Q96NY8 (PVRL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	510 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	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
Subcellular location	Cell membrane; Single-pass type I membrane protein Potential. Cell junction › adherens 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.10
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.

Ontologies

Keywords
Biological process	Cell adhesion Host-virus interaction
Cellular component	Cell junction Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Ectodermal dysplasia
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adherens junction organization Traceable author statement. Source: Reactome cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell junction assembly Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	adherens junction Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
H	Q786F2	2	EBI-4314784,EBI-5323300	From a different organism.
PVRL1	Q15223	2	EBI-4314784,EBI-1771314
TIGIT	Q495A1	2	EBI-4314784,EBI-4314807

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Potential

Chain

32 – 510

479

Poliovirus receptor-related protein 4

PRO_0000297673

Chain

32 – ?

Processed poliovirus receptor-related protein 4

PRO_0000311086

Regions

Topological domain

32 – 349

318

Extracellular Potential

Transmembrane

350 – 370

21

Helical; Potential

Topological domain

371 – 510

140

Cytoplasmic Potential

Domain

32 – 144

113

Ig-like V-type 1

Domain

148 – 237

90

Ig-like C2-type 1

Domain

248 – 331

84

Ig-like C2-type 2

Amino acid modifications

Modified residue

426

1

Phosphoserine By similarity

Glycosylation

281

1

N-linked (GlcNAc...) Potential

Disulfide bond

171 ↔ 223

By similarity

Disulfide bond

270 ↔ 315

By similarity

Natural variations

Natural variant

53

1

F → L.
Corresponds to variant rs3737786 [ dbSNP | Ensembl ].

VAR_034669

Natural variant

185

1

T → M in EDSS1. Ref.10

VAR_064189

Experimental info

Sequence conflict

35

1

E → G in BAB55344. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

510

Helix Strand Turn

Details...

Beta strand

38 – 41

4

Beta strand

46 – 50

5

Beta strand

62 – 69

8

Beta strand

72 – 74

3

Beta strand

78 – 82

5

Beta strand

84 – 86

3

Beta strand

87 – 90

4

Helix

92 – 94

3

Turn

95 – 97

3

Beta strand

112 – 116

5

Beta strand

119 – 121

3

Beta strand

123 – 134

12

Beta strand

136 – 144

9

Beta strand

152 – 155

4

Beta strand

165 – 177

13

Beta strand

180 – 187

8

Beta strand

190 – 197

8

Beta strand

199 – 210

12

Helix

214 – 216

3

Beta strand

220 – 226

7

Beta strand

234 – 239

6

Sequences

	Sequence		Length	Mass (Da)
	Q96NY8 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: DCF5E1D794F227FA	FASTA	510	55,454
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00043992.

RefSeq

NP_112178.2. NM_030916.2.

UniGene

Hs.492490.
Hs.732297.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4FRW	X-ray	3.50	A/B/C/D/E/F	32-243	[»]
4GJT	X-ray	3.10	B/C	32-146	[»]

ProteinModelPortal

Q96NY8.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41492N.

IntAct

Q96NY8. 4 interactions.

MINT

MINT-237395.

STRING

9606.ENSP00000356991.

PTM databases

PhosphoSite

Q96NY8.

Polymorphism databases

DMDM

74761016.

Proteomic databases

PaxDb

Q96NY8.

PRIDE

Q96NY8.

Protocols and materials databases

DNASU

81607.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368012; ENSP00000356991; ENSG00000143217.

GeneID

81607.

KEGG

hsa:81607.

UCSC

uc001fxo.2. human.

Organism-specific databases

CTD

81607.

GeneCards

GC01M161040.

H-InvDB

HIX0001228.

HGNC

HGNC:19688. PVRL4.

HPA

HPA010775.

MIM

609607. gene.
613573. phenotype.

neXtProt

NX_Q96NY8.

Orphanet

247820. Ectodermal dysplasia - syndactyly syndrome.

PharmGKB

PA134991624.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG149403.

HOGENOM

HOG000115806.

HOVERGEN

HBG108310.

InParanoid

Q96NY8.

KO

K06593.

OMA

QDEGIKQ.

OrthoDB

EOG4QFWD2.

PhylomeDB

Q96NY8.

Enzyme and pathway databases

Reactome

REACT_111155. Cell-Cell communication.

Gene expression databases

ArrayExpress

Q96NY8.

Bgee

Q96NY8.

CleanEx

HS_PRR4.
HS_PVRL4.

Genevestigator

Q96NY8.

Family and domain databases

Gene3D

2.60.40.10. 3 hits.

InterPro

IPR013162. 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]

Pfam

PF08205. C2-set_2. 1 hit.
PF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

81607.

NextBio

71924.

SOURCE

Search...

Entry information

Entry name

PVRL4_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 104 of the entry and version 1 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.