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Q96NY8 (PVRL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Poliovirus receptor-related protein 4
Alternative name(s):
Ig superfamily receptor LNIR
Nectin-4

Cleaved into the following chain:

  1. Processed poliovirus receptor-related protein 4
Gene names
Name:PVRL4
Synonyms:LNIR, PRR4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length510 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with PVRL2/nectin-1. Does not act as receptor for alpha-herpesvirus entry into cells.

Subunit structure

Self-associates. Interacts via its Ig-like V-type domain with PVRL1/nectin-1 Ig-like V-type domain. Interacts via its C-terminus with MLLT4. Binds to Measles virus protein H and acts as a receptor for this virus. Ref.1 Ref.6 Ref.9 Ref.10 Ref.11

Subcellular location

Cell membrane; Single-pass type I membrane protein Potential. Cell junctionadherens junction. Note: Colocalizes with MLLT4 at cadherin-based adherens junctions. Ref.1

Processed poliovirus receptor-related protein 4: Secreted. Note: The secreted form is found in breast tumor patients. Ref.1

Tissue specificity

Predominantly expressed in placenta. Not detected in normal breast epithelium but expressed in breast carcinoma. Ref.1 Ref.8

Post-translational modification

The soluble form is produced by proteolytic cleavage at the cell surface (shedding), probably by ADAM17/TACE.

Involvement in disease

Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) [MIM:613573]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDSS1 is characterized by the association of hair and teeth abnormalities with cutaneous syndactyly of the hands and/or feet. Hair morphologic abnormalities include twists at irregular intervals (pilli torti) and swelling along the shafts, particularly associated with areas of breakage. Dental findings consist of abnormally widely spaced teeth, with peg-shaped and conical crowns. Patients have normal sweating.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities

Belongs to the nectin family.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HQ786F22EBI-4314784,EBI-5323300From a different organism.
PVRL1Q152232EBI-4314784,EBI-1771314
TIGITQ495A12EBI-4314784,EBI-4314807

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Potential
Chain32 – 510479Poliovirus receptor-related protein 4
PRO_0000297673
Chain32 – ?Processed poliovirus receptor-related protein 4PRO_0000311086

Regions

Topological domain32 – 349318Extracellular Potential
Transmembrane350 – 37021Helical; Potential
Topological domain371 – 510140Cytoplasmic Potential
Domain32 – 144113Ig-like V-type 1
Domain148 – 23790Ig-like C2-type 1
Domain248 – 33184Ig-like C2-type 2

Amino acid modifications

Glycosylation2811N-linked (GlcNAc...) Potential
Disulfide bond52 ↔ 127 Ref.10 Ref.11
Disulfide bond171 ↔ 223 Ref.10 Ref.11
Disulfide bond270 ↔ 315 By similarity

Natural variations

Natural variant531F → L.
Corresponds to variant rs3737786 [ dbSNP | Ensembl ].
VAR_034669
Natural variant1851T → M in EDSS1. Ref.12
VAR_064189

Experimental info

Sequence conflict351E → G in BAB55344. Ref.2

Secondary structure

........................................ 510
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96NY8 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: DCF5E1D794F227FA

FASTA51055,454
        10         20         30         40         50         60 
MPLSLGAEMW GPEAWLLLLL LLASFTGRCP AGELETSDVV TVVLGQDAKL PCFYRGDSGE 

        70         80         90        100        110        120 
QVGQVAWARV DAGEGAQELA LLHSKYGLHV SPAYEGRVEQ PPPPRNPLDG SVLLRNAVQA 

       130        140        150        160        170        180 
DEGEYECRVS TFPAGSFQAR LRLRVLVPPL PSLNPGPALE EGQGLTLAAS CTAEGSPAPS 

       190        200        210        220        230        240 
VTWDTEVKGT TSSRSFKHSR SAAVTSEFHL VPSRSMNGQP LTCVVSHPGL LQDQRITHIL 

       250        260        270        280        290        300 
HVSFLAEASV RGLEDQNLWH IGREGAMLKC LSEGQPPPSY NWTRLDGPLP SGVRVDGDTL 

       310        320        330        340        350        360 
GFPPLTTEHS GIYVCHVSNE FSSRDSQVTV DVLDPQEDSG KQVDLVSASV VVVGVIAALL 

       370        380        390        400        410        420 
FCLLVVVVVL MSRYHRRKAQ QMTQKYEEEL TLTRENSIRR LHSHHTDPRS QPEESVGLRA 

       430        440        450        460        470        480 
EGHPDSLKDN SSCSVMSEEP EGRSYSTLTT VREIETQTEL LSPGSGRAEE EEDQDEGIKQ 

       490        500        510 
AMNHFVQENG TLRAKPTGNG IYINGRGHLV 

« Hide

References

« Hide 'large scale' references
[1]"Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction."
Reymond N., Fabre S., Lecocq E., Adelaide J., Dubreuil P., Lopez M.
J. Biol. Chem. 276:43205-43215(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH MLLT4 AND PVRL1.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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. expand/collapse author list , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[6]"Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C-C'-C'-D beta-strands of the nectin1 V domain."
Fabre S., Reymond N., Cocchi F., Menotti L., Dubreuil P., Campadelli-Fiume G., Lopez M.
J. Biol. Chem. 277:27006-27013(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PVLR1.
[7]"Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM-17."
Fabre-Lafay S., Garrido-Urbani S., Reymond N., Goncalves A., Dubreuil P., Lopez M.
J. Biol. Chem. 280:19543-19550(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING.
[8]"Nectin-4 is a new histological and serological tumor associated marker for breast cancer."
Fabre-Lafay S., Monville F., Garrido-Urbani S., Berruyer-Pouyet C., Ginestier C., Reymond N., Finetti P., Sauvan R., Adelaide J., Geneix J., Lecocq E., Popovici C., Dubreuil P., Viens P., Goncalves A., Charafe-Jauffret E., Jacquemier J., Birnbaum D., Lopez M.
BMC Cancer 7:73-73(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Adherens junction protein nectin-4 is the epithelial receptor for measles virus."
Muhlebach M.D., Mateo M., Sinn P.L., Prufer S., Uhlig K.M., Leonard V.H., Navaratnarajah C.K., Frenzke M., Wong X.X., Sawatsky B., Ramachandran S., McCray P.B. Jr., Cichutek K., von Messling V., Lopez M., Cattaneo R.
Nature 480:530-533(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MEASLES VIRUS PROTEIN H.
[10]"Nectin ectodomain structures reveal a canonical adhesive interface."
Harrison O.J., Vendome J., Brasch J., Jin X., Hong S., Katsamba P.S., Ahlsen G., Troyanovsky R.B., Troyanovsky S.M., Honig B., Shapiro L.
Nat. Struct. Mol. Biol. 19:906-915(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 32-243, SUBUNIT, DISULFIDE BONDS, IDENTIFICATION BY MASS SPECTROMETRY.
[11]"Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4."
Zhang X., Lu G., Qi J., Li Y., He Y., Xu X., Shi J., Zhang C.W., Yan J., Gao G.F.
Nat. Struct. Mol. Biol. 20:67-72(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 32-146 IN COMPLEX WITH WITH MEASLES VIRUS HEMAGGLUTININ, SUBUNIT, DISULFIDE BOND.
[12]"Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome."
Brancati F., Fortugno P., Bottillo I., Lopez M., Josselin E., Boudghene-Stambouli O., Agolini E., Bernardini L., Bellacchio E., Iannicelli M., Rossi A., Dib-Lachachi A., Stuppia L., Palka G., Mundlos S., Stricker S., Kornak U., Zambruno G., Dallapiccola B.
Am. J. Hum. Genet. 87:265-273(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EDSS1 MET-185.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF426163 mRNA. Translation: AAL23958.1.
AK027753 mRNA. Translation: BAB55344.1.
AL591806 Genomic DNA. Translation: CAI15376.1.
CH471121 Genomic DNA. Translation: EAW52665.1.
BC010423 mRNA. Translation: AAH10423.1.
RefSeqNP_112178.2. NM_030916.2.
UniGeneHs.492490.
Hs.732297.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4FRWX-ray3.50A/B/C/D/E/F32-243[»]
4GJTX-ray3.10B/C32-146[»]
4JJHX-ray2.25A/B32-153[»]
ProteinModelPortalQ96NY8.
SMRQ96NY8. Positions 32-335.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123544. 3 interactions.
DIPDIP-41492N.
IntActQ96NY8. 4 interactions.
MINTMINT-237395.
STRING9606.ENSP00000356991.

PTM databases

PhosphoSiteQ96NY8.

Polymorphism databases

DMDM74761016.

Proteomic databases

PaxDbQ96NY8.
PRIDEQ96NY8.

Protocols and materials databases

DNASU81607.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368012; ENSP00000356991; ENSG00000143217.
GeneID81607.
KEGGhsa:81607.
UCSCuc001fxo.2. human.

Organism-specific databases

CTD81607.
GeneCardsGC01M161040.
H-InvDBHIX0001228.
HGNCHGNC:19688. PVRL4.
HPAHPA010775.
MIM609607. gene.
613573. phenotype.
neXtProtNX_Q96NY8.
Orphanet247820. Ectodermal dysplasia - syndactyly syndrome.
PharmGKBPA134991624.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG149403.
HOGENOMHOG000115806.
HOVERGENHBG108310.
InParanoidQ96NY8.
KOK06593.
OMAQDEGIKQ.
OrthoDBEOG73RBB5.
PhylomeDBQ96NY8.
TreeFamTF338610.

Enzyme and pathway databases

ReactomeREACT_111155. Cell-Cell communication.

Gene expression databases

ArrayExpressQ96NY8.
BgeeQ96NY8.
CleanExHS_PRR4.
HS_PVRL4.
GenevestigatorQ96NY8.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
InterProIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
IPR013151. Immunoglobulin.
[Graphical view]
PfamPF08205. C2-set_2. 1 hit.
PF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi81607.
NextBio71924.
PROQ96NY8.
SOURCESearch...

Entry information

Entry namePVRL4_HUMAN
AccessionPrimary (citable) accession number: Q96NY8
Secondary accession number(s): Q96K15
Entry history
Integrated into UniProtKB/Swiss-Prot: August 21, 2007
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM