Q9NQS3 (PVRL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Poliovirus receptor-related protein 3

Alternative name(s):
CDw113
Nectin-3
CD_antigen=CD113

Gene names

Name:	PVRL3
Synonyms:	PRR3

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	549 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	Plays a role in cell-cell adhesion through heterophilic trans-interactions with nectin-like proteins or nectins, such as trans-interaction with PVRL2/nectin-2 at Sertoli-spermatid junctions. Trans-interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1. Also involved in the formation of cell-cell junctions, including adherens junctions and synapses. Induces endocytosis-mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation. Plays a role in the morphology of the ciliary body. Ref.5
Subunit structure	Cis- and trans-homodimer. Can form trans-heterodimers with PVRL1/nectin-1, PVRL2/nectin-2, PVR, IGSF4B/Necl-1 and with IGSF4. Interacts with MLLT4/afadin. Binds with low affinity to TIGIT. Ref.1 Ref.4 Ref.5 Ref.6
Subcellular location	Cell membrane; Single-pass membrane protein Potential.
Tissue specificity	Predominantly expressed in testis and placenta as well as in many cell lines, including epithelial cell lines. Ref.1
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.
Sequence caution	The sequence AAH17572.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adherens junction organization Traceable author statement. Source: Reactome cell junction assembly Traceable author statement. Source: Reactome fertilization Inferred from electronic annotation. Source: Compara homophilic cell adhesion Inferred from sequence or structural similarity. Source: HGNC lens morphogenesis in camera-type eye Inferred from electronic annotation. Source: Compara retina morphogenesis in camera-type eye Inferred from electronic annotation. Source: Compara
Cellular_component	apical junction complex Inferred from electronic annotation. Source: Compara cell-cell adherens junction Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from sequence or structural similarity. Source: HGNC
Molecular_function	protein homodimerization activity Inferred from sequence or structural similarity. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PVRL1	Q15223	2	EBI-2826725,EBI-1771314
PVRL2	Q92692	2	EBI-2826725,EBI-718419
TIGIT	Q495A1	2	EBI-2826725,EBI-4314807

Alternative products

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

Isoform 1 (identifier: Q9NQS3-1)

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: Q9NQS3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     357-366: DPPTTTTLQP → AYNSVASLNC
     367-549: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 57	57	Potential
	Chain	58 – 549	492	Poliovirus receptor-related protein 3		PRO_0000226372
Regions
	Topological domain	58 – 404	347	Extracellular Potential
	Transmembrane	405 – 425	21	Helical; Potential
	Topological domain	426 – 549	124	Cytoplasmic Potential
	Domain	59 – 165	107	Ig-like V-type
	Domain	170 – 258	89	Ig-like C2-type 1
	Domain	269 – 354	86	Ig-like C2-type 2
Amino acid modifications
	Glycosylation	73	1	N-linked (GlcNAc...) Potential
	Glycosylation	83	1	N-linked (GlcNAc...) Potential
	Glycosylation	125	1	N-linked (GlcNAc...) Potential
	Glycosylation	186	1	N-linked (GlcNAc...) Potential
	Glycosylation	222	1	N-linked (GlcNAc...) Potential
	Glycosylation	331	1	N-linked (GlcNAc...) Potential
	Disulfide bond	78 ↔ 148		By similarity
	Disulfide bond	193 ↔ 246		By similarity
	Disulfide bond	291 ↔ 338		By similarity
Natural variations
	Alternative sequence	357 – 366	10	DPPTTTTLQP → AYNSVASLNC in isoform 2.		VSP_017435
	Alternative sequence	367 – 549	183	Missing in isoform 2.		VSP_017436
	Natural variant	432	1	R → L. Corresponds to variant rs15611 [ dbSNP | Ensembl ].		VAR_049995
Experimental info
	Sequence conflict	251	1	P → Q in AAH67808. Ref.2
	Sequence conflict	386	1	K → E in AAH17572. Ref.2
	Sequence conflict	465	1	S → P in CAB43256. Ref.3
	Sequence conflict	519	1	K → R in CAB43256. Ref.3
	Sequence conflict	548	1	Y → C in CAB43256. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 6D1104CCB4A9D731	FASTA	549	61,002
	10 20 30 40 50 60 MARTLRPSPL CPGGGKAQLS SASLLGAGLL LQPPTPPPLL LLLFPLLLFS RLCGALAGPI 70 80 90 100 110 120 IVEPHVTAVW GKNVSLKCLI EVNETITQIS WEKIHGKSSQ TVAVHHPQYG FSVQGEYQGR 130 140 150 160 170 180 VLFKNYSLND ATITLHNIGF SDSGKYICKA VTFPLGNAQS STTVTVLVEP TVSLIKGPDS 190 200 210 220 230 240 LIDGGNETVA AICIAATGKP VAHIDWEGDL GEMESTTTSF PNETATIISQ YKLFPTRFAR 250 260 270 280 290 300 GRRITCVVKH PALEKDIRYS FILDIQYAPE VSVTGYDGNW FVGRKGVNLK CNADANPPPF 310 320 330 340 350 360 KSVWSRLDGQ WPDGLLASDN TLHFVHPLTF NYSGVYICKV TNSLGQRSDQ KVIYISDPPT 370 380 390 400 410 420 TTTLQPTIQW HPSTADIEDL ATEPKKLPFP LSTLATIKDD TIATIIASVV GGALFIVLVS 430 440 450 460 470 480 VLAGIFCYRR RRTFRGDYFA KNYIPPSDMQ KESQIDVLQQ DELDSYPDSV KKENKNPVNN 490 500 510 520 530 540 LIRKDYLEEP EKTQWNNVEN LNRFERPMDY YEDLKMGMKF VSDEHYDENE DDLVSHVDGS VISRREWYV
	Isoform 2 [UniParc]. Checksum: 091C0A4640DB8661	FASTA	366	39,692
	10 20 30 40 50 60 MARTLRPSPL CPGGGKAQLS SASLLGAGLL LQPPTPPPLL LLLFPLLLFS RLCGALAGPI 70 80 90 100 110 120 IVEPHVTAVW GKNVSLKCLI EVNETITQIS WEKIHGKSSQ TVAVHHPQYG FSVQGEYQGR 130 140 150 160 170 180 VLFKNYSLND ATITLHNIGF SDSGKYICKA VTFPLGNAQS STTVTVLVEP TVSLIKGPDS 190 200 210 220 230 240 LIDGGNETVA AICIAATGKP VAHIDWEGDL GEMESTTTSF PNETATIISQ YKLFPTRFAR 250 260 270 280 290 300 GRRITCVVKH PALEKDIRYS FILDIQYAPE VSVTGYDGNW FVGRKGVNLK CNADANPPPF 310 320 330 340 350 360 KSVWSRLDGQ WPDGLLASDN TLHFVHPLTF NYSGVYICKV TNSLGQRSDQ KVIYISAYNS VASLNC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that interacts with afadin." Reymond N., Borg J.-P., Lecocq E., Adelaide J., Campadelli-Fiume G., Dubreuil P., Lopez M. Gene 255:347-355(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH MLLT4.
[2]	"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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 246-549 (ISOFORM 1). Tissue: Brain, Cervix and Kidney.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 143-549 (ISOFORM 1). Tissue: Fetal kidney.
[4]	"Recruitment of nectin-3 to cell-cell junctions through trans-heterophilic interaction with CD155, a vitronectin and poliovirus receptor that localizes to alpha(v)beta3 integrin-containing membrane microdomains." Mueller S., Wimmer E. J. Biol. Chem. 278:31251-31260(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PVR.
[5]	"Inhibition of cell movement and proliferation by cell-cell contact-induced interaction of Necl-5 with nectin-3." Fujito T., Ikeda W., Kakunaga S., Minami Y., Kajita M., Sakamoto Y., Monden M., Takai Y. J. Cell Biol. 171:165-173(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PVR.
[6]	"The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells." Yu X., Harden K., Gonzalez L.C., Francesco M., Chiang E., Irving B., Tom I., Ivelja S., Refino C.J., Clark H., Eaton D., Grogan J.L. Nat. Immunol. 10:48-57(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TIGIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF282874 mRNA. Translation: AAF97597.1.
BC001336 mRNA. Translation: AAH01336.1.
BC017572 mRNA. Translation: AAH17572.1. Different initiation.
BC067808 mRNA. Translation: AAH67808.1.
AL050071 mRNA. Translation: CAB43256.1.

IPI

IPI00022959.
IPI00736191.

PIR

T08732.

RefSeq

NP_001230215.1. NM_001243286.1.
NP_056295.1. NM_015480.2.

UniGene

Hs.293917.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4FOM	X-ray	3.93	A	58-359	[»]

ProteinModelPortal

Q9NQS3.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41491N.

IntAct

Q9NQS3. 4 interactions.

MINT

MINT-147327.

STRING

9606.ENSP00000418070.

Protein family/group databases

MEROPS

I43.001.

PTM databases

PhosphoSite

Q9NQS3.

Polymorphism databases

DMDM

74762752.

Proteomic databases

PaxDb

Q9NQS3.

PRIDE

Q9NQS3.

Protocols and materials databases

DNASU

25945.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000319792; ENSP00000321514; ENSG00000177707.
ENST00000485303; ENSP00000418070; ENSG00000177707.

GeneID

25945.

KEGG

hsa:25945.

UCSC

uc003dxt.2. human.
uc021xch.1. human.

Organism-specific databases

CTD

25945.

GeneCards

GC03P110788.

HGNC

HGNC:17664. PVRL3.

HPA

CAB009869.
HPA011038.

MIM

607147. gene.

neXtProt

NX_Q9NQS3.

PharmGKB

PA134969621.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47602.

HOGENOM

HOG000115805.

HOVERGEN

HBG082234.

InParanoid

Q9NQS3.

KO

K06592.

OrthoDB

EOG4X6C8C.

PhylomeDB

Q9NQS3.

Enzyme and pathway databases

Reactome

REACT_111155. Cell-Cell communication.

Gene expression databases

ArrayExpress

Q9NQS3.

Bgee

Q9NQS3.

CleanEx

HS_PRR3.
HS_PVRL3.

Genevestigator

Q9NQS3.

GermOnline

ENSG00000177707. Homo sapiens.

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.
IPR013106. Ig_V-set.
[Graphical view]

Pfam

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

SMART

SM00409. IG. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PVRL3. human.

GenomeRNAi

25945.

NextBio

47534.

SOURCE

Search...

Entry information

Entry name

PVRL3_HUMAN

Accession

Primary (citable) accession number: Q9NQS3
Secondary accession number(s): Q6NVZ3 , Q8WVU4, Q9BVA9, Q9Y412

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 93 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.