PODXL_MOUSE
ID PODXL_MOUSE Reviewed; 503 AA.
AC Q9R0M4; Q9ESZ1;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2001, sequence version 2.
DT 03-AUG-2022, entry version 139.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10591182; DOI=10.1016/s1074-7613(00)80132-6;
RA Hara T., Nakano Y., Tanaka M., Tamura K., Sekiguchi T., Minehata K.,
RA Copeland N.G., Jenkins N.A., Okabe M., Kogo H., Mukouyama Y., Miyajima A.;
RT "Identification of podocalyxin-like protein 1 as a novel cell surface
RT marker for hemangioblasts in the murine aorta-gonad-mesonephros region.";
RL Immunity 11:567-578(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kershaw D.B., Li J.;
RT "Gene structure of mouse podocalyxin.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=11435469; DOI=10.1084/jem.194.1.13;
RA Doyonnas R., Kershaw D.B., Duhme C., Merkens H., Chelliah S., Graf T.,
RA McNagny K.M.;
RT "Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-
RT related protein podocalyxin.";
RL J. Exp. Med. 194:13-27(2001).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17311105; DOI=10.1371/journal.pone.0000237;
RA Nielsen J.S., Graves M.L., Chelliah S., Vogl A.W., Roskelley C.D.,
RA McNagny K.M.;
RT "The CD34-related molecule podocalyxin is a potent inducer of microvillus
RT formation.";
RL PLoS ONE 2:E237-E237(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-463, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(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 {ECO:0000269|PubMed:11435469, ECO:0000269|PubMed:17311105}.
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 -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:17311105}. Cell projection, microvillus
CC {ECO:0000269|PubMed:17311105}. Membrane raft {ECO:0000250}. Cell
CC projection, lamellipodium {ECO:0000250}. Cell projection, filopodium
CC {ECO:0000250}. Cell projection, ruffle {ECO:0000250}. Membrane
CC {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}.
CC Note=In single attached epithelial cells is restricted to a preapical
CC pole on the free plasma membrane whereas other apical and basolateral
CC proteins are not yet polarized. Colocalizes with SLC9A3R2 at the apical
CC plasma membrane during epithelial polarization. Colocalizes with
CC SLC9A3R1 at the trans-Golgi network (transiently) and at the apical
CC plasma membrane. Its association with the membrane raft is transient.
CC Forms granular, punctuated pattern, forming patches, preferentially
CC adopting a polar distribution, located on the migrating poles of the
CC cell or forming clusters along the terminal ends of filipodia
CC establishing contact with the endothelial cells. Colocalizes with the
CC submembrane actin of lamellipodia, particularly associated with
CC ruffles. Colocalizes with vinculin at protrusions of cells. Colocalizes
CC with ITGB1. Colocalizes with EZR and SLC9A3R2 at the apical cell
CC membrane of glomerular epithelium cells (By similarity). Colocalizes
CC with actin filaments, EZR and SLC9A3R1 in a punctate pattern at the
CC apical cell surface where microvilli form. 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 (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in liver cells and hematopoietic cells
CC (at protein level). Glomerular epithelium cell (podocyte).
CC {ECO:0000269|PubMed:11435469}.
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 -!- DISRUPTION PHENOTYPE: Die within the first 24 h of postnatal life from
CC profound defects in kidney and/or gut formation. They are anuric (no
CC measurable urine in the bladder), and fail to generate the extensive
CC interdigitated foot process and instead retain cell junctions between
CC immature podocytes. {ECO:0000269|PubMed:11435469}.
CC -!- SIMILARITY: Belongs to the podocalyxin family. {ECO:0000305}.
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DR EMBL; AB028048; BAA86912.1; -; mRNA.
DR EMBL; AF290209; AAG02458.1; -; mRNA.
DR EMBL; BC052442; AAH52442.1; -; mRNA.
DR EMBL; BC054530; AAH54530.1; -; mRNA.
DR CCDS; CCDS19983.1; -.
DR RefSeq; NP_038751.2; NM_013723.3.
DR AlphaFoldDB; Q9R0M4; -.
DR STRING; 10090.ENSMUSP00000026698; -.
DR GlyGen; Q9R0M4; 8 sites.
DR iPTMnet; Q9R0M4; -.
DR PhosphoSitePlus; Q9R0M4; -.
DR SwissPalm; Q9R0M4; -.
DR jPOST; Q9R0M4; -.
DR MaxQB; Q9R0M4; -.
DR PaxDb; Q9R0M4; -.
DR PRIDE; Q9R0M4; -.
DR ProteomicsDB; 291765; -.
DR Antibodypedia; 971; 1211 antibodies from 45 providers.
DR DNASU; 27205; -.
DR Ensembl; ENSMUST00000026698; ENSMUSP00000026698; ENSMUSG00000025608.
DR GeneID; 27205; -.
DR KEGG; mmu:27205; -.
DR UCSC; uc009bgh.2; mouse.
DR CTD; 5420; -.
DR MGI; MGI:1351317; Podxl.
DR VEuPathDB; HostDB:ENSMUSG00000025608; -.
DR eggNOG; ENOG502S2JU; Eukaryota.
DR GeneTree; ENSGT00730000111314; -.
DR HOGENOM; CLU_032485_0_0_1; -.
DR InParanoid; Q9R0M4; -.
DR OMA; NWTKCEA; -.
DR OrthoDB; 1404598at2759; -.
DR PhylomeDB; Q9R0M4; -.
DR TreeFam; TF333564; -.
DR BioGRID-ORCS; 27205; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Podxl; mouse.
DR PRO; PR:Q9R0M4; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9R0M4; protein.
DR Bgee; ENSMUSG00000025608; Expressed in renal corpuscle and 281 other tissues.
DR ExpressionAtlas; Q9R0M4; baseline and differential.
DR Genevisible; Q9R0M4; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0044297; C:cell body; ISO:MGI.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
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; IMP:UniProtKB.
DR GO; GO:0072175; P:epithelial tube formation; ISS:UniProtKB.
DR GO; GO:0050900; P:leukocyte migration; IMP:MGI.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IMP: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; IDA: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..503
FT /note="Podocalyxin"
FT /id="PRO_0000024755"
FT TOPO_DOM 22..404
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 405..425
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 426..503
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 19..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 463
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 482
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00592"
FT MOD_RES 501
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O00592"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 78
FT /note="S -> F"
SQ SEQUENCE 503 AA; 53389 MW; 786A1ECF65484D1F CRC64;
MPPTTALSAL LLLLLSPASH SHNGNETSTS AIKSSTVQSH QSATTSTEVT TGHPVASTLA
STQPSNPTPF TTSTQSPSMP TSTPNPTSNQ SGGNLTSSVS EVDKTKTSSP SSTAFTSSSG
QTASSGGKSG DSFTTAPTTT LGLINVSSQP TDLNTTSKLL STPTTDNTTS PQQPVDSSPS
TASHPVGQHT PAAVPSSSGS TPSTDNSTLT WKPTTHKPLG TSEATQPLTS QTPGITTLPV
STLQQSMAST VGTTTEEFTH LISNGTPVAP PGPSTPSPIW AFGNYQLNCE PPIRPDEELL
ILNLTRASLC ERSPLDEKEK LVELLCHSVK ASFKPAEDLC TLHVAPILDN QAVAVKRIII
ETKLSPKAVY ELLKDRWDDL TEAGVSDMKL GKEGPPEVNE DRFSLPLIIT IVCMASFLLL
VAALYGCCHQ RISQRKDQQR LTEELQTVEN GYHDNPTLEV METPSEMQEK KVVNLNGELG
DSWIVPLDNL TKDDLDEEED THL
