PODXL_CANLF
ID PODXL_CANLF Reviewed; 571 AA.
AC Q52S86;
DT 15-JUN-2010, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Podocalyxin;
DE AltName: Full=Gp135;
DE AltName: Full=Podocalyxin-like protein 1;
DE Short=PC;
DE Short=PC-like protein 1;
DE Short=PCLP-1;
DE Short=cPCLP1;
DE Flags: Precursor;
GN Name=PODXL; Synonyms=PCLP, PCLP1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 398-406; 448-466 AND
RP 525-538, FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-199; ASN-373
RP AND ASN-383, MUTAGENESIS OF ASN-123; ASN-199; ASN-373 AND ASN-383, AND
RP TISSUE SPECIFICITY.
RX PubMed=15814834; DOI=10.1681/asn.2004121145;
RA Cheng H.Y., Lin Y.Y., Yu C.Y., Chen J.Y., Shen K.F., Lin W.L., Liao H.K.,
RA Chen Y.J., Liu C.H., Pang V.F., Jou T.S.;
RT "Molecular identification of canine podocalyxin-like protein 1 as a renal
RT tubulogenic regulator.";
RL J. Am. Soc. Nephrol. 16:1612-1622(2005).
RN [2]
RP FUNCTION, INTERACTION WITH SLC9A3R2, AND SUBCELLULAR LOCATION.
RX PubMed=15642748; DOI=10.1083/jcb.200407072;
RA Meder D., Shevchenko A., Simons K., Fuellekrug J.;
RT "Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical
RT domain during polarization of MDCK cells.";
RL J. Cell Biol. 168:303-313(2005).
RN [3]
RP SUBUNIT, INTERACTION WITH SLC9A3R1, GLYCOSYLATION AT ASN-199; ASN-373 AND
RP ASN-383, AND MUTAGENESIS OF ASN-199; ASN-373 AND ASN-383.
RX PubMed=17332505; DOI=10.1091/mbc.e06-07-0629;
RA Yu C.Y., Chen J.Y., Lin Y.Y., Shen K.F., Lin W.L., Chien C.L.,
RA ter Beest M.B., Jou T.S.;
RT "A bipartite signal regulates the faithful delivery of apical domain marker
RT podocalyxin/Gp135.";
RL Mol. Biol. Cell 18:1710-1722(2007).
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 {ECO:0000269|PubMed:15642748, ECO:0000269|PubMed:15814834}.
CC -!- SUBUNIT: Found in a complex with EZR, PODXL and SLC9A3R2. Associates
CC with the actin cytoskeleton through complex formation with EZR and
CC SLC9A3R2. Interacts (via the C-terminal PDZ-binding motif DTHL) with
CC SLC9A3R1 (via the PDZ domains); interaction is not detected in
CC glomerular epithelium cells. Interacts (via the C-terminal PDZ-binding
CC motif DTHL) with SLC9A3R2 (via the PDZ 1 domain); interaction is
CC detected in glomerular epithelium cells. Interacts with EZR (By
CC similarity). Monomer; when associated with the membrane raft. Oligomer;
CC when integrated in the apical membrane. Interacts with SLC9A3R2.
CC Interacts (via the C-terminal PDZ-binding motif DTHL) with SLC9A3R1
CC (via the PDZ domains); the interaction take place early in the
CC secretory pathway and is necessary for its apical membrane sorting.
CC {ECO:0000250, ECO:0000269|PubMed:15642748,
CC ECO:0000269|PubMed:17332505}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane. Membrane raft. Cell
CC projection, lamellipodium {ECO:0000250}. Cell projection, filopodium
CC {ECO:0000250}. Cell projection, ruffle {ECO:0000250}. Cell projection,
CC microvillus {ECO:0000250}. Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Note=Forms granular, punctuated
CC pattern, forming patches, preferentially adopting a polar distribution,
CC located on the migrating poles of the cell or forming clusters along
CC the terminal ends of filipodia establishing contact with the
CC endothelial cells. Colocalizes with the submembrane actin of
CC lamellipodia, particularly associated with ruffles. Colocalizes with
CC vinculin at protrusions of cells. Colocalizes with ITGB1. Colocalizes
CC with actin filaments, ezrin and SLC9A3R1 in a punctate pattern at the
CC apical cell surface where microvilli form. Colocalizes with EZR and
CC SLC9A3R2 at the apical cell membrane of glomerular epithelium cells (By
CC similarity). In single attached epithelial cells is restricted to a
CC preapical pole on the free plasma membrane whereas other apical and
CC basolateral proteins are not yet polarized. Colocalizes with SLC9A3R2
CC 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. Colocalizes with PARD3, PRKCI, EXOC5, OCLN, RAB11A and
CC RAB8A in apical membrane initiation sites (AMIS) during the generation
CC of apical surface and luminogenesis (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in glomerular and tubular epithelial
CC cells and peritubular capillaries of the kidney (at protein level).
CC Expressed in heart, lung, renal cortex and medulla, kidney and muscle.
CC {ECO:0000269|PubMed:15814834}.
CC -!- DOMAIN: The large highly anionic extracellular domain allows to
CC maintain open filtration pathways between neighboring podocyte foot
CC processes. The cytoplasmic C-terminus PDZ-binding motif (DTHL) is
CC essential for interaction with SLC9A3R1 and for targeting SLC9A3R1 to
CC the apical cell membrane. The extracellular domain is necessary for
CC microvillus formation (By similarity). Both the O-glycan-rich domain of
CC the extracellular domain and the C-terminus PDZ-binding motif (DTHL) in
CC the cytoplasmic tail harbor an apical sorting signal. The cytoplasmic
CC domain is necessary for the apical membrane targeting and renal
CC tubulogenesis. {ECO:0000250}.
CC -!- PTM: N- and O-linked glycosylated. Sialoglycoprotein.
CC {ECO:0000269|PubMed:15814834, ECO:0000269|PubMed:17332505}.
CC -!- SIMILARITY: Belongs to the podocalyxin family. {ECO:0000305}.
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DR EMBL; AY970669; AAX93749.1; -; mRNA.
DR RefSeq; NP_001018645.1; NM_001020809.1.
DR AlphaFoldDB; Q52S86; -.
DR STRING; 9612.ENSCAFP00000041563; -.
DR iPTMnet; Q52S86; -.
DR PaxDb; Q52S86; -.
DR Ensembl; ENSCAFT00000002169; ENSCAFP00000002008; ENSCAFG00000001403.
DR GeneID; 482252; -.
DR KEGG; cfa:482252; -.
DR CTD; 5420; -.
DR VGNC; VGNC:54792; PODXL.
DR eggNOG; ENOG502S2JU; Eukaryota.
DR InParanoid; Q52S86; -.
DR OrthoDB; 1404598at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA: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; IDA: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; Direct protein sequencing;
KW Glycoprotein; Membrane; Phosphoprotein; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..571
FT /note="Podocalyxin"
FT /id="PRO_5000095844"
FT TOPO_DOM 23..474
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 475..495
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 496..571
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 94..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 94..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 531
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0M4"
FT MOD_RES 550
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00592"
FT MOD_RES 569
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O00592"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15814834,
FT ECO:0000269|PubMed:17332505"
FT CARBOHYD 373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15814834,
FT ECO:0000269|PubMed:17332505"
FT CARBOHYD 383
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15814834,
FT ECO:0000269|PubMed:17332505"
FT MUTAGEN 123
FT /note="N->Q: Does not reduce N-glycosylation."
FT /evidence="ECO:0000269|PubMed:15814834"
FT MUTAGEN 199
FT /note="N->Q: Reduces N-glycosylation but not apical
FT targeting. Reduces strongly N-glycosylation but not apical
FT targeting; when associated with Q-373 and Q-383."
FT /evidence="ECO:0000269|PubMed:15814834,
FT ECO:0000269|PubMed:17332505"
FT MUTAGEN 373
FT /note="N->Q: Reduces N-glycosylation but not apical
FT targeting. Reduces strongly N-glycosylation but not apical
FT targeting; when associated with Q-199 and Q-383."
FT /evidence="ECO:0000269|PubMed:15814834,
FT ECO:0000269|PubMed:17332505"
FT MUTAGEN 383
FT /note="N->Q: Reduces N-glycosylation but not apical
FT targeting. Reduces strongly N-glycosylation but not apical
FT targeting; when associated with Q-199 and Q-373."
FT /evidence="ECO:0000269|PubMed:15814834,
FT ECO:0000269|PubMed:17332505"
SQ SEQUENCE 571 AA; 59906 MW; EA23F38263093539 CRC64;
MRPAPPPPLL LLLLLLPPPS LSHDGTIIAA TSPTSGQPST ELPGGKGLIT TAKTIQNTDL
AITGEKVMSA TVSKGPLPGS SNSVSMTLAP TQKNTVIAPD QDEKVSTNPT IATSDSKGIP
DLNKSILPSA TNSMKPDTPV TQTAGPGAQG NPGTTVSHMT SENTEQTTSQ PPPQVKPSSI
TPALTSIITP TSPRQPSANS TTLKPPESSS ESPDKSHTAS SSLGTKVVPS SSLYGTSPTR
TSSVTFWGGP QSSSGTPPVP APTPRPAATS SSTPGISSVP GTTSLPSETE SLESPSSESP
SQPPKLRPTG PPSSGSSGPA ASLPDEGPRS SSTQRAATAP RAPSVPSPTS AQGDDRIKCE
SPGRLTDKML LLNLTRSGLC AGNNSDDKLI TLLCRAAKAT FNPAQDQCHI RLVPIQDTQA
VAIKEITVQT NLLPRDVYEL LKDKWDELKE VGVSNMKLGD QGPPEETEDR FSMPLIITIV
CMASFLLLVA ALYGCCHQRL SQRKDQQRLT EELQTVENGY HDNPTLEVME TSSEMQEKKV
VNLNGELGDS WIVPLDNLAK DDLDEEEDTH L
