CD213a1 IL13Rα1 (interleukin 13 receptor, alpha 1)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
B Cell
Monocyte
Fibroblast
Endothelial Cell
Peripheral blood
Tonsil
Heart
Liver
Skeletal muscle
Ovary
Hematopoietic Progenitor Cell
Nonhematopoietic Cell
Carcinoma Cell
Colon
B Lymphocyte
Pancreas
Cancer cell
Lymph Node
Skin
Placenta
Prostate
Small intestine
Nervous system
65 / 65

Expression
CD213a1 is expressed on mature B cells, monocytes, fibroblasts and endothelial cells.  Expression is on hematopoietic progenitor cells and non-hematopoietic human tumor cell lines including renal cell carcinoma, glioblastoma, ovarian cancer, epidermoid carcinoma, colon carcinoma, AIDS asssociated Kaposi's sarcoma, head and neck tumors, prostate tumors and erythroleukemia cells.  Expression is also detected on cord blood lymphocytes, subpopulations of PBL, peripheral B lymphocytes and lymphoma cells and lymphocytes from patients with AIDS.  Positive cells are found in the tonsil, lymph node, colon, skin, skin lymphoma, Crohn disease and ulcerative colitis.  Transcription is reported to be upregulated in cisplatin-resistant cancer cells.  Expression is also detected in the nervous system, placenta, pancreas, spleen, thymus, prostate, testis, small intestine, peripheral blood and mononuclear cells.  The highest expression is in heart, liver, skeletal muscle and ovary, while the lowest expression is observed in brain, lung and kidney.  mRNA for CD213a1 is upregulated in human B lymphocytes by anti-immunoglobulin and anti-CD40 antibodies.  Expression is in adult mouse tissue except skeletal muscle.


Structure
MOLECULAR FAMILY NAME: Belongs to the type 1 cytokine receptor family.

CD213α1 is a single-pass type-1 406 aa glycoprotein.  It contains a putative 21 aa signal peptide, a 324 aa  extracellular domain which contains 4 conserved cysteine residues followed by a cytokine receptor domain and a fibronectin type-3 domain that includes the WSXWS motif which appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding, a 23 aa transmembrane domain and a 59 aa  cytoplasmic domain.  The extracellular domain is closely related to that of CD213a2 but the residue cytoplasmic domain is much longer suggesting that the 2 receptors are functionally distinct.  It is structurally similar to the CD125(IL-5Ra) chain with a 51% aa sequence similarity and a 27% identity. Similar to CD125, the extracellular region of the IL-13Ra chain consists of a N-terminal region of about 100 aa with a sequence similarity to the equivalent portion of the CD123 (IL-3Ra) chain and the CD116 (GM-CSFRa) chain.  The open reading frame of human CD213a1 has 81% nucleotide and 76% aa identity with murine sequence and contains 3 additional aa.  In addition, 57 aa of 60 aa in the cytoplasmic domain, 95% are identical between murine and human CD213a.

MOLECULAR MASS
Cell Type Unreduced Reduced
Human T cell lymphotropic virus-I-transfected MT-2 cells 65 kDa

POST-TRANSCRIPTIONAL MODIFICATION

CD213α1 may be generated by alternate splicing but not by proteolysis since it is a cDNA sequence.  Another soluble human CD213a1 cytoplasmic domain is secreted from peripheral T cells.

POST-TRANSLATIONAL MODIFICATION

CD213a1 has 11 potential N-linked glycosylation sites.  125I - IL-13 crosslinked CD213a1 migrates like a ~80 kDa protein although the calculated Mr is ~62 kDa (~49 kDa - CD213a1) + (~13 kDa - IL-13).  The presence of multiple glycosylation sites explains the slower migration on gels and apparent difference in molecular weight.

Ligands
The human IL-13Ra chain expressed in COS-7 cells binds human IL-13 with a high affinity of kDa = 220-280 pM, whereas COS-7 cells transfected with the mouse IL-13Ra chain cDNA bind mouse IL-13 with a low affinity of kDa = 2-10 nM. In both species, the IL-13Ra chain also associates with CD124 to form a receptor capable of binding both IL-13 and IL-4 with a high affinity and mediating signal transduction events.  This interaction may explain the apparent discrepancy in the ability of the human, but not mouse, IL-13Ra chain to bind IL-13 with high affinity.  Untransfected COS-7 cells express low levels of CD124 which might associate with the transfected human, but not mouse, IL-13Ra chain to form a functional high-affinity binding site for IL-13.  Crosslinking experiments have identified an IL-13 binding protein of approximately 60 kDa-70 kDa, which probably corresponds to the IL-13Ra chain.

LIGANDS AND MOLECULES ASSOCIATED WITH CD213a1
Molecule Comment
IL-4Ra Upon ligation CD213a1 interacts with IL-4Ra to make a high affinity functional IL-13 receptor as well as an IL-4R
IL-13 IL-13 interacts with CD213a1
IL-4 IL-4 interacts with CD213a1
STAT3 The cytoplasmic domain of murine CD213a1 appears to be constitutively associated with STAT3 and Tyk2
Tyk2 The cytoplasmic domain of murine CD213a1 appears to be constitutively associated with STAT3 and Tyk2


Function
IL-13 binds cells through either a combination with CD213α1 and CD124 or through CD213α2.  In both cases, the common γ chain appears to be necessary for signaling.  IL-13 though its receptors regulates, inflammation, cell signaling and immune regulation.  It inhibits the production of pro-inflammatory cytokines and chemokines from monocytes and macrophages.  IL-13 upregulates several cell-surface molecules, including MHC class II and CD23 and it can act as a costimulus for B-cell proliferation and Ig synthesis and class switching.  IL-13 is not restricted in function to lymphocytes and has activities on progenitor cells and endothelial.  CD213α1 is a necessary component for IL-4-induced signal transduction in the type-2 IL-4 receptor system but they do not regulate T cell functions.  The cytoplasmic domain of CD213α1 has been implicated in murine B-cell activation and differentiation.  The protein encoded by CD213α1 is a subunit of the IL-13 receptor.  This subunit forms a receptor complex with IL-4 receptor α, a subunit shared by IL-13 and IL-4 receptors.  The subunit serves as a primary IL-13-binding subunit of the IL-13 receptor, and may be a component of IL-4 receptors.  This protein has been shown to bind tyrosine kinase TYK2, and thus may mediate the signaling processes that lead to the activation of JAK1, STAT3 ande STAT6 induced by IL-13 and IL-4.

BIOCHEMICAL ACTIVITY

CD213a1 is one of the signaling subunits of the IL-13 receptor complex.  It binds IL-13 with a weak affinity, however, with the IL-4R chain, known as IL-4Rb, it can form a functional receptor for IL-13.  CD213α1 also serves as an alternate accessory protein to the common cytokine receptor gamma chain for IL-4 signaling but cannot replace the function of gamma C in allowing enhanced IL-2 binding activity. 

DISEASE RELEVANCE AND FUNCTION OF CD213a1 IN INTACT ANIMAL

The CD213a1 antibody has a potential as a therapeutic target for glioma whereas soluble CD213α2 can reverse IL-13 airway hyper-responsiveness suggesting a possible use in asthma.  CD213α2 is widely expressed on human tumor cell lines including renal cell carcinoma, glioblastoma, ovarian cancer, epidermoid carcinoma, colon carcinoma, AIDS-associated Kaposi's sarcoma and erythroleukemia.  This chain appears to be present in tumor cells and normal cells and because this chain is hypothesized it may have a role in oncogenesis. 

Comments
The human and mouse IL-13Ra chain sequences share the same overall topology, but show only limited aa sequence identity.  It remains to be determined whether additional IL-13R subunits exist and whether, in fact, these molecules are true species orthologues.  The accession numbers and aa sequences are given in CD124.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD213a1: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD213a1 : No information.

ADDITIONAL INSIGHTS

CD213a1 was first cloned in mice and was originally termed as IL-13Ra.  In the same year, human orthologue of CD213a was cloned.  Since another IL-13 binding protein, CD213a2 was also cloned simultaneously from a independent laboratory, CD213a was termed IL-13Ra' or IL-13a1 to distinquish a1 from a2.  The following year, some researchers used the same term IL13Ra for a1 and a2 without distinquishing both forms resulting in a confusion of terminology.  While some researchers proposed terms IL-13Ra1 and IL-13Ra2, other publications have used terms IL-13Ra and IL-13RA respectively.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3597P78552
Antibodies

Revised June 25, 2008


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