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REG4 Gene

protein-coding   GIFtS: 50
GCID: GC01M120336

Regenerating Islet-Derived Family, Member 4

  See REG4-related disease
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
Regenerating Islet-Derived Family, Member 41 2     REG-42 3
Regenerating Gene Type IV1 2     RELP2 3
Gastrointestinal Secretory Protein2 3     REG-Like Protein2 3
Reg IV2 3      Gastrointestinal Secretory Protein1
Regenerating Islet-Derived Protein IV2 3     REG-IV2
GISP2 3     Regenerating Islet-Derived Protein 42

External Ids:    HGNC: 229771   Entrez Gene: 839982   Ensembl: ENSG000001341937   OMIM: 6098465   UniProtKB: Q9BYZ83   

Export aliases for REG4 gene to outside databases

Previous GC identifers: GC01M119483 GC01M119683 GC01M120048 GC01M120138 GC01M118195


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for REG4 Gene:
REG4 (regenerating islet-derived family, member 4) is a protein-coding gene. Diseases associated with REG4 include pseudomyxoma peritonei. GO annotations related to this gene include carbohydrate binding. An important paralog of this gene is REG3A.

UniProtKB/Swiss-Prot: REG4_HUMAN, Q9BYZ8
Function: Calcium-independent lectin displaying mannose-binding specificity and able to maintain carbohydrate
recognition activity in an acidic environment. May be involved in inflammatory and metaplastic responses of the
gastrointestinal epithelium

Gene Wiki entry for REG4 Gene


(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 at NCBI GenBank:
NC_000001.10  NT_032977.10  NC_018912.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the REG4 gene promoter:
         LHX3b/Lhx3b   AML1a   AP-1   ATF-2   FOXO4   FOXJ2 (long isoform)   Cart-1   LHX3a/Lhx3a   c-Jun   FOXJ2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidREG4 promoter sequence
   Search Chromatin IP Primers for REG4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat REG4


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

Entrez Gene cytogenetic band: 1p13.1-p12   Ensembl cytogenetic band:  1p12   HGNC cytogenetic band: 1p13.1-p12

REG4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
REG4 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01M120336:  view genomic region     (about GC identifiers)

Start:
120,336,641 bp from pter      End:
120,354,283 bp from pter
Size:
17,643 bases      Orientation:
minus 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, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: REG4_HUMAN, Q9BYZ8 (See protein sequence)
Recommended Name: Regenerating islet-derived protein 4 precursor  
Size: 158 amino acids; 18230 Da
Sequence caution: Sequence=AAM95599.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;
1 PDB 3D structure from and Proteopedia for REG4:
2KV3 (3D)    
Secondary accessions: Q8NER6 Q8NER7
Alternative splicing: 2 isoforms:  Q9BYZ8-1   Q9BYZ8-2   

Explore the universe of human proteins at neXtProt for REG4: NX_Q9BYZ8

Explore proteomics data for REG4 at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn50

  • See REG4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001152824.1  NP_001152825.1  NP_114433.1  

    ENSEMBL proteins: 
     ENSP00000346158   ENSP00000256585   ENSP00000437135   ENSP00000358409  

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    Cloud-Clone Corp. Proteins for REG4

     
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    antibodies-online proteins for REG4 (16 products) 

     
    Search antibodies-online for peptides for REG4

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    antibodies-online antibodies for REG4 (28 products) 

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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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    4 InterPro protein domains:
     IPR016187 C-type_lectin_fold
     IPR018378 C-type_lectin_CS
     IPR016186 C-type_lectin-like
     IPR001304 C-type_lectin

    Graphical View of Domain Structure for InterPro Entry Q9BYZ8

    ProtoNet protein and cluster: Q9BYZ8

    1 Blocks protein domain: IPB003990 Pancreatitis-associated protein signature

    UniProtKB/Swiss-Prot: REG4_HUMAN, Q9BYZ8
    Similarity: Contains 1 C-type lectin domain


    Find genes that share domains with REG4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: REG4_HUMAN, Q9BYZ8
    Function: Calcium-independent lectin displaying mannose-binding specificity and able to maintain carbohydrate
    recognition activity in an acidic environment. May be involved in inflammatory and metaplastic responses of the
    gastrointestinal epithelium
    Induction: Up-regulated by mucosal injury from active Crohn's disease or ulcerative colitis. Up-regulated in
    colorectal tumors. Up-regulated in epithelial cells at regenerating margins of peptic ulcers in the stomach and
    duodenum

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005509NOT calcium ion binding IDA--
    GO:0008201heparin binding IDA--
    GO:0030246carbohydrate binding ----
    GO:2001065mannan binding IDA--
         
    Find genes that share ontologies with REG4           About GenesLikeMe


    Phenotypes:
         1 MGI phenotypic allele for Reg4 (no phenotypes)

    Find genes that share phenotypes with REG4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Reg4tm1Lex for REG4

       genOway: Develop your customized and physiologically relevant rodent model for REG4

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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 UniProtKB/Swiss-Prot
    REG4_HUMAN, Q9BYZ8: Secreted
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5

    Gene Ontology (GO): 2 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IEA--
    GO:0005737cytoplasm IDA12819006

    Find genes that share ontologies with REG4           About GenesLikeMe


    (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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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for REG4
    Interactions:

        GeneGlobe Interaction Network for REG4

    STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

    1 Interacting protein for REG4 (ENSP000002565854) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CUBNENSP000003670644STRING: ENSP00000367064
    About this table

    (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 REG4

    1 Novoseek inferred chemical compound relationship for REG4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    calcium 4.37 3 15553756 (1), 16315915 (1), 19699332 (1)



    Find genes that share compounds with REG4           About GenesLikeMe



    (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, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for REG4 gene (3 alternative transcripts): 
    NM_001159352.1  NM_001159353.1  NM_032044.3  

    Unigene Cluster for REG4:

    Regenerating islet-derived family, member 4
    Hs.660883  [show with all ESTs]
    Unigene Representative Sequence: AY126670
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000354219(uc001eig.3 uc001eif.3) ENST00000256585 ENST00000530654
    ENST00000369401(uc001eih.1)
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    Additional mRNA sequence: 

    AF254415.1 AF345934.1 AY007243.1 AY126670.1 AY126671.1 AY126672.1 BC017089.2 

    6 DOTS entries:

    DT.417427  DT.92068854  DT.99927244  DT.100742664  DT.95167160  DT.95217366 

    Selected AceView cDNA sequences (see all 199):

    AA315069 AA307789 BM792702 BM852931 AF254415 AA307590 BM790284 AA316634 
    BM852851 BC017089 BM769915 AA314779 AW853800 AY007243 BM769042 BM769144 
    BM773135 AA315757 CD633572 AA315990 AI791286 BM798142 BQ084350 AA313549 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for REG4    About this scheme

    ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b
    SP1:                                -                           
    SP2:              -                 -                           
    SP3:              -                                             


    ECgene alternative splicing isoforms for REG4

    (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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    REG4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GGAAGGTTTA
    REG4 Expression
    About this image

    REG4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    REG4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.660883

    UniProtKB/Swiss-Prot: REG4_HUMAN, Q9BYZ8
    Tissue specificity: Highly expressed in the gastrointestinal tract including the duodenum, jejunum, ileum,
    ileocecum, appendix, descending colon, pancreas and small intestine. Weakly expressed in normal colon and
    stomach. Strongly expressed in most colorectal tumors than in normal colon. Preferentially expressed in mucinous
    tumors and in some cases neuro-endocrine tumors. Expressed in mucus-secreting cells and enterocyte-like cells. In
    small intestine expressed at the basal perinuclear zone of goblet cells

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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 chordates.

    Orthologs for REG4 gene from Selected species (see all 8)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Reg41 , 5 regenerating islet-derived family, member 41, 5 77.35(n)1
    66.67(a)1
      3 (42.73 cM)5
    677091  NM_026328.21  NP_080604.21 
     982221565 
    chicken
    (Gallus gallus)
    Aves REG41 regenerating islet-derived family, member 4 51.75(n)
    39.16(a)
      424379  NM_001277527.1  NP_001264456.1 
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia LOC1004854851 regenerating islet-derived protein 4-like 52.11(n)
    46.84(a)
      100485485  XM_002934583.2  XP_002934629.1 


    ENSEMBL Gene Tree for REG4 (if available)
    TreeFam Gene Tree for REG4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for REG4 gene
    REG3A2  REG3G2  REG1B2  REG1A2  
    9 SIMAP similar genes for REG4 using alignment to 2 protein entries:     REG4_HUMAN (see all proteins):
    REG1B    REG1A    PAP    REG3A    CD209    ASGR2
    CLEC4M    HBXBP    REG3G

    Find genes that share paralogs with REG4           About GenesLikeMe



    (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 REG4 (see all 488)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs66988131,2
    C,F,A,H--120336182(+) CTTGTA/CTGGTG 2 -- ds500111Minor allele frequency- C:0.50NA WA CSA EA 374
    rs1932226431,2
    --120336244(+) AATCAC/TTGAGT 2 -- ds50010--------
    rs46592371,2
    C,F,A,H--120336278(+) ACCACG/TCAGAT 2 -- ds500110Minor allele frequency- T:0.50NA WA CSA EA 371
    rs1856420211,2
    --120336367(+) TGCAAA/TCCTCA 2 -- ds50010--------
    rs1894375501,2
    --120336384(+) AAAGAC/GAGTCA 2 -- ds50010--------
    rs1167000791,2
    --120336561(+) CACCTG/TCATCT 2 -- ds50010--------
    rs1508216641,2
    --120336600(+) GGGGTA/GGAGGA 2 -- ds50010--------
    rs1807858811,2
    C--120336735(+) TAAAGA/GAATGT 2 -- ut310--------
    rs10529721,2
    C,F,A,H--120336785(-) GCCATG/AGGAAG 2 -- ut3131Minor allele frequency- A:0.43NS EA NA WA CSA EU 4815
    rs413061731,2
    C--120336857(+) AGAAGC/GGTGTA 2 -- ut310--------

    HapMap Linkage Disequilibrium report for REG4 (120336641 - 120354283 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for REG4:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv831215CNV Gain17160897
    nsv524681CNV Gain19592680
    nsv428201CNV Gain18775914
    nsv831226CNV Gain+Loss17160897
    dgv94e1CNV Complex17122850
    dgv93e1CNV Complex17122850

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 609846    OMIM disorders: --

    1 disease for REG4:    
    About MalaCards
    pseudomyxoma peritonei


    Find genes that share disorders with REG4           About GenesLikeMe

    7 Novoseek inferred disease relationships for REG4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    inflammatory bowel diseases 55.1 2 16086444 (1), 18754868 (1)
    colon cancer 52.2 8 17260007 (2), 19136934 (1), 19740514 (1)
    colitis ulcerative 32.2 3 17260007 (2), 12819006 (1)
    gastric cancer 25.3 13 15553756 (4), 16315915 (3)
    cancer 2.36 5 16086444 (1), 18754868 (1), 17260007 (1)
    metastasis 0 2 16315915 (1)
    tumors 0 2 18754868 (1), 12455032 (1)

    Genetic Association Database (GAD): REG4

    Export disorders for REG4 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 REG4 gene, integrated from 10 sources (see all 52):
    (articles sorted by number of sources associating them with REG4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas. (PubMed id 12455032)1, 2, 3, 9 Violette S.... Lesuffleur T. (Int. J. Cancer 2003)
    2. Isolation and characterization of a cDNA encoding a novel member of the human regenerating protein family: Reg IV. (PubMed id 11311942)1, 2, 3 Hartupee J.C.... Dieckgraefe B.K. (Biochim. Biophys. Acta 2001)
    3. RELP, a novel human REG-like protein with up-regulated expression in inflammatory and metaplastic gastrointestinal mucosa. (PubMed id 12819006)1, 2, 9 Kaemaeraeinen M....Andersson L.C. (Am. J. Pathol. 2003)
    4. Human RegIV protein adopts a typical C-type lectin fold but binds mannan with two calcium-independent sites. (PubMed id 20692269)1, 2 Ho M.R.... Chen C. (J. Mol. Biol. 2010)
    5. The DNA sequence and biological annotation of human chromosome 1. (PubMed id 16710414)1, 2 Gregory S.G.... Bentley D.R. (Nature 2006)
    6. Signal peptide prediction based on analysis of experimentally verified cleavage sites. (PubMed id 15340161)1, 2 Zhang Z. and Henzel W.J. (Protein Sci. 2004)
    7. 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. (Genome Res. 2004)
    8. The role of Reg IV gene and its encoding product in gastric carcinogenesis. (PubMed id 19740514)1, 9 Zheng H.C....Takano Y. (Hum. Pathol. 2010)
    9. REG4 is associated with carcinogenesis in the 'intestinal' pathway of intraductal papillary mucinous neoplasms. (PubMed id 19136934)1, 9 Nakata K....Tsuneyoshi M. (Mod. Pathol. 2009)
    10. High expression of RELP (Reg IV) in neoplastic goblet cells of appendiceal mucinous cystadenoma and pseudomyxoma peritonei. (PubMed id 16323007)1, 9 Heiskala K....Andersson L.C. (Virchows Arch. 2006)

    (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: 83998 HGNC: 22977 AceView: REG4 Ensembl:ENSG00000134193 euGenes: HUgn83998
    ECgene: REG4 H-InvDB: REG4

    (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 REG4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for REG4 Genetics and Cytogenetics in Oncology and Haematology
    Functional Glycomics Gateway - Glycan Bindinghttp://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_257

    (Patent information from GeneIP,
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    Patent Information for REG4 gene:
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