CD30 TNFRSF8 (tumor necrois factor superfamily member 8), Ki-1 antigen, Ber-H2 antigen
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Thymus
Carcinoma Cell
Lymphoid Cell
Lymph Node
Reed-Sternberg Cell
Tonsil
T Lymphocyte
NK Cell
Monocyte
Lymphoma Cell
B Lymphocyte
Tumor Cell
105 / 105
120 / 120

Expression
CD30 is expressed on activated T and B lymphocytes, NK cells, and monocytes.  In normal tissues, the antigen is found on large lymphoid cells in sections of lymph node, tonsil, thymus, thymus decidua and endometrial cells with decidual change.  Cell lines that express CD30 are HUT102, CEM, Jurkat JY, MOLT4, NALM6, RPMI 8226, FLG 29.1, U937 and YT.  It is present on malignant cells such as Hodgkin's lymphoma - Reed-Sternberg cells, Hodgkin cells, non-Hodgkin's lymphoma - anaplastic large cell lymphoma (ALCL), medium to large  pleomorphic cells, immunoblastic lymphoma, embryonal carcinoma, and mixed germ cell tumors.


Structure
MOLECULAR FAMILY NAME: Belongs to the tumor necrosis factor growth receptor family.

CD30 is a single-pass type-1 glycoprotein.  It contains a 362 aa extracellular domain, a transmembrane domain and a cytoplasmic domain.  The extracellular domain contains 5 cysteine-rich repeats with a central hinge sequence and 2 N-linked glycosylation sites in cysteine repeats.  The central hinge region and the membrane-proximal region are sites for O-glycosylation by virtue of the high content of Ser, Thr and Pro residues.  In cell lines, CD30 is phosphorylated on serine and tyrosine residues.  The mouse and rat CD30 cDNA encodes 498 aa and 493 aa proteins, respectively.  In the human CD30 which lack 90 aa it is thought to be partially duplicated from 1 of the cysteine-rich domains.   The 5 repeats are interrupted after repeat 3 by a hinge sequence of about 60 aa that may have derived from the central region of another TNFR repeat.  This is proposed because there are 2 Cys residues at the end of this region which are surrounded by sequence patterns typical of TNFR repeats.  Repeats 2 and 5 show particular sequences similarities, suggesting that CD30 may have evolved by gene duplication of a precursor structure with 3 repeats.  Biochemical analysis of CD30 revealed the presence of O-linked sugars accounting for 4 kDa on SDS-PAGE. 

MOLECULAR MASS
Cell Type Unreduced Reduced
Unspecified 120 kDa 105 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.  A variant form of CD30, CD30v, having only the cytoplasmic domain, is expressed in alveolar macrophages.  CD30v mRNA is transcribed from an alternative promoter located in the intron.

POST-TRANSLATIONAL MODIFICATION

There is a soluble form of Mr 85,000 produced by metalloproteinase and constitutive phosphorylation. The hinge region and the area proximal to the membrane are likely O-glycosylated.

Ligands
CD30 binds to CD153 (also known as CD30 ligand), a member of the TNF superfamily.

LIGANDS AND MOLECULES ASSOCIATED WITH CD30
Molecule Comment
CD153 (CD30L) Present on neutorphils, activated T cells, macrophages and monocytes.
TRAF1 The cytoplasmic tail of CD30 associates with TRAF1, 2, 3 and 5 but not with TRAF6
TRAF2 The cytoplasmic tail of CD30 associates with TRAF1, 2, 3 and 5 but not with TRAF6
TRAF3 The cytoplasmic tail of CD30 associates with TRAF1, 2, 3 and 5 but not with TRAF6
TRAF5 The cytoplasmic tail of CD30 associates with TRAF1, 2, 3 and 5 but not with TRAF6



Function
CD30 may attenuate autoreactive T lymphocyte proliferation.  Its expression in T cells is upregulated by CD153 (CD30L).  The CD153-CD30 interaction costimulates T cell proliferation and upregulates the expression of adhesion molecules and cytokine release.  CD30+ T cell clones produce TH2-type cytokines.  A role for the CD153-CD30 interaction in TH2-type autoimmune disease has been suggested.  Pleiotropic effects on CD30-positive lymphoma cell lines ranging from cell proliferation to cell death.  It is thought to be involved in negative selection of T-cells in the thymus and to be involved in TCR-mediated cell death and the reduction in cytolytic activity.  CD30 null mice gave increased numbers of thymocytes whereas overexpression in mice results in increased thymocyte apoptosis following TCR binding.  CD30 is a member of the TNFR family of molecules which activates NF-kB, Jun N-terminal kinase (JNK) and p38 via its interaction with TRAF2 to TRAF5 although TRAF-independent activation of NF-κB has been shown.  It also activates extracellular regulated kinase (ERK) by an as yet unknown mechanism.  CD30 is a positive regulator of apoptosis and has been shown to limit the proliferative potential of autoreactive CD8 effector T cells and protect the body against autoimmunity.  Although it was thought at one time to represent a marker on TH2 cells, it has been identified on TH0 and TH1 cells and at lower levels on CD8+ T-cells.  Overexpression of CD30v activates NF-kB in Jurkat cells and induces NBT reduction activity in HL-60 cells.  In the mouse, crosslinking causes IL-5 production but not IFNg.  Soluble CD30 interfers with CD30 signaling by binding CD153 and preventing its interaction with the membrane CD30.  Alternatively, it may form complexes with the membrane form that have greater negative influence on the cell.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD30 IN INTACT ANIMAL

CD30 was originally identified as Ki-1, an antigen expressed on Reed-Sternberg cells in Hodgkin's lymphomas and other non-Hodgkin's lymphomas.  Differential expression of CD30 and p80 between peripheral blood and bone marrow lymphomas is a property of small cell variant of anaplastic large cell lymphoma and immunoblastic lymophoma.  Cutaneous lymphoproliferative disorders expressing CD30 include lymphomatoid papulosis, peripheral T-cell lymphomas and anaplastic large cell lymphomas.  CD30 is marker of infection on lymphocytes infected with HIV, HTLV-1 or EBV.  Crosslinking on HIV infected T-cells causes activation of latent HIV production.  Soluble levels of CD30 are elevated and associated with prognosis in Hodgkin's disease and AIDS.  Elevated levels were reported in patients with ATL and a part of those with non-Hodgkin's lymphoma.  CD30+ lymphoma has a better prognosis.  Most recently it has been found expressed on the primary effusion lymphoma and Castleman's disease associated with the recently identified herpes homines virus 8 (HHV8) or Kaposi's sarcoma Herpes virus.  Elevated serum levels of soluble CD30 have also been identified in patients with hepatitis B infection, correlating with activity of disease.  Poxviruses encode soluble truncated homologues of CD30 that are capable of binding CD153.  The CD30/CD153 complex may play a role in autoimmune disease and graft versus host disease (GVHD) in transplant patients.

Comments
Truncated CD30 protein is released from the cell surface and found as a soluble protein in the serum of some patients with adult T cell leukemia or other CD30+ lymphomas. Levels of soluble CD30 correlated with disease.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD30

CD30 has a cryptic promoter in the intron which drives transcription of variant CD30 mRNA.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD30
MOLECULE Comment
Metalloproteinase

ADDITIONAL INSIGHTS ON CD30

CD30 is found on approximately 15% of CD45R0+ T-cells after activation which in humans appears to be the major subset producing g interferon.  This is inducible with IL-12 and inhibited by IL-10 or antibodies to IL-2. Both CD30+ and CD30- cells respond to IL-2 following activation, but only the CD30+ subset produces g interferon following IL-12 addition.  Considerable controversy about its precise role in delineating TH1 and TH2 subsets remains but the preponderance of the data suggest that both subsets can express this molecule.  Stimulated splenocytes express most of the CD30 on CD8+ cells, peaking at 4-5 days.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 943P28908
MouseU25416
Antibodies
Ber-H2   View Reactivity
BerH8   View Reactivity
HRS-4   View Reactivity

Revised June 25, 2008


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