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PROW: CD97
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PROW and IWHLDA present the GUIDE on:
CD97
Authors: Jorg Hamann; Rene AW van Lier
Reviewer: Kathleen Kelly
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OVERVIEW
SUMMARY SENTENCE  
CD97 is a member of the EGF-TM7 family of class II G-protein coupled receptors that can bind to CD55(DAF)

MOLECULAR FAMILIES  

  • Families in which CD97 is a member

    ALTERNATE NAMES  

  • CD97 [HUGO gene name]
  • CD97 antigen

    MAJOR LINKS  

  • NCBI LocusLink Record: 976
  • Mendelian Inheritance in Man (OMIM): 601211
  • SwissProt annotated protein record: P48960
  • AUTHOR'S ADDITIONAL INSIGHTS  
    CD97 is a member of a superfamily of class II G-protein coupled receptors with highly related 7TM sequences but diverse, large extracellular regions. The extracellular regions are generally unrelated in sequence but usually contain cell adhesion motifs. The family is conserved in Drosophila and C. elegans**

  • For receptors with N-terminal EGF domains the designation EGF-TM7 family has been introduced. Typically, isoforms with variable number of EGF domains exist. So far, the EGF-TM7 family consists of CD97 and EMR1, the human homologue of F4/80. Family members are preferentially expressed by cells of the immune system
    SYSTEM VIEW
    DISEASE RELEVANCE / FUNCTION IN INTACT  
  • High surface expression of CD97 has been found at sites of inflammation in skin and lung and in rheumatoid arthritis. At the same sites, elevated levels of soluble CD97 are detectable. Analysis of epithelial tumors revealed CD97 expression on the malignant cells in thyroid cancer and adenocarcinomas of the gastro-intestinal tract

    CELLULAR FUNCTION  
    - Unknown

    PROTEIN LOCATION  
    - plasma membrane

    CELLULAR EXPRESSION  

  • Activated B cells
  • Activated T cells
  • Monocytes/macrophages
  • Dendritic cells
  • Granulocytes
    GENE
    CHROMOSOMAL LOCATION  
    8 [mouse]
    19p13.2-p13.12 [human]

    GENE SEQUENCE LINKS  

  • GenBank Accession Code: X94630
  • GENE POLYMORPHISM  
    - No information

    TRANSCRIPTION REGULATING MOLECULES  
    - Unknown

    GENE ANNOTATION  
    - No information


    TRANSCRIPT
    TRANSCRIPT SEQUENCE LINKS  
  • GenBank Accession Code: NM_001784
  • POST-TRANSCRIPTIONAL MODIFICATION  

  • Alternative splicing of exons 5 and 6 results in three isoforms containing 3, 4, or 5 EGF domains*

    TRANSCRIPT ANNOTATION  
    - No information


    PROTEIN
    BIOCHEMICAL ACTIVITY  
    - Unknown

    PROTEIN SEQUENCE LINKS  

  • SwissProt annotated protein record: P48960
  • PROTEIN SEQUENCE ANNOTATION  

  • The three isoforms of CD97 consisting of 722, 766, or 815 amino acids contain the following:
  • Extracellular region of 433, 477, or 526 amino acids with 3, 4, or 5 EGF domains, respectively
  • Seven transmembrane (7TM) region of 243 amino acids
  • Intracellular region of 46 amino acids
  • All EGF domains except for the N-terminal one possess a calcium-binding site

    PROTEIN POLYMORPHISM  
    - No information

    PROTEIN PHYSICAL PROPERTIES  

    CELL TYPEMW UNREDUCEDMW REDUCEDComment
    Activated peripheral blood mononuclear cell (PBMC) 74-78,80-82,86-89 kDa 75-85 kDa CD97 alpha*
    Activated peripheral blood mononuclear cell (PBMC) 28 kDa 28kDa CD97 beta*

    POST-TRANSLATIONAL MODIFICATION  

  • Cleavage of an approximately 20 amino acid leader sequence*
  • Eight potential N-glycosylation sites
  • CD97 is translated as a single polypeptide and cleaved in the endoplasmic reticulum (ER) into two subunits (alpha and beta) which noncovalently associate on the cell surface**
  • CD97 alpha is the extracellular subunit and CD97 beta is the seven transmembrane (7TM) subunit. The exact cleavage site has not been determined, but it is approximately at aa 530 in the 4 EGF domain form**

    PROTEIN STRUCTURE LINKS  
    - No information


    MOLECULAR INTERACTIONS
    MOLECULAR PATHWAYS  
    - No information

    ENZYME FOR WHICH THIS IS A SUBSTRATE  
    - Unknown

    SUBSTRATES  
    - Unknown

    OTHER LIGANDS AND ASSOCIATED MOLECULES  

    MOLECULECOMMENT
    CD55 (DAF) The physiological role of this interaction is still unknown. The CD55-binding site is formed by the EGF domain region. Three tandemly arranged EGF domains are necessary for ligand binding. The smallest isoform with 3 EGF domains binds CD55 with higher affinity compared to the larger isoforms possessing 4 and 5 EGF domains. Remarkably, the interaction between CD97 and CD55 is phylogenetically restricted

    REAGENTS
    MODEL ANIMAL STRAINS  
    - No information

    MONOCLONAL ANTIBODIES  

    ReagentSupplierDescription
    MEM-180 Vaclav Horejsi, Prague  
    BL-Ac/F2   {Eichler_W/Hamann_D.1994.SJI}
    VIM3   {Pickl_WF/Knapp_W.1995.LTV}
    VIM3b   {Pickl_WF/Knapp_W.1995.LTV}
    VIM3c   {Pickl_WF/Knapp_W.1995.LTV}
    CLB-CD97/1   {Hamann_J/van_Lier_RA.1996.JEM}
    CLB-CD97/2 Jorg Hamann, Amsterdam  
    CLB-CD97/3 Jorg Hamann, Amsterdam  
    TP1/16 Francisco Sanchez-Madrid, Madrid  

    POLYCLONAL ANTIBODIES  
    - No information

    DRUGS AND SMALL MOLECULES  
    - No information

    GENETIC CONSTRUCTS  
    - No information

    PURIFIED PROTEIN  
    - No information

    REAGENTS MISC.  
    - No information


    REFERENCES
    REVIEWS  
    1. {Pickl_WF/Knapp_W.1995.LTV}
    Pickl WF, Majdic O, Mai I, Gadd S and Knapp W. 1995. Overview of CD97. In Schlossman SF, Boumsell L, Gilks W, Harlan JM, Kishimoto T, Morimoto C, Ritz J, Shaw S, Silverstein R, Springer T, Tedder TF and Todd RF. 1995. Leukocyte Typing V. OXFORD University Press p1151-1153
    2. {Hamann_J/van_Lier_RA..LTVI}
    Hamann J, Eichler W, Vogel B, Stortelers C, Hamann D, Horejsi V and van Lier RA. . CD97 workshop panel report. In Kishimoto T, Kikutani H, von dem Borne AE, Goyert SM, Mason DY, Miyasaka M, Moretta L, Okumura K, Shaw S, Springer TA, Sugamura K and Zola H. 1997. Leukocyte Typing VI. Garland Publishing, Inc. p527

    PRIMARY CITATIONS  
    3. {Aust_G/Hoang-Vu_C.1997.CR}
    Aust G, Eichler W, Laue S, Lehmann I, Heldin NE, Lotz O, Scherbaum WA, Dralle H and Hoang-Vu C. 1997. CD97: a dedifferentiation marker in human thyroid carcinomas. Cancer Res 57:1798-1806
    4. {Carver_EA/Stubbs_L.1999.MG}
    Carver EA, Hamann J, Olsen AS and Stubbs L. 1999. Physical mapping of EMR1 and CD97 in human chromosome 19 and assignment of Cd97 to mouse chromosome 8 suggest an ancient genomic duplication. Mamm Genome 10:1039-1040
    5. {Eichler_W/Hamann_D.1994.SJI}
    Eichler W, Aust G and Hamann D. 1994. Characterization of an early activation-dependent antigen on lymphocytes defined by the monoclonal antibody BL-Ac(F2). Scand J Immunol 39:111-115
    6. {Gray_JX/Kelly_K.1996.JI}
    Gray JX, Haino M, Roth MJ, Maguire JE, Jensen PN, Yarme A, Stetler-Stevenson MA, Siebenlist U and Kelly K. 1996. CD97 is a processed, seven-transmembrane, heterodimeric receptor associated with inflammation. J Immunol 157:5438-5447**
    7. {Hamann_J/van_Lier_RA.1995.JI}
    Hamann J, Eichler W, Hamann D, Kerstens HM, Poddighe PJ, Hoovers JM, Hartmann E, Strauss M and van Lier RA. 1995. Expression cloning and chromosomal mapping of the leukocyte activation antigen CD97, a new seven-span transmembrane molecule of the secretion receptor superfamily with an unusual extracellular domain. J Immunol 155:1942-1950
    8. {Hamann_J/van_Lier_RA.1996.GENOM}
    Hamann J, Hartmann E and van Lier RA. 1996. Structure of the human CD97 gene: exon shuffling has generated a new type of seven-span transmembrane molecule related to the secretin receptor superfamily. Genomics 32:144-147
    9. {Hamann_J/van_Lier_RA.1998.EJI}
    Hamann J, Stortelers C, Kiss-Toth E, Vogel B, Eichler W and van Lier RA. 1998. Characterization of the CD55 (DAF)-binding site on the seven-span transmembrane receptor CD97. Eur J Immunol 28:1701-1707
    10. {Hamann_J/van_Lier_RA.1996.JEM}
    Hamann J, Vogel B, van Schijndel GM and van Lier RA. 1996. The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J Exp Med 184:1185-1189
    11. {Hamann_J/Tak_PP.1999.AR}
    Hamann J, Wishaupt JO, van Lier RA, Smeets TJ, Breedveld FC and Tak PP. 1999. Expression of the activation antigen CD97 and its ligand CD55 in rheumatoid synovial tissue. Arthritis Rheum 42:650-658
    12. {McKnight_AJ/Gordon_S.1998.JLB}
    McKnight AJ and Gordon S. 1998. The EGF-TM7 family: unusual structures at the leukocyte surface. J Leukoc Biol 63:271-280
    13. {Qian_YM/Song_WC.1999.IMMUN}
    Qian YM, Haino M, Kelly K and Song WC. 1999. Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55). Immunology 98:303-311

    WWW RESOURCES  


    * indicates amended by reviewer, ** indicates added by reviewer
    Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission
    Modified 02/15/00   mpr@mail.nih.gov