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Protein

Nectin-3

Gene

NECTIN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays a role in cell-cell adhesion through heterophilic trans-interactions with nectin-like proteins or nectins, such as trans-interaction with NECTIN2 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.1 Publication

GO - Molecular functioni

  • cell adhesion molecule binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: HGNC
  • signaling receptor activity Source: GO_Central

GO - Biological processi

Keywordsi

Biological processCell adhesion

Enzyme and pathway databases

ReactomeiR-HSA-418990 Adherens junctions interactions
R-HSA-420597 Nectin/Necl trans heterodimerization

Names & Taxonomyi

Protein namesi
Recommended name:
Nectin-3
Alternative name(s):
CDw113
Nectin cell adhesion molecule 3Imported
Poliovirus receptor-related protein 3
CD_antigen: CD113
Gene namesi
Name:NECTIN3Imported
Synonyms:PRR3, PVRL3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000177707.10
HGNCiHGNC:17664 NECTIN3
MIMi607147 gene
neXtProtiNX_Q9NQS3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini58 – 404ExtracellularSequence analysisAdd BLAST347
Transmembranei405 – 425HelicalSequence analysisAdd BLAST21
Topological domaini426 – 549CytoplasmicSequence analysisAdd BLAST124

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Organism-specific databases

DisGeNETi25945
OpenTargetsiENSG00000177707
PharmGKBiPA134969621

Polymorphism and mutation databases

BioMutaiPVRL3
DMDMi74762752

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 57Sequence analysisAdd BLAST57
ChainiPRO_000022637258 – 549Nectin-3Add BLAST492

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi73N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi78 ↔ 148PROSITE-ProRule annotation
Glycosylationi83N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi125N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi186N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi193 ↔ 246PROSITE-ProRule annotation
Glycosylationi222N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi291 ↔ 338PROSITE-ProRule annotation
Glycosylationi331N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9NQS3
MaxQBiQ9NQS3
PaxDbiQ9NQS3
PeptideAtlasiQ9NQS3
PRIDEiQ9NQS3
ProteomicsDBi82178
82179 [Q9NQS3-2]

PTM databases

iPTMnetiQ9NQS3
PhosphoSitePlusiQ9NQS3

Expressioni

Tissue specificityi

Predominantly expressed in testis and placenta as well as in many cell lines, including epithelial cell lines.1 Publication

Gene expression databases

BgeeiENSG00000177707 Expressed in 186 organ(s), highest expression level in chorionic villus
CleanExiHS_PRR3
HS_PVRL3
ExpressionAtlasiQ9NQS3 baseline and differential
GenevisibleiQ9NQS3 HS

Organism-specific databases

HPAiCAB009869
HPA011038

Interactioni

Subunit structurei

Cis- and trans-homodimer. Can form trans-heterodimers with NECTIN1, NECTIN2, PVR, IGSF4B/Necl-1 and with IGSF4. Interaction between NECTIN1 and NECTIN3 on the pre- and postsynaptic sites, respectively, initiates the formation of puncta adherentia junctions between axons and dendrites. Interacts (via Cytoplasmic domain) with AFDN, providing a connection with the actin cytoskeleton. Binds with low affinity to TIGIT.5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117441, 40 interactors
CORUMiQ9NQS3
DIPiDIP-41491N
IntActiQ9NQS3, 32 interactors
MINTiQ9NQS3
STRINGi9606.ENSP00000418070

Structurei

3D structure databases

ProteinModelPortaliQ9NQS3
SMRiQ9NQS3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini59 – 165Ig-like V-typeAdd BLAST107
Domaini170 – 258Ig-like C2-type 1Add BLAST89
Domaini269 – 354Ig-like C2-type 2Add BLAST86

Sequence similaritiesi

Belongs to the nectin family.Curated

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IGR7 Eukaryota
ENOG410ZRVN LUCA
GeneTreeiENSGT00900000140811
HOGENOMiHOG000115805
HOVERGENiHBG082234
InParanoidiQ9NQS3
KOiK06592
OMAiTHKPPPM
OrthoDBiEOG091G0BLQ
PhylomeDBiQ9NQS3
TreeFamiTF331051

Family and domain databases

Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR013162 CD80_C2-set
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set
IPR033319 Nectin-3
PANTHERiPTHR23277:SF12 PTHR23277:SF12, 1 hit
PfamiView protein in Pfam
PF08205 C2-set_2, 1 hit
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 3 hits

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9NQS3-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MARTLRPSPL CPGGGKAQLS SASLLGAGLL LQPPTPPPLL LLLFPLLLFS
60 70 80 90 100
RLCGALAGPI IVEPHVTAVW GKNVSLKCLI EVNETITQIS WEKIHGKSSQ
110 120 130 140 150
TVAVHHPQYG FSVQGEYQGR VLFKNYSLND ATITLHNIGF SDSGKYICKA
160 170 180 190 200
VTFPLGNAQS STTVTVLVEP TVSLIKGPDS LIDGGNETVA AICIAATGKP
210 220 230 240 250
VAHIDWEGDL GEMESTTTSF PNETATIISQ YKLFPTRFAR GRRITCVVKH
260 270 280 290 300
PALEKDIRYS FILDIQYAPE VSVTGYDGNW FVGRKGVNLK CNADANPPPF
310 320 330 340 350
KSVWSRLDGQ WPDGLLASDN TLHFVHPLTF NYSGVYICKV TNSLGQRSDQ
360 370 380 390 400
KVIYISDPPT TTTLQPTIQW HPSTADIEDL ATEPKKLPFP LSTLATIKDD
410 420 430 440 450
TIATIIASVV GGALFIVLVS VLAGIFCYRR RRTFRGDYFA KNYIPPSDMQ
460 470 480 490 500
KESQIDVLQQ DELDSYPDSV KKENKNPVNN LIRKDYLEEP EKTQWNNVEN
510 520 530 540
LNRFERPMDY YEDLKMGMKF VSDEHYDENE DDLVSHVDGS VISRREWYV
Length:549
Mass (Da):61,002
Last modified:October 1, 2000 - v1
Checksum:i6D1104CCB4A9D731
GO
Isoform 2 (identifier: Q9NQS3-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:366
Mass (Da):39,692
Checksum:i091C0A4640DB8661
GO
Isoform 3 (identifier: Q9NQS3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: MARTLRPSPL...PLLLFSRLCG → MAEGWRWCFVRRTPGLLRGPLLPRSFSGNPR
     357-549: DPPTTTTLQP...SVISRREWYV → DVPFKQTSSI...VYIDPREHYV

Show »
Length:487
Mass (Da):54,375
Checksum:iA59BE81140C93511
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JMW3C9JMW3_HUMAN
Nectin-3
NECTIN3
168Annotation score:
H7C4L0H7C4L0_HUMAN
Nectin-3
NECTIN3
244Annotation score:
C9J795C9J795_HUMAN
Nectin-3
NECTIN3
130Annotation score:
H7C5G5H7C5G5_HUMAN
Nectin-3
NECTIN3
31Annotation score:
C9IZE6C9IZE6_HUMAN
Nectin-3
NECTIN3
17Annotation score:

Sequence cautioni

The sequence AAH17572 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
Isoform 3 : The sequence BAC11404 differs from that shown. Reason: Erroneous termination at position 268. Translated as Cys.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti251P → Q in AAH67808 (PubMed:15489334).Curated1
Sequence conflicti284R → G in BAC11404 (PubMed:14702039).Curated1
Sequence conflicti386K → E in AAH17572 (PubMed:15489334).Curated1
Sequence conflicti465S → P in CAB43256 (PubMed:17974005).Curated1
Sequence conflicti519K → R in CAB43256 (PubMed:17974005).Curated1
Sequence conflicti548Y → C in CAB43256 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049995432R → L. Corresponds to variant dbSNP:rs15611Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0468931 – 54MARTL…SRLCG → MAEGWRWCFVRRTPGLLRGP LLPRSFSGNPR in isoform 3. 1 PublicationAdd BLAST54
Alternative sequenceiVSP_046894357 – 549DPPTT…REWYV → DVPFKQTSSIAVAGAVIGAV LALFIIAIFVTVLLTPRKKR PSYLDKVIDLPPTHKPPPLY EERSPPLPQKDLFQPEHLPL QTQFKEREVGNLQHSNGLNS RSFDYEDENPVGEDGIQQMY PLYNQMCYQDRSPGKHHQNN DPKRVYIDPREHYV in isoform 3. 1 PublicationAdd BLAST193
Alternative sequenceiVSP_017435357 – 366DPPTTTTLQP → AYNSVASLNC in isoform 2. 1 Publication10
Alternative sequenceiVSP_017436367 – 549Missing in isoform 2. 1 PublicationAdd BLAST183

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF282874 mRNA Translation: AAF97597.1
AK075105 mRNA Translation: BAC11404.1 Different termination.
AC133436 Genomic DNA No translation available.
AC133477 Genomic DNA No translation available.
AC137833 Genomic DNA No translation available.
BC001336 mRNA Translation: AAH01336.1
BC017572 mRNA Translation: AAH17572.1 Different initiation.
BC067808 mRNA Translation: AAH67808.1
AL050071 mRNA Translation: CAB43256.1
CCDSiCCDS2957.1 [Q9NQS3-1]
CCDS58842.1 [Q9NQS3-2]
CCDS58843.1 [Q9NQS3-3]
PIRiT08732
RefSeqiNP_001230215.1, NM_001243286.1 [Q9NQS3-2]
NP_001230217.1, NM_001243288.1 [Q9NQS3-3]
NP_056295.1, NM_015480.2 [Q9NQS3-1]
UniGeneiHs.293917
Hs.656767

Genome annotation databases

EnsembliENST00000319792; ENSP00000321514; ENSG00000177707 [Q9NQS3-2]
ENST00000485303; ENSP00000418070; ENSG00000177707 [Q9NQS3-1]
ENST00000493615; ENSP00000420579; ENSG00000177707 [Q9NQS3-3]
GeneIDi25945
KEGGihsa:25945
UCSCiuc003dxt.3 human [Q9NQS3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF282874 mRNA Translation: AAF97597.1
AK075105 mRNA Translation: BAC11404.1 Different termination.
AC133436 Genomic DNA No translation available.
AC133477 Genomic DNA No translation available.
AC137833 Genomic DNA No translation available.
BC001336 mRNA Translation: AAH01336.1
BC017572 mRNA Translation: AAH17572.1 Different initiation.
BC067808 mRNA Translation: AAH67808.1
AL050071 mRNA Translation: CAB43256.1
CCDSiCCDS2957.1 [Q9NQS3-1]
CCDS58842.1 [Q9NQS3-2]
CCDS58843.1 [Q9NQS3-3]
PIRiT08732
RefSeqiNP_001230215.1, NM_001243286.1 [Q9NQS3-2]
NP_001230217.1, NM_001243288.1 [Q9NQS3-3]
NP_056295.1, NM_015480.2 [Q9NQS3-1]
UniGeneiHs.293917
Hs.656767

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4FOMX-ray3.93A58-359[»]
ProteinModelPortaliQ9NQS3
SMRiQ9NQS3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117441, 40 interactors
CORUMiQ9NQS3
DIPiDIP-41491N
IntActiQ9NQS3, 32 interactors
MINTiQ9NQS3
STRINGi9606.ENSP00000418070

PTM databases

iPTMnetiQ9NQS3
PhosphoSitePlusiQ9NQS3

Polymorphism and mutation databases

BioMutaiPVRL3
DMDMi74762752

Proteomic databases

EPDiQ9NQS3
MaxQBiQ9NQS3
PaxDbiQ9NQS3
PeptideAtlasiQ9NQS3
PRIDEiQ9NQS3
ProteomicsDBi82178
82179 [Q9NQS3-2]

Protocols and materials databases

DNASUi25945
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000319792; ENSP00000321514; ENSG00000177707 [Q9NQS3-2]
ENST00000485303; ENSP00000418070; ENSG00000177707 [Q9NQS3-1]
ENST00000493615; ENSP00000420579; ENSG00000177707 [Q9NQS3-3]
GeneIDi25945
KEGGihsa:25945
UCSCiuc003dxt.3 human [Q9NQS3-1]

Organism-specific databases

CTDi25945
DisGeNETi25945
EuPathDBiHostDB:ENSG00000177707.10
GeneCardsiNECTIN3
HGNCiHGNC:17664 NECTIN3
HPAiCAB009869
HPA011038
MIMi607147 gene
neXtProtiNX_Q9NQS3
OpenTargetsiENSG00000177707
PharmGKBiPA134969621
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGR7 Eukaryota
ENOG410ZRVN LUCA
GeneTreeiENSGT00900000140811
HOGENOMiHOG000115805
HOVERGENiHBG082234
InParanoidiQ9NQS3
KOiK06592
OMAiTHKPPPM
OrthoDBiEOG091G0BLQ
PhylomeDBiQ9NQS3
TreeFamiTF331051

Enzyme and pathway databases

ReactomeiR-HSA-418990 Adherens junctions interactions
R-HSA-420597 Nectin/Necl trans heterodimerization

Miscellaneous databases

ChiTaRSiNECTIN3 human
GeneWikiiPVRL3
GenomeRNAii25945
PROiPR:Q9NQS3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177707 Expressed in 186 organ(s), highest expression level in chorionic villus
CleanExiHS_PRR3
HS_PVRL3
ExpressionAtlasiQ9NQS3 baseline and differential
GenevisibleiQ9NQS3 HS

Family and domain databases

Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR013162 CD80_C2-set
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set
IPR033319 Nectin-3
PANTHERiPTHR23277:SF12 PTHR23277:SF12, 1 hit
PfamiView protein in Pfam
PF08205 C2-set_2, 1 hit
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiNECT3_HUMAN
AccessioniPrimary (citable) accession number: Q9NQS3
Secondary accession number(s): E9PFR0
, Q6NVZ3, Q8NC05, Q8WVU4, Q9BVA9, Q9Y412
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: October 1, 2000
Last modified: November 7, 2018
This is version 144 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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