ID   IGSF2_HUMAN             Reviewed;        1021 AA.
AC   Q93033; Q15856;
DT   17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2009, sequence version 2.
DT   24-JAN-2024, entry version 171.
DE   RecName: Full=Immunoglobulin superfamily member 2;
DE            Short=IgSF2;
DE   AltName: Full=Cell surface glycoprotein V7;
DE   AltName: Full=Glu-Trp-Ile EWI motif-containing protein 101;
DE            Short=EWI-101;
DE   AltName: CD_antigen=CD101;
DE   Flags: Precursor;
GN   Name=CD101; Synonyms=EWI101, IGSF2, V7;
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], TISSUE SPECIFICITY, AND VARIANT VAL-415.
RX   PubMed=7722300;
RA   Ruegg C.L., Rivas A., Madani N.D., Zeitung J., Laus R., Engleman E.G.;
RT   "V7, a novel leukocyte surface protein that participates in T cell
RT   activation. II. Molecular cloning and characterization of the V7 gene.";
RL   J. Immunol. 154:4434-4443(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
RP   FUNCTION, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX   PubMed=7722299;
RA   Rivas A., Ruegg C.L., Zeitung J., Laus R., Warnke R., Benike C.,
RA   Engleman E.G.;
RT   "V7, a novel leukocyte surface protein that participates in T cell
RT   activation. I. Tissue distribution and functional studies.";
RL   J. Immunol. 154:4423-4433(1995).
RN   [4]
RP   FUNCTION.
RX   PubMed=9233604;
RA   Soares L.R.B., Rivas A., Tsavaler L., Engleman E.G.;
RT   "Ligation of the V7 molecule on T cells blocks anergy induction through a
RT   CD28-independent mechanism.";
RL   J. Immunol. 159:1115-1124(1997).
RN   [5]
RP   TISSUE SPECIFICITY, AND FUNCTION.
RX   PubMed=9389317; DOI=10.1111/j.1399-0039.1997.tb02898.x;
RA   Bagot M., Martinel I., Charue D., Weill F., Boulland M.-L., Wechsler J.,
RA   Freeman G.J., Bensussan A., Boumsell L.;
RT   "CD101 is expressed by skin dendritic cells. Role in T-lymphocyte
RT   activation.";
RL   Tissue Antigens 50:439-448(1997).
RN   [6]
RP   FUNCTION.
RX   PubMed=9647226;
RA   Soares L.R.B., Tsavaler L., Rivas A., Engleman E.G.;
RT   "V7 (CD101) ligation inhibits TCR/CD3-induced IL-2 production by blocking
RT   Ca2+ flux and nuclear factor of activated T cell nuclear translocation.";
RL   J. Immunol. 161:209-217(1998).
RN   [7]
RP   FUNCTION.
RX   PubMed=11093127;
RX   DOI=10.1002/1521-4141(200011)30:11<3132::aid-immu3132>3.0.co;2-e;
RA   Bouloc A., Bagot M., Delaire S., Bensussan A., Boumsell L.;
RT   "Triggering CD101 molecule on human cutaneous dendritic cells inhibits T
RT   cell proliferation via IL-10 production.";
RL   Eur. J. Immunol. 30:3132-3139(2000).
RN   [8]
RP   TISSUE SPECIFICITY.
RX   PubMed=10692025; DOI=10.1046/j.1365-2559.2000.00827.x;
RA   Bouloc A., Boulland M.-L., Geissmann F., Fraitag S., Andry P., Teillac D.,
RA   Bensussan A., Revuz J., Boumsell L., Wechsler J., Bagot M.;
RT   "CD101 expression by Langerhans cell histiocytosis cells.";
RL   Histopathology 36:229-232(2000).
RN   [9]
RP   DOMAIN EWI MOTIF.
RX   PubMed=11504738; DOI=10.1074/jbc.m107338200;
RA   Stipp C.S., Kolesnikova T.V., Hemler M.E.;
RT   "EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein
RT   subfamily.";
RL   J. Biol. Chem. 276:40545-40554(2001).
RN   [10]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=15737213; DOI=10.1111/j.0022-202x.2005.23617.x;
RA   Meyer N., Petrella T., Poszepczynska-Guigne E., Boumsell L., Wechsler J.,
RA   Bensussan A., Bagot M.;
RT   "CD4+ CD56+ blastic tumor cells express CD101 molecules.";
RL   J. Invest. Dermatol. 124:668-669(2005).
CC   -!- FUNCTION: Plays a role as inhibitor of T-cells proliferation induced by
CC       CD3. Inhibits expression of IL2RA on activated T-cells and secretion of
CC       IL2. Inhibits tyrosine kinases that are required for IL2 production and
CC       cellular proliferation. Inhibits phospholipase C-gamma-1/PLCG1
CC       phosphorylation and subsequent CD3-induced changes in intracellular
CC       free calcium. Prevents nuclear translocation of nuclear factor of
CC       activated T-cell to the nucleus. Plays a role in the inhibition of T-
CC       cell proliferation via IL10 secretion by cutaneous dendritic cells. May
CC       be a marker of CD4(+) CD56(+) leukemic tumor cells.
CC       {ECO:0000269|PubMed:11093127, ECO:0000269|PubMed:15737213,
CC       ECO:0000269|PubMed:7722299, ECO:0000269|PubMed:9233604,
CC       ECO:0000269|PubMed:9389317, ECO:0000269|PubMed:9647226}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in lung, thymus and small intestine.
CC       Detected in cutaneous dendritic cells, activated T-cells, monocytes and
CC       granulocytes as well as with epithelial cells with dendritic
CC       morphology. Expressed in some leukemic cells, the CD4(+) CD56(+)
CC       blastic tumor cells, as well as in Langerhans cells from LCH
CC       (Langerhans cell histiocytosis) patients. {ECO:0000269|PubMed:10692025,
CC       ECO:0000269|PubMed:15737213, ECO:0000269|PubMed:7722299,
CC       ECO:0000269|PubMed:7722300, ECO:0000269|PubMed:9389317}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:7722299}.
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DR   EMBL; Z33642; CAA83923.1; -; mRNA.
DR   EMBL; AL445231; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS891.1; -.
DR   PIR; I39207; I39207.
DR   RefSeq; NP_001243035.1; NM_001256106.2.
DR   RefSeq; NP_001243038.1; NM_001256109.2.
DR   RefSeq; NP_004249.2; NM_004258.5.
DR   AlphaFoldDB; Q93033; -.
DR   BioGRID; 114795; 6.
DR   IntAct; Q93033; 4.
DR   STRING; 9606.ENSP00000358482; -.
DR   GlyCosmos; Q93033; 2 sites, No reported glycans.
DR   GlyGen; Q93033; 4 sites.
DR   iPTMnet; Q93033; -.
DR   PhosphoSitePlus; Q93033; -.
DR   BioMuta; CD101; -.
DR   DMDM; 223590070; -.
DR   EPD; Q93033; -.
DR   jPOST; Q93033; -.
DR   MassIVE; Q93033; -.
DR   PaxDb; 9606-ENSP00000358482; -.
DR   PeptideAtlas; Q93033; -.
DR   ProteomicsDB; 75672; -.
DR   Antibodypedia; 20186; 415 antibodies from 33 providers.
DR   DNASU; 9398; -.
DR   Ensembl; ENST00000256652.8; ENSP00000256652.4; ENSG00000134256.13.
DR   Ensembl; ENST00000369470.1; ENSP00000358482.1; ENSG00000134256.13.
DR   Ensembl; ENST00000682167.1; ENSP00000508039.1; ENSG00000134256.13.
DR   GeneID; 9398; -.
DR   KEGG; hsa:9398; -.
DR   MANE-Select; ENST00000682167.1; ENSP00000508039.1; NM_001256106.3; NP_001243035.1.
DR   UCSC; uc010oxc.3; human.
DR   AGR; HGNC:5949; -.
DR   CTD; 9398; -.
DR   DisGeNET; 9398; -.
DR   GeneCards; CD101; -.
DR   HGNC; HGNC:5949; CD101.
DR   HPA; ENSG00000134256; Tissue enhanced (bone marrow, intestine, lung).
DR   MIM; 604516; gene.
DR   neXtProt; NX_Q93033; -.
DR   OpenTargets; ENSG00000134256; -.
DR   PharmGKB; PA29762; -.
DR   VEuPathDB; HostDB:ENSG00000134256; -.
DR   eggNOG; ENOG502QRRB; Eukaryota.
DR   GeneTree; ENSGT00940000161722; -.
DR   HOGENOM; CLU_005187_0_0_1; -.
DR   InParanoid; Q93033; -.
DR   OMA; SKWVNQA; -.
DR   OrthoDB; 5347942at2759; -.
DR   PhylomeDB; Q93033; -.
DR   TreeFam; TF332702; -.
DR   PathwayCommons; Q93033; -.
DR   Reactome; R-HSA-202433; Generation of second messenger molecules.
DR   SignaLink; Q93033; -.
DR   BioGRID-ORCS; 9398; 21 hits in 1147 CRISPR screens.
DR   ChiTaRS; CD101; human.
DR   GeneWiki; IGSF2; -.
DR   GenomeRNAi; 9398; -.
DR   Pharos; Q93033; Tbio.
DR   PRO; PR:Q93033; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q93033; Protein.
DR   Bgee; ENSG00000134256; Expressed in monocyte and 95 other cell types or tissues.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR   GO; GO:0016812; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides; IEA:InterPro.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0002763; P:positive regulation of myeloid leukocyte differentiation; IEA:Ensembl.
DR   CDD; cd00099; IgV; 3.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 7.
DR   InterPro; IPR002195; Dihydroorotase_CS.
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; IPR013106; Ig_V-set.
DR   PANTHER; PTHR12207:SF25; IMMUNOGLOBULIN SUPERFAMILY MEMBER 2; 1.
DR   PANTHER; PTHR12207; V-SET AND TRANSMEMBRANE DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF07686; V-set; 3.
DR   SMART; SM00409; IG; 7.
DR   SMART; SM00406; IGv; 4.
DR   SUPFAM; SSF48726; Immunoglobulin; 7.
DR   PROSITE; PS50835; IG_LIKE; 7.
DR   Genevisible; Q93033; HS.
PE   1: Evidence at protein level;
KW   Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW   Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..1021
FT                   /note="Immunoglobulin superfamily member 2"
FT                   /id="PRO_0000253539"
FT   TOPO_DOM        21..954
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        955..975
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        976..1021
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          22..139
FT                   /note="Ig-like C2-type 1"
FT   DOMAIN          144..265
FT                   /note="Ig-like C2-type 2"
FT   DOMAIN          279..389
FT                   /note="Ig-like C2-type 3"
FT   DOMAIN          408..525
FT                   /note="Ig-like C2-type 4"
FT   DOMAIN          541..651
FT                   /note="Ig-like C2-type 5"
FT   DOMAIN          656..794
FT                   /note="Ig-like C2-type 6"
FT   DOMAIN          808..925
FT                   /note="Ig-like C2-type 7"
FT   MOTIF           253..255
FT                   /note="EWI motif"
FT   CARBOHYD        44
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        322
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        43..121
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        168..249
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        304..377
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        434..511
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        562..640
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        697..778
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        834..909
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   VARIANT         157
FT                   /note="G -> S (in dbSNP:rs34999087)"
FT                   /id="VAR_054434"
FT   VARIANT         225
FT                   /note="N -> S (in dbSNP:rs3754112)"
FT                   /id="VAR_028371"
FT   VARIANT         415
FT                   /note="M -> V (in dbSNP:rs2249265)"
FT                   /evidence="ECO:0000269|PubMed:7722300"
FT                   /id="VAR_028372"
FT   VARIANT         518
FT                   /note="R -> Q (in dbSNP:rs17235766)"
FT                   /id="VAR_028373"
FT   VARIANT         525
FT                   /note="S -> R (in dbSNP:rs17235773)"
FT                   /id="VAR_028374"
FT   VARIANT         631
FT                   /note="T -> S (in dbSNP:rs34510762)"
FT                   /id="VAR_054435"
FT   VARIANT         933
FT                   /note="R -> Q (in dbSNP:rs12093834)"
FT                   /id="VAR_054436"
FT   VARIANT         955
FT                   /note="L -> F (in dbSNP:rs34223095)"
FT                   /id="VAR_054437"
FT   VARIANT         965
FT                   /note="V -> I (in dbSNP:rs12097758)"
FT                   /id="VAR_028375"
FT   VARIANT         988
FT                   /note="R -> C (in dbSNP:rs12067543)"
FT                   /id="VAR_028376"
FT   VARIANT         992
FT                   /note="R -> W (in dbSNP:rs34248572)"
FT                   /id="VAR_054438"
FT   CONFLICT        91
FT                   /note="S -> G (in Ref. 1; CAA83923)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        129
FT                   /note="K -> N (in Ref. 1; CAA83923)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        135
FT                   /note="S -> R (in Ref. 1; CAA83923)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        352
FT                   /note="V -> L (in Ref. 1; CAA83923)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        684
FT                   /note="V -> G (in Ref. 1; CAA83923)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1021 AA;  115109 MW;  12A07C648D21EB91 CRC64;
     MAGISYVASF FLLLTKLSIG QREVTVQKGP LFRAEGYPVS IGCNVTGHQG PSEQHFQWSV
     YLPTNPTQEV QIISTKDAAF SYAVYTQRVR SGDVYVERVQ GNSVLLHISK LQMKDAGEYE
     CHTPNTDEKY YGSYSAKTNL IVIPDTLSAT MSSQTLGKEE GEPLALTCEA SKATAQHTHL
     SVTWYLTQDG GGSQATEIIS LSKDFILVPG PLYTERFAAS DVQLNKLGPT TFRLSIERLQ
     SSDQGQLFCE ATEWIQDPDE TWMFITKKQT DQTTLRIQPA VKDFQVNITA DSLFAEGKPL
     ELVCLVVSSG RDPQLQGIWF FNGTEIAHID AGGVLGLKND YKERASQGEL QVSKLGPKAF
     SLKIFSLGPE DEGAYRCVVA EVMKTRTGSW QVLQRKQSPD SHVHLRKPAA RSVVMSTKNK
     QQVVWEGETL AFLCKAGGAE SPLSVSWWHI PRDQTQPEFV AGMGQDGIVQ LGASYGVPSY
     HGNTRLEKMD WATFQLEITF TAITDSGTYE CRVSEKSRNQ ARDLSWTQKI SVTVKSLESS
     LQVSLMSRQP QVMLTNTFDL SCVVRAGYSD LKVPLTVTWQ FQPASSHIFH QLIRITHNGT
     IEWGNFLSRF QKKTKVSQSL FRSQLLVHDA TEEETGVYQC EVEVYDRNSL YNNRPPRASA
     ISHPLRIAVT LPESKLKVNS RSQVQELSIN SNTDIECSIL SRSNGNLQLA IIWYFSPVST
     NASWLKILEM DQTNVIKTGD EFHTPQRKQK FHTEKVSQDL FQLHILNVED SDRGKYHCAV
     EEWLLSTNGT WHKLGEKKSG LTELKLKPTG SKVRVSKVYW TENVTEHREV AIRCSLESVG
     SSATLYSVMW YWNRENSGSK LLVHLQHDGL LEYGEEGLRR HLHCYRSSST DFVLKLHQVE
     MEDAGMYWCR VAEWQLHGHP SKWINQASDE SQRMVLTVLP SEPTLPSRIC SSAPLLYFLF
     ICPFVLLLLL LISLLCLYWK ARKLSTLRSN TRKEKALWVD LKEAGGVTTN RREDEEEDEG
     N
//