iUUCD 2.0 - integrated annotations for ubiquitin and ubiquitin-like conjugation database

Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEO	ArrayExpress	GXD
DNA & RNA Element
AREsite	miRTarBase	microRNA	TRANSFAC
RepTar	RAID2
Protein-protein Interaction
IID	iRefIndex	HINT	Mentha
Protein 3D Structure
PDB	MMDB
Post-translational Modifications (PTMs)
dbPAF	PhosphositePlus	dbPTM	UniProt
Protein Expression/Proteomics
GPMDB

Status

Unreviewed

Classification

Family	Identity	E-Value	Score	Source Orthology
DUB/Other	82.14	0.00e+00	815.00	IUUC-Hsa-046924
UBD/Other/Other	82.14	0.00e+00	815.00	IUUC-Hsa-046924

Active Site

Position(s)	Description	Evidence
N/A	N/A	N/A

Organism

Mus musculus

Functional Description
(View)

Functional Description

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 (PubMed:26000482). 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 (PubMed:19322177, PubMed:21115689, PubMed:23185455, PubMed:26000482). 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) (PubMed:23706741). Self regulates by destabilizing its own mRNA (PubMed:22037600). 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 (PubMed:19322177, PubMed:23185455, PubMed:23706741, PubMed:26000482, PubMed:26134560). 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 (PubMed:21115689). 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 (PubMed:21115689). 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 (PubMed:21971051). Plays a role in the regulation of macrophage polarization; promotes IL4-induced polarization of macrophages M1 into anti-inflammatory M2 state (PubMed:25934862). May also act as a transcription factor that regulates the expression of multiple genes involved in inflammatory response, angiogenesis, adipogenesis and apoptosis (PubMed:18178554, PubMed:19666473, PubMed:22739135). 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 (PubMed:21616078).

Protein Sequence
(Fasta)

MSDPCGTKPV QESNPTMSLW SLEDRHSSQG RPQPDQDPVA KEAPTSELQM KVDFFRKLGY 60
SSSEIHSVLQ KLGVQADTNT VLGELVKHGS ATERECQALT APSPQPPLVP RGGSTPKPST 120

It may take some time, please wait.

Nucleotide Sequence
(Fasta)

GCTACGAAGG TGCCGTCAGA GCCCGAGACT CGGCTCCATG GACACCTTAC AGACGACGTC 60
CGGCGCTCAG CGGGGTGAGT GCTACCGGGT GGAACGGGTG CTGCGCTGCG TTGGGTCTGA 120

It may take some time, please wait.

Sequence Source

Ensembl

Keyword

KW-0002--3D-structure
KW-0037--Angiogenesis
KW-0053--Apoptosis
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0217--Developmental protein
KW-0221--Differentiation
KW-0227--DNA damage
KW-0238--DNA-binding
KW-0255--Endonuclease
KW-0256--Endoplasmic reticulum
KW-0378--Hydrolase
KW-0391--Immunity
KW-0395--Inflammatory response
KW-0460--Magnesium
KW-0472--Membrane
KW-0479--Metal-binding
KW-0524--Neurogenesis
KW-0540--Nuclease
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-1185--Reference proteome
KW-0694--RNA-binding
KW-0346--Stress response
KW-0832--Ubl conjugation
KW-0862--Zinc
KW-0863--Zinc-finger

Interpro

IPR021869--RNase_Zc3h12_NYN

Pfam

PF11977--RNase_Zc3h12a

Gene Ontology

GO:0005737--C:cytoplasm
GO:0005856--C:cytoskeleton
GO:0042406--C:extrinsic component of endoplasmic reticulum membrane
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0000932--C:P-body
GO:0043234--C:protein complex
GO:0005791--C:rough endoplasmic reticulum
GO:0030867--C:rough endoplasmic reticulum membrane
GO:0003682--F:chromatin binding
GO:0003677--F:DNA binding
GO:0004521--F:endoribonuclease activity
GO:0004532--F:exoribonuclease activity
GO:0046872--F:metal ion binding
GO:0035198--F:miRNA binding
GO:0035925--F:mRNA 3'-UTR AU-rich region binding
GO:0003730--F:mRNA 3'-UTR binding
GO:0003729--F:mRNA binding
GO:0004540--F:ribonuclease activity
GO:0043022--F:ribosome binding
GO:0003723--F:RNA binding
GO:0035613--F:RNA stem-loop binding
GO:0004843--F:thiol-dependent ubiquitin-specific protease activity
GO:0061158--P:3'-UTR-mediated mRNA destabilization
GO:0001525--P:angiogenesis
GO:0006915--P:apoptotic process
GO:0030154--P:cell differentiation
GO:1990869--P:cellular response to chemokine
GO:0006974--P:cellular response to DNA damage stimulus
GO:0042149--P:cellular response to glucose starvation
GO:0071347--P:cellular response to interleukin-1
GO:1904637--P:cellular response to ionomycin
GO:0071222--P:cellular response to lipopolysaccharide
GO:0034599--P:cellular response to oxidative stress
GO:1904628--P:cellular response to phorbol 13-acetate 12-myristate
GO:1903936--P:cellular response to sodium arsenite
GO:0071356--P:cellular response to tumor necrosis factor
GO:0098586--P:cellular response to virus
GO:0002376--P:immune system process
GO:0006954--P:inflammatory response
GO:0044828--P:negative regulation by host of viral genome replication
GO:0055118--P:negative regulation of cardiac muscle contraction
GO:1900016--P:negative regulation of cytokine production involved in inflammatory response
GO:0010629--P:negative regulation of gene expression
GO:0043124--P:negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:1902714--P:negative regulation of interferon-gamma secretion
GO:0050713--P:negative regulation of interleukin-1 beta secretion
GO:0032715--P:negative regulation of interleukin-6 production
GO:1900165--P:negative regulation of interleukin-6 secretion
GO:0010656--P:negative regulation of muscle cell apoptotic process
GO:0042347--P:negative regulation of NF-kappaB import into nucleus
GO:0032088--P:negative regulation of NF-kappaB transcription factor activity
GO:0045019--P:negative regulation of nitric oxide biosynthetic process
GO:1903799--P:negative regulation of production of miRNAs involved in gene silencing by miRNA
GO:0001933--P:negative regulation of protein phosphorylation
GO:0032720--P:negative regulation of tumor necrosis factor production
GO:1904468--P:negative regulation of tumor necrosis factor secretion
GO:0007399--P:nervous system development
GO:0000294--P:nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay
GO:0045766--P:positive regulation of angiogenesis
GO:0010508--P:positive regulation of autophagy
GO:0010942--P:positive regulation of cell death
GO:0002230--P:positive regulation of defense response to virus by host
GO:0010595--P:positive regulation of endothelial cell migration
GO:1900119--P:positive regulation of execution phase of apoptosis
GO:0045600--P:positive regulation of fat cell differentiation
GO:0010628--P:positive regulation of gene expression
GO:0010884--P:positive regulation of lipid storage
GO:2000627--P:positive regulation of miRNA catabolic process
GO:0061014--P:positive regulation of mRNA catabolic process
GO:1900745--P:positive regulation of p38MAPK cascade
GO:1903003--P:positive regulation of protein deubiquitination
GO:0042307--P:positive regulation of protein import into nucleus
GO:2000379--P:positive regulation of reactive oxygen species metabolic process
GO:0045944--P:positive regulation of transcription from RNA polymerase II promoter
GO:0016579--P:protein deubiquitination
GO:0051259--P:protein oligomerization
GO:0010468--P:regulation of gene expression
GO:0090501--P:RNA phosphodiester bond hydrolysis
GO:0090502--P:RNA phosphodiester bond hydrolysis, endonucleolytic

KEGG

mmu:230738

Orthology

iUUCD ID	Species	Identity	E-value	Score
IUUC-Aml-002223	Ailuropoda melanoleuca	80.98	0.00e+00	778.00
IUUC-Apl-003631	Anas platyrhynchos	66.75	5.00e-151	527.00
IUUC-Aca-005301	Anolis carolinensis	53.62	2.00e-148	519.00
IUUC-Ame-010867	Astyanax mexicanus	68.69	5.00e-121	428.00
IUUC-Bta-012505	Bos taurus	80.96	0.00e+00	815.00
IUUC-Cja-019490	Callithrix jacchus	80.98	0.00e+00	821.00
IUUC-Cfa-021149	Canis familiaris	76.84	0.00e+00	772.00
IUUC-Cpo-021301	Cavia porcellus	83.88	0.00e+00	850.00
IUUC-Csa-023367	Chlorocebus sabaeus	81.86	0.00e+00	852.00
IUUC-Cin-025756	Ciona intestinalis	67.12	1.00e-16	79.70
IUUC-Dre-027579	Danio rerio	70.90	3.00e-121	427.00
IUUC-Dno-030064	Dasypus novemcinctus	79.06	0.00e+00	754.00
IUUC-Dor-031093	Dipodomys ordii	72.79	0.00e+00	741.00
IUUC-Ete-032302	Echinops telfairi	65.38	5.00e-163	567.00
IUUC-Eca-033237	Equus caballus	81.48	0.00e+00	835.00
IUUC-Eeu-035130	Erinaceus europaeus	76.06	0.00e+00	656.00
IUUC-Fca-035416	Felis catus	81.65	0.00e+00	791.00
IUUC-Fal-037281	Ficedula albicollis	56.31	4.00e-162	565.00
IUUC-Fso-038424	Fusarium solani	31.11	4.30e-02	32.00
IUUC-Gmo-039204	Gadus morhua	48.44	6.00e-116	411.00
IUUC-Gac-041980	Gasterosteus aculeatus	48.89	2.00e-130	459.00
IUUC-Ggo-044933	Gorilla gorilla	81.64	0.00e+00	830.00
IUUC-Hsa-046924	Homo sapiens	81.30	0.00e+00	831.00
IUUC-Itr-048614	Ictidomys tridecemlineatus	80.63	0.00e+00	835.00
IUUC-Lch-050063	Latimeria chalumnae	57.66	2.00e-169	589.00
IUUC-Loc-051993	Lepisosteus oculatus	53.02	3.00e-149	522.00
IUUC-Laf-053400	Loxodonta africana	80.10	0.00e+00	801.00
IUUC-Mcc-054768	Macaca mulatta	82.20	0.00e+00	838.00
IUUC-Meu-056059	Macropus eugenii	52.85	3.00e-130	459.00
IUUC-Mga-059707	Meleagris gallopavo	59.86	1.00e-172	599.00
IUUC-Mvi-060339	Microbotryum violaceum	36.36	1.10e+00	25.80
IUUC-Mmr-061391	Microcebus murinus	83.31	0.00e+00	830.00
IUUC-Mdo-062040	Monodelphis domestica	66.78	0.00e+00	667.00
IUUC-Mpu-066099	Mustela putorius furo	80.96	0.00e+00	759.00
IUUC-Mlu-067979	Myotis lucifugus	79.56	0.00e+00	821.00
IUUC-Nle-069830	Nomascus leucogenys	79.80	0.00e+00	800.00
IUUC-Opr-071005	Ochotona princeps	80.27	2.00e-177	615.00
IUUC-Ont-072306	Oreochromis niloticus	48.78	5.00e-135	474.00
IUUC-Oan-073138	Ornithorhynchus anatinus	62.85	2.00e-172	598.00
IUUC-Ocu-073908	Oryctolagus cuniculus	87.71	0.00e+00	635.00
IUUC-Ola-087280	Oryzias latipes	46.11	4.00e-126	444.00
IUUC-Oga-088418	Otolemur garnettii	81.64	0.00e+00	842.00
IUUC-Oar-090414	Ovis aries	83.67	0.00e+00	645.00
IUUC-Ptr-091275	Pan troglodytes	81.47	0.00e+00	828.00
IUUC-Pan-092541	Papio anubis	82.03	0.00e+00	830.00
IUUC-Psi-094002	Pelodiscus sinensis	61.36	1.00e-179	622.00
IUUC-Pab-098538	Pongo abelii	81.97	0.00e+00	842.00
IUUC-Pca-100137	Procavia capensis	79.86	1.00e-174	605.00
IUUC-Pva-102367	Pteropus vampyrus	83.26	0.00e+00	652.00
IUUC-Rno-105133	Rattus norvegicus	92.79	0.00e+00	1036.00
IUUC-Sha-106603	Sarcophilus harrisii	65.90	6.00e-157	547.00
IUUC-Tgu-117358	Taeniopygia guttata	60.68	9.00e-143	499.00
IUUC-Tru-118112	Takifugu rubripes	48.08	2.00e-126	446.00
IUUC-Tsy-119005	Tarsius syrichta	75.07	2.00e-150	525.00
IUUC-Ttr-129314	Tursiops truncatus	80.74	0.00e+00	836.00

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence