Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

ADGRE5 (CD97 molecule)

Written2007-10Gabriela Aust
University of Leipzig, Faculty of Medicine, Research Laboratories, Center of Surgery, Liebigstr. 20, Leipzig, D-04103, Germany

(Note : for Links provided by Atlas : click)

Identity

Alias_namesCD97
CD97 antigen
CD97 molecule
Alias_symbol (synonym)TM7LN1
Other alias
HGNC (Hugo) ADGRE5
LocusID (NCBI) 976
Atlas_Id 996
Location 19p13.12  [Link to chromosome band 19p13]
Location_base_pair Starts at 14381144 and ends at 14408725 bp from pter ( according to hg19-Feb_2009)  [Mapping ADGRE5.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ADGRE5 (19p13.12) / ATP2A2 (12q24.11)ADGRE5 (19p13.12) / SDC3 (1p35.2)CCDC88B (11q13.1) / ADGRE5 (19p13.12)

DNA/RNA

 
  Genomic organization of CD97 (drawn to scale), boxes represent exons.
Description DNA contains 27.322 kb composed of 20 coding exons. Exons 1-2 encode the 5' untranslated region and the signal peptide, exons 3-7 the five EGF domains, exons 8-13 the extracellular stalk, exons 14-18 the seven-span transmembrane (TM7) domains and exons 19-20 the intracellular part and the 3' untranslated region.
Transcription 3247 bp mRNA transcribed in telomeric to centromeric orientation; 2508 bp open reading frame. Human CD97 exists in three isoforms that result from alternative splicing of exons 5 and 6 and thus contain different numbers of EGF domains in the extracellular part of the molecule. The isoforms are designated as CD97(EGF1,2,5), CD97(EGF1,2,3,5) and CD97(EGF1-5) in human.
Pseudogene No pseudogenes reported.

Protein

 
  Structure of CD97. Three isoforms containing 3, 4, or 5 EGF domains exist. N-glycosylation sites in the EGF domains are indicated.
Description CD97 belongs to the B family of G protein-coupled receptors (GCPRs). Subfamily B2 contains cell surface molecules with long extracellular N-termini (LNB-TM7) known also as adhesion class of heptahelical receptors.
CD97 is the founding member of a small subfamily within the adhesion class called EGF-TM7 family. All EGF-TM7 receptors (CD97, EMR1, EMR2, EMR3, EMR4) consist of extracellular tandemly arranged EGF domains, a stalk, the seven-span transmembrane (TM7) und a short intracellular part. They are expressed as heterodimers of a non-covalently bound alpha- and beta-chain resulting from intracellular autocatalytic cleavage at a conserved GCPR proteolytic site (GPS). The alpha-chain represents the extracellular region with the varying numbers of EGF domains and the main part of the stalk and the beta-chain consists of the stalk residue, the TM7 and intracellular part.
Three CD97 isoforms containing 3, 4 or 5 EGF domains are described. The mature full length proteins contain either 722, 766 or 815 amino acids (aa). After cleavage the (secretory) alpha-chains contain 420, 464, or 513 aa. The beta-chain theoretically contains 305 aa with a molecular weight of 34.3 kDa. However, immunoprecipitation of the beta-chain yielded a molecular weight of approximately 28 kDa. The discrepancy between the theoretical and actual molecular weight of the beta-chain is not yet clarified.
Depending on the cell type and transformation status of the cell, CD97 is completely or partly N-glycosylated or naked. In normal muscle cells CD97 is not or only slightly N-glycosylated. The molecular weight for the respective naked alpha-chain of the various CD97 isoforms are 45.6, 50.5 and 55.8 kDa. In hematopoetic cells CD97 is N-glycosylated at the EGF domains resulting in molecular weights of 74-78, 80-82, and 86-89 kDa for the alpha-chains of the respective isoform. During tumor transformation CD97 may get N-glycosylated. Although the CD97 stalk contains many Ser or Thr residues the molecule seems not to be O-glycosylated.
Expression Broad, not cell-type specific.
  • Hematopoetic system: strong in peripheral blood myeloid cells and activated lymphocytes, moderately in subsets of tissue-derived leukocytes;
  • Strong in smooth muscle cells (except for arterial vascular smooth muscle cells), skeletal muscle cells (stronger in slow-twitch fibers), heart muscle cells;
  • Fat cells;
  • Low in normal intestinal, thyroidal epithelial cells, moderately in duct cells of the pancreas, parotis gland and in bile duct cells of the liver.
  • Localisation Usually at the cell membrane; soluble CD97 (sCD97) representing the CD97 alpha-chain in body fluids;
    Skeletal muscle cells: at the sarcolemm and intracellularly in the sacroendoplasmatic reticulum (SR).
    Function CD97 has the ability to bind cellular and extracellular matrix ligands. The first two EGF domains of CD97 bind CD55 (decay accelerating factor). The fourth EGF domain of CD97 and thus only the longest CD97 isoform interacts with the glycosaminoglycan chondroitin sulfate B. CD97 binds to alpha5beta1 and alphavbeta3 integrins through interaction with the CD97 stalk region.
  • Hematopoetic cells: Functional studies indicate a role of CD97 in leukocyte trafficking. CD97 antibodies block tissue localization of immune cells in vivo leading to impaired protection against bacteria and amelioration of autoimmune pathology.
  • Tumor cells: In vitro CD97 increases single cell random motility and directed migration and invasion of tumor cells in 2D and 3D matrices. CD97 enhances proteolytic activity of matrix metalloproteinases (MMPs) and secretion of chemokines in an isoform-specific manner. CD97 (EGF 1,2,5) overexpression promotes tumor growth in scid mice.
    The alpha-chain of the longest CD97 (EGF1-5) isoform (sCD97) enhances angiogenesis in in vivo tumor models.
  • Muscle, fat, duct cells: function unknown.
  • Homology H. sapiens: CD97
    P. troglodytes: CD97
    B. taurus: CD97
    S. scrofa: CD97
    C. lupus: CD97
    M. musculus: CD97
    R. norvegicus: CD97
    Exists only in mammals.

    Mutations

    Note unknown

    Implicated in

    Note
    Note Note for all tumors:
    Antibodies to various epitopes of CD97 vary strongly in their staining pattern and cross-reactivity to other EGF-TM7 molecules. The first group of monoclonal antibodies, which includes BL-Ac/F2, VIM-3b and CLB-CD97/1, binds to the EGF domains of CD97 (CD97EGF antibodies). These antibodies also detect EMR2, another member of the EGF-TM7 family. In most cases, this cross-reactivity will not influence the results obtained for CD97 staining in tumors since EMR2 is strongly restricted to myeloid cells. CD97 antibodies MEM-180 and CLB-CD97/3 bind to the stalk region of CD97 (CD97stalk) and do not bind EMR2.
    CD97EGF epitope accessibility depends on cell type-specific N-glycosylation (see above). CD97EGF antibodies detect only N-glycosylated CD97. During tumor transformation, not only the CD97 protein expression level but also the degree of CD97 N-glycosylation varies. Thus, the selection of the CD97 antibody strongly influences the result in immunohistological studies focused on the correlation between CD97 and histopathological subtypes, diagnosis, progression, or prognosis of tumors.
    CD97 in tumors is strongly regulated at the post-trancriptional level.
      
      
    Entity Thyroid cancer
    Note In normal thyroid tissue, no or low immunoreactivity of CD97 is found. In differentiated follicular thyroid carcinoma or papillary thyroid carcinoma, CD97 expression is also either lacking or low. Most undifferentiated anaplastic carcinomas reveal high CD97 presentation. CD97 is absent or only weakly present in patients with postoperative T1 tumors but increased greatly with the progression to postoperative T4 tumors. Until now, only antibodies against CD97 EGF domains (CD97EGF antibodies, see above) have been used in studies of thyroid carcinomas.
    Prognosis not determined
    Cytogenetics not determined
    Oncogenesis Overexpression of CD97 might be important for the progression of thyroid cancer.
      
      
    Entity Colorectal cancer
    Note Normal human colorectal epithelium is slightly CD97-positive. Most colorectal carcinomas express CD97. The strongest staining for CD97 occurs in scattered tumor cells at the invasion front compared to cells located within solid tumor formations of the same tumor. Carcinomas with more strongly CD97-stained scattered tumor cells show a poorer clinical stage as well as increased lymph vessel invasion compared to cases with uniform CD97 staining.
    Prognosis not determined
    Cytogenetics not determined
    Oncogenesis Overexpression of CD97 might be important for invasion and metastasis of colorectal cancer.
      
      
    Entity Gastric cancer
    Note CD97 is present in normal parietal cells of gastric mucosa. It is stronger expressed by most gastric carcinomas. Half of the tumors show scattered tumor cells at the invasion front with stronger CD97 expression than tumor cells located in solid tumor formations.
    Prognosis not determined
    Cytogenetics not determined
      
      
    Entity Leiomyosarcoma
    Note Normal smooth muscle cells are CD97-positive. In this cell type CD97 is not N-glycosylated. Thus, monoclonal antibodies that detect an N-glycosylation dependent epitop of CD97 do not react with normal smooth muscle cells (CD97EGF antibodies). During transformation CD97 get partly N-glyocosylated in most uterine leiomyoma and or completely N-glyocosylated in nearly 25% of the leiomyosarcomas. These tumors are now positive for CD97EGF antibodies. However, one third of leiomyosarcomas are completely devoid of CD97.
    Prognosis not determined
    Cytogenetics not determined
      

    Bibliography

    CD97: a dedifferentiation marker in human thyroid carcinomas.
    Aust G, Eichler W, Laue S, Lehmann I, Heldin NE, Lotz O, Scherbaum WA, Dralle H, Hoang-Vu C
    Cancer research. 1997 ; 57 (9) : 1798-1806.
    PMID 9135025
     
    CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric, pancreatic, and esophageal carcinomas.
    Aust G, Steinert M, Schütz A, Boltze C, Wahlbuhl M, Hamann J, Wobus M
    American journal of clinical pathology. 2002 ; 118 (5) : 699-707.
    PMID 12428789
     
    Individual cell-based models of tumor-environment interactions: Multiple effects of CD97 on tumor invasion.
    Galle J, Sittig D, Hanisch I, Wobus M, Wandel E, Loeffler M, Aust G
    The American journal of pathology. 2006 ; 169 (5) : 1802-1811.
    PMID 17071601
     
    Comparative study of gill neuroepithelial cells and their innervation in teleosts and Xenopus tadpoles.
    Saltys HA, Jonz MG, Nurse CA
    Cell and tissue research. 2006 ; 323 (1) : 1-10.
    PMID 16163489
     
    Expression and regulation of CD97 in colorectal carcinoma cell lines and tumor tissues.
    Steinert M, Wobus M, Boltze C, Schütz A, Wahlbuhl M, Hamann J, Aust G
    The American journal of pathology. 2002 ; 161 (5) : 1657-1667.
    PMID 12414513
     
    CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells.
    Wang T, Ward Y, Tian L, Lake R, Guedez L, Stetler-Stevenson WG, Kelly K
    Blood. 2005 ; 105 (7) : 2836-2844.
    PMID 15576472
     

    Citation

    This paper should be referenced as such :
    Aust, G
    CD97 (CD97 molecule)
    Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):201-203.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/CD97ID996ch19p13.html


    External links

    Nomenclature
    HGNC (Hugo)ADGRE5   1711
    Cards
    AtlasCD97ID996ch19p13
    Entrez_Gene (NCBI)ADGRE5  976  adhesion G protein-coupled receptor E5
    AliasesCD97; TM7LN1
    GeneCards (Weizmann)ADGRE5
    Ensembl hg19 (Hinxton)ENSG00000123146 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000123146 [Gene_View]  chr19:14381144-14408725 [Contig_View]  ADGRE5 [Vega]
    ICGC DataPortalENSG00000123146
    TCGA cBioPortalADGRE5
    AceView (NCBI)ADGRE5
    Genatlas (Paris)ADGRE5
    WikiGenes976
    SOURCE (Princeton)ADGRE5
    Genetics Home Reference (NIH)ADGRE5
    Genomic and cartography
    GoldenPath hg38 (UCSC)ADGRE5  -     chr19:14381144-14408725 +  19p13.12   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)ADGRE5  -     19p13.12   [Description]    (hg19-Feb_2009)
    EnsemblADGRE5 - 19p13.12 [CytoView hg19]  ADGRE5 - 19p13.12 [CytoView hg38]
    Mapping of homologs : NCBIADGRE5 [Mapview hg19]  ADGRE5 [Mapview hg38]
    OMIM601211   
    Gene and transcription
    Genbank (Entrez)AI890331 AK097264 AK225655 AK225677 AK292159
    RefSeq transcript (Entrez)NM_001025160 NM_001784 NM_078481
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)ADGRE5
    Cluster EST : UnigeneHs.466039 [ NCBI ]
    CGAP (NCI)Hs.466039
    Alternative Splicing GalleryENSG00000123146
    Gene ExpressionADGRE5 [ NCBI-GEO ]   ADGRE5 [ EBI - ARRAY_EXPRESS ]   ADGRE5 [ SEEK ]   ADGRE5 [ MEM ]
    Gene Expression Viewer (FireBrowse)ADGRE5 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)976
    GTEX Portal (Tissue expression)ADGRE5
    Human Protein AtlasENSG00000123146-ADGRE5 [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP48960   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtP48960  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProP48960
    Splice isoforms : SwissVarP48960
    PhosPhoSitePlusP48960
    Domaine pattern : Prosite (Expaxy)ASX_HYDROXYL (PS00010)    EGF_3 (PS50026)    EGF_CA (PS01187)    G_PROTEIN_RECEP_F2_2 (PS00650)    G_PROTEIN_RECEP_F2_4 (PS50261)    GPS (PS50221)   
    Domains : Interpro (EBI)EGF-like_Ca-bd_dom    EGF-like_dom    EGF-type_Asp/Asn_hydroxyl_site    EGF_Ca-bd_CS    GPCR_2-like    GPCR_2_CD97    GPCR_2_secretin-like    GPCR_2_secretin-like_CS    GPS    Growth_fac_rcpt_   
    Domain families : Pfam (Sanger)7tm_2 (PF00002)    EGF_CA (PF07645)    GPS (PF01825)   
    Domain families : Pfam (NCBI)pfam00002    pfam07645    pfam01825   
    Domain families : Smart (EMBL)EGF (SM00181)  EGF_CA (SM00179)  GPS (SM00303)  
    Conserved Domain (NCBI)ADGRE5
    DMDM Disease mutations976
    Blocks (Seattle)ADGRE5
    SuperfamilyP48960
    Human Protein Atlas [tissue]ENSG00000123146-ADGRE5 [tissue]
    Peptide AtlasP48960
    HPRD03130
    IPIIPI00397229   IPI00299412   IPI00397230   IPI00872746   
    Protein Interaction databases
    DIP (DOE-UCLA)P48960
    IntAct (EBI)P48960
    FunCoupENSG00000123146
    BioGRIDADGRE5
    STRING (EMBL)ADGRE5
    ZODIACADGRE5
    Ontologies - Pathways
    QuickGOP48960
    Ontology : AmiGOtransmembrane signaling receptor activity  G-protein coupled receptor activity  calcium ion binding  protein binding  extracellular space  plasma membrane  integral component of plasma membrane  focal adhesion  movement of cell or subcellular component  inflammatory response  immune response  cell adhesion  cell surface receptor signaling pathway  G-protein coupled receptor signaling pathway  cell-cell signaling  membrane  secretory granule membrane  neutrophil degranulation  extracellular exosome  
    Ontology : EGO-EBItransmembrane signaling receptor activity  G-protein coupled receptor activity  calcium ion binding  protein binding  extracellular space  plasma membrane  integral component of plasma membrane  focal adhesion  movement of cell or subcellular component  inflammatory response  immune response  cell adhesion  cell surface receptor signaling pathway  G-protein coupled receptor signaling pathway  cell-cell signaling  membrane  secretory granule membrane  neutrophil degranulation  extracellular exosome  
    NDEx NetworkADGRE5
    Atlas of Cancer Signalling NetworkADGRE5
    Wikipedia pathwaysADGRE5
    Orthology - Evolution
    OrthoDB976
    GeneTree (enSembl)ENSG00000123146
    Phylogenetic Trees/Animal Genes : TreeFamADGRE5
    HOVERGENP48960
    HOGENOMP48960
    Homologs : HomoloGeneADGRE5
    Homology/Alignments : Family Browser (UCSC)ADGRE5
    Gene fusions - Rearrangements
    Tumor Fusion PortalADGRE5
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerADGRE5 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)ADGRE5
    dbVarADGRE5
    ClinVarADGRE5
    1000_GenomesADGRE5 
    Exome Variant ServerADGRE5
    ExAC (Exome Aggregation Consortium)ENSG00000123146
    GNOMAD BrowserENSG00000123146
    Genetic variants : HAPMAP976
    Genomic Variants (DGV)ADGRE5 [DGVbeta]
    DECIPHERADGRE5 [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisADGRE5 
    Mutations
    ICGC Data PortalADGRE5 
    TCGA Data PortalADGRE5 
    Broad Tumor PortalADGRE5
    OASIS PortalADGRE5 [ Somatic mutations - Copy number]
    Mutations and Diseases : HGMDADGRE5
    BioMutasearch ADGRE5
    DgiDB (Drug Gene Interaction Database)ADGRE5
    DoCM (Curated mutations)ADGRE5 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)ADGRE5 (select a term)
    intoGenADGRE5
    NCG5 (London)ADGRE5
    Cancer3DADGRE5(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM601211   
    Orphanet
    DisGeNETADGRE5
    MedgenADGRE5
    Genetic Testing Registry ADGRE5
    NextProtP48960 [Medical]
    TSGene976
    GENETestsADGRE5
    Target ValidationADGRE5
    Huge Navigator ADGRE5 [HugePedia]
    snp3D : Map Gene to Disease976
    BioCentury BCIQADGRE5
    ClinGenADGRE5
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD976
    Chemical/Pharm GKB GenePA26248
    Clinical trialADGRE5
    Miscellaneous
    canSAR (ICR)ADGRE5 (select the gene name)
    Other databaseFamily 2 or B of the G-protein-coupled receptors (GCPRs)
    Probes
    Litterature
    PubMed65 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineADGRE5
    EVEXADGRE5
    GoPubMedADGRE5
    iHOPADGRE5
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Tue Nov 21 14:46:26 CET 2017

    Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.