Q7Z7D3 (VTCN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
V-set domain-containing T-cell activation inhibitor 1

Alternative name(s):
B7h.5
Immune costimulatory protein B7-H4
Protein B7S1
T-cell costimulatory molecule B7x

Gene names

Name:	VTCN1
Synonyms:	B7H4
ORF Names:	UNQ659/PRO1291

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	282 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	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. Ref.12 Ref.13 Ref.16 Ref.17 UniProtKB Q7TSP5
Subcellular location	Cell membrane; Single-pass type I membrane protein Potential. Note: Expressed at the cell surface. A soluble form has also been detected. Ref.1 Ref.3 Ref.12
Tissue specificity	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. Ref.1 Ref.3 Ref.11 Ref.12 Ref.13 Ref.15 Ref.17
Induction	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). Ref.13 Ref.14 Ref.16
Post-translational modification	N-glycosylated. Ref.12
Miscellaneous	May serve as a predictive marker for renal cell carcinoma. Ref.15
Sequence similarities	Belongs to the immunoglobulin superfamily. BTN/MOG family. UniProtKB Q5ZPR3 Contains 2 Ig-like V-type (immunoglobulin-like) domains.
Caution	The mouse ortholog has been shown (PubMed:12818166) 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.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 (identifier: Q7Z7D3-1)

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 Ref.3 (identifier: Q7Z7D3-2)

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

Isoform 3 Ref.4 (identifier: Q7Z7D3-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 282	258	V-set domain-containing T-cell activation inhibitor 1		PRO_0000339237
Regions
	Topological domain	25 – 259	235	Extracellular Potential
	Transmembrane	260 – 280	21	Helical; Potential
	Topological domain	281 – 282	2	Cytoplasmic Potential
	Domain	35 – 146	112	Ig-like V-type 1
	Domain	153 – 241	89	Ig-like V-type 2
Amino acid modifications
	Glycosylation	216	1	N-linked (GlcNAc...) Potential
	Disulfide bond	56 ↔ 130		By similarity
	Disulfide bond	168 ↔ 225		By similarity
Natural variations
	Alternative sequence	33 – 148	116	Missing in isoform 2. Ref.3		VSP_052841
	Alternative sequence	33 – 87	55	GRHSI…FKEGK → EVSVWLSAMKGWCRSSKASL SIDLCFLNFRETLHHSHYCR LSWEHWGGWNPELHF in isoform 3. Ref.4		VSP_052842
	Alternative sequence	88 – 282	195	Missing in isoform 3. Ref.4		VSP_052843
Experimental info
	Sequence conflict	29	1	F → L in ABI16083. Ref.10
	Sequence conflict	54	1	L → Q in BAB15349. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: 1C9C565A9242E78C	FASTA	282	30,878
	10 20 30 40 50 60 MASLGQILFW SIISIIIILA GAIALIIGFG ISGRHSITVT TVASAGNIGE DGILSCTFEP 70 80 90 100 110 120 DIKLSDIVIQ WLKEGVLGLV HEFKEGKDEL SEQDEMFRGR TAVFADQVIV GNASLRLKNV 130 140 150 160 170 180 QLTDAGTYKC YIITSKGKGN ANLEYKTGAF SMPEVNVDYN ASSETLRCEA PRWFPQPTVV 190 200 210 220 230 240 WASQVDQGAN FSEVSNTSFE LNSENVTMKV VSVLYNVTIN NTYSCMIEND IAKATGDIKV 250 260 270 280 TESEIKRRSH LQLLNSKASL CVSSFFAISW ALLPLSPYLM LK
	Isoform 2 [UniParc]. Checksum: 30FFF157B8C66DE2	FASTA	166	18,275
	10 20 30 40 50 60 MASLGQILFW SIISIIIILA GAIALIIGFG ISAFSMPEVN VDYNASSETL RCEAPRWFPQ 70 80 90 100 110 120 PTVVWASQVD QGANFSEVSN TSFELNSENV TMKVVSVLYN VTINNTYSCM IENDIAKATG 130 140 150 160 DIKVTESEIK RRSHLQLLNS KASLCVSSFF AISWALLPLS PYLMLK
	Isoform 3 [UniParc]. Checksum: 1006690A861AB006	FASTA	87	9,875
	10 20 30 40 50 60 MASLGQILFW SIISIIIILA GAIALIIGFG ISEVSVWLSA MKGWCRSSKA SLSIDLCFLN 70 80 FRETLHHSHY CRLSWEHWGG WNPELHF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"B7-H4, a molecule of the B7 family, negatively regulates T cell immunity." Sica G.L., Choi I.-H., Zhu G., Tamada K., Wang S.-D., Tamura H., Chapoval A.I., Flies D.B., Bajorath J., Chen L. Immunity 18:849-861(2003) [PubMed: 12818165] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Placenta.
[2]	"B7x: a widely expressed B7 family member that inhibits T cell activation." Zang X., Loke P., Kim J., Murphy K., Waitz R., Allison J.P. Proc. Natl. Acad. Sci. U.S.A. 100:10388-10392(2003) [PubMed: 12920180] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"B7-H3 and B7-H4 expression in non-small-cell lung cancer." Sun Y., Wang Y., Zhao J., Gu M., Giscombe R., Lefvert A.K., Wang X. Lung Cancer 53:143-151(2006) [PubMed: 16782226] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"A new splice variant of B7-H4." Mao Y., Zhang X. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[5]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Kidney epithelium.
[7]	"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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[10]	Huang G., Bai Y., Zhang L., Zhang L., Song M. Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-167 (ISOFORM 1). Tissue: Peripheral blood.
[11]	"Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family." Choi I.-H., Zhu G., Sica G.L., Strome S.E., Cheville J.C., Lau J.S., Zhu Y., Flies D.B., Tamada K., Chen L. J. Immunol. 171:4650-4654(2003) [PubMed: 14568939] [Abstract] Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[12]	"The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation." Salceda S., Tang T., Kmet M., Munteanu A., Ghosh M., Macina R., Liu W., Pilkington G., Papkoff J. Exp. Cell Res. 306:128-141(2005) [PubMed: 15878339] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION.
[13]	"B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma." Kryczek I., Zou L., Rodriguez P., Zhu G., Wei S., Mottram P., Brumlik M., Cheng P., Curiel T., Myers L., Lackner A., Alvarez X., Ochoa A., Chen L., Zou W. J. Exp. Med. 203:871-881(2006) [PubMed: 16606666] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[14]	"Induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells." Kryczek I., Wei S., Zou L., Zhu G., Mottram P., Xu H., Chen L., Zou W. J. Immunol. 177:40-44(2006) [PubMed: 16785496] [Abstract] Cited for: INDUCTION.
[15]	"B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival." Krambeck A.E., Thompson R.H., Dong H., Lohse C.M., Park E.S., Kuntz S.M., Leibovich B.C., Blute M.L., Cheville J.C., Kwon E.D. Proc. Natl. Acad. Sci. U.S.A. 103:10391-10396(2006) [PubMed: 16798883] [Abstract] Cited for: TISSUE SPECIFICITY, USE AS A MARKER FOR RENAL CELL CANCER.
[16]	"Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma." Kryczek I., Wei S., Zhu G., Myers L., Mottram P., Cheng P., Chen L., Coukos G., Zou W. Cancer Res. 67:8900-8905(2007) [PubMed: 17875732] [Abstract] Cited for: FUNCTION, INDUCTION.
[17]	"B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration." Miyatake T., Tringler B., Liu W., Liu S.-H., Papkoff J., Enomoto T., Torkko K.C., Dehn D.L., Swisher A., Shroyer K.R. Gynecol. Oncol. 106:119-127(2007) [PubMed: 17509674] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. AL391476 Genomic DNA. Translation: CAI12739.1. CH471122 Genomic DNA. Translation: EAW56672.1. BC074729 mRNA. Translation: AAH74729.1. DQ836392 mRNA. Translation: ABI16083.1.
IPI	IPI00479574. IPI00640575. IPI00644574.
RefSeq	NP_078902.2. NM_024626.2.
UniGene	Hs.546434.
3D structure databases
HSSP	HSSP built from PDB template 1PKO based on UniProtKB Q63345.
ProteinModelPortal	Q7Z7D3.
SMR	Q7Z7D3. Positions 35-246.
ModBase	Search...
Protein-protein interaction databases
STRING	Q7Z7D3.
Polymorphism databases
DMDM	74759262.
Proteomic databases
PRIDE	Q7Z7D3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000369458; ENSP00000358470; ENSG00000134258.
GeneID	79679.
KEGG	hsa:79679.
UCSC	uc001ehb.1. human. uc009whf.1. human.
Organism-specific databases
CTD	79679.
GeneCards	GC01M117686.
H-InvDB	HIX0000935.
HGNC	HGNC:28873. VTCN1.
MIM	608162. gene.
neXtProt	NX_Q7Z7D3.
PharmGKB	PA142670611.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000063710.
HOVERGEN	HBG097943.
InParanoid	Q7Z7D3.
OrthoDB	EOG4MGS84.
PhylomeDB	Q7Z7D3.
Gene expression databases
ArrayExpress	Q7Z7D3.
Bgee	Q7Z7D3.
CleanEx	HS_VTCN1.
Genevestigator	Q7Z7D3.
Family and domain databases
InterPro	IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013106. Ig_V-set. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 2 hits.
KO	K06747.
Pfam	PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	68926.
SOURCE	Search...

Entry information

Entry name

VTCN1_HUMAN

Accession

Primary (citable) accession number: Q7Z7D3
Secondary accession number(s): Q0GN76 , Q45VN0, Q5WPZ3, Q9H6B2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 10, 2008
Last sequence update:	October 1, 2003
Last modified:	January 25, 2012
This is version 85 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.