Patients may manifest other features, such as hypotonia, seizures and delayed bone age. {ECO:0000269\|PubMed:18252223, ECO:0000269\|PubMed:25985138, ECO:0000269\|PubMed:27130160, ECO:0000269\|PubMed:27884935, ECO:0000269\|PubMed:29180823}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the UPL family. TOM1/PTR1 subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAC62492.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAF28950.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAF28950.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAB13404.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA, contains the C-terminal part of ATP5ME.; Evidence={ECO:0000305}; Sequence=BAC06833.1; Type=Frameshift; Evidence={ECO:0000305};