Q9R0M4 (PODXL_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 91. History...
Names and origin
|Protein names||Recommended name:|
Podocalyxin-like protein 1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||503 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Involved in the regulation of both adhesion and cell morphology and cancer progression. Function as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell-cell contacts in an integrin-dependent manner. Induces the formation of apical actin-dependent microvilli. Involved in the formation of a preapical plasma membrane subdomain to set up inital epithelial polarization and the apical lumen formation during renal tubulogenesis. Plays a role in cancer development and aggressiveness by inducing cell migration and invasion through its interaction with the actin-binding protein EZR. Affects EZR-dependent signaling events, leading to increased activities of the MAPK and PI3K pathways in cancer cells. Ref.4 Ref.5
Monomer; when associated with the membrane raft. Oligomer; when integrated in the apical membrane. Found in a complex with EZR, PODXL and SLC9A3R2. Associates with the actin cytoskeleton through complex formation with EZR and SLC9A3R2. Interacts (via the C-terminal PDZ-binding motif DTHL) with SLC9A3R1 (via the PDZ domains); interaction is not detected in glomerular epithelium cells, take place early in the secretory pathway and is necessary for its apical membrane sorting. Interacts (via the C-terminal PDZ-binding motif DTHL) with SLC9A3R2 (via the PDZ 1 domain); interaction is detected in glomerular epithelium cells. Interacts with EZR By similarity.
Apical cell membrane. Cell projection › microvillus. Membrane raft By similarity. Cell projection › lamellipodium By similarity. Cell projection › filopodium By similarity. Cell projection › ruffle By similarity. Membrane; Single-pass type I membrane protein Potential. Note: In single attached epithelial cells is restricted to a preapical pole on the free plasma membrane whereas other apical and basolateral proteins are not yet polarized. Colocalizes with SLC9A3R2 at the apical plasma membrane during epithelial polarization. Colocalizes with SLC9A3R1 at the trans-Golgi network (transiently) and at the apical plasma membrane. Its association with the membrane raft is transient. Forms granular, punctuated pattern, forming patches, preferentially adopting a polar distribution, located on the migrating poles of the cell or forming clusters along the terminal ends of filipodia establishing contact with the endothelial cells. Colocalizes with the submembrane actin of lamellipodia, particularly associated with ruffles. Colocalizes with vinculin at protrusions of cells. Colocalizes with ITGB1. Colocalizes with EZR and SLC9A3R2 at the apical cell membrane of glomerular epithelium cells By similarity. Colocalizes with actin filaments, EZR and SLC9A3R1 in a punctate pattern at the apical cell surface where microvilli form. Colocalizes with PARD3, PRKCI, EXOC5, OCLN, RAB11A and RAB8A in apical membrane initiation sites (AMIS) during the generation of apical surface and luminogenesis By similarity. Ref.5
Expressed in liver cells and hematopoietic cells (at protein level). Glomerular epithelium cell (podocyte). Ref.4
Both the O-glycan-rich domain of the extracellular domain and the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal. The cytoplasmic domain is necessary for the apical membrane targeting and renal tubulogenesis. The large highly anionic extracellular domain allows to maintain open filtration pathways between neighboring podocyte foot processes. The cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with SLC9A3R1 and for targeting SLC9A3R1 to the apical cell membrane. The extracellular domain is necessary for microvillus formation By similarity.
N- and O-linked glycosylated. Sialoglycoprotein By similarity.
Die within the first 24 h of postnatal life from profound defects in kidney and/or gut formation. They are anuric (no measurable urine in the bladder), and fail to generate the extensive interdigitated foot process and instead retain cell junctions between immature podocytes. Ref.4
Belongs to the podocalyxin family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 21||21||Potential|
|Chain||22 – 503||482||Podocalyxin||PRO_0000024755|
|Topological domain||22 – 404||383||Extracellular Potential|
|Transmembrane||405 – 425||21||Helical; Potential|
|Topological domain||426 – 503||78||Cytoplasmic Potential|
|Compositional bias||27 – 259||233||Ser/Thr-rich|
Amino acid modifications
|Modified residue||482||1||Phosphoserine By similarity|
|Modified residue||501||1||Phosphothreonine By similarity|
|Glycosylation||25||1||N-linked (GlcNAc...) Potential|
|Glycosylation||89||1||N-linked (GlcNAc...) Potential|
|Glycosylation||94||1||N-linked (GlcNAc...) Potential|
|Glycosylation||145||1||N-linked (GlcNAc...) Potential|
|Glycosylation||154||1||N-linked (GlcNAc...) Potential|
|Glycosylation||167||1||N-linked (GlcNAc...) Potential|
|Glycosylation||206||1||N-linked (GlcNAc...) Potential|
|Glycosylation||303||1||N-linked (GlcNAc...) Potential|
|Natural variant||78||1||S → F.|
|||"Identification of podocalyxin-like protein 1 as a novel cell surface marker for hemangioblasts in the murine aorta-gonad-mesonephros region."|
Hara T., Nakano Y., Tanaka M., Tamura K., Sekiguchi T., Minehata K., Copeland N.G., Jenkins N.A., Okabe M., Kogo H., Mukouyama Y., Miyajima A.
Immunity 11:567-578(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Gene structure of mouse podocalyxin."|
Kershaw D.B., Li J.
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||"Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin."|
Doyonnas R., Kershaw D.B., Duhme C., Merkens H., Chelliah S., Graf T., McNagny K.M.
J. Exp. Med. 194:13-27(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
|||"The CD34-related molecule podocalyxin is a potent inducer of microvillus formation."|
Nielsen J.S., Graves M.L., Chelliah S., Vogl A.W., Roskelley C.D., McNagny K.M.
PLoS ONE 2:E237-E237(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
|+||Additional computationally mapped references.|
|AB028048 mRNA. Translation: BAA86912.1.|
AF290209 mRNA. Translation: AAG02458.1.
BC052442 mRNA. Translation: AAH52442.1.
BC054530 mRNA. Translation: AAH54530.1.
|RefSeq||NP_038751.2. NM_013723.3. |
3D structure databases
Protein-protein interaction databases
|IntAct||Q9R0M4. 3 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000026698; ENSMUSP00000026698; ENSMUSG00000025608. |
|UCSC||uc009bgh.2. mouse. |
|MGI||MGI:1351317. Podxl. |
Gene expression databases
Family and domain databases
|InterPro||IPR013836. CD34/Podocalyxin. |
|Pfam||PF06365. CD34_antigen. 1 hit. |
|PIRSF||PIRSF038143. Podocalyxin-like_p1. 1 hit. |
|Accession||Primary (citable) accession number: Q9R0M4|
Secondary accession number(s): Q9ESZ1
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|