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Protein

V-set domain-containing T-cell activation inhibitor 1

Gene

VTCN1

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

Functioni

Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells (Treg), in the suppression of tumor-associated antigen-specific T-cell immunity. Involved in promoting epithelial cell transformation.By similarity4 Publications

Miscellaneous

May serve as a predictive marker for renal cell carcinoma.1 Publication

Caution

The mouse ortholog has been shown to be a GPI-anchored protein but the Gly residue which is predicted to be the modified site in mouse and rat is not conserved in human.Curated

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • interferon-gamma secretion Source: Ensembl
  • interleukin-4 secretion Source: Ensembl
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of T cell activation Source: UniProtKB
  • negative regulation of T cell proliferation Source: UniProtKB
  • positive regulation of interleukin-2 secretion Source: Ensembl
  • positive regulation of T cell proliferation Source: Ensembl
  • response to protozoan Source: Ensembl

Keywordsi

Biological processAdaptive immunity, Immunity

Names & Taxonomyi

Protein namesi
Recommended name:
V-set domain-containing T-cell activation inhibitor 1
Alternative name(s):
B7 homolog 4
Short name:
B7-H4
B7h.5
Immune costimulatory protein B7-H4
Protein B7S1
T-cell costimulatory molecule B7x
Gene namesi
Name:VTCN1Imported
Synonyms:B7H4Imported
ORF Names:UNQ659/PRO1291
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000134258.16
HGNCiHGNC:28873 VTCN1
MIMi608162 gene
neXtProtiNX_Q7Z7D3

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 domaini25 – 259ExtracellularSequence analysisAdd BLAST235
Transmembranei260 – 280HelicalSequence analysisAdd BLAST21
Topological domaini281 – 282CytoplasmicSequence analysis2

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi79679
OpenTargetsiENSG00000134258
PharmGKBiPA142670611

Polymorphism and mutation databases

BioMutaiVTCN1
DMDMi74759262

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000033923725 – 282V-set domain-containing T-cell activation inhibitor 1Sequence analysisAdd BLAST258

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi56 ↔ 130PROSITE-ProRule annotation
Disulfide bondi168 ↔ 225PROSITE-ProRule annotation
Glycosylationi216N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein

Proteomic databases

PaxDbiQ7Z7D3
PeptideAtlasiQ7Z7D3
PRIDEiQ7Z7D3
ProteomicsDBi69518
69519 [Q7Z7D3-2]
69520 [Q7Z7D3-3]

PTM databases

iPTMnetiQ7Z7D3
PhosphoSitePlusiQ7Z7D3

Expressioni

Tissue specificityi

Overexpressed in breast, ovarian, endometrial, renal cell (RCC) and non-small-cell lung cancers (NSCLC). Expressed on activated T- and B-cells, monocytes and dendritic cells, but not expressed in most normal tissues (at protein level). Widely expressed, including in kidney, liver, lung, ovary, placenta, spleen and testis.7 Publications

Inductioni

Up-regulated by IL6/interleukin-6 and IL10/interleukin-10 and inhibited by CSF2/GM-CSF and IL4/interleukin-4 on antigen-presenting cells (APCs).3 Publications

Gene expression databases

BgeeiENSG00000134258
CleanExiHS_VTCN1
ExpressionAtlasiQ7Z7D3 baseline and differential
GenevisibleiQ7Z7D3 HS

Organism-specific databases

HPAiHPA054200

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122803, 1 interactor
STRINGi9606.ENSP00000358470

Structurei

Secondary structure

1282
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi39 – 42Combined sources4
Beta strandi44 – 47Combined sources4
Beta strandi52 – 58Combined sources7
Helixi64 – 66Combined sources3
Beta strandi68 – 73Combined sources6
Beta strandi77 – 84Combined sources8
Helixi95 – 97Combined sources3
Beta strandi101 – 103Combined sources3
Turni105 – 107Combined sources3
Helixi108 – 110Combined sources3
Beta strandi115 – 119Combined sources5
Helixi122 – 124Combined sources3
Beta strandi126 – 134Combined sources9
Beta strandi137 – 148Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4GOSX-ray1.59A30-148[»]
ProteinModelPortaliQ7Z7D3
SMRiQ7Z7D3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 146Ig-like V-type 1Sequence analysisAdd BLAST112
Domaini153 – 241Ig-like V-type 2Sequence analysisAdd BLAST89

Sequence similaritiesi

Belongs to the immunoglobulin superfamily. BTN/MOG family.By similarity

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKB5 Eukaryota
ENOG4111T2B LUCA
GeneTreeiENSGT00700000104325
HOGENOMiHOG000139645
HOVERGENiHBG097943
InParanoidiQ7Z7D3
KOiK06747
PhylomeDBiQ7Z7D3
TreeFamiTF331083

Family and domain databases

Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 2 hits

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 17 Publications (identifier: Q7Z7D3-1) [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
MASLGQILFW SIISIIIILA GAIALIIGFG ISGRHSITVT TVASAGNIGE
60 70 80 90 100
DGILSCTFEP DIKLSDIVIQ WLKEGVLGLV HEFKEGKDEL SEQDEMFRGR
110 120 130 140 150
TAVFADQVIV GNASLRLKNV QLTDAGTYKC YIITSKGKGN ANLEYKTGAF
160 170 180 190 200
SMPEVNVDYN ASSETLRCEA PRWFPQPTVV WASQVDQGAN FSEVSNTSFE
210 220 230 240 250
LNSENVTMKV VSVLYNVTIN NTYSCMIEND IAKATGDIKV TESEIKRRSH
260 270 280
LQLLNSKASL CVSSFFAISW ALLPLSPYLM LK
Length:282
Mass (Da):30,878
Last modified:October 1, 2003 - v1
Checksum:i1C9C565A9242E78C
GO
Isoform 21 Publication (identifier: Q7Z7D3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     33-148: Missing.

Show »
Length:166
Mass (Da):18,275
Checksum:i30FFF157B8C66DE2
GO
Isoform 31 Publication (identifier: Q7Z7D3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     33-87: GRHSITVTTV...GLVHEFKEGK → EVSVWLSAMK...WGGWNPELHF
     88-282: Missing.

Show »
Length:87
Mass (Da):9,875
Checksum:i1006690A861AB006
GO
Isoform 4 (identifier: Q7Z7D3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-95: Missing.

Show »
Length:187
Mass (Da):20,743
Checksum:i9AED6155AEED4E63
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti29F → L in ABI16083 (Ref. 10) Curated1
Sequence conflicti54L → Q in BAB15349 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0454231 – 95Missing in isoform 4. 2 PublicationsAdd BLAST95
Alternative sequenceiVSP_05284133 – 148Missing in isoform 2. 1 PublicationAdd BLAST116
Alternative sequenceiVSP_05284233 – 87GRHSI…FKEGK → EVSVWLSAMKGWCRSSKASL SIDLCFLNFRETLHHSHYCR LSWEHWGGWNPELHF in isoform 3. 1 PublicationAdd BLAST55
Alternative sequenceiVSP_05284388 – 282Missing in isoform 3. 1 PublicationAdd BLAST195

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY280972 mRNA Translation: AAP37283.1
AY346100 mRNA Translation: AAQ24206.1
DQ103757 mRNA Translation: AAZ17406.1
AY442303 mRNA Translation: AAS13400.1
AY358352 mRNA Translation: AAQ88718.1
AK026071 mRNA Translation: BAB15349.1
AK303466 mRNA Translation: BAH13967.1
AL391476 Genomic DNA Translation: CAI12739.1
CH471122 Genomic DNA Translation: EAW56672.1
CH471122 Genomic DNA Translation: EAW56673.1
BC065717 mRNA Translation: AAH65717.1
BC074729 mRNA Translation: AAH74729.1
DQ836392 mRNA Translation: ABI16083.1
CCDSiCCDS58019.1 [Q7Z7D3-4]
CCDS58020.1 [Q7Z7D3-2]
CCDS894.1 [Q7Z7D3-1]
RefSeqiNP_001240778.1, NM_001253849.1 [Q7Z7D3-4]
NP_001240779.1, NM_001253850.1 [Q7Z7D3-2]
NP_078902.2, NM_024626.3 [Q7Z7D3-1]
UniGeneiHs.546434

Genome annotation databases

EnsembliENST00000328189; ENSP00000328168; ENSG00000134258 [Q7Z7D3-2]
ENST00000369458; ENSP00000358470; ENSG00000134258 [Q7Z7D3-1]
ENST00000539893; ENSP00000444724; ENSG00000134258 [Q7Z7D3-4]
GeneIDi79679
KEGGihsa:79679
UCSCiuc001ehb.4 human [Q7Z7D3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiVTCN1_HUMAN
AccessioniPrimary (citable) accession number: Q7Z7D3
Secondary accession number(s): Q0GN76
, Q45VN0, Q5WPZ3, Q6P097, Q9H6B2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: October 1, 2003
Last modified: June 20, 2018
This is version 132 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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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