PLVAP_HUMAN
ID PLVAP_HUMAN Reviewed; 442 AA.
AC Q9BX97; Q86VP0; Q8N8Y0; Q8ND68; Q8TER8; Q9BZD5;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Plasmalemma vesicle-associated protein;
DE AltName: Full=Fenestrated endothelial-linked structure protein;
DE AltName: Full=Plasmalemma vesicle protein 1;
DE Short=PV-1;
GN Name=PLVAP; Synonyms=FELS, PV1;
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], AND TISSUE SPECIFICITY.
RX PubMed=11401446; DOI=10.1006/geno.2000.6489;
RA Stan R.-V., Arden K.C., Palade G.E.;
RT "cDNA and protein sequence, genomic organization, and analysis of cis
RT regulatory elements of mouse and human PLVAP genes.";
RL Genomics 72:304-313(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Mesak F.M., Schoecklmann H., Hallmann R.;
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS;
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 [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=15155804; DOI=10.1091/mbc.e03-08-0593;
RA Stan R.-V., Tkachenko E., Niesman I.R.;
RT "PV1 is a key structural component for the formation of the stomatal and
RT fenestral diaphragms.";
RL Mol. Biol. Cell 15:3615-3630(2004).
RN [7]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=15971170; DOI=10.1002/path.1805;
RA Strickland L.A., Jubb A.M., Hongo J.-A., Zhong F., Burwick J., Fu L.,
RA Frantz G.D., Koeppen H.;
RT "Plasmalemmal vesicle-associated protein (PLVAP) is expressed by tumour
RT endothelium and is upregulated by vascular endothelial growth factor-A
RT (VEGF).";
RL J. Pathol. 206:466-475(2005).
RN [8]
RP INVOLVEMENT IN DIAR10, VARIANT DIAR10 358-ARG--GLY-442 DEL, AND
RP CHARACTERIZATION OF VARIANT DIAR10 358-ARG--GLY-442 DEL.
RX PubMed=26207260; DOI=10.1016/j.jcmgh.2015.05.001;
RA Elkadri A., Thoeni C., Deharvengt S.J., Murchie R., Guo C.,
RA Stavropoulos J.D., Marshall C.R., Wales P., Bandsma R., Cutz E.,
RA Roifman C.M., Chitayat D., Avitzur Y., Stan R.V., Muise A.M.;
RT "Mutations in plasmalemma vesicle associated protein result in sieving
RT protein-losing enteropathy characterized by hypoproteinemia,
RT hypoalbuminemia, and hypertriglyceridemia.";
RL Cell. Mol. Gastroenterol. Hepatol. 1:381-394(2015).
RN [9]
RP INVOLVEMENT IN DIAR10, AND VARIANT DIAR10 330-GLN--GLY-442 DEL.
RX PubMed=29661969; DOI=10.1136/jmedgenet-2018-105262;
RA Broekaert I.J., Becker K., Gottschalk I., Koerber F., Doetsch J.,
RA Thiele H., Altmueller J., Nuernberg P., Huenseler C., Cirak S.;
RT "Mutations in plasmalemma vesicle-associated protein cause severe syndromic
RT protein-losing enteropathy.";
RL J. Med. Genet. 55:637-640(2018).
RN [10]
RP INVOLVEMENT IN DIAR10, AND VARIANT DIAR10 PRO-34.
RX PubMed=29875123; DOI=10.1136/jmedgenet-2018-105299;
RA Kurolap A., Eshach-Adiv O., Gonzaga-Jauregui C., Dolnikov K., Mory A.,
RA Paperna T., Hershkovitz T., Overton J.D., Kaplan M., Glaser F., Zohar Y.,
RA Shuldiner A.R., Berger G., Baris H.N.;
RT "Establishing the role of PLVAP in protein-losing enteropathy: a homozygous
RT missense variant leads to an attenuated phenotype.";
RL J. Med. Genet. 55:779-784(2018).
CC -!- FUNCTION: Endothelial cell-specific membrane protein involved in the
CC formation of the diaphragms that bridge endothelial fenestrae. It is
CC also required for the formation of stomata of caveolae and
CC transendothelial channels. Functions in microvascular permeability,
CC endothelial fenestrae contributing to the passage of water and solutes
CC and regulating transcellular versus paracellular flow in different
CC organs. Plays a specific role in embryonic development.
CC {ECO:0000250|UniProtKB:Q91VC4}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9WV78}.
CC -!- INTERACTION:
CC Q9BX97; A0A1U9X8X8; NbExp=3; IntAct=EBI-2803560, EBI-17234977;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9WV78};
CC Single-pass type II membrane protein {ECO:0000255}. Membrane, caveola
CC {ECO:0000250|UniProtKB:Q9WV78}; Single-pass type II membrane protein
CC {ECO:0000255}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q9WV78}. Note=Membrane-associated protein of
CC caveolae. Found in fenestral and stomatal diaphragms in fenestrated
CC endothelia and transendothelial channels. Also colocalized with CAV1 in
CC perinuclear region. {ECO:0000250|UniProtKB:Q9WV78}.
CC -!- TISSUE SPECIFICITY: Expressed in lung, kidney, heart, aorta, placenta,
CC muscle, pituitary gland, adrenals, mammary gland, bladder, lymph node,
CC bone marrow, trachea, digestive tract, liver and tumor-associated
CC endothelium. {ECO:0000269|PubMed:11401446,
CC ECO:0000269|PubMed:15971170}.
CC -!- INDUCTION: By phorbol myristate acetate (PMA) or VEGF in endothelial
CC cell culture. {ECO:0000269|PubMed:15155804,
CC ECO:0000269|PubMed:15971170}.
CC -!- DISEASE: Diarrhea 10, protein-losing enteropathy type (DIAR10)
CC [MIM:618183]: An autosomal recessive, congenital diarrheal disorder
CC characterized by intractable secretory diarrhea with massive protein
CC loss due to leaky fenestrated capillaries, severe hypoalbuminemia,
CC hypogammaglobulinemia, hypertriglyceridemia, and electrolyte
CC abnormalities. Disease severity is variable and death in infancy may
CC occur in severe cases. Some patients show facial dysmorphic features,
CC and cardiac and renal abnormalities. {ECO:0000269|PubMed:26207260,
CC ECO:0000269|PubMed:29661969, ECO:0000269|PubMed:29875123}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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; AF348827; AAK20040.1; -; mRNA.
DR EMBL; AF326591; AAK11226.1; -; mRNA.
DR EMBL; AK074054; BAB84880.1; -; mRNA.
DR EMBL; AK096030; BAC04681.1; -; mRNA.
DR EMBL; AL834363; CAD39027.2; -; mRNA.
DR EMBL; BC050365; AAH50365.2; -; mRNA.
DR EMBL; BC056414; AAH56414.1; -; mRNA.
DR CCDS; CCDS32952.1; -.
DR RefSeq; NP_112600.1; NM_031310.2.
DR AlphaFoldDB; Q9BX97; -.
DR SMR; Q9BX97; -.
DR BioGRID; 123668; 14.
DR IntAct; Q9BX97; 15.
DR STRING; 9606.ENSP00000252590; -.
DR GlyGen; Q9BX97; 6 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q9BX97; -.
DR PhosphoSitePlus; Q9BX97; -.
DR BioMuta; PLVAP; -.
DR DMDM; 73921753; -.
DR jPOST; Q9BX97; -.
DR MassIVE; Q9BX97; -.
DR PaxDb; Q9BX97; -.
DR PeptideAtlas; Q9BX97; -.
DR PRIDE; Q9BX97; -.
DR ProteomicsDB; 79389; -.
DR Antibodypedia; 973; 212 antibodies from 23 providers.
DR DNASU; 83483; -.
DR Ensembl; ENST00000252590.9; ENSP00000252590.3; ENSG00000130300.9.
DR GeneID; 83483; -.
DR KEGG; hsa:83483; -.
DR MANE-Select; ENST00000252590.9; ENSP00000252590.3; NM_031310.3; NP_112600.1.
DR UCSC; uc002ngk.2; human.
DR CTD; 83483; -.
DR DisGeNET; 83483; -.
DR GeneCards; PLVAP; -.
DR HGNC; HGNC:13635; PLVAP.
DR HPA; ENSG00000130300; Tissue enhanced (thyroid).
DR MalaCards; PLVAP; -.
DR MIM; 607647; gene.
DR MIM; 618183; phenotype.
DR neXtProt; NX_Q9BX97; -.
DR OpenTargets; ENSG00000130300; -.
DR Orphanet; 329242; Congenital chronic diarrhea with protein-losing enteropathy.
DR PharmGKB; PA33424; -.
DR VEuPathDB; HostDB:ENSG00000130300; -.
DR eggNOG; ENOG502S1PR; Eukaryota.
DR GeneTree; ENSGT00390000006166; -.
DR HOGENOM; CLU_049986_0_0_1; -.
DR InParanoid; Q9BX97; -.
DR OMA; HLTCESQ; -.
DR OrthoDB; 1080934at2759; -.
DR PhylomeDB; Q9BX97; -.
DR TreeFam; TF337332; -.
DR PathwayCommons; Q9BX97; -.
DR SignaLink; Q9BX97; -.
DR BioGRID-ORCS; 83483; 19 hits in 1068 CRISPR screens.
DR ChiTaRS; PLVAP; human.
DR GeneWiki; PLVAP; -.
DR GenomeRNAi; 83483; -.
DR Pharos; Q9BX97; Tbio.
DR PRO; PR:Q9BX97; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9BX97; protein.
DR Bgee; ENSG00000130300; Expressed in left lobe of thyroid gland and 158 other tissues.
DR ExpressionAtlas; Q9BX97; baseline and differential.
DR Genevisible; Q9BX97; HS.
DR GO; GO:0005901; C:caveola; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0032502; P:developmental process; ISS:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IDA:UniProtKB.
DR GO; GO:0002693; P:positive regulation of cellular extravasation; IMP:UniProtKB.
DR GO; GO:0043114; P:regulation of vascular permeability; IBA:GO_Central.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.
DR InterPro; IPR009538; PV-1.
DR PANTHER; PTHR21687; PTHR21687; 1.
DR Pfam; PF06637; PV-1; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Coiled coil; Cytoplasm; Disease variant; Glycoprotein;
KW Membrane; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..442
FT /note="Plasmalemma vesicle-associated protein"
FT /id="PRO_0000058462"
FT TOPO_DOM 1..27
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 28..48
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 49..442
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 301..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 57..77
FT /evidence="ECO:0000255"
FT COILED 202..225
FT /evidence="ECO:0000255"
FT COILED 280..387
FT /evidence="ECO:0000255"
FT CARBOHYD 83
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 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 34
FT /note="L -> P (in DIAR10; dbSNP:rs1568378665)"
FT /evidence="ECO:0000269|PubMed:29875123"
FT /id="VAR_081738"
FT VARIANT 330..442
FT /note="Missing (in DIAR10)"
FT /evidence="ECO:0000269|PubMed:29661969"
FT /id="VAR_081739"
FT VARIANT 358..442
FT /note="Missing (in DIAR10; the protein is not expressed in
FT the patient biopsy tissues)"
FT /evidence="ECO:0000269|PubMed:26207260"
FT /id="VAR_081740"
FT CONFLICT 130
FT /note="Q -> H (in Ref. 2; AAK11226)"
FT /evidence="ECO:0000305"
FT CONFLICT 328..332
FT /note="Missing (in Ref. 3; BAC04681)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="P -> L (in Ref. 3; BAC04681)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 442 AA; 50594 MW; D89ADBC9309A46FA CRC64;
MGLAMEHGGS YARAGGSSRG CWYYLRYFFL FVSLIQFLII LGLVLFMVYG NVHVSTESNL
QATERRAEGL YSQLLGLTAS QSNLTKELNF TTRAKDAIMQ MWLNARRDLD RINASFRQCQ
GDRVIYTNNQ RYMAAIILSE KQCRDQFKDM NKSCDALLFM LNQKVKTLEV EIAKEKTICT
KDKESVLLNK RVAEEQLVEC VKTRELQHQE RQLAKEQLQK VQALCLPLDK DKFEMDLRNL
WRDSIIPRSL DNLGYNLYHP LGSELASIRR ACDHMPSLMS SKVEELARSL RADIERVARE
NSDLQRQKLE AQQGLRASQE AKQKVEKEAQ AREAKLQAEC SRQTQLALEE KAVLRKERDN
LAKELEEKKR EAEQLRMELA IRNSALDTCI KTKSQPMMPV SRPMGPVPNP QPIDPASLEE
FKRKILESQR PPAGIPVAPS SG
