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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

RHBDL2 Gene

protein-coding   GIFtS: 48
GCID: GC01M039351

rhomboid, veinlet-like 2 (Drosophila)

(Previous names: rhomboid (veinlet, Drosophila)-like 2 )
 Explore 3 diseases affiliated with
RHBDL2 via our new
 Human Malady Compendium 
Biological research products
for RHBDL2
    

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
Rhomboid, Veinlet-Like 2 (Drosophila)1 2     FLJ204351
Rhomboid (Veinlet, Drosophila)-Like 21 2     Rhomboid Protease 22
Rhomboid-Like Protein 22 3     Rhomboid-Related Protein 22
RRP22 3     EC 3.4.21.1053

External Ids:    HGNC: 160831   Entrez Gene: 549332   Ensembl: ENSG000001583157   OMIM: 6089625   UniProtKB: Q9NX523   

Export aliases for RHBDL2 gene to outside databases

Previous GC identifers: GC01M039276 GC01M038359 GC01M038815 GC01M038765 GC01M039021 GC01M039124 GC01M037469


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for RHBDL2:
The protein encoded by this gene is a member of the rhomboid family of integral membrane proteins. This family contains
proteins that are related to Drosophila rhomboid protein. Members of this family are found in both prokaryotes and
eukaryotes and are thought to function as intramembrane serine proteases. The encoded protein is thought to release
soluble growth factors by proteolytic cleavage of certain membrane-bound substrates, including ephrin B2 and ephrin
B3. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: RHBL2_HUMAN, Q9NX52
Function: Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from
their membrane anchors. Known substrate: EFNB3




(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000001.10  NC_018912.1  NT_032977.9  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the RHBDL2 gene promoter:
         Bach1   Roaz   NF-AT   NF-AT4   POU2F1   NF-AT2   POU2F1a   NF-AT3   MRF-2   NF-AT1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidRHBDL2 promoter sequence
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Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat RHBDL2


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

Entrez Gene cytogenetic band: 1p34.3   Ensembl cytogenetic band:  1p34.3   HGNC cytogenetic band: 1p35.1

RHBDL2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RHBDL2 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01M039351:  view genomic region     (about GC identifiers)

Start:
39,351,479 bp from pter      End:
39,407,471 bp from pter
Size:
55,993 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: RHBL2_HUMAN, Q9NX52 (See protein sequence)
Recommended Name: Rhomboid-related protein 2  
Size: 303 amino acids; 34021 Da
Subcellular location: Rhomboid-related protein 2, C-terminal fragment: Cell membrane; Multi-pass membrane protein
Sequence caution: Sequence=AAH13103.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Sequence=BAA91168.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Secondary accessions: B2RNT3 B9EH75 Q6P175 Q8NER8 Q96E02
Alternative splicing: 2 isoforms:  Q9NX52-1   Q9NX52-3   (May be due to an intron retention. No experimental confirmation available)

Explore the universe of human proteins at neXtProt for RHBDL2: NX_Q9NX52

Post-translational modifications:

  • Proteolytic processing of the proenzyme produces a N-terminal fragment (NTF) and a C-terminal fragment (CTF). The
  • processing is required for activation of the protease1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q9NX52

  • RHBDL2 Protein expression data from MOPED and PaxDb:    About this image 
    RHBDL2 Protein Expression
    REFSEQ proteins: NP_060291.2  
    ENSEMBL proteins: 
     ENSP00000289248   ENSP00000441097   ENSP00000362076   ENSP00000439227   ENSP00000362081  

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    Uscn Proteins for RHBDL2

    Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005886plasma membrane IDA19850051
    GO:0016021integral to membrane IEA--

    RHBDL2 for ontologies           About GeneDecksing



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    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    RHBDL2 for domains           About GeneDecksing

    3 InterPro domains/families:
     IPR022764 Peptidase_S54_rhomboid_dom
     IPR002610 Peptidase_S54_rhomboid
     IPR017213 Peptidase_S54_rhomboid_met

    Graphical View of Domain Structure for InterPro Entry Q9NX52

    ProtoNet protein and cluster: Q9NX52

    1 Blocks protein family: IPB002610 Rhomboid-like protein

    UniProtKB/Swiss-Prot: RHBL2_HUMAN, Q9NX52
    Similarity: Belongs to the peptidase S54 family


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: RHBL2_HUMAN, Q9NX52
    Function: Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from
    their membrane anchors. Known substrate: EFNB3
    Catalytic activity: Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that
    are contributed by different transmembrane domains

         Enzyme Number (IUBMB): EC 3.4.21.1051

         Gene Ontology (GO): 1 molecular function term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004252serine-type endopeptidase activity IDA19850051
         
    RHBDL2 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for RHBDL2:
     Synthetic lethal with Ras 

    Animal Models:
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    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section



    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for RHBDL2

    STRING Interaction Network Preview (showing 3 interactants - click image to see more details)

    3 Interacting proteins for RHBDL2 (Q9NX523 ENSP000002892484) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    EFNB2P527993, ENSP000002453234I2D: score=1 STRING: ENSP00000245323
    EFNB3Q157683, ENSP000002260914I2D: score=2 STRING: ENSP00000226091
    POP4ENSP000002217704STRING: ENSP00000221770
    About this table

    Gene Ontology (GO): 1 biological process term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006508proteolysis IEA--

    RHBDL2 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
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    Search CenterWatch for drugs/clinical trials and news about RHBDL2 / RHBL2 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
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    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for RHBDL2 gene: 
    NM_017821.3  

    Unigene Cluster for RHBDL2:

    Rhomboid, veinlet-like 2 (Drosophila)
    Hs.524626  [show with all ESTs]
    Unigene Representative Sequence: AK097621
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000289248 ENST00000540558(uc001ccv.3) ENST00000372985 ENST00000538156
    ENST00000372990(uc010oin.1 uc010oio.1 uc001ccu.1)

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    Additional cDNA sequence: 

    AK097621.1 AK294115.1 AY126343.1 BC013103.1 BC137108.1 BC137110.1 BC144476.1 BC144477.1 

    7 DOTS entries:

    DT.121348336  DT.87016578  DT.91938592  DT.102822514  DT.86849383  DT.65286529  DT.102822513 

    24/538 AceView cDNA sequences (see all 538):

    CB132041 AI076839 AA165138 AF271261 AI148118 BQ777715 BU071030 AI765647 
    AI418896 CA307952 CB160441 BM791108 AI797354 AA581659 BM312296 AA904343 
    AA504831 CR608844 NM_030772 BC016668 NM_017821 AA352872 BI770903 AA505988 

    GeneLoc Exon Structure


    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    RHBDL2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: AGTTCAAGAC
    RHBDL2 Expression
    About this image
    See RHBDL2 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for RHBDL2

    SOURCE GeneReport for Unigene cluster: Hs.524626
        SABiosciences Custom PCR Arrays for RHBDL2

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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)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for RHBDL2 gene from 4/16 species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    lizard
    (Anolis carolinensis)
    Reptilia RHBDL26
    --
    68(a)
    1 ↔ 1
    GL343426.1(764151-768701)
    zebrafish
    (Danio rerio)
    Actinopterygii zgc555332 similar to rhomboid, veinlet-like 2 (Drosophila) 76.31(n)   394179  BC048048.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta ru6
    rho6
    (see all 4)
    rhomboid
    (see all 4)
    26(a)
    25(a)
    (see all 4)
    many ↔ many
    many ↔ many
    (see all 4)
    3L(1370628-1387437)
    3L(1463811-1468944)
    worm
    (Caenorhabditis elegans)
    Secernentea rom-11 Protein ROM-1 52(n)
    40(a)
      184989  NM_065628.2  NP_498029.2 


    ENSEMBL Gene Tree for RHBDL2 (if available)
    TreeFam Gene Tree for RHBDL2 (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for RHBDL2 gene
    RHBDL12  RHBDL32  
    2 SIMAP similar genes for RHBDL2 using alignment to 3 protein entries:     RHBL2_HUMAN (see all proteins):
    RHBDL1    RHBDL3

    RHBDL2 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/1077 NCBI SNPs in RHBDL2 are shown (see all 1077    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1892582261,2
    --39351016(+) AGATGA/CGAATC 1 -- ds50010--------
    rs1809419111,2
    --39351154(+) CATTCA/GTGGTG 1 -- ds50010--------
    rs580043081,2
    C--39351386(+) GATAA-/TATTATCA 1 -- ds50010--------
    rs795182991,2
    C--39351388(+) TAATAA/TTATCA 1 -- ds50010--------
    rs1995130981,2
    C--39351389(-) TTGATA/GANNNN 1 -- ds50010--------
    rs1381361481,2
    --39351577(+) GTTTTA/GTAGAA 1 -- ut310--------
    rs1860621231,2
    --39351692(+) ATCTCG/TGCTCA 1 -- ut310--------
    rs1913382151,2
    --39351714(+) GCCTCC/GCAGGT 1 -- ut310--------
    rs1832964751,2
    --39351857(+) ATGACC/GTCAGG 1 -- ut310--------
    rs1460892041,2
    C--39351918(+) NNNNGC/TGCCTG 1 -- ut310--------

    HapMap Linkage Disequilibrium report for RHBDL2 (39351479 - 39407471 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 1 variation for RHBDL2
         1 CNV: 23108

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    (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.)
    About This Section

    RHBDL2 for disorders           About GeneDecksing

    OMIM gene information: 608962    OMIM disorders: --

    3 diseases for RHBDL2:    About MalaCards
    lyme disease    prostate cancer    prostatitis

    Human Genome Epidemiology (HuGE) Navigator: RHBDL2 (1 document)

    Export disorders for RHBDL2 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)
    About This Section

    PubMed articles for RHBDL2 gene, integrated from 9 sources (see all 13):
    (articles sorted by number of sources associating them with RHBDL2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL2. (PubMed id 15047175)1, 2, 9 Pascall J.C. and Brown K.D. (2004)
    2. The processing of human rhomboid intramembrane serine protease RHBDL2 is required for its proteolytic activity. (PubMed id 19850051)1, 2 Lei X. and Li Y.M. (2009)
    3. The DNA sequence and biological annotation of human chromosome 1. (PubMed id 16710414)1, 2 Gregory S.G.... Bentley D.R. (2006)
    4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
    5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (2004)
    6. Drosophila Rhomboid-1 defines a family of putative intramembrane serine proteases. (PubMed id 11672525)1, 2 Urban S.... Freeman M. (2001)
    7. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. (PubMed id 22267201)1 Stolk L....Lunetta K.L. (2012)
    8. Mammalian EGF receptor activation by the rhomboid pro tease RHBDL2. (PubMed id 21494248)1 Adrain C....Freeman M. (2011)
    9. Functions of rhomboid family protease RHBDL2 and thro mbomodulin in wound healing. (PubMed id 21833011)1 Cheng T.L....Wu H.L. (2011)
    10. Inherited genetic variant predisposes to aggressive b ut not indolent prostate cancer. (PubMed id 20080650)1 Xu J....Isaacs W.B. (2010)

    (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)
    About This Section
    Entrez Gene: 54933 HGNC: 16083 AceView: MYCBPandRHBDL2andRRAGCandGJA10 Ensembl:ENSG00000158315 euGenes: HUgn54933
    ECgene: RHBDL2 H-InvDB: RHBDL2

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for RHBDL2 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for RHBDL2 gene:
    Search GeneIP for patents involving RHBDL2

    GeneCards and IP:
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