| UniProt functional annotation for Q9H0M0 | |||
| UniProt code: Q9H0M0. |
| 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 accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Ubiquitinates ERBB4 isoforms JM-A CYT-1 and JM-B CYT-1, KLF2, KLF5 and TP63 and promotes their proteasomal degradation. Ubiquitinates RNF11 without targeting it for degradation. Ubiquitinates and promotes degradation of TGFBR1; the ubiquitination is enhanced by SMAD7. Ubiquitinates SMAD6 and SMAD7. Ubiquitinates and promotes degradation of SMAD2 in response to TGF-beta signaling, which requires interaction with TGIF. {ECO:0000269|PubMed:12535537, ECO:0000269|PubMed:15221015, ECO:0000269|PubMed:15359284}. | |
| 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; | |
| Activity regulation: | Activated by NDFIP1- and NDFIP2-binding. | |
| Pathway: | Protein modification; protein ubiquitination. | |
| Subunit: | Binds KLF2 AND HIVEP3 (By similarity). Binds SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2, DRPLA and adenovirus type 2 PIII. Interacts with RNF11 (By similarity). Interacts with SPART. Interacts with ERBB4 isoforms JM-B CYT-1 and JM-A CYT-1. Interacts with SMAD1, SMAD2, SMAD3, SMAD5, SMAD6, SMAD7, TGFBR1 AND TGFBR2. Associates with the TGFBR1:TGFBR2 receptor complex in presence of SMAD7. Interacts with SKIL isoform 1. Interacts with TP63 isoform 1 and isoform 2. Interacts with STAMBP and RNF11. Interacts with NDFIP1 and NDFIP2 (Probable); this interaction activates the E3 ubiquitin-protein ligase. Interacts with TGIF. Interacts (via WW domains) with ARRDC1, ARRDC2 and ARRDC3 (PubMed:21191027). {ECO:0000250, ECO:0000269|PubMed:12450395, ECO:0000269|PubMed:15221015, ECO:0000269|PubMed:15359284, ECO:0000269|PubMed:19561640, ECO:0000269|PubMed:19580544, ECO:0000269|PubMed:21191027, ECO:0000269|PubMed:9169421, ECO:0000269|PubMed:9647693}. | |
| Subunit: | (Microbial infection) Interacts with HTLV-1 protein Gag. {ECO:0000269|PubMed:17609263}. | |
| Subunit: | (Microbial infection) Interacts with ebola virus protein VP40. {ECO:0000269|PubMed:28768865}. | |
| Subcellular location: | Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus {ECO:0000250}. | |
| Tissue specificity: | Detected in heart, placenta, pancreas, kidney, liver, skeletal muscle, bone marrow, fetal brain, and at much lower levels in adult brain and lung. Isoform 1 and isoform 5 predominate in all tissues tested, except in testis and bone marrow, where isoform 5 is expressed at much higher levels than isoform 1. {ECO:0000269|PubMed:11779188, ECO:0000269|PubMed:9647693}. | |
| Domain: | The WW domains mediate interaction with PPxY motif-containing proteins. {ECO:0000269|PubMed:21191027}. | |
| Ptm: | Auto-ubiquitinated and ubiquitinated by RNF11. {ECO:0000269|PubMed:15359284, ECO:0000269|PubMed:18724389, ECO:0000269|PubMed:19343052}. | |
Annotations taken from UniProtKB at the EBI.