KLRB1_HUMAN
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 03-AUG-2022, entry version 147.
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";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 GlyGen; Q12918; 1 site.
DR BioMuta; KLRB1; -.
DR DMDM; 74722301; -.
DR MassIVE; Q12918; -.
DR PaxDb; Q12918; -.
DR PeptideAtlas; Q12918; -.
DR PRIDE; Q12918; -.
DR ProteomicsDB; 59026; -.
DR Antibodypedia; 11606; 930 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 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; TEIRWIC; -.
DR OrthoDB; 1341815at2759; -.
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 1060 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 119 other tissues.
DR Genevisible; Q12918; HS.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; -; 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 Pfam; PF00059; Lectin_C; 1.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
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
