VSIG4_HUMAN
ID VSIG4_HUMAN Reviewed; 399 AA.
AC Q9Y279; Q6UXI4;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=V-set and immunoglobulin domain-containing protein 4;
DE AltName: Full=Protein Z39Ig;
DE Flags: Precursor;
GN Name=VSIG4; Synonyms=CRIg, Z39IG; ORFNames=UNQ317/PRO362;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=11004523; DOI=10.1016/s0167-4781(00)00131-7;
RA Langnaese K., Colleaux L., Kloos D.U., Fontes M., Wieacker P.;
RT "Cloning of Z39Ig, a novel gene with immunoglobulin-like domains located on
RT human chromosome X.";
RL Biochim. Biophys. Acta 1492:522-525(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 20-34.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17016562; DOI=10.1172/jci25673;
RA Vogt L., Schmitz N., Kurrer M.O., Bauer M., Hinton H.I., Behnke S.,
RA Gatto D., Sebbel P., Beerli R.R., Sonderegger I., Kopf M., Saudan P.,
RA Bachmann M.F.;
RT "VSIG4, a B7 family-related protein, is a negative regulator of T cell
RT activation.";
RL J. Clin. Invest. 116:2817-2826(2006).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 19-137 IN COMPLEX WITH C3B AND
RP C3C, FUNCTION, AND DISULFIDE BOND.
RX PubMed=17051150; DOI=10.1038/nature05263;
RA Wiesmann C., Katschke K.J., Yin J., Helmy K.Y., Steffek M.,
RA Fairbrother W.J., McCallum S.A., Embuscado L., DeForge L., Hass P.E.,
RA van Lookeren Campagne M.;
RT "Structure of C3b in complex with CRIg gives insights into regulation of
RT complement activation.";
RL Nature 444:217-220(2006).
CC -!- FUNCTION: Phagocytic receptor, strong negative regulator of T-cell
CC proliferation and IL2 production. Potent inhibitor of the alternative
CC complement pathway convertases. {ECO:0000269|PubMed:17016562,
CC ECO:0000269|PubMed:17051150}.
CC -!- INTERACTION:
CC Q9Y279; Q969F0: FATE1; NbExp=3; IntAct=EBI-903131, EBI-743099;
CC Q9Y279; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-903131, EBI-10266796;
CC Q9Y279; O95183: VAMP5; NbExp=3; IntAct=EBI-903131, EBI-10191195;
CC Q9Y279-1; P01024: C3; NbExp=5; IntAct=EBI-903144, EBI-905851;
CC Q9Y279-2; P01024: C3; NbExp=2; IntAct=EBI-903148, EBI-905851;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y279-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y279-2; Sequence=VSP_012813;
CC Name=3;
CC IsoId=Q9Y279-3; Sequence=VSP_041213;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in several fetal tissues. In
CC adult tissues, highest expression in lung and placenta. Expressed in
CC resting macrophages. {ECO:0000269|PubMed:11004523,
CC ECO:0000269|PubMed:17016562}.
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DR EMBL; AJ132502; CAB51536.1; -; mRNA.
DR EMBL; AY358341; AAQ88707.1; -; mRNA.
DR EMBL; AL034397; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR607860; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC010525; AAH10525.1; -; mRNA.
DR CCDS; CCDS14383.1; -. [Q9Y279-1]
DR CCDS; CCDS48132.1; -. [Q9Y279-3]
DR CCDS; CCDS55435.1; -. [Q9Y279-2]
DR RefSeq; NP_001093901.1; NM_001100431.1. [Q9Y279-3]
DR RefSeq; NP_001171759.1; NM_001184830.1. [Q9Y279-2]
DR RefSeq; NP_001171760.1; NM_001184831.1.
DR RefSeq; NP_001244332.1; NM_001257403.1.
DR RefSeq; NP_009199.1; NM_007268.2. [Q9Y279-1]
DR PDB; 2ICC; X-ray; 1.20 A; A=19-137.
DR PDB; 2ICE; X-ray; 3.10 A; S/T=19-137.
DR PDB; 2ICF; X-ray; 4.10 A; S=19-137.
DR PDB; 5IMK; X-ray; 1.23 A; A=19-232.
DR PDB; 5IML; X-ray; 1.80 A; A=19-232.
DR PDBsum; 2ICC; -.
DR PDBsum; 2ICE; -.
DR PDBsum; 2ICF; -.
DR PDBsum; 5IMK; -.
DR PDBsum; 5IML; -.
DR AlphaFoldDB; Q9Y279; -.
DR SMR; Q9Y279; -.
DR BioGRID; 116455; 207.
DR IntAct; Q9Y279; 39.
DR STRING; 9606.ENSP00000363869; -.
DR GlyGen; Q9Y279; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y279; -.
DR PhosphoSitePlus; Q9Y279; -.
DR BioMuta; VSIG4; -.
DR DMDM; 59799152; -.
DR jPOST; Q9Y279; -.
DR MassIVE; Q9Y279; -.
DR PaxDb; Q9Y279; -.
DR PeptideAtlas; Q9Y279; -.
DR PRIDE; Q9Y279; -.
DR ProteomicsDB; 85683; -. [Q9Y279-1]
DR ProteomicsDB; 85684; -. [Q9Y279-2]
DR ProteomicsDB; 85685; -. [Q9Y279-3]
DR ABCD; Q9Y279; 1 sequenced antibody.
DR Antibodypedia; 13115; 218 antibodies from 32 providers.
DR DNASU; 11326; -.
DR Ensembl; ENST00000374737.9; ENSP00000363869.4; ENSG00000155659.15. [Q9Y279-1]
DR Ensembl; ENST00000412866.2; ENSP00000394143.2; ENSG00000155659.15. [Q9Y279-3]
DR Ensembl; ENST00000455586.6; ENSP00000411581.2; ENSG00000155659.15. [Q9Y279-2]
DR GeneID; 11326; -.
DR KEGG; hsa:11326; -.
DR MANE-Select; ENST00000374737.9; ENSP00000363869.4; NM_007268.3; NP_009199.1.
DR UCSC; uc004dwh.3; human. [Q9Y279-1]
DR CTD; 11326; -.
DR DisGeNET; 11326; -.
DR GeneCards; VSIG4; -.
DR HGNC; HGNC:17032; VSIG4.
DR HPA; ENSG00000155659; Tissue enhanced (lung).
DR MIM; 300353; gene.
DR neXtProt; NX_Q9Y279; -.
DR OpenTargets; ENSG00000155659; -.
DR PharmGKB; PA134986421; -.
DR VEuPathDB; HostDB:ENSG00000155659; -.
DR eggNOG; ENOG502S07Y; Eukaryota.
DR GeneTree; ENSGT00390000001432; -.
DR HOGENOM; CLU_058836_0_0_1; -.
DR InParanoid; Q9Y279; -.
DR OMA; NDYSEDP; -.
DR OrthoDB; 816499at2759; -.
DR PhylomeDB; Q9Y279; -.
DR TreeFam; TF336175; -.
DR PathwayCommons; Q9Y279; -.
DR SignaLink; Q9Y279; -.
DR BioGRID-ORCS; 11326; 9 hits in 696 CRISPR screens.
DR ChiTaRS; VSIG4; human.
DR EvolutionaryTrace; Q9Y279; -.
DR GenomeRNAi; 11326; -.
DR Pharos; Q9Y279; Tbio.
DR PRO; PR:Q9Y279; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9Y279; protein.
DR Bgee; ENSG00000155659; Expressed in right lung and 177 other tissues.
DR ExpressionAtlas; Q9Y279; baseline and differential.
DR Genevisible; Q9Y279; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0032991; C:protein-containing complex; IPI:UniProtKB.
DR GO; GO:0001851; F:complement component C3b binding; IPI:UniProtKB.
DR GO; GO:0006957; P:complement activation, alternative pathway; IEA:UniProtKB-KW.
DR GO; GO:0045957; P:negative regulation of complement activation, alternative pathway; IPI:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IBA:GO_Central.
DR GO; GO:0043031; P:negative regulation of macrophage activation; IEA:InterPro.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IBA:GO_Central.
DR CDD; cd16089; IgV_CRIg; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR039939; VSIG4.
DR InterPro; IPR039944; VSIG4_IgV.
DR PANTHER; PTHR15466; PTHR15466; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complement alternate pathway;
KW Direct protein sequencing; Disulfide bond; Immunity; Immunoglobulin domain;
KW Innate immunity; Membrane; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 20..399
FT /note="V-set and immunoglobulin domain-containing protein
FT 4"
FT /id="PRO_0000015006"
FT TOPO_DOM 20..283
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 284..304
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..399
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..131
FT /note="Ig-like 1"
FT DOMAIN 143..226
FT /note="Ig-like 2"
FT DISULFID 41..113
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:17051150"
FT DISULFID 165..211
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 138..232
FT /note="LSVSKPTVTTGSGYGFTVPQGMRISLQCQARGSPPISYIWYKQQTNNQEPIK
FT VATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHSDIVKFVVKD -> H (in
FT isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_041213"
FT VAR_SEQ 322..399
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_012813"
FT VARIANT 108
FT /note="R -> W (in dbSNP:rs34581041)"
FT /id="VAR_049956"
FT VARIANT 272
FT /note="G -> E (in dbSNP:rs34222730)"
FT /id="VAR_049957"
FT VARIANT 279
FT /note="G -> E (in dbSNP:rs17315645)"
FT /id="VAR_049958"
FT VARIANT 397
FT /note="S -> I (in dbSNP:rs35553694)"
FT /id="VAR_049959"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:5IMK"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:2ICC"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:2ICC"
FT STRAND 50..58
FT /evidence="ECO:0007829|PDB:2ICC"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:2ICC"
FT STRAND 65..71
FT /evidence="ECO:0007829|PDB:2ICC"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:2ICC"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:2ICC"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:2ICC"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:2ICC"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:2ICC"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:2ICC"
FT STRAND 109..118
FT /evidence="ECO:0007829|PDB:2ICC"
FT STRAND 124..136
FT /evidence="ECO:0007829|PDB:2ICC"
SQ SEQUENCE 399 AA; 43987 MW; 735CA3BC58185035 CRC64;
MGILLGLLLL GHLTVDTYGR PILEVPESVT GPWKGDVNLP CTYDPLQGYT QVLVKWLVQR
GSDPVTIFLR DSSGDHIQQA KYQGRLHVSH KVPGDVSLQL STLEMDDRSH YTCEVTWQTP
DGNQVVRDKI TELRVQKLSV SKPTVTTGSG YGFTVPQGMR ISLQCQARGS PPISYIWYKQ
QTNNQEPIKV ATLSTLLFKP AVIADSGSYF CTAKGQVGSE QHSDIVKFVV KDSSKLLKTK
TEAPTTMTYP LKATSTVKQS WDWTTDMDGY LGETSAGPGK SLPVFAIILI ISLCCMVVFT
MAYIMLCRKT SQQEHVYEAA RAHAREANDS GETMRVAIFA SGCSSDEPTS QNLGNNYSDE
PCIGQEYQII AQINGNYARL LDTVPLDYEF LATEGKSVC
