User:Jacob A. Ray/Sandbox 1
From Proteopedia
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<StructureSection load='4pz4' size='340' side='right' caption='Hyaluronan Binding Domain of Human CD44 (pdb: 4pz4)' scene=''> | <StructureSection load='4pz4' size='340' side='right' caption='Hyaluronan Binding Domain of Human CD44 (pdb: 4pz4)' scene=''> | ||
== Function == | == Function == | ||
| - | <scene name='10/1079558/Link_domain/2'>CD44</scene> is a highly glycosylated multifunctional cell surface receptor that is involved in cell-cell interaction and maintenance of the extracellular matrix.<ref> | + | <scene name='10/1079558/Link_domain/2'>CD44</scene> is a highly glycosylated multifunctional cell surface receptor that is involved in cell-cell interaction and maintenance of the extracellular matrix.<ref name="frontier">PMID: 28326306</ref> The primary ligand for CD44 is hyaluronan (HA), but it has also been found to interact with other molecules including osteopontin, collagens, and fibronectin. <ref>DOI 10.1136/mp.52.4.189</ref> CD44 is a single chain protein containing four distinct regions: the N-terminal HA binding Link domain<ref>DOI 10.1016/S1097-2765(04)00080-2</ref>, a flexible variable domain, a transmembrane domain, and an intracellular signaling domain.<ref name="frontier" /> The <scene name='10/1079558/Link_Highlight/2'>Link domain</scene> is an approximately 100 amino acid domain consisting of two antiparallel β-sheets, two α-helicies, and two disulfide bonds.<ref>DOI 10.1016/S1097-2765(04)00080-2</ref> This domain is found in most HA binding proteins, including aggrecan, versican, brevican, and tumor necrosis factor-inducible gene 6.<ref>DOI 10.1006/prep.1998.0971</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|right|200px]] | [[Image:Consurf_key_small.gif|right|200px]] | ||
| - | <scene name='10/1079558/CD44_ConSurf/4'>Evolutionary conservation</scene> of CD44 residues, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. | + | <scene name='10/1079558/CD44_ConSurf/4'>Evolutionary conservation</scene> of CD44 residues, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. 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. |
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| - | 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 == | == 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 | + | 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 name="frontier"> 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 peptides expressed. |
[[Image:CD44 Isoforms.png|1000 px|]] | [[Image:CD44 Isoforms.png|1000 px|]] | ||
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== Substrate Binding == | == 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> | 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> | ||
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| - | Due to its key role in interacting with the extracellular matrix, altered expression of CD44 in tumors is associated with an increased risk of metastasis.<ref>DOI 10.1083/jcb.124.1.71</ref> For example, benign human prostate cell express CD44v5, but after neoplasia they shift to express soluble CD44 which contains no variable peptides. CD44 expression on vascular endothelial cells contributes to the regulation of angiogenesis and may be leveraged by tumors to increase local blood supply.<ref | + | == Clinical Significance == |
| + | Due to its key role in interacting with the extracellular matrix, altered expression of CD44 in tumors is associated with an increased risk of metastasis.<ref>DOI 10.1083/jcb.124.1.71</ref> For example, benign human prostate cell express CD44v5, but after neoplasia they shift to express soluble CD44 which contains no variable peptides. CD44 expression on vascular endothelial cells contributes to the regulation of angiogenesis and may be leveraged by tumors to increase local blood supply.<ref name="frontier"> | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 20:59, 4 May 2025
CD44
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References
- ↑ 1.0 1.1 1.2 1.3 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
- ↑ 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
- ↑ 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
- ↑ 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
