| Identification |
|---|
| BMDB Protein ID
| BMDBP00469 |
| Secondary Accession Numbers
| None |
| Name
| Ribonuclease ZC3H12A |
| Synonyms
|
Not Available
|
| Gene Name
| ZC3H12A |
| Protein Type
| Enzyme |
| Biological Properties |
|---|
| General Function
| Involved in endonuclease activity |
| Specific Function
| Endoribonuclease involved in various biological functions such as cellular inflammatory response and immune homeostasis, glial differentiation of neuroprogenitor cells, cell death of cardiomyocytes, adipogenesis and angiogenesis. Functions as an endoribonuclease involved in mRNA decay. Modulates the inflammatory response by promoting the degradation of a set of translationally active cytokine-induced inflammation-related mRNAs, such as IL6 and IL12B, during the early phase of inflammation. Prevents aberrant T-cell-mediated immune reaction by degradation of multiple mRNAs controlling T-cell activation, such as those encoding cytokines (IL6 and IL2), cell surface receptors (ICOS, TNFRSF4 and TNFR2) and transcription factor (REL). Inhibits cooperatively with ZC3H12A the differentiation of helper T cells Th17 in lungs. They repress target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A (By similarity). Together with RC3H1, destabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR (By similarity). Self regulates by destabilizing its own mRNA. Cleaves mRNA harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-dependent manner (By similarity). Plays a role in the inhibition of microRNAs (miRNAs) biogenesis (By similarity). Cleaves the terminal loop of a set of precursor miRNAs (pre-miRNAs) important for the regulation of the inflammatory response leading to their degradation, and thus preventing the biosynthesis of mature miRNAs (By similarity). Plays also a role in promoting angiogenesis in response to inflammatory cytokines by inhibiting the production of antiangiogenic microRNAs via its anti-dicer RNase activity (By similarity). Affects the overall ubiquitination of cellular proteins. Positively regulates deubiquitinase activity promoting the cleavage at 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains on TNF receptor-associated factors (TRAFs), preventing JNK and NF-kappa-B signaling pathway activation, and hence negatively regulating macrophage-mediated inflammatory response and immune homeostasis (By similarity). Induces also deubiquitination of the transcription factor HIF1A, probably leading to its stabilization and nuclear import, thereby positively regulating the expression of proangiogenic HIF1A-targeted genes. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (By similarity). Prevents stress granules (SGs) formation and promotes macrophage apoptosis under stress conditions, including arsenite-induced oxidative stress, heat shock, and energy deprivation. Plays a role in the regulation of macrophage polarization; promotes IL4-induced polarization of macrophages M1 into anti-inflammatory M2 state. May also act as a transcription factor that regulates the expression of multiple genes involved in inflammatory response, angiogenesis, adipogenesis and apoptosis (By similarity). Functions as a positive regulator of glial differentiation of neuroprogenitor cells through an amyloid precursor protein (APP)-dependent signaling pathway (By similarity). Attenuates septic myocardial contractile dysfunction in response to lipopolysaccharide (LPS) by reducing I-kappa-B-kinase (IKK)-mediated NF-kappa-B activation, and hence myocardial proinflammatory cytokine production (By similarity). |
| Pathways
|
Not Available
|
| Reactions
| Not Available |
| GO Classification
|
Not Available
|
| Cellular Location
|
Not Available
|
| Gene Properties |
|---|
| Chromosome Location
| 3 |
| Locus
| Not Available |
| SNPs
| ZC3H12A |
| Gene Sequence
|
>1752 bp
ATGAGCCTGTGGGAACTTGAAGACCGCCGAAGCTGCCAGGGGACCCCCAGGCCGGCCCAG
GAGCCCACGGCCGAGGAGGCAACGACTGCAGAGTTGCAGATGAAGGTTGACTTCTTCCGG
AAGCTGGGCTACTCATCTGCTGAGATCCACAGTGTCCTGCAGAAGCTGGGCATCCAGGCA
GACACCAACACAGTGCTGGGGGAGCTGGTTAAACATGGGTCAGCGGCCGAGCGGGAGCGC
CAGGCATCGCCGGACCCCTGCCCTCAGCTGCCTCTGGTCCCCCGGGGTGGGGGCACCCCC
AAGGCTCCCACCGTGGAGACTTATCCACCCGAGGAAGACAAGGAGGGCAGTGACCTGAGA
CCCATAGTCATCGATGGGAGCAACGTGGCCATGAGCCATGGGAACAAGGACGTCTTCTCC
TGCCGGGGGATCCTCCTGGCAGTGAATTGGTTCCTGGAGCGGGGCCACACAGACATCACC
GTGTTTGTGCCGTCCTGGAGGAAAGAGCAGCCTCGCCCAGATGTGCCCATCACTGATCAG
CACATCCTGCGGGACCTGGAGAAGAAGAAGATCTTGGTGTTCACACCGTCGCGGCGGGTG
GGTGGCAAGCGGGTAGTCTGCTATGACGACCGCTTCATCGTGAAGCTGGCCTTTGAGTCG
GACGGCATCGTGGTCTCCAATGACACGTACCGGGACCTGCAGGGCGAGCGGCAGGAGTGG
AAGCGTTTCATCGAGGAGCGGCTGCTCATGTACTCCTTTGTCAATGACAAGTTCATGCCC
CCCGATGACCCTTTGGGCCGTCATGGGCCGAGCCTGGACAACTTCCTGCGTAAGAAGCCG
CTCACATCAGAGCACAAGAAGCAGCCGTGTCCCTATGGGAGGAAATGCACCTACGGGATC
AAGTGCCGATTCTTGCACCCCGAGCGGCCGAGCCGGCCCCAGCGCTCCGTGGCCGACGAG
CTCCGCGCCAACGCCCTGCTGCCACCCTCCAGGGCCGCGAGCAAAGACAAAAACAGCCGG
CGGCCTTCACCCTCCTCTCAGCCCGGCTCTCTGCCAACAGAGCACGAGCAGTGCAGCCCG
GACAGGAAGAAGCTGGGGGCCCAGGCGTCTCCAGGAACCCCCCGGGAGGGCCTGATGCAG
ACCTTTGCCCCGACAGGCAGGAGCCTCCCTCCTAGTGGGAGCAGTGGCGGCAGCTTCGGG
CCCTCAGAGTGGTTCCCGCAGACCCTGGACTCTCTCCCCTACGCCTCCCAGGACTGCCTG
GACTCGGGCATCGGCTCCCTGGAGAGCCAGATGTCAGAACTCTGGGGGGTTCGAGGAGGG
GGCCCTGGCGAGCCGGGCCCACCTCGGGGCCCTTATGCCGGCTACTGCACCTACGGGGCA
GAGCTCCCTGCCACCCCGGCCTTCTCGGCCTTCAGCCGGGCCCTGGGTGCCGGCCACTTC
AGCGTCCCCGCTGACTATGCACCCCCGCCGGCCGCCTTTCCACCTCGGGAATACTGGTCT
GAGCCATACCAGCTGCCCCCGCCCACCCAACGCCTGCAGGAGCCCCAGGCACCTGGCCCA
GGAGCTGACAGGGGCCCCTGGGGTGGGGCAGGCAGGCTGGCGAAGGAGCGAGCCAGCGTG
TACACTAAGCTGTGTGGAGTCTTCCCCCCACACCTGGTGGAGGCCGTGATGTCGCGCTTC
CCGCAGCTCCTGGACCCCCAGCAGCTGGCCGCCGAGATCCTCTCCTACAAGTCCCAGCAC
CTCAGTGAATAA
|
| Protein Properties |
|---|
| Number of Residues
| 583 |
| Molecular Weight
| 64263.0 |
| Theoretical pI
| 7.89 |
| Pfam Domain Function
|
Not Available |
| Signals
|
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
>Ribonuclease ZC3H12A
MSLWELEDRRSCQGTPRPAQEPTAEEATTAELQMKVDFFRKLGYSSAEIHSVLQKLGIQA
DTNTVLGELVKHGSAAERERQASPDPCPQLPLVPRGGGTPKAPTVETYPPEEDKEGSDLR
PIVIDGSNVAMSHGNKDVFSCRGILLAVNWFLERGHTDITVFVPSWRKEQPRPDVPITDQ
HILRDLEKKKILVFTPSRRVGGKRVVCYDDRFIVKLAFESDGIVVSNDTYRDLQGERQEW
KRFIEERLLMYSFVNDKFMPPDDPLGRHGPSLDNFLRKKPLTSEHKKQPCPYGRKCTYGI
KCRFLHPERPSRPQRSVADELRANALLPPSRAASKDKNSRRPSPSSQPGSLPTEHEQCSP
DRKKLGAQASPGTPREGLMQTFAPTGRSLPPSGSSGGSFGPSEWFPQTLDSLPYASQDCL
DSGIGSLESQMSELWGVRGGGPGEPGPPRGPYAGYCTYGAELPATPAFSAFSRALGAGHF
SVPADYAPPPAAFPPREYWSEPYQLPPPTQRLQEPQAPGPGADRGPWGGAGRLAKERASV
YTKLCGVFPPHLVEAVMSRFPQLLDPQQLAAEILSYKSQHLSE
|
| External Links |
|---|
| GenBank ID Protein
| AAI49868.1 |
| UniProtKB/Swiss-Prot ID
| A6QQJ8 |
| UniProtKB/Swiss-Prot Entry Name
| ZC12A_BOVIN |
| PDB IDs
|
Not Available |
| GenBank Gene ID
| BC149867 |
| GeneCard ID
| ZC3H12A |
| GenAtlas ID
| Not Available |
| HGNC ID
| Not Available |
| References |
|---|
| General References
| Not Available |
