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RNF181 Gene

protein-coding   GIFtS: 50
GCID: GC02P085822

Ring Finger Protein 181

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Ring Finger Protein 1811 2 3
E3 Ubiquitin-Protein Ligase RNF1812
EC 6.3.2.-3

External Ids:    HGNC: 280371   Entrez Gene: 512552   Ensembl: ENSG000001688947   OMIM: 6124905   UniProtKB: Q9P0P03   

Export aliases for RNF181 gene to outside databases

Previous GC identifers: GC02P085676 GC02P085719


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for RNF181 Gene:
RNF181 binds the integrin alpha-IIb (ITGA2B; MIM 607759)/beta-3 (ITGB3; MIM 173470) complex and has E3 ubiquitin
ligase activity (Brophy et al., 2008 (PubMed 18331836)).(supplied by OMIM, Dec 2008)

GeneCards Summary for RNF181 Gene:
RNF181 (ring finger protein 181) is a protein-coding gene. Diseases associated with RNF181 include intrahepatic cholangiocarcinoma, and cholangiocarcinoma. GO annotations related to this gene include ligase activity. An important paralog of this gene is PJA2.

UniProtKB/Swiss-Prot: RN181_HUMAN, Q9P0P0
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




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000002.12  NT_022184.16  NC_018913.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the RNF181 gene promoter:
         c-Fos   AP-1   FosB   Nkx2-5   E47   FOXC1   E2F   E2F-1   Msx-1   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidRNF181 promoter sequence
   Search Chromatin IP Primers for RNF181

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat RNF181


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2p11.2   Ensembl cytogenetic band:  2p11.2   HGNC cytogenetic band: 2p11.2

RNF181 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RNF181 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02P085822:  view genomic region     (about GC identifiers)

Start:
85,822,837 bp from pter      End:
85,824,831 bp from pter
Size:
1,995 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: RN181_HUMAN, Q9P0P0 (See protein sequence)
Recommended Name: E3 ubiquitin-protein ligase RNF181  
Size: 153 amino acids; 17909 Da
Subunit: Directly interacts with ITGA2B and, as a result, with integrin ITGA2B/ITGB3. There is no evidence that
integrin ITGA2B/ITGB3 is an endogenous substrate for RNF181-directed ubiquitination
Secondary accessions: Q53H81

Explore the universe of human proteins at neXtProt for RNF181: NX_Q9P0P0

Explore proteomics data for RNF181 at MOPED

Post-translational modifications: 

  • Auto-ubiquitinated as part of the enzymatic reaction1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See RNF181 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_057578.1  
    ENSEMBL proteins: 
     ENSP00000412025   ENSP00000306906   ENSP00000397109   ENSP00000391326   ENSP00000415246  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    RNF: RING-type (C3HC4) zinc fingers

    2 InterPro protein domains:
     IPR001841 Znf_RING
     IPR013083 Znf_RING/FYVE/PHD

    Graphical View of Domain Structure for InterPro Entry Q9P0P0

    ProtoNet protein and cluster: Q9P0P0

    1 Blocks protein domain: IPB001841 Zn-finger

    UniProtKB/Swiss-Prot: RN181_HUMAN, Q9P0P0
    Similarity: Belongs to the RNF181 family
    Similarity: Contains 1 RING-type zinc finger


    RNF181 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: RN181_HUMAN, Q9P0P0
    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

         Enzyme Number (IUBMB): EC 6.3.2.-1

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding ----
    GO:0008270zinc ion binding IEA--
    GO:0016874ligase activity IEA--
    GO:0046872metal ion binding ----
         
    RNF181 for ontologies           About GeneDecksing


    Phenotypes:
         3 GenomeRNAi human phenotypes for RNF181:
     Cell cycle / mitosis defect  G0/1 arrest  Increased G1 DNA content 

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for RNF181
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       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for RNF181

    miRNA
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    miRTarBase miRNAs that target RNF181:
    hsa-mir-92b-3p (MIRT040738), hsa-mir-877-3p (MIRT036911)

    Block miRNA regulation of human, mouse, rat RNF181 using miScript Target Protectors
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular3
    cytosol2
    nucleus1

    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    UniProtKB/Swiss-Prot: RN181_HUMAN, Q9P0P0
    Pathway: Protein modification; protein ubiquitination

        Pathway & Disease-focused RT2 Profiler PCR Array including RNF181: 

              Ubiquitin Ligases in human mouse rat

    Interactions:

        Search GeneGlobe Interaction Network for RNF181

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for RNF181 (Q9P0P03 ENSP000003069064) via UniProtKB, MINT, STRING, and/or I2D (see all 32)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    UBE2D2P628373, ENSP000003817174I2D: score=2 STRING: ENSP00000381717
    UBE2D3P610773, ENSP000003497224I2D: score=2 STRING: ENSP00000349722
    UBE2UQ5VVX93, ENSP000003601164I2D: score=2 STRING: ENSP00000360116
    ITGA2BP085143, ENSP000002624074I2D: score=1 STRING: ENSP00000262407
    UBE2D1P516683, ENSP000003630194I2D: score=2 STRING: ENSP00000363019
    About this table

    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0016567protein ubiquitination IEA--

    RNF181 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for RNF181 (RN181)



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for RNF181 gene: 
    NM_016494.3  

    Unigene Cluster for RNF181:

    Ring finger protein 181
    Hs.356187  [show with all ESTs]
    Unigene Representative Sequence: CD242398
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000461845 ENST00000441634(uc002spv.1) ENST00000306368 ENST00000414390
    ENST00000443647 ENST00000456023
    miRNA
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      QuantiTect SYBR Green Assays in human, mouse, rat RNF181
      QuantiFast Probe-based Assays in human, mouse, rat RNF181

    Additional mRNA sequence: 

    AF151072.1 AK222700.1 BC002803.2 CR457165.1 

    15 DOTS entries:

    DT.449021  DT.100824128  DT.95174634  DT.100824132  DT.95174642  DT.100824130  DT.95174636  DT.100032387 
    DT.99954127  DT.100036784  DT.120929939  DT.92436844  DT.92436847  DT.95174637  DT.97859068 

    Selected AceView cDNA sequences (see all 265):

    BG488504 AI185447 BF691565 AA370418 AI685629 AA035385 CA950240 H69071 
    AI015971 H47715 H73233 AI885762 AW961040 AA888074 BC002803 CB109323 
    AA669683 AW026542 AV709283 AI720442 BP432921 AA923809 W76429 BM550405 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for RNF181 (see all 8)    About this scheme

    ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b · 7c
    SP1:                                      -                 -                           
    SP2:                                      -                 -                           
    SP3:                                      -     -           -                           
    SP4:                                      -     -     -     -                           
    SP5:                                      -                 -     -                     


    ECgene alternative splicing isoforms for RNF181

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    RNF181 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TACACGTGAG
    RNF181 Expression
    About this image


    RNF181 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 20) fully expand
     
     Testis (Reproductive System)
             Pre-Sertoli Cells Testis Cord
     
     Brain (Nervous System)
             Cerebral Cortex
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Heart (Cardiovascular System)
             Atrioventricular Canal Cells Atrioventricular Canal
     
     Colon (Gastrointestinal Tract)
    RNF181 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    RNF181 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.356187

    UniProtKB/Swiss-Prot: RN181_HUMAN, Q9P0P0
    Tissue specificity: Widely expressed, with highest levels in liver and heart and lowest levels in brain and
    skeletal muscle. Expressed in platelets (at protein level)

        Pathway & Disease-focused RT2 Profiler PCR Array including RNF181: 
              Ubiquitin Ligases in human mouse rat

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for RNF181 gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Rnf1811 , 5 ring finger protein 1811, 5 86.18(n)1
    86.18(a)1
      6 (32.27 cM)5
    665101  NM_025607.31  NP_079883.31 
     723597145 
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.334902 Xenopus laevis transcribed sequence with weak similarity more 78.83(n)    CF549335.1 
    zebrafish
    (Danio rerio)
    Actinopterygii zgc564242 hypothetical protein MGC56424 73.25(n)   393276  BC050161.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG76946
    --
    37(a)
    1 ↔ 1
    3R(14398817-14416448)


    ENSEMBL Gene Tree for RNF181 (if available)
    TreeFam Gene Tree for RNF181 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for RNF181 gene
    PJA22  RNF1152  RNF1262  PJA12  
    7 SIMAP similar genes for RNF181 using alignment to 6 protein entries:     RN181_HUMAN (see all proteins):
    PJA2    RNF115    RNF167    PJA1    RNF126    SCAF11
    TRIM39

    RNF181 for paralogs           About GeneDecksing


    2 Pseudogenes.org Pseudogenes for RNF181
    PGOHUM00000242531 PGOHUM00000233516


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for RNF181 (see all 107)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1441787961,2
    --85821102(+) CCTTCA/CGAAGT 1 -- us2k10--------
    rs67428871,2
    C,F,H--85821204(+) TTCCCA/GCTCCT 1 -- us2k19Minor allele frequency- G:0.03NS EA NA WA 1208
    rs1888346141,2
    --85821474(+) CCACCA/GTGTCC 1 -- us2k10--------
    rs37550101,2
    C,F,A,H--85821526(+) CCAGGG/CAGGCA 1 -- us2k13Minor allele frequency- C:0.18WA NA EA 358
    rs37550111,2
    C,F,A,H--85821599(+) ACCAAG/TACTGT 1 -- us2k111Minor allele frequency- T:0.27EA NS WA CSA NA 2067
    rs729230211,2
    C,F--85821676(+) GAATTC/TAGGGT 1 -- us2k12Minor allele frequency- T:0.12WA 120
    rs116882331,2
    C,F,H--85821714(+) CTGGGT/AAAAGT 1 -- us2k17Minor allele frequency- A:0.06NS EA NA 536
    rs1460761091,2
    --85821750(+) AAGCCC/TGAGTT 1 -- us2k10--------
    rs15623221,2
    C,F,A,H--85821956(-) CGCTCG/AATCAT 1 -- us2k129Minor allele frequency- A:0.21NS MN EA NA WA CSA 4388
    rs1399625661,2
    --85821963(+) AGCGTA/GTAAAA 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for RNF181 (85822837 - 85824831 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for RNF181:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv992753CNV Deletion20482838

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing RNF181
    DNA2.0 Custom Variant and Variant Library Synthesis for RNF181

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 612490    OMIM disorders: --

    5 diseases for RNF181:    
    About MalaCards
    intrahepatic cholangiocarcinoma    cholangiocarcinoma    hepatocellular carcinoma    prostate cancer
    prostatitis


    RNF181 for disorders           About GeneDecksing


    Export disorders for RNF181 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for RNF181 gene, integrated from 10 sources (see all 19):
    (articles sorted by number of sources associating them with RNF181)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. (PubMed id 11042152)1, 2, 3 Zhang Q.-H.... Chen Z. (Genome Res. 2000)
    2. RN181, a novel ubiquitin E3 ligase that interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3. (PubMed id 18331836)1, 2 Brophy T.M.... Moran N. (Biochem. Biophys. Res. Commun. 2008)
    3. Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks. (PubMed id 22493164)1 Woodsmith J....Sanderson C.M. (amp 2012)
    4. Initial characterization of the human central proteome. (PubMed id 21269460)2 Burkard T.R.... Colinge J. (BMC Syst. Biol. 2011)
    5. Toward an understanding of the protein interaction network of the human liver. (PubMed id 21988832)1 Wang J....Yang X. (Mol. Syst. Biol. 2011)
    6. RN181 suppresses hepatocellular carcinoma growth by inhibition of the ERK/MAPK pathway. (PubMed id 21391225)1 Wang S....Li M. (Hepatology 2011)
    7. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. (PubMed id 21743467)1 Kote-Jarai Z....TybjA ( 2011)
    8. Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. (PubMed id 21139048)1 Danielsen J.M....Nielsen M.L. (amp 2011)
    9. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. (PubMed id 20068231)2 Olsen J.V....Mann M. (Sci. Signal. 2010)
    10. [Construction of recombinant eukaryotic expression vector pDsRed1-C3/LOC51255 and subcellular localization of LOC51255 protein in HePG2 cell line]. (PubMed id 19426595)1 Huang X....Li M. (Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 51255 HGNC: 28037 AceView: LOC51255 Ensembl:ENSG00000168894 euGenes: HUgn51255
    ECgene: RNF181 H-InvDB: RNF181

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for RNF181 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    IP news from LifeMap Sciences, Inc.)
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    Patent Information for RNF181 gene:
    Search GeneIP for patents involving RNF181

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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