RNF133

Summary

RNF133 (ring finger protein 133, HGNC:21154) is a protein-coding gene on chromosome 7q31.32, encoding E3 ubiquitin-protein ligase RNF133 (Q8WVZ7). Has E3 ubiquitin-protein ligase activity.

The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene has no intron.

Source: NCBI Gene 168433 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_139175

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21154
Approved symbol	RNF133
Name	ring finger protein 133
Location	7q31.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188050
Ensembl biotype	protein_coding
OMIM	620556
Entrez	168433

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000340112

RefSeq mRNA: 1 — MANE Select: NM_139175 NM_139175

CCDS: CCDS5784

Canonical transcript exons

ENST00000340112 — 1 exons

Exon	Start	End
ENSE00001366015	122697735	122699117

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 98.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0322 / max 27.0651, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85949	0.0228	3
85948	0.0054	2
85950	0.0040	2

Top tissues by expression

233 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.17	gold quality
left testis	UBERON:0004533	91.46	gold quality
right testis	UBERON:0004534	91.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.01	gold quality
testis	UBERON:0000473	88.48	gold quality
adult organism	UBERON:0007023	76.66	gold quality
bone marrow cell	CL:0002092	62.13	gold quality
adrenal tissue	UBERON:0018303	61.93	gold quality
calcaneal tendon	UBERON:0003701	60.56	gold quality
mucosa of stomach	UBERON:0001199	57.10	gold quality
left ventricle myocardium	UBERON:0006566	56.97	gold quality
cerebellar vermis	UBERON:0004720	55.86	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
epithelial cell of pancreas	CL:0000083	53.40	gold quality
tendon	UBERON:0000043	52.83	gold quality
nasal cavity epithelium	UBERON:0005384	52.26	gold quality
right lung	UBERON:0002167	52.09	gold quality
tibialis anterior	UBERON:0001385	51.64	silver quality
ileal mucosa	UBERON:0000331	51.09	silver quality
cerebellar cortex	UBERON:0002129	51.02	gold quality
left uterine tube	UBERON:0001303	50.92	gold quality
cerebellar hemisphere	UBERON:0002245	50.70	gold quality
myocardium	UBERON:0002349	50.54	gold quality
upper lobe of left lung	UBERON:0008952	50.54	gold quality
cerebellum	UBERON:0002037	50.18	gold quality
upper lobe of lung	UBERON:0008948	50.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	49.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	49.69	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.27

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnf133	ENSMUSG00000051956
rattus_norvegicus	Rnf133	ENSRNOG00000065130

Paralogs (9): RNF13 (ENSG00000082996), RNF215 (ENSG00000099999), ZNRF4 (ENSG00000105428), RNF167 (ENSG00000108523), RNF130 (ENSG00000113269), RNF128 (ENSG00000133135), RNF149 (ENSG00000163162), RNF150 (ENSG00000170153), RNF148 (ENSG00000235631)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF133 — Q8WVZ7 (reviewed: Q8WVZ7)

Alternative names: RING finger protein 133, RING-type E3 ubiquitin transferase RNF133

All UniProt accessions (1): Q8WVZ7

UniProt curated annotations — full annotation on UniProt →

Function. Has E3 ubiquitin-protein ligase activity. Plays a role in male fecundity through the interaction with the E2 ubituitin-protein ligase UBE2J1.

Subunit / interactions. Interacts with E3 ligase UBE2J1.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expression is testis-specific.

Post-translational modifications. Auto-ubiquitinated.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (1): NP_631914* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR003137	PA_domain	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR046450	PA_dom_sf	Homologous_superfamily

Pfam: PF02225, PF13639

UniProt features (7 total): chain 1, transmembrane region 1, domain 1, zinc finger region 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVZ7-F1	77.48	0.41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_511, TAL1ALPHAE47_01, CAGGTCC_MIR492, GOBP_PROTEIN_AUTOUBIQUITINATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_CATABOLIC_PROCESS, TGGAAA_NFAT_Q4_01, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_PROTEOLYSIS, GOCC_ORGANELLE_SUBCOMPARTMENT, chr7q31, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY

GO Biological Process (3): ubiquitin-dependent protein catabolic process (GO:0006511), protein autoubiquitination (GO:0051865), protein ubiquitination (GO:0016567)

GO Molecular Function (4): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): cytoplasm (GO:0005737), late endosome (GO:0005770), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	2
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
endosome	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF133	RNF151	Q2KHN1	554
RNF133	UBE2J1	Q9Y385	450
RNF133	OR1C1	Q15619	419
RNF133	DYNLT4	Q5JR98	398
RNF133	C10orf71	Q711Q0	398
RNF133	ZNF275	Q9NSD4	396
RNF133	OR4M2	Q8NGB6	395
RNF133	FAM89B	Q8N5H3	393
RNF133	CIMAP1D	Q3SX64	392
RNF133	ZNRF4	Q8WWF5	386
RNF133	DDX25	Q9UHL0	378
RNF133	OR4N4	Q8N0Y3	378
RNF133	ZSWIM2	Q8NEG5	376
RNF133	SPAG11A	Q6PDA7	359
RNF133	C1orf21	Q9H246	356

IntAct

5 interactions, top by confidence:

A	B	Type	Score
UBE2H	RNF133	psi-mi:“MI:0915”(physical association)	0.370
RNF133	UBE2I	psi-mi:“MI:0915”(physical association)	0.370
RNF133	CD14	psi-mi:“MI:0914”(association)	0.350
RNF133	NME2P1	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): DISP1 (Affinity Capture-MS), CD14 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), GBF1 (Affinity Capture-MS), ARMC9 (Affinity Capture-MS), ACP2 (Affinity Capture-MS), PTPRD (Affinity Capture-MS), RNF149 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), MECR (Affinity Capture-MS), GLRB (Affinity Capture-MS), ANO6 (Affinity Capture-MS), NUP35 (Affinity Capture-MS)

ESM2 similar proteins: A1A697, F4HZZ4, F4HZZ5, F4I2Y3, G3X9R7, O22243, O24585, O43567, O54965, O60106, O80963, P87139, P93825, Q09499, Q0VD51, Q0WPW5, Q10R93, Q14B02, Q1EHT7, Q26261, Q2TA44, Q3U2C5, Q5RCV8, Q5XIL0, Q66HG0, Q69U49, Q6AY01, Q6NRX0, Q75J39, Q84RR2, Q8AWW4, Q8GUU2, Q8L9W3, Q8N7C7, Q8VZ14, Q8WVZ7, Q90972, Q91XF4, Q95K04, Q9C7E9

Diamond homologs: A0A3L6DPG1, A5WWA0, A6HD62, D3ZSP7, F1QB30, G3X9R7, O13797, O16259, O35814, O54981, O88196, P31948, P53041, P53042, P53804, Q06003, Q0JL44, Q14B02, Q29RU0, Q2TA44, Q388N2, Q3U2C5, Q3ZBZ8, Q496Y0, Q4R8N7, Q54DA8, Q566M8, Q5DTZ6, Q5QLR5, Q5R8D8, Q5RF74, Q5SPX3, Q5XEP2, Q5Z880, Q5ZHY5, Q60676, Q60864, Q6AY01, Q6DGE9, Q6NPT7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF133	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

0 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

222 predictions. Top by Δscore:

Variant	Effect	Δscore
7:122697770:T:TA	donor_gain	0.9800
7:122698080:T:C	acceptor_gain	0.8400
7:122697771:C:A	donor_gain	0.8200
7:122698981:T:C	acceptor_gain	0.7800
7:122698195:C:CT	donor_gain	0.6900
7:122698196:T:TT	donor_gain	0.6900
7:122698410:C:CA	donor_gain	0.6800
7:122697810:T:TA	donor_gain	0.6600
7:122698079:CT:C	acceptor_gain	0.6500
7:122698080:TT:T	acceptor_gain	0.6500
7:122697756:A:C	donor_gain	0.6200
7:122697736:TAGG:T	donor_gain	0.5700
7:122697737:AGGA:A	donor_gain	0.5700
7:122697754:A:AC	donor_gain	0.5700
7:122697755:C:CC	donor_gain	0.5700
7:122697814:C:CT	donor_gain	0.5600
7:122697815:T:TT	donor_gain	0.5600
7:122698448:G:C	donor_gain	0.5600
7:122697752:A:T	donor_gain	0.5500
7:122698284:C:CC	acceptor_gain	0.5500
7:122698080:T:TC	acceptor_gain	0.5400
7:122697784:G:A	donor_gain	0.5300
7:122698022:A:AC	donor_gain	0.5300
7:122698195:CTA:C	donor_gain	0.5300
7:122698968:GTTGA:G	acceptor_gain	0.5300
7:122698975:ATT:A	acceptor_gain	0.5300
7:122699091:C:CC	acceptor_gain	0.5200
7:122698981:T:TC	acceptor_gain	0.5100
7:122699090:A:AC	acceptor_gain	0.5100
7:122698969:TTGAC:T	acceptor_gain	0.4900

AlphaMissense

2477 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:122698733:A:C	F62L	0.983
7:122698733:A:T	F62L	0.983
7:122698735:A:G	F62L	0.983
7:122698461:A:T	V153D	0.975
7:122698611:G:T	A103E	0.974
7:122698590:C:G	C110S	0.968
7:122698591:A:T	C110S	0.968
7:122698536:A:G	I128T	0.966
7:122698085:G:C	F278L	0.965
7:122698085:G:T	F278L	0.965
7:122698087:A:G	F278L	0.965
7:122698536:A:C	I128S	0.964
7:122698536:A:T	I128N	0.964
7:122698734:A:C	F62C	0.963
7:122698526:G:C	N131K	0.962
7:122698526:G:T	N131K	0.962
7:122698643:G:C	F92L	0.961
7:122698643:G:T	F92L	0.961
7:122698645:A:G	F92L	0.961
7:122698574:T:A	K115N	0.959
7:122698574:T:G	K115N	0.959
7:122698563:G:T	A119E	0.958
7:122698608:A:G	L104P	0.957
7:122698575:T:A	K115I	0.953
7:122698644:A:C	F92C	0.953
7:122698441:C:G	G160R	0.952
7:122698591:A:G	C110R	0.951
7:122698616:C:A	W101C	0.951
7:122698616:C:G	W101C	0.951
7:122698695:A:T	I75K	0.951

dbSNP variants (sampled 300 via entrez): RS1000087056 (7:122700985 G>A), RS1001661032 (7:122698991 G>A,T), RS1003607926 (7:122697656 C>T), RS1004107593 (7:122697289 T>A,C,G), RS1004712669 (7:122698352 G>A), RS1005396408 (7:122699791 A>C), RS1005448972 (7:122699442 TAAA>T,TAA,TAAAA), RS1006548076 (7:122700179 C>T), RS1006990008 (7:122700370 G>A,C), RS1007783582 (7:122698045 T>A), RS1008269834 (7:122699124 T>C), RS1009018112 (7:122697637 T>A), RS1010467581 (7:122699192 A>C), RS1011253204 (7:122698395 G>C,T), RS1012981287 (7:122700768 C>T)

Disease associations

OMIM: gene MIM:620556 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methyleugenol	decreases expression	1
arsenite	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.