UniProt functional annotation for P68036



	UniProt functional annotation for P68036

UniProt code: P68036.

Organism: Homo sapiens (Human).

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

Function: Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PRKN and ARIH1, that function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down- regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis. {ECO:0000269|PubMed:10888878, ECO:0000269|PubMed:15367689, ECO:0000269|PubMed:17003263, ECO:0000269|PubMed:18946090, ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:21532592}.

Catalytic activity: Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin- activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin- conjugating enzyme]-L-cysteine.; EC=2.3.2.23; Evidence={ECO:0000255|PROSITE-ProRule:PRU00388, ECO:0000255|PROSITE- ProRule:PRU10133, ECO:0000269|PubMed:20061386};

Pathway: Protein modification; protein ubiquitination. {ECO:0000255|PROSITE-ProRule:PRU00388}.

Subunit: Interacts with PRKN; involved in ubiquitination and degradation of misfolded proteins. Interacts with UBE3A; used by the papilloma virus HPV-16 E6 protein to ubiquitinate p53/TP53. Interacts with CCNB1IP1, CBL, ZAP70, RNF19A, RNF19B and RNF144B. Interacts with ARIH1. Interacts with ARIH2 (via RING-type 1). Interacts with NCOA1; they functionally interact to regulate progesterone receptor transcriptional activity. May interact with NR3C1. Interacts with NDFIP1 (via N-terminus); the interaction mediates recruitment of UBE2L3 to ITCH and causes MAP3K7 ubiquitination (PubMed:25632008). {ECO:0000269|PubMed:10558980, ECO:0000269|PubMed:10888878, ECO:0000269|PubMed:10966114, ECO:0000269|PubMed:11237715, ECO:0000269|PubMed:11278816, ECO:0000269|PubMed:12612082, ECO:0000269|PubMed:15367689, ECO:0000269|PubMed:16427630, ECO:0000269|PubMed:16709802, ECO:0000269|PubMed:17003263, ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:25632008}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11278816, ECO:0000269|PubMed:17003263}. Cytoplasm {ECO:0000269|PubMed:11278816, ECO:0000269|PubMed:17003263}.

Tissue specificity: Ubiquitous, with highest expression in testis.

Domain: In contrast to other ubiquitin-conjugating enzymes E2, residues essential for lysine reactivity are absent: Pro and a His residues are present instead of an Asp and an Asp residues in positions 88 and 119, respectively. {ECO:0000269|PubMed:21532592}.

Ptm: Ubiquitinated. The alteration of UBE2L3 protein levels during the S-phase of the cell cycle is due to ubiquitin-dependent proteasomal degradation. Autoubiquitinated in vitro (PubMed:22496338). {ECO:0000269|PubMed:18946090, ECO:0000269|PubMed:22496338}.

Similarity: Belongs to the ubiquitin-conjugating enzyme family. {ECO:0000255|PROSITE-ProRule:PRU00388}.

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:		Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PRKN and ARIH1, that function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down- regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis. {ECO:0000269\|PubMed:10888878, ECO:0000269\|PubMed:15367689, ECO:0000269\|PubMed:17003263, ECO:0000269\|PubMed:18946090, ECO:0000269\|PubMed:19340006, ECO:0000269\|PubMed:20061386, ECO:0000269\|PubMed:21532592}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin- activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin- conjugating enzyme]-L-cysteine.; EC=2.3.2.23; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00388, ECO:0000255\|PROSITE- ProRule:PRU10133, ECO:0000269\|PubMed:20061386};
Pathway:		Protein modification; protein ubiquitination. {ECO:0000255\|PROSITE-ProRule:PRU00388}.
Subunit:		Interacts with PRKN; involved in ubiquitination and degradation of misfolded proteins. Interacts with UBE3A; used by the papilloma virus HPV-16 E6 protein to ubiquitinate p53/TP53. Interacts with CCNB1IP1, CBL, ZAP70, RNF19A, RNF19B and RNF144B. Interacts with ARIH1. Interacts with ARIH2 (via RING-type 1). Interacts with NCOA1; they functionally interact to regulate progesterone receptor transcriptional activity. May interact with NR3C1. Interacts with NDFIP1 (via N-terminus); the interaction mediates recruitment of UBE2L3 to ITCH and causes MAP3K7 ubiquitination (PubMed:25632008). {ECO:0000269\|PubMed:10558980, ECO:0000269\|PubMed:10888878, ECO:0000269\|PubMed:10966114, ECO:0000269\|PubMed:11237715, ECO:0000269\|PubMed:11278816, ECO:0000269\|PubMed:12612082, ECO:0000269\|PubMed:15367689, ECO:0000269\|PubMed:16427630, ECO:0000269\|PubMed:16709802, ECO:0000269\|PubMed:17003263, ECO:0000269\|PubMed:19340006, ECO:0000269\|PubMed:21532592, ECO:0000269\|PubMed:25632008}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11278816, ECO:0000269\|PubMed:17003263}. Cytoplasm {ECO:0000269\|PubMed:11278816, ECO:0000269\|PubMed:17003263}.
Tissue specificity:		Ubiquitous, with highest expression in testis.
Domain:		In contrast to other ubiquitin-conjugating enzymes E2, residues essential for lysine reactivity are absent: Pro and a His residues are present instead of an Asp and an Asp residues in positions 88 and 119, respectively. {ECO:0000269\|PubMed:21532592}.
Ptm:		Ubiquitinated. The alteration of UBE2L3 protein levels during the S-phase of the cell cycle is due to ubiquitin-dependent proteasomal degradation. Autoubiquitinated in vitro (PubMed:22496338). {ECO:0000269\|PubMed:18946090, ECO:0000269\|PubMed:22496338}.
Similarity:		Belongs to the ubiquitin-conjugating enzyme family. {ECO:0000255\|PROSITE-ProRule:PRU00388}.