Q9Y279 (VSIG4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
V-set and immunoglobulin domain-containing protein 4

Alternative name(s):
Protein Z39Ig

Gene names

Name:	VSIG4
Synonyms:	CRIg, Z39IG
ORF Names:	UNQ317/PRO362

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	399 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	Phagocytic receptor, strong negative regulator of T-cell proliferation and IL2 production. Potent inhibitor of the alternative complement pathway convertases. Ref.7 Ref.8
Subcellular location	Membrane; Single-pass type I membrane protein Probable.
Tissue specificity	Abundantly expressed in several fetal tissues. In adult tissues, highest expression in lung and placenta. Expressed in resting macrophages. Ref.1 Ref.7
Sequence similarities	Contains 2 Ig-like (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Complement alternate pathway Immunity Innate immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	complement activation, alternative pathway Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of T cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of interleukin-2 production Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
C3	P01024	5	EBI-903144,EBI-905851

Alternative products

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

Isoform 1 (identifier: Q9Y279-1)

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: Q9Y279-2)

The sequence of this isoform differs from the canonical sequence as follows:
     322-399: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9Y279-3)

The sequence of this isoform differs from the canonical sequence as follows:
     138-232: LSVSKPTVTT...SDIVKFVVKD → H

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.6

Chain

20 – 399

380

V-set and immunoglobulin domain-containing protein 4

PRO_0000015006

Regions

Topological domain

20 – 283

264

Extracellular Potential

Transmembrane

284 – 304

21

Helical; Potential

Topological domain

305 – 399

95

Cytoplasmic Potential

Domain

21 – 131

111

Ig-like 1

Domain

143 – 226

84

Ig-like 2

Amino acid modifications

Disulfide bond

41 ↔ 113

Ref.8

Disulfide bond

165 ↔ 211

By similarity

Natural variations

Alternative sequence

138 – 232

95

LSVSK…FVVKD → H in isoform 3.

VSP_041213

Alternative sequence

322 – 399

78

Missing in isoform 2.

VSP_012813

Natural variant

108

1

R → W.
Corresponds to variant rs34581041 [ dbSNP | Ensembl ].

VAR_049956

Natural variant

272

1

G → E.
Corresponds to variant rs34222730 [ dbSNP | Ensembl ].

VAR_049957

Natural variant

279

1

G → E.
Corresponds to variant rs17315645 [ dbSNP | Ensembl ].

VAR_049958

Natural variant

397

1

S → I.
Corresponds to variant rs35553694 [ dbSNP | Ensembl ].

VAR_049959

Secondary structure

1

.

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399

Helix Strand Turn

Details...

Beta strand

27 – 32

6

Beta strand

37 – 39

3

Beta strand

50 – 58

9

Beta strand

60 – 63

4

Beta strand

65 – 71

7

Beta strand

74 – 77

4

Helix

80 – 82

3

Turn

83 – 85

3

Beta strand

86 – 88

3

Beta strand

98 – 100

3

Helix

105 – 107

3

Beta strand

109 – 118

10

Beta strand

124 – 136

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 735CA3BC58185035	FASTA	399	43,987
	10 20 30 40 50 60 MGILLGLLLL GHLTVDTYGR PILEVPESVT GPWKGDVNLP CTYDPLQGYT QVLVKWLVQR 70 80 90 100 110 120 GSDPVTIFLR DSSGDHIQQA KYQGRLHVSH KVPGDVSLQL STLEMDDRSH YTCEVTWQTP 130 140 150 160 170 180 DGNQVVRDKI TELRVQKLSV SKPTVTTGSG YGFTVPQGMR ISLQCQARGS PPISYIWYKQ 190 200 210 220 230 240 QTNNQEPIKV ATLSTLLFKP AVIADSGSYF CTAKGQVGSE QHSDIVKFVV KDSSKLLKTK 250 260 270 280 290 300 TEAPTTMTYP LKATSTVKQS WDWTTDMDGY LGETSAGPGK SLPVFAIILI ISLCCMVVFT 310 320 330 340 350 360 MAYIMLCRKT SQQEHVYEAA RAHAREANDS GETMRVAIFA SGCSSDEPTS QNLGNNYSDE 370 380 390 PCIGQEYQII AQINGNYARL LDTVPLDYEF LATEGKSVC
	Isoform 2 [UniParc]. Checksum: B2AB2E3151D39C6E	FASTA	321	35,544
	10 20 30 40 50 60 MGILLGLLLL GHLTVDTYGR PILEVPESVT GPWKGDVNLP CTYDPLQGYT QVLVKWLVQR 70 80 90 100 110 120 GSDPVTIFLR DSSGDHIQQA KYQGRLHVSH KVPGDVSLQL STLEMDDRSH YTCEVTWQTP 130 140 150 160 170 180 DGNQVVRDKI TELRVQKLSV SKPTVTTGSG YGFTVPQGMR ISLQCQARGS PPISYIWYKQ 190 200 210 220 230 240 QTNNQEPIKV ATLSTLLFKP AVIADSGSYF CTAKGQVGSE QHSDIVKFVV KDSSKLLKTK 250 260 270 280 290 300 TEAPTTMTYP LKATSTVKQS WDWTTDMDGY LGETSAGPGK SLPVFAIILI ISLCCMVVFT 310 320 MAYIMLCRKT SQQEHVYEAA R
	Isoform 3 [UniParc]. Checksum: 12C57C74CCD69134	FASTA	305	33,857
	10 20 30 40 50 60 MGILLGLLLL GHLTVDTYGR PILEVPESVT GPWKGDVNLP CTYDPLQGYT QVLVKWLVQR 70 80 90 100 110 120 GSDPVTIFLR DSSGDHIQQA KYQGRLHVSH KVPGDVSLQL STLEMDDRSH YTCEVTWQTP 130 140 150 160 170 180 DGNQVVRDKI TELRVQKHSS KLLKTKTEAP TTMTYPLKAT STVKQSWDWT TDMDGYLGET 190 200 210 220 230 240 SAGPGKSLPV FAIILIISLC CMVVFTMAYI MLCRKTSQQE HVYEAARAHA REANDSGETM 250 260 270 280 290 300 RVAIFASGCS SDEPTSQNLG NNYSDEPCIG QEYQIIAQIN GNYARLLDTV PLDYEFLATE GKSVC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of Z39Ig, a novel gene with immunoglobulin-like domains located on human chromosome X." Langnaese K., Colleaux L., Kloos D.U., Fontes M., Wieacker P. Biochim. Biophys. Acta 1492:522-525(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Placenta.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] 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] (ISOFORM 1). Tissue: Brain.
[6]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-34.
[7]	"VSIG4, a B7 family-related protein, is a negative regulator of T cell activation." Vogt L., Schmitz N., Kurrer M.O., Bauer M., Hinton H.I., Behnke S., Gatto D., Sebbel P., Beerli R.R., Sonderegger I., Kopf M., Saudan P., Bachmann M.F. J. Clin. Invest. 116:2817-2826(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]	"Structure of C3b in complex with CRIg gives insights into regulation of complement activation." Wiesmann C., Katschke K.J., Yin J., Helmy K.Y., Steffek M., Fairbrother W.J., McCallum S.A., Embuscado L., DeForge L., Hass P.E., van Lookeren Campagne M. Nature 444:217-220(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 19-137 IN COMPLEX WITH C3B AND C3C, FUNCTION, DISULFIDE BOND.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ132502 mRNA. Translation: CAB51536.1.
AY358341 mRNA. Translation: AAQ88707.1.
AL034397 Genomic DNA. Translation: CAB46921.1.
CR607860 mRNA. No translation available.
BC010525 mRNA. Translation: AAH10525.1.

IPI

IPI00027038.
IPI00552123.
IPI00641261.

RefSeq

NP_001093901.1. NM_001100431.1.
NP_001171759.1. NM_001184830.1.
NP_001171760.1. NM_001184831.1.
NP_001244332.1. NM_001257403.1.
NP_009199.1. NM_007268.2.

UniGene

Hs.8904.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ICC	X-ray	1.20	A	19-137	[»]
2ICE	X-ray	3.10	S/T	19-137	[»]
2ICF	X-ray	4.10	S	19-137	[»]

ProteinModelPortal

Q9Y279.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y279. 2 interactions.

STRING

9606.ENSP00000363869.

PTM databases

PhosphoSite

Q9Y279.

Polymorphism databases

DMDM

59799152.

Proteomic databases

PaxDb

Q9Y279.

PRIDE

Q9Y279.

Protocols and materials databases

DNASU

11326.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000374737; ENSP00000363869; ENSG00000155659.
ENST00000412866; ENSP00000394143; ENSG00000155659.
ENST00000455586; ENSP00000411581; ENSG00000155659.

GeneID

11326.

KEGG

hsa:11326.

UCSC

uc004dwh.2. human.
uc004dwi.2. human.

Organism-specific databases

CTD

11326.

GeneCards

GC0XM065241.

HGNC

HGNC:17032. VSIG4.

HPA

CAB026000.
HPA003903.

MIM

300353. gene.

neXtProt

NX_Q9Y279.

PharmGKB

PA134986421.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39012.

HOGENOM

HOG000137602.

HOVERGEN

HBG055008.

InParanoid

Q9Y279.

OMA

LCCMVVF.

OrthoDB

EOG41JZC8.

Gene expression databases

ArrayExpress

Q9Y279.

Bgee

Q9Y279.

CleanEx

HS_VSIG4.

Genevestigator

Q9Y279.

GermOnline

ENSG00000155659. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 2 hits.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
[Graphical view]

Pfam

PF07686. V-set. 1 hit.
[Graphical view]

SMART

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

PROSITE

PS50835. IG_LIKE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9Y279.

GenomeRNAi

11326.

NextBio

43025.

SOURCE

Search...

Entry information

Entry name

VSIG4_HUMAN

Accession

Primary (citable) accession number: Q9Y279
Secondary accession number(s): Q6UXI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 15, 2005
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 110 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.