PODXL_RABIT
ID PODXL_RABIT Reviewed; 551 AA.
AC Q28645;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Podocalyxin;
DE AltName: Full=Podocalyxin-like protein 1;
DE Short=PC;
DE Short=PCLP-1;
DE Flags: Precursor;
GN Name=PODXL; Synonyms=PCLP1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=New Zealand white;
RX PubMed=7493982; DOI=10.1074/jbc.270.49.29439;
RA Kershaw D.B., Thomas P.E., Wharram B.L., Goyal M., Wiggins J.E.,
RA Whiteside C.I., Wiggins R.C.;
RT "Molecular cloning, expression, and characterization of podocalyxin-like
RT protein 1 from rabbit as a transmembrane protein of glomerular podocytes
RT and vascular endothelium.";
RL J. Biol. Chem. 270:29439-29446(1995).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=20890297; DOI=10.1038/ncb2106;
RA Bryant D.M., Datta A., Rodriguez-Fraticelli A.E., Peraenen J.,
RA Martin-Belmonte F., Mostov K.E.;
RT "A molecular network for de novo generation of the apical surface and
RT lumen.";
RL Nat. Cell Biol. 12:1035-1045(2010).
CC -!- FUNCTION: Involved in the regulation of both adhesion and cell
CC morphology and cancer progression. Functions as an anti-adhesive
CC molecule that maintains an open filtration pathway between neighboring
CC foot processes in the podocyte by charge repulsion. Acts as a pro-
CC adhesive molecule, enhancing the adherence of cells to immobilized
CC ligands, increasing the rate of migration and cell-cell contacts in an
CC integrin-dependent manner. Induces the formation of apical actin-
CC dependent microvilli. Involved in the formation of a preapical plasma
CC membrane subdomain to set up initial epithelial polarization and the
CC apical lumen formation during renal tubulogenesis. Plays a role in
CC cancer development and aggressiveness by inducing cell migration and
CC invasion through its interaction with the actin-binding protein EZR.
CC Affects EZR-dependent signaling events, leading to increased activities
CC of the MAPK and PI3K pathways in cancer cells.
CC -!- SUBUNIT: Monomer; when associated with the membrane raft. Oligomer;
CC when integrated in the apical membrane. Found in a complex with EZR,
CC PODXL and SLC9A3R2. Associates with the actin cytoskeleton through
CC complex formation with EZR and SLC9A3R2. Interacts (via the C-terminal
CC PDZ-binding motif DTHL) with SLC9A3R1 (via the PDZ domains);
CC interaction is not detected in glomerular epithelium cells, take place
CC early in the secretory pathway and is necessary for its apical membrane
CC sorting. Interacts (via the C-terminal PDZ-binding motif DTHL) with
CC SLC9A3R2 (via the PDZ 1 domain); interaction is detected in glomerular
CC epithelium cells. Interacts with EZR (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q28645; Q8SQG9: SLC9A3R2; NbExp=7; IntAct=EBI-8375591, EBI-1174758;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000250}. Cell
CC projection, microvillus {ECO:0000250}. Membrane raft {ECO:0000250}.
CC Cell projection, lamellipodium {ECO:0000250}. Cell projection,
CC filopodium {ECO:0000250}. Cell projection, ruffle {ECO:0000250}.
CC Membrane {ECO:0000305}; Single-pass type I membrane protein
CC {ECO:0000305}. Note=In single attached epithelial cells is restricted
CC to a preapical pole on the free plasma membrane whereas other apical
CC and basolateral proteins are not yet polarized. Colocalizes with
CC SLC9A3R2 at the apical plasma membrane during epithelial polarization.
CC Colocalizes with SLC9A3R1 at the trans-Golgi network (transiently) and
CC at the apical plasma membrane. Its association with the membrane raft
CC is transient. Forms granular, punctuated pattern, forming patches,
CC preferentially adopting a polar distribution, located on the migrating
CC poles of the cell or forming clusters along the terminal ends of
CC filipodia establishing contact with the endothelial cells. Colocalizes
CC with the submembrane actin of lamellipodia, particularly associated
CC with ruffles. Colocalizes with vinculin at protrusions of cells.
CC Colocalizes with ITGB1. Colocalizes with EZR and SLC9A3R2 at the apical
CC cell membrane of glomerular epithelium cells. Colocalizes with actin
CC filaments, EZR and SLC9A3R1 in a punctate pattern at the apical cell
CC surface where microvilli form (By similarity). Colocalizes with PARD3,
CC PRKCI, EXOC5, OCLN, RAB11A and RAB8A in apical membrane initiation
CC sites (AMIS) during the generation of apical surface and luminogenesis.
CC {ECO:0000250, ECO:0000269|PubMed:20890297}.
CC -!- TISSUE SPECIFICITY: Glomerular epithelium cell (podocyte) and
CC endothelial cells. {ECO:0000269|PubMed:7493982}.
CC -!- DOMAIN: Both the O-glycan-rich domain of the extracellular domain and
CC the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor
CC an apical sorting signal. The cytoplasmic domain is necessary for the
CC apical membrane targeting and renal tubulogenesis. The large highly
CC anionic extracellular domain allows to maintain open filtration
CC pathways between neighboring podocyte foot processes. The cytoplasmic
CC C-terminus PDZ-binding motif (DTHL) is essential for interaction with
CC SLC9A3R1 and for targeting SLC9A3R1 to the apical cell membrane. The
CC extracellular domain is necessary for microvillus formation (By
CC similarity). {ECO:0000250}.
CC -!- PTM: N- and O-linked glycosylated. Sialoglycoprotein (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the podocalyxin family. {ECO:0000305}.
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DR EMBL; U35239; AAC48489.1; -; mRNA.
DR RefSeq; NP_001076235.1; NM_001082766.1.
DR AlphaFoldDB; Q28645; -.
DR IntAct; Q28645; 1.
DR MINT; Q28645; -.
DR STRING; 9986.ENSOCUP00000021702; -.
DR PRIDE; Q28645; -.
DR GeneID; 100009552; -.
DR KEGG; ocu:100009552; -.
DR CTD; 5420; -.
DR eggNOG; ENOG502S2JU; Eukaryota.
DR InParanoid; Q28645; -.
DR OrthoDB; 1404598at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0031528; C:microvillus membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0036057; C:slit diaphragm; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0072175; P:epithelial tube formation; ISS:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0072015; P:podocyte development; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0033634; P:positive regulation of cell-cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0032534; P:regulation of microvillus assembly; ISS:UniProtKB.
DR InterPro; IPR013836; CD34/Podocalyxin.
DR InterPro; IPR017403; PODXL.
DR PANTHER; PTHR12067; PTHR12067; 1.
DR Pfam; PF06365; CD34_antigen; 1.
DR PIRSF; PIRSF038143; Podocalyxin-like_p1; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Cell projection; Glycoprotein; Membrane;
KW Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..551
FT /note="Podocalyxin"
FT /id="PRO_0000024756"
FT TOPO_DOM 22..452
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 453..473
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 474..551
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 18..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 55..105
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..188
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 197..244
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..271
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..314
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 511
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0M4"
FT MOD_RES 530
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00592"
FT MOD_RES 549
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O00592"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 551 AA; 57041 MW; E9B8AE168CDFB8C5 CRC64;
MRSALALAAL LLLLLSPPSL SQEKSPQPGP TPMATSTSTR PAPASAPAPK SSVAASVPAE
QNTTPMTTKA PATQSPSASP GSSVENSAPA QGSTTTQQSL SVTTKAEAKD AGGVPTAHVT
GSARPVTSGS QVAAQDPAAS KAPSNHSITT KPLATEATSQ APRQTTDVGT PGPTAPPVTN
STSPDLLGHA TPKPSEGPQL SFPTAAGSLG PVTGSGTGSG TLSTPQGKPA TLTPVASSAE
TQGMPSPMPP SPASPSSSPF PSSPSPSPAL QPSGPSAAGT EDTTGRGPTS SSTELASTAL
HGPSTLSPTS AVRDQRVSCG PPERPTEQLL ILNLTRSSPC IHVFQRQSQG EGETEISMHS
TDSLPEDKLV TLLCRAAKPT FNPAQDQCHV LLAPMLGSHA VVVKEITIKT NLLPTAVFEL
LKDRWDDLRE EGVSDMQLGD QGPPEETEDR FSLPLIITIV CMASFLLLVA ALYGCCHQRL
SHRKDQQRLT EELQTVENGY HDNPTLEVME TSAEMQEKKV VNLNGELGDS WIVPLDNLTK
DDLDEEEDTH L
