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   27-MAR-2024, entry version 153.
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), PROTEIN SEQUENCE OF 33-38, TISSUE
RP   SPECIFICITY, AND 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 AT SER-79, SIALIC ACID CONTENT, AND MUTAGENESIS OF TYR-97;
RP   TYR-118 AND 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: O-glycosylated; contains chondroitin sulfate. Displays sialylated
CC       O-linked oligosaccharides. {ECO:0000269|PubMed:10722749,
CC       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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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; 59.
DR   IntAct; Q9NZ53; 17.
DR   STRING; 9606.ENSP00000345359; -.
DR   GlyConnect; 687; 1 O-Linked glycan (1 site).
DR   GlyCosmos; Q9NZ53; 6 sites, 3 glycans.
DR   GlyGen; Q9NZ53; 16 sites, 4 O-linked glycans (12 sites).
DR   iPTMnet; Q9NZ53; -.
DR   PhosphoSitePlus; Q9NZ53; -.
DR   SwissPalm; Q9NZ53; -.
DR   BioMuta; PODXL2; -.
DR   DMDM; 74734719; -.
DR   EPD; Q9NZ53; -.
DR   jPOST; Q9NZ53; -.
DR   MassIVE; Q9NZ53; -.
DR   MaxQB; Q9NZ53; -.
DR   PaxDb; 9606-ENSP00000345359; -.
DR   PeptideAtlas; Q9NZ53; -.
DR   ProteomicsDB; 83326; -. [Q9NZ53-1]
DR   ProteomicsDB; 83327; -. [Q9NZ53-2]
DR   Pumba; Q9NZ53; -.
DR   Antibodypedia; 46650; 300 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   AGR; HGNC:17936; -.
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; WHMPPEE; -.
DR   OrthoDB; 5354759at2759; -.
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 1159 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 99 other cell types or tissues.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0005886; C: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; PODOCALYXIN-LIKE PROTEIN 2; 1.
DR   PANTHER; PTHR15594:SF1; PODOCALYXIN-LIKE PROTEIN 2; 1.
DR   Pfam; PF06365; CD34_antigen; 1.
DR   Genevisible; Q9NZ53; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell adhesion; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Membrane; Phosphoprotein; Proteoglycan;
KW   Reference proteome; Sialic acid; Signal; Sulfation; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000269|PubMed:10722749"
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        79
FT                   /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT                   /evidence="ECO:0000269|PubMed:12889478"
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: Reduced sialylation."
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
//