PDXL2_HUMAN
ID PDXL2_HUMAN Reviewed; 605 AA.
AC Q9NZ53; Q6UVY4; Q8WUV6;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Podocalyxin-like protein 2;
DE AltName: Full=Endoglycan;
DE Flags: Precursor;
GN Name=PODXL2; ORFNames=UNQ1861/PRO3742;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP GLYCOSYLATION.
RC TISSUE=Brain;
RX PubMed=10722749; DOI=10.1074/jbc.275.12.9001;
RA Sassetti C., Van Zante A., Rosen S.D.;
RT "Identification of endoglycan, a member of the CD34/podocalyxin family of
RT sialomucins.";
RL J. Biol. Chem. 275:9001-9010(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Melanoma, and Neuroblastoma;
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 INTERACTION WITH SELL, SUBUNIT, SULFATION AT TYR-97 AND TYR-118,
RP GLYCOSYLATION, SIALIC ACID CONTENT, AND MUTAGENESIS OF TYR-97; TYR-118 AND
RP THR-124.
RX PubMed=12889478; DOI=10.1074/jbc.m304204200;
RA Fieger C.B., Sassetti C.M., Rosen S.D.;
RT "Endoglycan, a member of the CD34 family, functions as an L-selectin ligand
RT through modification with tyrosine sulfation and sialyl Lewis x.";
RL J. Biol. Chem. 278:27390-27398(2003).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-596, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [6]
RP FUNCTION, INTERACTION WITH SELL; SELE AND SELP, GLYCOSYLATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=18606703; DOI=10.4049/jimmunol.181.2.1480;
RA Kerr S.C., Fieger C.B., Snapp K.R., Rosen S.D.;
RT "Endoglycan, a member of the CD34 family of sialomucins, is a ligand for
RT the vascular selectins.";
RL J. Immunol. 181:1480-1490(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-596, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570 AND SER-596, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-596, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP GLYCOSYLATION AT SER-144, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23234360; DOI=10.1021/pr300963h;
RA Halim A., Ruetschi U., Larson G., Nilsson J.;
RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT of human cerebrospinal fluid glycoproteins.";
RL J. Proteome Res. 12:573-584(2013).
CC -!- FUNCTION: Acts as a ligand for vascular selectins. Mediates rapid
CC rolling of leukocytes over vascular surfaces through high affinity
CC divalent cation-dependent interactions with E-, P- and L-selectins.
CC {ECO:0000269|PubMed:18606703}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with SELL, SELE and
CC SELP. {ECO:0000269|PubMed:12889478, ECO:0000269|PubMed:18606703}.
CC -!- INTERACTION:
CC Q9NZ53-2; Q92876: KLK6; NbExp=3; IntAct=EBI-25887738, EBI-2432309;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NZ53-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NZ53-2; Sequence=VSP_020876;
CC -!- TISSUE SPECIFICITY: Expressed in T-cells, B-cells and monocytes.
CC Expression is higher on memory and germinal center cells than on naive
CC B-cells (at protein level). Highly expressed in brain. Moderately
CC expressed in pancreas, kidney and lymphoid node. Weakly expressed in
CC liver. Detected in both endothelial cells and CD34+ bone marrow cells.
CC {ECO:0000269|PubMed:10722749, ECO:0000269|PubMed:18606703}.
CC -!- PTM: Glycosylated; contains chondroitin sulfate. Displays sialylated O-
CC linked oligosaccharides. {ECO:0000269|PubMed:12889478}.
CC -!- PTM: Sulfation is necessary for interaction with SELL. Sialylated O-
CC linked oligosaccharides are necessary for interaction with SELL, SELE
CC and SELP. {ECO:0000269|PubMed:12889478}.
CC -!- SIMILARITY: Belongs to the podocalyxin family. {ECO:0000305}.
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DR EMBL; AF219137; AAF44629.1; -; mRNA.
DR EMBL; AY359096; AAQ89454.1; -; mRNA.
DR EMBL; BC019330; AAH19330.1; -; mRNA.
DR EMBL; BC052585; AAH52585.1; -; mRNA.
DR CCDS; CCDS3044.1; -. [Q9NZ53-1]
DR RefSeq; NP_056535.1; NM_015720.3. [Q9NZ53-1]
DR AlphaFoldDB; Q9NZ53; -.
DR SMR; Q9NZ53; -.
DR BioGRID; 119082; 55.
DR IntAct; Q9NZ53; 15.
DR STRING; 9606.ENSP00000345359; -.
DR GlyConnect; 687; 1 O-Linked glycan (1 site).
DR GlyGen; Q9NZ53; 7 sites, 3 O-linked glycans (4 sites).
DR iPTMnet; Q9NZ53; -.
DR PhosphoSitePlus; Q9NZ53; -.
DR BioMuta; PODXL2; -.
DR DMDM; 74734719; -.
DR EPD; Q9NZ53; -.
DR jPOST; Q9NZ53; -.
DR MassIVE; Q9NZ53; -.
DR MaxQB; Q9NZ53; -.
DR PaxDb; Q9NZ53; -.
DR PeptideAtlas; Q9NZ53; -.
DR PRIDE; Q9NZ53; -.
DR ProteomicsDB; 83326; -. [Q9NZ53-1]
DR ProteomicsDB; 83327; -. [Q9NZ53-2]
DR Antibodypedia; 46650; 259 antibodies from 30 providers.
DR DNASU; 50512; -.
DR Ensembl; ENST00000342480.7; ENSP00000345359.6; ENSG00000114631.11. [Q9NZ53-1]
DR GeneID; 50512; -.
DR KEGG; hsa:50512; -.
DR MANE-Select; ENST00000342480.7; ENSP00000345359.6; NM_015720.4; NP_056535.1.
DR UCSC; uc003ejq.4; human. [Q9NZ53-1]
DR CTD; 50512; -.
DR GeneCards; PODXL2; -.
DR HGNC; HGNC:17936; PODXL2.
DR HPA; ENSG00000114631; Tissue enhanced (brain, pituitary gland).
DR MIM; 616627; gene.
DR neXtProt; NX_Q9NZ53; -.
DR OpenTargets; ENSG00000114631; -.
DR PharmGKB; PA134860950; -.
DR VEuPathDB; HostDB:ENSG00000114631; -.
DR eggNOG; ENOG502QTNA; Eukaryota.
DR GeneTree; ENSGT00730000111323; -.
DR HOGENOM; CLU_039299_0_0_1; -.
DR InParanoid; Q9NZ53; -.
DR OMA; DTWAVGG; -.
DR OrthoDB; 1103853at2759; -.
DR PhylomeDB; Q9NZ53; -.
DR TreeFam; TF333564; -.
DR PathwayCommons; Q9NZ53; -.
DR Reactome; R-HSA-156584; Cytosolic sulfonation of small molecules.
DR SignaLink; Q9NZ53; -.
DR BioGRID-ORCS; 50512; 10 hits in 1079 CRISPR screens.
DR ChiTaRS; PODXL2; human.
DR GenomeRNAi; 50512; -.
DR Pharos; Q9NZ53; Tbio.
DR PRO; PR:Q9NZ53; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NZ53; protein.
DR Bgee; ENSG00000114631; Expressed in cortical plate and 97 other tissues.
DR Genevisible; Q9NZ53; HS.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005539; F:glycosaminoglycan binding; TAS:ProtInc.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IDA:UniProtKB.
DR InterPro; IPR013836; CD34/Podocalyxin.
DR InterPro; IPR042397; PODXL2.
DR PANTHER; PTHR15594; PTHR15594; 1.
DR Pfam; PF06365; CD34_antigen; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Disulfide bond; Glycoprotein;
KW Membrane; Phosphoprotein; Reference proteome; Sialic acid; Signal;
KW Sulfation; Transmembrane; Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..605
FT /note="Podocalyxin-like protein 2"
FT /id="PRO_0000252129"
FT TOPO_DOM 33..500
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 501..521
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 522..605
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 129..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 129..134
FT /note="O-glycosylated at one site"
FT REGION 554..605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 162..192
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 200..219
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 230..267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 554..568
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 590..605
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 97
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:12889478"
FT MOD_RES 118
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:12889478"
FT MOD_RES 570
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 596
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT CARBOHYD 144
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 336..411
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020876"
FT VARIANT 456
FT /note="V -> A (in dbSNP:rs34117815)"
FT /id="VAR_053599"
FT MUTAGEN 97
FT /note="Y->F: Remains sulfated. Not sulfated and reduced
FT rolling of Jurkat T-cells by more than 50%; when associated
FT with F-118. The rolling of Jurkat T-cells is reduced by
FT more than 80%; when associated with F-118 and A-124."
FT /evidence="ECO:0000269|PubMed:12889478"
FT MUTAGEN 118
FT /note="Y->F: Remains sulfated. Not sulfated and reduced
FT rolling of Jurkat T-cells by more than 50%; when associated
FT with F-97. The rolling of Jurkat T-cells is reduced by more
FT than 80%; when associated with F-97 and A-124."
FT /evidence="ECO:0000269|PubMed:12889478"
FT MUTAGEN 124
FT /note="T->A: Not sialylated O-linked."
FT /evidence="ECO:0000269|PubMed:12889478"
FT CONFLICT 77
FT /note="P -> S (in Ref. 2; AAQ89454)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 605 AA; 65076 MW; 2F9B8DC51F7FC22A CRC64;
MGRLLRAARL PPLLSPLLLL LVGGAFLGAC VAGSDEPGPE GLTSTSLLDL LLPTGLEPLD
SEEPSETMGL GAGLGAPGSG FPSEENEESR ILQPPQYFWE EEEELNDSSL DLGPTADYVF
PDLTEKAGSI EDTSQAQELP NLPSPLPKMN LVEPPWHMPP REEEEEEEEE EEREKEEVEK
QEEEEEEELL PVNGSQEEAK PQVRDFSLTS SSQTPGATKS RHEDSGDQAS SGVEVESSMG
PSLLLPSVTP TTVTPGDQDS TSQEAEATVL PAAGLGVEFE APQEASEEAT AGAAGLSGQH
EEVPALPSFP QTTAPSGAEH PDEDPLGSRT SASSPLAPGD MELTPSSATL GQEDLNQQLL
EGQAAEAQSR IPWDSTQVIC KDWSNLAGKN YIILNMTENI DCEVFRQHRG PQLLALVEEV
LPRHGSGHHG AWHISLSKPS EKEQHLLMTL VGEQGVVPTQ DVLSMLGDIR RSLEEIGIQN
YSTTSSCQAR ASQVRSDYGT LFVVLVVIGA ICIIIIALGL LYNCWQRRLP KLKHVSHGEE
LRFVENGCHD NPTLDVASDS QSEMQEKHPS LNGGGALNGP GSWGALMGGK RDPEDSDVFE
EDTHL
