User:Jacob A. Ray/Sandbox 1: Difference between revisions

Revision as of 04:12, 30 April 2025

CD44

Function

CD44 is a highly glycosylated multifunctional cell surface receptor that is involved in cell-cell interaction and maintenance of the extracellular matrix.^[1] The primary ligand for CD44 is hyaluronan (HA), but it has also been found to interact with other molecules including osteopontin (OPN), collagens, and fibronectin. ^[2] CD44 is a single chain protein containing four distinct regions: the N-terminal HA binding Link domain^[3], a flexible variable domain, a transmembrane domain, and an intracellular signaling domain.^[4] The Link domain is an approximately 100 amino acid domain consisting of two antiparallel β-sheets, two α-helicies, and two disulfide bonds.^[5] This domain is found in most HA binding proteins, including aggrecan, versican, brevican, and tumor necrosis factor-inducible gene 6.^[6]

Evolutionary Conservation

Evolutionary conservation of CD44 residues, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Residues proximal to the HA binding site tend to be the most conserved across species while residues that fall outside of the canonical Link domain are the most variable.

Isoforms

The CD44 gene encodes a total of 20 exons but only exons 1-5 (HA binding domain) and 16-20 (transmembrane domain and cytosolic region) are constitutively expressed.^[7] Exons 6-15 are variably expressed within and across cell types creating diversity in available N- and O-glycosylation sites.^[8]^[9] Variable exons are termed 1v-10v. Standard CD44 contains no variable regions while variants are termed CD44vX where 'vX' identifies the variable exons expressed.

Substrate Binding

The HA binding domain of murine CD44 is well characterized. Interactions with tyrosine, alanine, and cysteine residues in the HA binding cleft appear to be the most impactful.^[10]

Cancer

Altered expression of CD44 in tumors is associated with an increased risk of metastasis.

↑ Senbanjo LT, Chellaiah MA. CD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. Front Cell Dev Biol. 2017 Mar 7;5:18. PMID:28326306 doi:10.3389/fcell.2017.00018
↑ Goodison S, Urquidi V, Tarin D. CD44 cell adhesion molecules. Mol Pathol. 1999 Aug;52(4):189-96. PMID:10694938 doi:10.1136/mp.52.4.189
↑ doi: https://dx.doi.org/10.1016/S1097-2765(04)00080-2
↑ Senbanjo LT, Chellaiah MA. CD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. Front Cell Dev Biol. 2017 Mar 7;5:18. PMID:28326306 doi:10.3389/fcell.2017.00018
↑ doi: https://dx.doi.org/10.1016/S1097-2765(04)00080-2
↑ Banerji S, Day AJ, Kahmann JD, Jackson DG. Characterization of a functional hyaluronan-binding domain from the human CD44 molecule expressed in Escherichia coli. Protein Expr Purif. 1998 Dec;14(3):371-81. PMID:9882571 doi:10.1006/prep.1998.0971
↑ Senbanjo LT, Chellaiah MA. CD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. Front Cell Dev Biol. 2017 Mar 7;5:18. PMID:28326306 doi:10.3389/fcell.2017.00018
↑ Mackay CR, Terpe HJ, Stauder R, Marston WL, Stark H, Günthert U. Expression and modulation of CD44 variant isoforms in humans. J Cell Biol. 1994 Jan;124(1-2):71-82. PMID:7507492 doi:10.1083/jcb.124.1.71
↑ Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018 May 10;11(1):64. PMID:29747682 doi:10.1186/s13045-018-0605-5
↑ Banerji S, Wright AJ, Noble M, Mahoney DJ, Campbell ID, Day AJ, Jackson DG. Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction. Nat Struct Mol Biol. 2007 Mar;14(3):234-9. Epub 2007 Feb 11. PMID:17293874 doi:10.1038/nsmb1201

References

Proteopedia Page Contributors and Editors (what is this?)

Jacob A. Ray

[1] Senbanjo LT, Chellaiah MA. CD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. Front Cell Dev Biol. 2017 Mar 7;5:18. PMID:28326306 doi:10.3389/fcell.2017.00018

[2] Goodison S, Urquidi V, Tarin D. CD44 cell adhesion molecules. Mol Pathol. 1999 Aug;52(4):189-96. PMID:10694938 doi:10.1136/mp.52.4.189

[3] : https://dx.doi.org/10.1016/S1097-2765(04)00080-2

[4] Senbanjo LT, Chellaiah MA. CD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. Front Cell Dev Biol. 2017 Mar 7;5:18. PMID:28326306 doi:10.3389/fcell.2017.00018

[5] : https://dx.doi.org/10.1016/S1097-2765(04)00080-2

[6] Banerji S, Day AJ, Kahmann JD, Jackson DG. Characterization of a functional hyaluronan-binding domain from the human CD44 molecule expressed in Escherichia coli. Protein Expr Purif. 1998 Dec;14(3):371-81. PMID:9882571 doi:10.1006/prep.1998.0971

[7] Senbanjo LT, Chellaiah MA. CD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. Front Cell Dev Biol. 2017 Mar 7;5:18. PMID:28326306 doi:10.3389/fcell.2017.00018

[8] Mackay CR, Terpe HJ, Stauder R, Marston WL, Stark H, Günthert U. Expression and modulation of CD44 variant isoforms in humans. J Cell Biol. 1994 Jan;124(1-2):71-82. PMID:7507492 doi:10.1083/jcb.124.1.71

[9] Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018 May 10;11(1):64. PMID:29747682 doi:10.1186/s13045-018-0605-5

[10] Banerji S, Wright AJ, Noble M, Mahoney DJ, Campbell ID, Day AJ, Jackson DG. Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction. Nat Struct Mol Biol. 2007 Mar;14(3):234-9. Epub 2007 Feb 11. PMID:17293874 doi:10.1038/nsmb1201

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@@ Line 10: / Line 10: @@
 of the method and the full data available from
 [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4pz4 ConSurf].
-Residues proximal to the HA binding site tend to be the most conserved across species while residues that fall outside of the cannonical Link domain are the most variable.
+Residues proximal to the HA binding site tend to be the most conserved across species while residues that fall outside of the canonical Link domain are the most variable.
 == Isoforms ==
-The CD44 gene encodes a total of 20 exons but only exons 1-5 (HA binding domain) and 16-20 (transmembrane domain and cytosolic region) are constitutively expressed.<ref>DOI 10.3389/fcell.2017.00018</ref> Exons 6-15 are variably expressed within and across cell types creating diversity in available N- and O-glycosylation sites.<ref>DOI 10.1083/jcb.124.1.71</ref><ref>DOI 10.1186/s13045-018-0605-5</ref> The standard isoform of CD44 contains no variable region peptides.
+The CD44 gene encodes a total of 20 exons but only exons 1-5 (HA binding domain) and 16-20 (transmembrane domain and cytosolic region) are constitutively expressed.<ref>DOI 10.3389/fcell.2017.00018</ref> Exons 6-15 are variably expressed within and across cell types creating diversity in available N- and O-glycosylation sites.<ref>DOI 10.1083/jcb.124.1.71</ref><ref>DOI 10.1186/s13045-018-0605-5</ref> Variable exons are termed 1v-10v. Standard CD44 contains no variable regions while variants are termed CD44vX where 'vX' identifies the variable exons expressed.
 [[Image:CD44 Isoforms.png|1000 px|]]
 == Substrate Binding ==
 The HA binding domain of <scene name='10/1079558/Mcd44/1'>murine CD44</scene> is well characterized. Interactions with tyrosine, alanine, and cysteine residues in the <scene name='10/1079558/HA_Bind_Res/1'>HA binding cleft</scene> appear to be the most impactful.<ref>DOI 10.1038/nsmb1201</ref>
 == Cancer ==
+Altered expression of CD44 in tumors is associated with an increased risk of metastasis.
 </StructureSection>
 == References ==
 <references/>

User:Jacob A. Ray/Sandbox 1: Difference between revisions

Revision as of 04:12, 30 April 2025

CD44

Contents

Function

Evolutionary Conservation

Isoforms

Substrate Binding

Cancer

References

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