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PODXL

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PODXL
Identifiers
AliasesPODXL, Gp200, PC, PCLP, PCLP-1, podocalyxin like, PODXL1, PDX, gp135
External IDsOMIM: 602632; HomoloGene: 136790; GeneCards: PODXL; OMA:PODXL - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005397
NM_001018111

n/a

RefSeq (protein)

NP_001018121
NP_005388

n/a

Location (UCSC)Chr 7: 131.5 – 131.56 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Podocalyxin-like protein 1 is a protein that in humans is encoded by the PODXL gene.[3]

Function

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This gene encodes a member of the CD34 sialomucin protein family.[4] 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.[5] 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.[3]

Expression

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The expression and localisation of PODXL in human cells, tissues and organs have been investigated by the Human Protein Atlas consortium.[6] 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.[7] Based on confocal microscopy,[8] the protein is mainly localised to the plasma membrane and microtubule organizing center and in addition localized to vesicles.[9]

Interactions

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PODXL has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2.[10][11][12]

Clinical significance

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Podocalyxin is upregulated in a number of cancers and is frequently associated with poor prognosis.[13] Based on patient survival data,[14] high level of PODXL transcripts in tumor cells is associated with poor prognosis in renal cancer.

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000128567Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b "Entrez Gene: PODXL podocalyxin-like".
  4. ^ Nielsen JS, McNagny KM (November 2008). "Novel functions of the CD34 family". Journal of Cell Science. 121 (Pt 22): 3683–92. doi:10.1242/jcs.037507. PMID 18987355. S2CID 18154561.
  5. ^ Doyonnas R, Kershaw DB, Duhme C, Merkens H, Chelliah S, Graf T, McNagny KM (July 2001). "Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin". The Journal of Experimental Medicine. 194 (1): 13–27. doi:10.1084/jem.194.1.13. PMC 2193439. PMID 11435469.
  6. ^ Uhlen et al (2015) Science 347: 1260419. https://doi.org/doi:10.1126/science.1260419
  7. ^ "Tissue expression of PODXL - Summary - the Human Protein Atlas".
  8. ^ Thul et al (2017) Science 356 (6340): eaal3321. https://doi.org/doi:10.1126/science.aal3321
  9. ^ "Cell atlas - PODXL - the Human Protein Atlas".
  10. ^ Meder D, Shevchenko A, Simons K, Füllekrug J (Jan 2005). "Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical domain during polarization of MDCK cells". The Journal of Cell Biology. 168 (2): 303–13. doi:10.1083/jcb.200407072. PMC 2171597. PMID 15642748.
  11. ^ Takeda T, McQuistan T, Orlando RA, Farquhar MG (Jul 2001). "Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton". The Journal of Clinical Investigation. 108 (2): 289–301. doi:10.1172/JCI12539. PMC 203027. PMID 11457882.
  12. ^ Li Y, Li J, Straight SW, Kershaw DB (Jun 2002). "PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2". American Journal of Physiology. Renal Physiology. 282 (6): F1129–39. doi:10.1152/ajprenal.00131.2001. PMID 11997330.
  13. ^ 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 (March 2015). "Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy". Breast Cancer Research. 17 (1): 46. doi:10.1186/s13058-015-0562-7. PMC 4423095. PMID 25887862.
  14. ^ Uhlen et al (2017) Science 357 (6352): eaan2507. https://doi.org/doi:10.1126/science.aan2507

Further reading

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