PODXL

This gene encodes a member of the CD34 sialomucin protein family.{{cite journal | vauthors = Nielsen JS, McNagny KM | title = Novel functions of the CD34 family | journal = Journal of Cell Science | volume = 121 | issue = Pt 22 | pages = 3683–92 | date = November 2008 | pmid = 18987355 | doi = 10.1242/jcs.037507 | s2cid = 18154561 | doi-access = }} The encoded protein was originally identified as an important component of glomerular podocytes. Inactivation of the encoding gene in mice leads to anuria, omphalocele and perinatal death.{{cite journal | vauthors = Doyonnas R, Kershaw DB, Duhme C, Merkens H, Chelliah S, Graf T, McNagny KM | title = Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin | journal = The Journal of Experimental Medicine | volume = 194 | issue = 1 | pages = 13–27 | date = July 2001 | pmid = 11435469 | pmc = 2193439 | doi = 10.1084/jem.194.1.13 }} Podocytes are highly differentiated epithelial cells with interdigitating foot processes covering the outer aspect of the glomerular basement membrane. Other biological activities of the encoded protein include: binding in a membrane protein complex with Na+/H+ exchanger regulatory factor to intracellular cytoskeletal elements, playing a role in hematopoietic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin.

The expression and localisation of PODXL in human cells, tissues and organs have been investigated by the Human Protein Atlas consortium.Uhlen et al (2015) Science 347: 1260419. https://doi.org/doi:10.1126/science.1260419 According to antibody-based profiling, the protein is present in glomerular podocytes, endothelial cells, glandular cells in fallopian tube, uterus and seminal vesicle and according to RNA expression analysis, the PODXL transcripts are present in all analysed human tissues.{{Cite web | url=http://www.proteinatlas.org/ENSG00000128567-PODXL/tissue | title=Tissue expression of PODXL - Summary - the Human Protein Atlas}} Based on confocal microscopy,Thul et al (2017) Science 356 (6340): eaal3321. https://doi.org/doi:10.1126/science.aal3321 the protein is mainly localised to the plasma membrane and microtubule organizing center and in addition localized to vesicles.{{Cite web | url=http://www.proteinatlas.org/ENSG00000128567-PODXL/cell | title=Cell atlas - PODXL - the Human Protein Atlas}}

PODXL has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2.{{cite journal | vauthors = Meder D, Shevchenko A, Simons K, Füllekrug J | title = Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical domain during polarization of MDCK cells | journal = The Journal of Cell Biology | volume = 168 | issue = 2 | pages = 303–13 | date = Jan 2005 | pmid = 15642748 | pmc = 2171597 | doi = 10.1083/jcb.200407072 }}{{cite journal | vauthors = Takeda T, McQuistan T, Orlando RA, Farquhar MG | title = Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton | journal = The Journal of Clinical Investigation | volume = 108 | issue = 2 | pages = 289–301 | date = Jul 2001 | pmid = 11457882 | pmc = 203027 | doi = 10.1172/JCI12539 }}{{cite journal | vauthors = Li Y, Li J, Straight SW, Kershaw DB | title = PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2 | journal = American Journal of Physiology. Renal Physiology | volume = 282 | issue = 6 | pages = F1129–39 | date = Jun 2002 | pmid = 11997330 | doi = 10.1152/ajprenal.00131.2001 }}

Podocalyxin is upregulated in a number of cancers and is frequently associated with poor prognosis.{{cite journal | vauthors = Snyder KA, Hughes MR, Hedberg B, Brandon J, Hernaez DC, Bergqvist P, Cruz F, Po K, Graves ML, Turvey ME, Nielsen JS, Wilkins JA, McColl SR, Babcook JS, Roskelley CD, McNagny KM | title = Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy | journal = Breast Cancer Research | volume = 17 | issue = 1 | pages = 46 | date = March 2015 | pmid = 25887862 | doi = 10.1186/s13058-015-0562-7 | pmc=4423095 | doi-access = free }} Based on patient survival data,Uhlen et al (2017) Science 357 (6352): eaan2507. https://doi.org/doi:10.1126/science.aan2507 high level of PODXL transcripts in tumor cells is associated with poor prognosis in renal cancer.

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