BTNL2_HUMAN
ID BTNL2_HUMAN Reviewed; 455 AA.
AC Q9UIR0; A0PJV5; B0UYW9; B0V0N6; O98261; Q08E96; Q58R22; Q58R23; Q5JYF9;
AC Q5MP42; Q5MP43; Q5RIF8; Q5SP08; Q5SP09; Q5SRW3; Q5SRW4; Q5SU36; Q95HK0;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Butyrophilin-like protein 2;
DE Short=BTL-II;
GN Name=BTNL2;
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 [GENOMIC DNA].
RX PubMed=10803852; DOI=10.1007/s002510050633;
RA Stammers M., Rowen L., Rhodes D., Trowsdale J., Beck S.;
RT "BTL-II: a polymorphic locus with homology to the butyrophilin gene family,
RT located at the border of the major histocompatibility complex class II and
RT class III regions in human and mouse.";
RL Immunogenetics 51:373-382(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, ALTERNATIVE
RP SPLICING, TISSUE SPECIFICITY, INDUCTION, AND INVOLVEMENT IN SS2.
RX PubMed=15735647; DOI=10.1038/ng1519;
RA Valentonyte R., Hampe J., Huse K., Rosenstiel P., Albrecht M., Stenzel A.,
RA Nagy M., Gaede K.I., Franke A., Haesler R., Koch A., Lengauer T.,
RA Seegert D., Reiling N., Ehlers S., Schwinger E., Platzer M., Krawczak M.,
RA Mueller-Quernheim J., Schuermann M., Schreiber S.;
RT "Sarcoidosis is associated with a truncating splice site mutation in
RT BTNL2.";
RL Nat. Genet. 37:357-364(2005).
RN [3]
RP ERRATUM OF PUBMED:15735647.
RA Valentonyte R., Hampe J., Huse K., Rosenstiel P., Albrecht M., Stenzel A.,
RA Nagy M., Gaede K.I., Franke A., Haesler R., Koch A., Lengauer T.,
RA Seegert D., Reiling N., Ehlers S., Schwinger E., Platzer M., Krawczak M.,
RA Mueller-Quernheim J., Schuermann M., Schreiber S.;
RL Nat. Genet. 37:652-652(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS GLU-196 AND
RP LEU-334.
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5).
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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-109 (ISOFORMS 1/2/3/6).
RX PubMed=15516930; DOI=10.1038/ng1469;
RA Hiller M., Huse K., Szafranski K., Jahn N., Hampe J., Schreiber S.,
RA Backofen R., Platzer M.;
RT "Widespread occurrence of alternative splicing at NAGNAG acceptors
RT contributes to proteome plasticity.";
RL Nat. Genet. 36:1255-1257(2004).
CC -!- FUNCTION: Negative regulator of T-cell proliferation. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9UIR0-4; Q96CV9: OPTN; NbExp=3; IntAct=EBI-25911105, EBI-748974;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15735647}; Single-
CC pass type II membrane protein {ECO:0000269|PubMed:15735647}.
CC Note=Isoform 2 is present in the nuclear, vesicle and plasma membranes,
CC isoform 3 is found in cytoplasmic vesicle structures and is not
CC membrane bound.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q9UIR0-1; Sequence=Displayed;
CC Name=2; Synonyms=Long;
CC IsoId=Q9UIR0-2; Sequence=VSP_027186, VSP_027191;
CC Name=3; Synonyms=Short;
CC IsoId=Q9UIR0-3; Sequence=VSP_027186, VSP_027189, VSP_027190;
CC Name=4;
CC IsoId=Q9UIR0-4; Sequence=VSP_027185;
CC Name=5;
CC IsoId=Q9UIR0-5; Sequence=VSP_027184;
CC Name=6;
CC IsoId=Q9UIR0-6; Sequence=VSP_027187, VSP_027188;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver, pancreas,
CC ovary, leukocyte, small intestine, testis and thymus.
CC {ECO:0000269|PubMed:15735647}.
CC -!- INDUCTION: By pro-inflammatory cytokines such as TNF and
CC IL1B/interleukin-1 beta. {ECO:0000269|PubMed:15735647}.
CC -!- DISEASE: Sarcoidosis 2 (SS2) [MIM:612387]: An idiopathic, systemic,
CC inflammatory disease characterized by the formation of immune
CC granulomas in involved organs. Granulomas predominantly invade the
CC lungs and the lymphatic system, but also skin, liver, spleen, eyes and
CC other organs may be involved. {ECO:0000269|PubMed:15735647}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry. A nucleotide transition affecting a
CC splice donor site results in the use of an alternative splice site and
CC the production of isoform 3. Individuals expressing isoform 3 have a
CC higher risk for sarcoidosis.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. BTN/MOG family.
CC {ECO:0000305}.
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DR EMBL; AF186593; AAF05530.1; -; Genomic_DNA.
DR EMBL; AF186588; AAF05530.1; JOINED; Genomic_DNA.
DR EMBL; AF186589; AAF05530.1; JOINED; Genomic_DNA.
DR EMBL; AF186591; AAF05530.1; JOINED; Genomic_DNA.
DR EMBL; AF186592; AAF05530.1; JOINED; Genomic_DNA.
DR EMBL; AF186590; AAF05530.1; JOINED; Genomic_DNA.
DR EMBL; AY881999; AAX35330.1; -; Genomic_DNA.
DR EMBL; AY881999; AAX35331.1; -; Genomic_DNA.
DR EMBL; AL034394; CAI42180.1; -; Genomic_DNA.
DR EMBL; Z84814; CAI42180.1; JOINED; Genomic_DNA.
DR EMBL; Z84814; CAC69895.2; -; Genomic_DNA.
DR EMBL; AL034394; CAC69895.2; JOINED; Genomic_DNA.
DR EMBL; AL662796; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL670296; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL935032; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX255945; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR753634; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC119668; AAI19669.1; -; mRNA.
DR EMBL; BC127642; AAI27643.1; -; mRNA.
DR EMBL; AY684332; AAV91022.1; -; mRNA.
DR EMBL; AY684333; AAV91023.1; -; mRNA.
DR RefSeq; NP_001291490.1; NM_001304561.1.
DR AlphaFoldDB; Q9UIR0; -.
DR BioGRID; 121112; 179.
DR IntAct; Q9UIR0; 1.
DR STRING; 9606.ENSP00000390613; -.
DR GlyGen; Q9UIR0; 2 sites.
DR iPTMnet; Q9UIR0; -.
DR PhosphoSitePlus; Q9UIR0; -.
DR BioMuta; BTNL2; -.
DR DMDM; 73921189; -.
DR EPD; Q9UIR0; -.
DR jPOST; Q9UIR0; -.
DR MassIVE; Q9UIR0; -.
DR PaxDb; Q9UIR0; -.
DR PeptideAtlas; Q9UIR0; -.
DR PRIDE; Q9UIR0; -.
DR ProteomicsDB; 84559; -. [Q9UIR0-6]
DR Antibodypedia; 50239; 133 antibodies from 19 providers.
DR DNASU; 56244; -.
DR Ensembl; ENST00000544175.3; ENSP00000443364.2; ENSG00000204290.11.
DR Ensembl; ENST00000548253.2; ENSP00000447733.1; ENSG00000224242.7.
DR Ensembl; ENST00000548717.3; ENSP00000449356.1; ENSG00000225412.7.
DR Ensembl; ENST00000548832.5; ENSP00000448852.2; ENSG00000229741.7. [Q9UIR0-4]
DR Ensembl; ENST00000549560.2; ENSP00000448550.2; ENSG00000226127.7. [Q9UIR0-5]
DR Ensembl; ENST00000549852.4; ENSP00000446915.2; ENSG00000225845.7.
DR Ensembl; ENST00000549943.2; ENSP00000449578.2; ENSG00000224770.7. [Q9UIR0-5]
DR Ensembl; ENST00000550327.5; ENSP00000447985.1; ENSG00000226127.7. [Q9UIR0-1]
DR Ensembl; ENST00000550531.3; ENSP00000448023.1; ENSG00000229597.7. [Q9UIR0-1]
DR Ensembl; ENST00000550698.3; ENSP00000447616.1; ENSG00000229597.7. [Q9UIR0-5]
DR Ensembl; ENST00000551095.2; ENSP00000449546.1; ENSG00000229741.7. [Q9UIR0-1]
DR Ensembl; ENST00000551669.4; ENSP00000446794.1; ENSG00000224242.7.
DR Ensembl; ENST00000551686.5; ENSP00000450139.1; ENSG00000225412.7.
DR Ensembl; ENST00000552479.5; ENSP00000449365.1; ENSG00000224770.7. [Q9UIR0-1]
DR Ensembl; ENST00000553032.5; ENSP00000447291.2; ENSG00000229741.7. [Q9UIR0-5]
DR GeneID; 56244; -.
DR KEGG; hsa:56244; -.
DR UCSC; uc003obg.1; human. [Q9UIR0-1]
DR CTD; 56244; -.
DR DisGeNET; 56244; -.
DR GeneCards; BTNL2; -.
DR HGNC; HGNC:1142; BTNL2.
DR HPA; ENSG00000204290; Not detected.
DR MalaCards; BTNL2; -.
DR MIM; 606000; gene.
DR MIM; 612387; phenotype.
DR neXtProt; NX_Q9UIR0; -.
DR Orphanet; 797; Sarcoidosis.
DR PharmGKB; PA25463; -.
DR VEuPathDB; HostDB:ENSG00000204290; -.
DR eggNOG; ENOG502QSRZ; Eukaryota.
DR HOGENOM; CLU_032563_1_0_1; -.
DR InParanoid; Q9UIR0; -.
DR OrthoDB; 522383at2759; -.
DR PhylomeDB; Q9UIR0; -.
DR TreeFam; TF331083; -.
DR PathwayCommons; Q9UIR0; -.
DR Reactome; R-HSA-8851680; Butyrophilin (BTN) family interactions.
DR SignaLink; Q9UIR0; -.
DR BioGRID-ORCS; 56244; 1 hit in 199 CRISPR screens.
DR GeneWiki; BTNL2; -.
DR GenomeRNAi; 56244; -.
DR Pharos; Q9UIR0; Tbio.
DR PRO; PR:Q9UIR0; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9UIR0; protein.
DR Bgee; ENSG00000204290; Expressed in sural nerve and 83 other tissues.
DR ExpressionAtlas; Q9UIR0; baseline and differential.
DR Genevisible; Q9UIR0; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0001817; P:regulation of cytokine production; IBA:GO_Central.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 2.
DR SMART; SM00409; IG; 3.
DR SMART; SM00407; IGc1; 1.
DR SMART; SM00406; IGv; 2.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Membrane; Reference proteome; Repeat; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..455
FT /note="Butyrophilin-like protein 2"
FT /id="PRO_0000014537"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..23
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 24..455
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 29..140
FT /note="Ig-like V-type 1"
FT DOMAIN 142..234
FT /note="Ig-like V-type 2"
FT DOMAIN 236..355
FT /note="Ig-like V-type 3"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 427
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 50..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 164..218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 267..341
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..277
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027184"
FT VAR_SEQ 28..237
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027185"
FT VAR_SEQ 143..236
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_027186"
FT VAR_SEQ 244..259
FT /note="ASLKVNGPSQPILVRV -> GKYEVLAHTCGGSLCP (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_027187"
FT VAR_SEQ 260..455
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_027188"
FT VAR_SEQ 360..364
FT /note="SLGSS -> WVLPH (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_027189"
FT VAR_SEQ 365..455
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_027190"
FT VAR_SEQ 454..455
FT /note="GW -> ESRMTFLWKTLLVWGLLLAVAVGLPRKRS (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_027191"
FT VARIANT 94
FT /note="W -> R (in dbSNP:rs28362682)"
FT /id="VAR_033602"
FT VARIANT 181
FT /note="R -> Q (in dbSNP:rs28362681)"
FT /id="VAR_061307"
FT VARIANT 188
FT /note="V -> M (in dbSNP:rs9461742)"
FT /id="VAR_049837"
FT VARIANT 196
FT /note="K -> E (in dbSNP:rs2076523)"
FT /evidence="ECO:0000269|PubMed:14574404"
FT /id="VAR_021171"
FT VARIANT 202
FT /note="A -> V (in dbSNP:rs28362680)"
FT /id="VAR_061308"
FT VARIANT 283
FT /note="D -> V (in dbSNP:rs34423804)"
FT /id="VAR_033603"
FT VARIANT 334
FT /note="S -> L (in dbSNP:rs28362679)"
FT /evidence="ECO:0000269|PubMed:14574404"
FT /id="VAR_029128"
FT VARIANT 352
FT /note="A -> T (in dbSNP:rs35037492)"
FT /id="VAR_033604"
FT VARIANT 360
FT /note="S -> G (in dbSNP:rs2076530)"
FT /id="VAR_049838"
FT VARIANT 379
FT /note="P -> L (in dbSNP:rs28362678)"
FT /id="VAR_033605"
FT VARIANT 380
FT /note="M -> I (in dbSNP:rs28362677)"
FT /id="VAR_033606"
FT VARIANT 393
FT /note="P -> Q (in dbSNP:rs41521946)"
FT /id="VAR_033607"
FT CONFLICT 27
FT /note="Missing (in Ref. 6; AAV91023)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9UIR0-4:150
FT /note="S -> G (in Ref. 5; AAI27643)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9UIR0-5:83
FT /note="S -> G (in Ref. 5; AAI19669)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 455 AA; 50436 MW; 4194025C7416F839 CRC64;
MVDFPGYNLS GAVASFLFIL LTMKQSEDFR VIGPAHPILA GVGEDALLTC QLLPKRTTMH
VEVRWYRSEP STPVFVHRDG VEVTEMQMEE YRGWVEWIEN GIAKGNVALK IHNIQPSDNG
QYWCHFQDGN YCGETSLLLK VAGLGSAPSI HMEGPGESGV QLVCTARGWF PEPQVYWEDI
RGEKLLAVSE HRIQDKDGLF YAEATLVVRN ASAESVSCLV HNPVLTEEKG SVISLPEKLQ
TELASLKVNG PSQPILVRVG EDIQLTCYLS PKANAQSMEV RWDRSHRYPA VHVYMDGDHV
AGEQMAEYRG RTVLVSDAID EGRLTLQILS ARPSDDGQYR CLFEKDDVYQ EASLDLKVVS
LGSSPLITVE GQEDGEMQPM CSSDGWFPQP HVPWRDMEGK TIPSSSQALT QGSHGLFHVQ
TLLRVTNISA VDVTCSISIP FLGEEKIATF SLSGW
