ID   KLRB1_HUMAN             Reviewed;         225 AA.
AC   Q12918; Q24K24;
DT   14-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   24-JAN-2024, entry version 155.
DE   RecName: Full=Killer cell lectin-like receptor subfamily B member 1;
DE   AltName: Full=C-type lectin domain family 5 member B;
DE   AltName: Full=HNKR-P1a;
DE            Short=NKR-P1A;
DE   AltName: Full=Natural killer cell surface protein P1A;
DE   AltName: CD_antigen=CD161;
GN   Name=KLRB1; Synonyms=CLEC5B, NKRP1A;
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], GLYCOSYLATION, HOMODIMERIZATION, TISSUE
RP   SPECIFICITY, AND FUNCTION.
RX   PubMed=8077657;
RA   Lanier L.L., Chang C., Phillips J.H.;
RT   "Human NKR-P1A: a disulfide-linked homodimer of the C-type lectin
RT   superfamily expressed by a subset of NK and T lymphocytes.";
RL   J. Immunol. 153:2417-2428(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-168.
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   [3]
RP   INDUCTION BY IL12.
RX   PubMed=9603467;
RX   DOI=10.1002/(sici)1521-4141(199805)28:05<1611::aid-immu1611>3.0.co;2-6;
RA   Poggi A., Costa P., Tomasello E., Moretta L.;
RT   "IL-12-induced up-regulation of NKRP1A expression in human NK cells and
RT   consequent NKRP1A-mediated down-regulation of NK cell activation.";
RL   Eur. J. Immunol. 28:1611-1616(1998).
RN   [4]
RP   TISSUE SPECIFICITY.
RX   PubMed=12100027; DOI=10.1046/j.1365-2249.2002.01886.x;
RA   Iiai T., Watanabe H., Suda T., Okamoto H., Abo T., Hatakeyama K.;
RT   "CD161+ T (NT) cells exist predominantly in human intestinal epithelium as
RT   well as in liver.";
RL   Clin. Exp. Immunol. 129:92-98(2002).
RN   [5]
RP   INTERACTION WITH CLEC2D.
RX   PubMed=16339512; DOI=10.4049/jimmunol.175.12.7791;
RA   Aldemir H., Prod'homme V., Dumaurier M.-J., Retiere C., Poupon G.,
RA   Cazareth J., Bihl F., Braud V.M.;
RT   "Lectin-like transcript 1 is a ligand for the CD161 receptor.";
RL   J. Immunol. 175:7791-7795(2005).
RN   [6]
RP   INTERACTION WITH CLEC2D.
RX   PubMed=16339513; DOI=10.4049/jimmunol.175.12.7796;
RA   Rosen D.B., Bettadapura J., Alsharifi M., Mathew P.A., Warren H.S.,
RA   Lanier L.L.;
RT   "Lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A
RT   receptor.";
RL   J. Immunol. 175:7796-7799(2005).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH SMPD1.
RX   PubMed=16455998; DOI=10.4049/jimmunol.176.4.2397;
RA   Pozo D., Vales-Gomez M., Mavaddat N., Williamson S.C., Chisholm S.E.,
RA   Reyburn H.;
RT   "CD161 (human NKR-P1A) signaling in NK cells involves the activation of
RT   acid sphingomyelinase.";
RL   J. Immunol. 176:2397-2406(2006).
RN   [8]
RP   FUNCTION AS A LECTIN.
RX   PubMed=16925668; DOI=10.1111/j.1399-3089.2006.00332.x;
RA   Christiansen D., Mouhtouris E., Milland J., Zingoni A., Santoni A.,
RA   Sandrin M.S.;
RT   "Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161).";
RL   Xenotransplantation 13:440-446(2006).
RN   [9]
RP   INTERACTION WITH CLEC2D.
RX   PubMed=20843815; DOI=10.1074/jbc.m110.179622;
RA   Germain C., Bihl F., Zahn S., Poupon G., Dumaurier M.J., Rampanarivo H.H.,
RA   Padkjaer S.B., Spee P., Braud V.M.;
RT   "Characterization of alternatively spliced transcript variants of CLEC2D
RT   gene.";
RL   J. Biol. Chem. 285:36207-36215(2010).
CC   -!- FUNCTION: Plays an inhibitory role on natural killer (NK) cells
CC       cytotoxicity. Activation results in specific acid
CC       sphingomyelinase/SMPD1 stimulation with subsequent marked elevation of
CC       intracellular ceramide. Activation also leads to AKT1/PKB and
CC       RPS6KA1/RSK1 kinases stimulation as well as markedly enhanced T-cell
CC       proliferation induced by anti-CD3. Acts as a lectin that binds to the
CC       terminal carbohydrate Gal-alpha(1,3)Gal epitope as well as to the N-
CC       acetyllactosamine epitope. Binds also to CLEC2D/LLT1 as a ligand and
CC       inhibits NK cell-mediated cytotoxicity as well as interferon-gamma
CC       secretion in target cells. {ECO:0000269|PubMed:16455998,
CC       ECO:0000269|PubMed:16925668, ECO:0000269|PubMed:8077657}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with acid
CC       sphingomyelinase/SMPD1. {ECO:0000269|PubMed:16339512,
CC       ECO:0000269|PubMed:16339513, ECO:0000269|PubMed:16455998,
CC       ECO:0000269|PubMed:20843815}.
CC   -!- INTERACTION:
CC       Q12918; Q9UHP7-1: CLEC2D; NbExp=2; IntAct=EBI-2805465, EBI-13640978;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type II
CC       membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in a subset of NK cells predominantly in
CC       intestinal epithelium and liver. Detected in peripheral blood T-cells
CC       and preferentially in adult T-cells with a memory antigenic phenotype.
CC       {ECO:0000269|PubMed:12100027, ECO:0000269|PubMed:8077657}.
CC   -!- INDUCTION: By IL12/interleukin-12 in NK cells.
CC       {ECO:0000269|PubMed:9603467}.
CC   -!- PTM: N-glycosylated. Contains sialic acid residues.
CC       {ECO:0000269|PubMed:8077657}.
CC   -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC       Note=NKRP1;
CC       URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_248";
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DR   EMBL; U11276; AAA21605.1; -; mRNA.
DR   EMBL; BC113997; AAI13998.1; -; mRNA.
DR   EMBL; BC114516; AAI14517.1; -; mRNA.
DR   CCDS; CCDS8601.1; -.
DR   PIR; I38700; I38700.
DR   RefSeq; NP_002249.1; NM_002258.2.
DR   PDB; 5MGR; X-ray; 1.80 A; A/B=90-225.
DR   PDB; 5MGS; X-ray; 1.90 A; A/B/C/D/E/F/G/H=90-225.
DR   PDB; 5MGT; X-ray; 1.90 A; C/D/E/F=90-225.
DR   PDBsum; 5MGR; -.
DR   PDBsum; 5MGS; -.
DR   PDBsum; 5MGT; -.
DR   AlphaFoldDB; Q12918; -.
DR   SMR; Q12918; -.
DR   BioGRID; 110019; 75.
DR   IntAct; Q12918; 2.
DR   STRING; 9606.ENSP00000229402; -.
DR   UniLectin; Q12918; -.
DR   GlyCosmos; Q12918; 1 site, No reported glycans.
DR   GlyGen; Q12918; 1 site.
DR   BioMuta; KLRB1; -.
DR   DMDM; 74722301; -.
DR   MassIVE; Q12918; -.
DR   PaxDb; 9606-ENSP00000229402; -.
DR   PeptideAtlas; Q12918; -.
DR   ProteomicsDB; 59026; -.
DR   Antibodypedia; 11606; 1020 antibodies from 38 providers.
DR   DNASU; 3820; -.
DR   Ensembl; ENST00000229402.4; ENSP00000229402.3; ENSG00000111796.4.
DR   GeneID; 3820; -.
DR   KEGG; hsa:3820; -.
DR   MANE-Select; ENST00000229402.4; ENSP00000229402.3; NM_002258.3; NP_002249.1.
DR   UCSC; uc010sgt.3; human.
DR   AGR; HGNC:6373; -.
DR   CTD; 3820; -.
DR   DisGeNET; 3820; -.
DR   GeneCards; KLRB1; -.
DR   HGNC; HGNC:6373; KLRB1.
DR   HPA; ENSG00000111796; Tissue enhanced (bone marrow, lymphoid tissue).
DR   MIM; 602890; gene.
DR   neXtProt; NX_Q12918; -.
DR   OpenTargets; ENSG00000111796; -.
DR   PharmGKB; PA30162; -.
DR   VEuPathDB; HostDB:ENSG00000111796; -.
DR   eggNOG; KOG4297; Eukaryota.
DR   GeneTree; ENSGT00940000154685; -.
DR   HOGENOM; CLU_049894_8_2_1; -.
DR   InParanoid; Q12918; -.
DR   OMA; TENKWIC; -.
DR   OrthoDB; 4828219at2759; -.
DR   PhylomeDB; Q12918; -.
DR   TreeFam; TF337735; -.
DR   PathwayCommons; Q12918; -.
DR   Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR   SignaLink; Q12918; -.
DR   BioGRID-ORCS; 3820; 10 hits in 1140 CRISPR screens.
DR   GeneWiki; KLRB1; -.
DR   GenomeRNAi; 3820; -.
DR   Pharos; Q12918; Tbio.
DR   PRO; PR:Q12918; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q12918; Protein.
DR   Bgee; ENSG00000111796; Expressed in granulocyte and 120 other cell types or tissues.
DR   GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0030246; F:carbohydrate binding; TAS:ProtInc.
DR   GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0042269; P:regulation of natural killer cell mediated cytotoxicity; IBA:GO_Central.
DR   CDD; cd03593; CLECT_NK_receptors_like; 1.
DR   Gene3D; 3.10.100.10; Mannose-Binding Protein A, subunit A; 1.
DR   InterPro; IPR001304; C-type_lectin-like.
DR   InterPro; IPR016186; C-type_lectin-like/link_sf.
DR   InterPro; IPR016187; CTDL_fold.
DR   InterPro; IPR033992; NKR-like_CTLD.
DR   PANTHER; PTHR46784; KILLER CELL LECTIN-LIKE RECEPTOR SUBFAMILY B MEMBER 1; 1.
DR   PANTHER; PTHR46784:SF1; KILLER CELL LECTIN-LIKE RECEPTOR SUBFAMILY B MEMBER 1; 1.
DR   Pfam; PF00059; Lectin_C; 1.
DR   SMART; SM00034; CLECT; 1.
DR   SUPFAM; SSF56436; C-type lectin-like; 1.
DR   PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
DR   Genevisible; Q12918; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Disulfide bond; Glycoprotein; Lectin; Membrane; Receptor;
KW   Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN           1..225
FT                   /note="Killer cell lectin-like receptor subfamily B member
FT                   1"
FT                   /id="PRO_0000260000"
FT   TOPO_DOM        1..45
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        46..66
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        67..225
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          101..211
FT                   /note="C-type lectin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        94..105
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT   DISULFID        122..210
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT   DISULFID        189..202
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT   VARIANT         168
FT                   /note="I -> T (in dbSNP:rs1135816)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_028981"
FT   STRAND          92..94
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   STRAND          99..101
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   STRAND          104..108
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   HELIX           115..124
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   HELIX           135..142
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   STRAND          152..159
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   TURN            160..163
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   STRAND          164..167
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   STRAND          188..192
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   STRAND          197..201
FT                   /evidence="ECO:0007829|PDB:5MGR"
FT   STRAND          206..213
FT                   /evidence="ECO:0007829|PDB:5MGR"
SQ   SEQUENCE   225 AA;  25415 MW;  01BFA925445B83B0 CRC64;
     MDQQAIYAEL NLPTDSGPES SSPSSLPRDV CQGSPWHQFA LKLSCAGIIL LVLVVTGLSV
     SVTSLIQKSS IEKCSVDIQQ SRNKTTERPG LLNCPIYWQQ LREKCLLFSH TVNPWNNSLA
     DCSTKESSLL LIRDKDELIH TQNLIRDKAI LFWIGLNFSL SEKNWKWING SFLNSNDLEI
     RGDAKENSCI SISQTSVYSE YCSTEIRWIC QKELTPVRNK VYPDS
//