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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Podocalyxin-like protein 1''' is a [[protein]] that in humans is encoded by the ''PODXL'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PODXL podocalyxin-like| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5420| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Podocalyxin-like
| HGNCid = 9171
| Symbol = PODXL
| AltSymbols =; Gp200; MGC138240; PCLP
| OMIM = 602632
| ECnumber = 
| Homologene = 3937
| MGIid = 1351317
| GeneAtlas_image1 = PBB_GE_PODXL_201578_at_tn.png
| Function =  
| Component = {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process =
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5420
    | Hs_Ensembl = ENSG00000128567
    | Hs_RefseqProtein = NP_001018121
    | Hs_RefseqmRNA = NM_001018111
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 7
    | Hs_GenLoc_start = 130835563
    | Hs_GenLoc_end = 130891908
    | Hs_Uniprot = O00592
    | Mm_EntrezGene = 27205
    | Mm_Ensembl = ENSMUSG00000025608
    | Mm_RefseqmRNA = NM_013723
    | Mm_RefseqProtein = NP_038751
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 31449656
    | Mm_GenLoc_end = 31494074
    | Mm_Uniprot = Q3UYF4
  }}
}}
'''Podocalyxin-like''', also known as '''PODXL''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PODXL podocalyxin-like| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5420| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a member of the CD34 sialomucin protein family.<ref name="Nielsen_2008">{{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 | pmc =  | doi = 10.1242/jcs.037507 }}</ref> 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.<ref name="Doyonnas_2001">{{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 }}</ref> 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 hematopoetic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin.<ref name="entrez" />  
{{PBB_Summary
| section_title =  
| summary_text = This gene encodes a member of the sialomucin protein family. The encoded protein was originally identified as an important component of glomerular podocytes. 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 hematopoetic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin.<ref name="entrez">{{cite web | title = Entrez Gene: PODXL podocalyxin-like| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5420| accessdate = }}</ref>
}}


==References==
== Expression ==
{{reflist|2}}
 
==Further reading==
The expression and localisation of PODXL in human cells, tissues and organs have been investigated by the [[Human Protein Atlas]] consortium<ref>Uhlen et al (2015) Science 347: 1260419. https://doi.org/doi:10.1126/science.1260419</ref>. According to [[antibody]]-based profiling, the protein is present in [[Glomerulus_(kidney)|glomerular]] [[Podocyte|podocytes]], [[Endothelium|endothelial cells]], [[Gland|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<ref>http://www.proteinatlas.org/ENSG00000128567-PODXL/tissue</ref>. Based on [[confocal microscopy]]<ref>Thul et al (2017) Science 356 (6340): eaal3321. https://doi.org/doi:10.1126/science.aal3321</ref>, the protein is mainly localised to the [[Cell_membrane|plasma membrane]] and [[microtubule]] organizing center and in addition localized to [[Vesicle_(biology_and_chemistry)|vesicles]]<ref>http://www.proteinatlas.org/ENSG00000128567-PODXL/cell</ref>.
 
== Interactions ==
 
PODXL has been shown to [[Protein-protein interaction|interact]] with [[Sodium-hydrogen exchange regulatory cofactor 2]].<ref name=pmid15642748>{{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 }}</ref><ref name=pmid11457882>{{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 }}</ref><ref name=pmid11997330>{{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 }}</ref>
 
== Clinical significance ==
 
Podocalyxin is upregulated in a number of cancers and is frequently associated with poor prognosis<ref>{{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}}</ref><ref>{{cite book | vauthors = McNagny KM, Hughes MR, Graves ML, DeBruin EJ, Snyder K, Cipollone J, Turvey M, Tan PC, McColl S, Roskelley CD | year = 2012 | chapter = Podocalyxin in the Diagnosis and Treatment of Cancer | title = Advances in Cancer Management | veditors = Mohan R | isbn = 978-953-307-870-0 | publisher = InTech | doi = 10.5772/24274 }}</ref>. Based on patient survival data<ref>Uhlen et al (2017) Science 357 (6352): eaan2507. https://doi.org/doi:10.1126/science.aan2507</ref>, high level of PODXL transcripts in tumor cells is associated with poor prognosis in [http://www.proteinatlas.org/ENSG00000128567-PODXL/pathology/tissue/renal+cancer renal cancer].
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
| citations =
* {{cite journal | vauthors = Kershaw DB, Beck SG, Wharram BL, Wiggins JE, Goyal M, Thomas PE, Wiggins RC | title = Molecular cloning and characterization of human podocalyxin-like protein. Orthologous relationship to rabbit PCLP1 and rat podocalyxin | journal = The Journal of Biological Chemistry | volume = 272 | issue = 25 | pages = 15708–14 | date = Jun 1997 | pmid = 9188463 | doi = 10.1074/jbc.272.25.15708 }}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Kershaw DB, Wiggins JE, Wharram BL, Wiggins RC | title = Assignment of the human podocalyxin-like protein (PODXL) gene to 7q32-q33 | journal = Genomics | volume = 45 | issue = 1 | pages = 239–40 | date = Oct 1997 | pmid = 9339384 | doi = 10.1006/geno.1997.4934 }}
*{{cite journal | author=Kershaw DB, Beck SG, Wharram BL, ''et al.'' |title=Molecular cloning and characterization of human podocalyxin-like protein. Orthologous relationship to rabbit PCLP1 and rat podocalyxin. |journal=J. Biol. Chem. |volume=272 |issue= 25 |pages= 15708-14 |year= 1997 |pmid= 9188463 |doi= }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Kershaw DB, Wiggins JE, Wharram BL, Wiggins RC |title=Assignment of the human podocalyxin-like protein (PODXL) gene to 7q32-q33. |journal=Genomics |volume=45 |issue= 1 |pages= 239-40 |year= 1997 |pmid= 9339384 |doi= 10.1006/geno.1997.4934 }}
* {{cite journal | vauthors = Sassetti C, Tangemann K, Singer MS, Kershaw DB, Rosen SD | title = Identification of podocalyxin-like protein as a high endothelial venule ligand for L-selectin: parallels to CD34 | journal = The Journal of Experimental Medicine | volume = 187 | issue = 12 | pages = 1965–75 | date = Jun 1998 | pmid = 9625756 | pmc = 2212365 | doi = 10.1084/jem.187.12.1965 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
* {{cite journal | vauthors = Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ | title = Shotgun sequencing of the human transcriptome with ORF expressed sequence tags | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 7 | pages = 3491–6 | date = Mar 2000 | pmid = 10737800 | pmc = 16267 | doi = 10.1073/pnas.97.7.3491 }}
*{{cite journal | author=Sassetti C, Tangemann K, Singer MS, ''et al.'' |title=Identification of podocalyxin-like protein as a high endothelial venule ligand for L-selectin: parallels to CD34. |journal=J. Exp. Med. |volume=187 |issue= 12 |pages= 1965-75 |year= 1998 |pmid= 9625756 |doi= }}
* {{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 | author=Dias Neto E, Correa RG, Verjovski-Almeida S, ''et al.'' |title=Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 7 |pages= 3491-6 |year= 2000 |pmid= 10737800 |doi= }}
* {{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 }}
*{{cite journal | author=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=J. Clin. Invest. |volume=108 |issue= 2 |pages= 289-301 |year= 2001 |pmid= 11457882 |doi= }}
* {{cite journal | vauthors = Schopperle WM, Kershaw DB, DeWolf WC | title = Human embryonal carcinoma tumor antigen, Gp200/GCTM-2, is podocalyxin | journal = Biochemical and Biophysical Research Communications | volume = 300 | issue = 2 | pages = 285–90 | date = Jan 2003 | pmid = 12504081 | doi = 10.1016/S0006-291X(02)02844-9 }}
*{{cite journal | author=Li Y, Li J, Straight SW, Kershaw DB |title=PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2. |journal=Am. J. Physiol. Renal Physiol. |volume=282 |issue= 6 |pages= F1129-39 |year= 2002 |pmid= 11997330 |doi= 10.1152/ajprenal.00131.2001 }}
* {{cite journal | vauthors = Koop K, Eikmans M, Baelde HJ, Kawachi H, De Heer E, Paul LC, Bruijn JA | title = Expression of podocyte-associated molecules in acquired human kidney diseases | journal = Journal of the American Society of Nephrology | volume = 14 | issue = 8 | pages = 2063–71 | date = Aug 2003 | pmid = 12874460 | doi = 10.1097/01.ASN.0000078803.53165.C9 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW | title = Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation | journal = Nature Biotechnology | volume = 22 | issue = 6 | pages = 707–16 | date = Jun 2004 | pmid = 15146197 | doi = 10.1038/nbt971 }}
*{{cite journal | author=Schopperle WM, Kershaw DB, DeWolf WC |title=Human embryonal carcinoma tumor antigen, Gp200/GCTM-2, is podocalyxin. |journal=Biochem. Biophys. Res. Commun. |volume=300 |issue= 2 |pages= 285-90 |year= 2003 |pmid= 12504081 |doi= }}
* {{cite journal | vauthors = Economou CG, Kitsiou PV, Tzinia AK, Panagopoulou E, Marinos E, Kershaw DB, Kerjaschki D, Tsilibary EC | title = Enhanced podocalyxin expression alters the structure of podocyte basal surface | journal = Journal of Cell Science | volume = 117 | issue = Pt 15 | pages = 3281–94 | date = Jul 2004 | pmid = 15226400 | doi = 10.1242/jcs.01163 }}
*{{cite journal | author=Scherer SW, Cheung J, MacDonald JR, ''et al.'' |title=Human chromosome 7: DNA sequence and biology. |journal=Science |volume=300 |issue= 5620 |pages= 767-72 |year= 2003 |pmid= 12690205 |doi= 10.1126/science.1083423 }}
* {{cite journal | vauthors = Somasiri A, Nielsen JS, Makretsov N, McCoy ML, Prentice L, Gilks CB, Chia SK, Gelmon KA, Kershaw DB, Huntsman DG, McNagny KM, Roskelley CD | title = Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression | journal = Cancer Research | volume = 64 | issue = 15 | pages = 5068–73 | date = Aug 2004 | pmid = 15289306 | doi = 10.1158/0008-5472.CAN-04-0240 }}
*{{cite journal | author=Koop K, Eikmans M, Baelde HJ, ''et al.'' |title=Expression of podocyte-associated molecules in acquired human kidney diseases. |journal=J. Am. Soc. Nephrol. |volume=14 |issue= 8 |pages= 2063-71 |year= 2004 |pmid= 12874460 |doi= }}
* {{cite journal | vauthors = Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S | title = Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions | journal = Genome Research | volume = 14 | issue = 9 | pages = 1711–8 | date = Sep 2004 | pmid = 15342556 | pmc = 515316 | doi = 10.1101/gr.2435604 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
* {{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 | author=Brandenberger R, Wei H, Zhang S, ''et al.'' |title=Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. |journal=Nat. Biotechnol. |volume=22 |issue= 6 |pages= 707-16 |year= 2005 |pmid= 15146197 |doi= 10.1038/nbt971 }}
* {{cite journal | vauthors = Casey G, Neville PJ, Liu X, Plummer SJ, Cicek MS, Krumroy LM, Curran AP, McGreevy MR, Catalona WJ, Klein EA, Witte JS | title = Podocalyxin variants and risk of prostate cancer and tumor aggressiveness | journal = Human Molecular Genetics | volume = 15 | issue = 5 | pages = 735–41 | date = Mar 2006 | pmid = 16434482 | doi = 10.1093/hmg/ddi487 }}
*{{cite journal | author=Economou CG, Kitsiou PV, Tzinia AK, ''et al.'' |title=Enhanced podocalyxin expression alters the structure of podocyte basal surface. |journal=J. Cell. Sci. |volume=117 |issue= Pt 15 |pages= 3281-94 |year= 2005 |pmid= 15226400 |doi= 10.1242/jcs.01163 }}
* {{cite journal | vauthors = Butta N, Larrucea S, Alonso S, Rodriguez RB, Arias-Salgado EG, Ayuso MS, González-Manchón C, Parrilla R | title = Role of transcription factor Sp1 and CpG methylation on the regulation of the human podocalyxin gene promoter | journal = BMC Molecular Biology | volume = 7 | pages = 17 | year = 2006 | pmid = 16684343 | pmc = 1481587 | doi = 10.1186/1471-2199-7-17 }}
*{{cite journal | author=Somasiri A, Nielsen JS, Makretsov N, ''et al.'' |title=Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression. |journal=Cancer Res. |volume=64 |issue= 15 |pages= 5068-73 |year= 2004 |pmid= 15289306 |doi= 10.1158/0008-5472.CAN-04-0240 }}
*{{cite journal | author=Suzuki Y, Yamashita R, Shirota M, ''et al.'' |title=Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. |journal=Genome Res. |volume=14 |issue= 9 |pages= 1711-8 |year= 2004 |pmid= 15342556 |doi= 10.1101/gr.2435604 }}
*{{cite journal  | author=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=J. Cell Biol. |volume=168 |issue= 2 |pages= 303-13 |year= 2005 |pmid= 15642748 |doi= 10.1083/jcb.200407072 }}
*{{cite journal  | author=Casey G, Neville PJ, Liu X, ''et al.'' |title=Podocalyxin variants and risk of prostate cancer and tumor aggressiveness. |journal=Hum. Mol. Genet. |volume=15 |issue= 5 |pages= 735-41 |year= 2006 |pmid= 16434482 |doi= 10.1093/hmg/ddi487 }}
*{{cite journal  | author=Butta N, Larrucea S, Alonso S, ''et al.'' |title=Role of transcription factor Sp1 and CpG methylation on the regulation of the human podocalyxin gene promoter. |journal=BMC Mol. Biol. |volume=7 |issue=  |pages= 17 |year= 2006 |pmid= 16684343 |doi= 10.1186/1471-2199-7-17 }}
}}
{{refend}}
{{refend}}
{{protein-stub}}
{{WikiDoc Sources}}

Latest revision as of 15:52, 9 March 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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

Function

This gene encodes a member of the CD34 sialomucin protein family.[2] 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.[3] 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 hematopoetic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin.[1]

Expression

The expression and localisation of PODXL in human cells, tissues and organs have been investigated by the Human Protein Atlas consortium[4]. 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[5]. Based on confocal microscopy[6], the protein is mainly localised to the plasma membrane and microtubule organizing center and in addition localized to vesicles[7].

Interactions

PODXL has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2.[8][9][10]

Clinical significance

Podocalyxin is upregulated in a number of cancers and is frequently associated with poor prognosis[11][12]. Based on patient survival data[13], high level of PODXL transcripts in tumor cells is associated with poor prognosis in renal cancer.

References

  1. ↑ 1.0 1.1 "Entrez Gene: PODXL podocalyxin-like".
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ Uhlen et al (2015) Science 347: 1260419. https://doi.org/doi:10.1126/science.1260419
  5. ↑ http://www.proteinatlas.org/ENSG00000128567-PODXL/tissue
  6. ↑ Thul et al (2017) Science 356 (6340): eaal3321. https://doi.org/doi:10.1126/science.aal3321
  7. ↑ http://www.proteinatlas.org/ENSG00000128567-PODXL/cell
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ McNagny KM, Hughes MR, Graves ML, DeBruin EJ, Snyder K, Cipollone J, Turvey M, Tan PC, McColl S, Roskelley CD (2012). "Podocalyxin in the Diagnosis and Treatment of Cancer". In Mohan R. Advances in Cancer Management. InTech. doi:10.5772/24274. ISBN 978-953-307-870-0.
  13. ↑ Uhlen et al (2017) Science 357 (6352): eaan2507. https://doi.org/doi:10.1126/science.aan2507

Further reading

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