O00592 (PODXL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Podocalyxin

Alternative name(s):
GCTM-2 antigen
Gp200
Podocalyxin-like protein 1
Short name=PC
Short name=PCLP-1

Gene names

Name:	PODXL
Synonyms:	PCLP, PCLP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	558 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the regulation of both adhesion and cell morphology and cancer progression. Function as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell-cell contacts in an integrin-dependent manner. Induces the formation of apical actin-dependent microvilli. Involved in the formation of a preapical plasma membrane subdomain to set up inital epithelial polarization and the apical lumen formation during renal tubulogenesis. Plays a role in cancer development and aggressiveness by inducing cell migration and invasion through its interaction with the actin-binding protein EZR. Affects EZR-dependent signaling events, leading to increased activities of the MAPK and PI3K pathways in cancer cells. Ref.9 Ref.10
Subunit structure	Monomer; when associated with the membrane raft. Oligomer; when integrated in the apical membrane. Interacts (via the C-terminal PDZ-binding motif DTHL) with SLC9A3R1 (via the PDZ domains); the interaction is not detected in glomerular epithelium cells, take place early in the secretory pathway and is necessary for its apical membrane sorting. Found in a complex with EZR, PODXL and SLC9A3R2. Associates with the actin cytoskeleton through complex formation with EZR and SLC9A3R2. Interacts (via the C-terminal PDZ-binding motif DTHL) with SLC9A3R2 (via the PDZ 1 domain); interaction is detected in glomerular epithelium cells By similarity. Interacts with EZR. Ref.9
Subcellular location	Apical cell membrane. Cell projection › lamellipodium. Cell projection › filopodium. Cell projection › ruffle. Cell projection › microvillus By similarity. Membrane raft By similarity. Membrane; Single-pass type I membrane protein Potential. Note: In single attached epithelial cells is restricted to a preapical pole on the free plasma membrane whereas other apical and basolateral proteins are not yet polarized. Colocalizes with SLC9A3R2 at the apical plasma membrane during epithelial polarization. Colocalizes with SLC9A3R1 at the trans-Golgi network (transiently) and at the apical plasma membrane. Its association with the membrane raft is transient. Colocalizes with actin filaments, EZR and SLC9A3R1 in a punctate pattern at the apical cell surface where microvilli form. Colocalizes with EZR and SLC9A3R2 at the apical cell membrane of glomerular epithelium cells By similarity. Forms granular, punctuated pattern, forming patches, preferentially adopting a polar distribution, located on the migrating poles of the cell or forming clusters along the terminal ends of filipodia establishing contact with the endothelial cells. Colocalizes with the submembrane actin of lamellipodia, particularly associated with ruffles. Colocalizes with vinculin at protrusions of cells. Colocalizes with ITGB1. Colocalizes with PARD3, PRKCI, EXOC5, OCLN, RAB11A and RAB8A in apical membrane initiation sites (AMIS) during the generation of apical surface and luminogenesis By similarity. Ref.9 Ref.10
Tissue specificity	Glomerular epithelium cell (podocyte).
Domain	Both the O-glycan-rich domain of the extracellular domain and the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal. The cytoplasmic domain is necessary for the apical membrane targeting and renal tubulogenesis. The cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with SLC9A3R1 and for targeting SLC9A3R1 to the apical cell membrane. The extracellular domain is necessary for microvillus formation By similarity. The large highly anionic extracellular domain allows to maintain open filtration pathways between neighboring podocyte foot processes.
Post-translational modification	N- and O-linked glycosylated. Sialoglycoprotein By similarity.
Sequence similarities	Belongs to the podocalyxin family.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Cell projection Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW epithelial tube formation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell migration Inferred from direct assay Ref.10. Source: UniProtKB positive regulation of cell-cell adhesion mediated by integrin Inferred from direct assay Ref.10. Source: UniProtKB regulation of microvillus assembly Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	actin cytoskeleton Inferred from direct assay. Source: HPA apical plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB centrosome Inferred from direct assay. Source: HPA filopodium Inferred from direct assay Ref.10. Source: UniProtKB integral to plasma membrane Traceable author statement. Source: ProtInc lamellipodium Inferred from direct assay Ref.10. Source: UniProtKB membrane raft Inferred from electronic annotation. Source: UniProtKB-SubCell microvillus membrane Inferred from sequence or structural similarity. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA ruffle Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00592-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O00592-2)

The sequence of this isoform differs from the canonical sequence as follows:
     236-268: LETVFHHVSQAGLELLTSGDLPTLASQSAGITA → P

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 558	536	Podocalyxin		PRO_0000024754
Regions
	Topological domain	23 – 461	439	Extracellular Potential
	Transmembrane	462 – 482	21	Helical; Potential
	Topological domain	483 – 558	76	Cytoplasmic Potential
	Compositional bias	35 – 334	300	Thr-rich
Amino acid modifications
	Glycosylation	33	1	N-linked (GlcNAc...) Potential
	Glycosylation	43	1	N-linked (GlcNAc...) Potential
	Glycosylation	104	1	N-linked (GlcNAc...) Potential
	Glycosylation	144	1	N-linked (GlcNAc...) Potential
	Glycosylation	360	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	236 – 268	33	LETVF…AGITA → P in isoform 2.		VSP_037220
	Natural variant	60	1	T → R.		VAR_012236
	Natural variant	112	1	G → S. Corresponds to variant rs3735035 [ dbSNP | Ensembl ].		VAR_055237
	Natural variant	126	1	T → P. Corresponds to variant rs55698400 [ dbSNP | Ensembl ].		VAR_062136
	Natural variant	194	1	S → L. Ref.1 Corresponds to variant rs12670788 [ dbSNP | Ensembl ].		VAR_012237
	Natural variant	298	1	P → A. Corresponds to variant rs35893129 [ dbSNP | Ensembl ].		VAR_060090
	Natural variant	358	1	V → I. Ref.2 Corresponds to variant rs3212298 [ dbSNP | Ensembl ].		VAR_055238
Experimental info
	Sequence conflict	31	1	S → SPS in AAB61574. Ref.1
	Sequence conflict	404	1	G → Q AA sequence Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 8B1CF30D14D51691	FASTA	558	58,635
	10 20 30 40 50 60 MRCALALSAL LLLLSTPPLL PSSPSPSPSP SQNATQTTTD SSNKTAPTPA SSVTIMATDT 70 80 90 100 110 120 AQQSTVPTSK ANEILASVKA TTLGVSSDSP GTTTLAQQVS GPVNTTVARG GGSGNPTTTI 130 140 150 160 170 180 ESPKSTKSAD TTTVATSTAT AKPNTTSSQN GAEDTTNSGG KSSHSVTTDL TSTKAEHLTT 190 200 210 220 230 240 PHPTSPLSPR QPTSTHPVAT PTSSGHDHLM KISSSSSTVA IPGYTFTSPG MTTTLLETVF 250 260 270 280 290 300 HHVSQAGLEL LTSGDLPTLA SQSAGITASS VISQRTQQTS SQMPASSTAP SSQETVQPTS 310 320 330 340 350 360 PATALRTPTL PETMSSSPTA ASTTHRYPKT PSPTVAHESN WAKCEDLETQ TQSEKQLVLN 370 380 390 400 410 420 LTGNTLCAGG ASDEKLISLI CRAVKATFNP AQDKCGIRLA SVPGSQTVVV KEITIHTKLP 430 440 450 460 470 480 AKDVYERLKD KWDELKEAGV SDMKLGDQGP PEEAEDRFSM PLIITIVCMA SFLLLVAALY 490 500 510 520 530 540 GCCHQRLSQR KDQQRLTEEL QTVENGYHDN PTLEVMETSS EMQEKKVVSL NGELGDSWIV 550 PLDNLTKDDL DEEEDTHL
	Isoform 2 [UniParc]. Checksum: 3F14C259BDB3AC76	FASTA	526	55,386
	10 20 30 40 50 60 MRCALALSAL LLLLSTPPLL PSSPSPSPSP SQNATQTTTD SSNKTAPTPA SSVTIMATDT 70 80 90 100 110 120 AQQSTVPTSK ANEILASVKA TTLGVSSDSP GTTTLAQQVS GPVNTTVARG GGSGNPTTTI 130 140 150 160 170 180 ESPKSTKSAD TTTVATSTAT AKPNTTSSQN GAEDTTNSGG KSSHSVTTDL TSTKAEHLTT 190 200 210 220 230 240 PHPTSPLSPR QPTSTHPVAT PTSSGHDHLM KISSSSSTVA IPGYTFTSPG MTTTLPSSVI 250 260 270 280 290 300 SQRTQQTSSQ MPASSTAPSS QETVQPTSPA TALRTPTLPE TMSSSPTAAS TTHRYPKTPS 310 320 330 340 350 360 PTVAHESNWA KCEDLETQTQ SEKQLVLNLT GNTLCAGGAS DEKLISLICR AVKATFNPAQ 370 380 390 400 410 420 DKCGIRLASV PGSQTVVVKE ITIHTKLPAK DVYERLKDKW DELKEAGVSD MKLGDQGPPE 430 440 450 460 470 480 EAEDRFSMPL IITIVCMASF LLLVAALYGC CHQRLSQRKD QQRLTEELQT VENGYHDNPT 490 500 510 520 LEVMETSSEM QEKKVVSLNG ELGDSWIVPL DNLTKDDLDE EEDTHL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of human podocalyxin-like protein. Orthologous relationship to rabbit PCLP1 and rat podocalyxin." Kershaw D.B., Beck S.G., Wharram B.L., Wiggins J.E., Goyal M., Thomas P.E., Wiggins R.C. J. Biol. Chem. 272:15708-15714(1997) [PubMed: 9188463] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LEU-194.
[2]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ILE-358. Tissue: Heart.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Liver.
[7]	Suzuki Y., Yamashita R., Shirota M., Sakakibara Y., Chiba J., Nakai K., Sugano S. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 120-310 (ISOFORM 1).
[8]	"Human embryonal carcinoma tumor antigen, Gp200/GCTM-2, is podocalyxin." Schopperle W.M., Kershaw D.B., DeWolf W.C. Biochem. Biophys. Res. Commun. 300:285-290(2003) [PubMed: 12504081] [Abstract] Cited for: PROTEIN SEQUENCE OF 399-411 AND 445-372.
[9]	"Podocalyxin increases the aggressive phenotype of breast and prostate cancer cells in vitro through its interaction with ezrin." Sizemore S., Cicek M., Sizemore N., Ng K.P., Casey G. Cancer Res. 67:6183-6191(2007) [PubMed: 17616675] [Abstract] Cited for: FUNCTION, INTERACTION WITH EZR, SUBCELLULAR LOCATION.
[10]	"Expression of podocalyxin enhances the adherence, migration, and intercellular communication of cells." Larrucea S., Butta N., Arias-Salgado E.G., Alonso-Martin S., Ayuso M.S., Parrilla R. Exp. Cell Res. 314:2004-2015(2008) [PubMed: 18456258] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U97519 mRNA. Translation: AAB61574.1. AK223573 mRNA. Translation: BAD97293.1. AC008264 Genomic DNA. No translation available. CH236950 Genomic DNA. Translation: EAL24080.1. CH471070 Genomic DNA. Translation: EAW83786.1. BC093730 mRNA. Translation: AAH93730.1. BC112035 mRNA. Translation: AAI12036.1. BP234810 mRNA. No translation available.
IPI	IPI00299116. IPI01018674.
RefSeq	NP_001018121.1. NM_001018111.2. NP_005388.2. NM_005397.3.
UniGene	Hs.719018.
3D structure databases
ProteinModelPortal	O00592.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-58638N.
STRING	O00592.
PTM databases
PhosphoSite	O00592.
Proteomic databases
PRIDE	O00592.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378555; ENSP00000367817; ENSG00000128567.
GeneID	5420.
KEGG	hsa:5420.
Organism-specific databases
CTD	5420.
GeneCards	GC07M131185.
HGNC	HGNC:9171. PODXL.
HPA	CAB016169. HPA002110.
MIM	602632. gene.
neXtProt	NX_O00592.
PharmGKB	PA33493.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG08682.
GeneTree	ENSGT00570000079197.
HOVERGEN	HBG053629.
OMA	EITIHTK.
OrthoDB	EOG46WZ89.
Gene expression databases
ArrayExpress	O00592.
Bgee	O00592.
CleanEx	HS_PODXL.
Genevestigator	O00592.
GermOnline	ENSG00000128567. Homo sapiens.
Family and domain databases
InterPro	IPR013836. CD34/Podocalyxin. IPR017403. Podocalyxin-like_p1. [Graphical view]
KO	K06817.
Pfam	PF06365. CD34_antigen. 1 hit. [Graphical view]
PIRSF	PIRSF038143. Podocalyxin-like_p1. 1 hit.
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

PODXL_HUMAN

Accession

Primary (citable) accession number: O00592
Secondary accession number(s): A6NHX8, Q52LZ7, Q53ER6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2001
Last sequence update:	May 5, 2009
Last modified:	January 25, 2012
This is version 84 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.