CL12B_HUMAN
ID CL12B_HUMAN Reviewed; 276 AA.
AC Q2HXU8; Q6UWF2; Q6ZRG0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=C-type lectin domain family 12 member B;
DE AltName: Full=Macrophage antigen H {ECO:0000303|PubMed:17562706};
GN Name=CLEC12B {ECO:0000303|PubMed:34310951, ECO:0000312|HGNC:HGNC:31966};
GN ORFNames=UNQ5782/PRO16089;
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), FUNCTION, SUBCELLULAR LOCATION,
RP SUBUNIT, INTERACTION WITH PTPN6 AND PTPN11, TISSUE SPECIFICITY, INDUCTION,
RP DOMAIN, MUTAGENESIS OF TYR-7, PHOSPHORYLATION AT TYR-7, AND ALTERNATIVE
RP SPLICING.
RX PubMed=17562706; DOI=10.1074/jbc.m704250200;
RA Hoffmann S.C., Schellack C., Textor S., Konold S., Schmitz D., Cerwenka A.,
RA Pflanz S., Watzl C.;
RT "Identification of CLEC12B, an inhibitory receptor on myeloid cells.";
RL J. Biol. Chem. 282:22370-22375(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT LEU-116.
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 2), AND VARIANTS ASN-6 AND
RP LEU-116.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, PTM, INTERACTION WITH PTPN11, DOMAIN, AND
RP MUTAGENESIS OF TYR-7.
RX PubMed=34310951; DOI=10.1016/j.jid.2021.05.035;
RA Montaudie H., Sormani L., Dadone-Montaudie B., Heim M., Cardot-Leccia N.,
RA Tulic M.K., Beranger G., Gay A.S., Debayle D., Cheli Y., Raymond J.H.,
RA Sohier P., Petit V., Rocchi S., Gesbert F., Larue L., Passeron T.;
RT "CLEC12B Decreases Melanoma Proliferation by Repressing Signal Transducer
RT and Activator of Transcription 3.";
RL J. Invest. Dermatol. 142:425-434(2022).
CC -!- FUNCTION: Inhibitory receptor postulated to negatively regulate immune
CC and non-immune functions (PubMed:17562706, PubMed:34310951). Upon
CC phosphorylation, recruits SH2 domain-containing PTPN6 and PTPN11
CC phosphatases to its ITIM motif and antagonizes activation signals
CC (PubMed:17562706, PubMed:34310951). Although it inhibits KLRK1/NKG2D-
CC mediated signaling, it does not bind known ligands of KLRK1/NKG2D and
CC therefore is not its inhibitory counterpart (PubMed:17562706). May
CC limit activation of myeloid cell subsets in response to infection or
CC tissue inflammation (PubMed:17562706). May protect target cells against
CC natural killer cell-mediated lysis (PubMed:17562706). May negatively
CC regulate cell cycle and differentiation of melanocytes via inactivation
CC of STAT3 (PubMed:34310951). {ECO:0000269|PubMed:17562706,
CC ECO:0000269|PubMed:34310951}.
CC -!- SUBUNIT: Homodimer. Interacts (via ITIM motif) with PTPN6
CC (PubMed:17562706). Interacts (via ITIM motif) with PTPN11; this
CC interaction triggers dephosphorylation and activation of PTPN11
CC (PubMed:17562706, PubMed:34310951). {ECO:0000269|PubMed:17562706,
CC ECO:0000269|PubMed:34310951}.
CC -!- INTERACTION:
CC Q2HXU8-2; Q01638-2: IL1RL1; NbExp=3; IntAct=EBI-12811991, EBI-12838366;
CC Q2HXU8-2; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-12811991, EBI-10266796;
CC Q2HXU8-2; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-12811991, EBI-12033434;
CC Q2HXU8-2; Q8N112: LSMEM2; NbExp=3; IntAct=EBI-12811991, EBI-10264855;
CC Q2HXU8-2; Q13021: MALL; NbExp=3; IntAct=EBI-12811991, EBI-750078;
CC Q2HXU8-2; P35372-10: OPRM1; NbExp=3; IntAct=EBI-12811991, EBI-12807478;
CC Q2HXU8-2; Q9Y342: PLLP; NbExp=3; IntAct=EBI-12811991, EBI-3919291;
CC Q2HXU8-2; Q01453: PMP22; NbExp=3; IntAct=EBI-12811991, EBI-2845982;
CC Q2HXU8-2; O00767: SCD; NbExp=3; IntAct=EBI-12811991, EBI-2684237;
CC Q2HXU8-2; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-12811991, EBI-8652744;
CC Q2HXU8-2; Q3ZAQ7: VMA21; NbExp=3; IntAct=EBI-12811991, EBI-1055364;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17562706};
CC Single-pass type II membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q2HXU8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2HXU8-2; Sequence=VSP_030034, VSP_030035;
CC -!- TISSUE SPECIFICITY: Detected in colon, heart, kidney, liver, lung,
CC mammary gland, ovary, spleen and testis (PubMed:17562706). Expressed in
CC melanocytes (at protein level) (PubMed:34310951).
CC {ECO:0000269|PubMed:17562706, ECO:0000269|PubMed:34310951}.
CC -!- INDUCTION: Up-regulated upon differentiation of monocytes to
CC macrophages. {ECO:0000269|PubMed:17562706}.
CC -!- DOMAIN: Contains 1 copy of a cytoplasmic motif that is referred to as
CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is
CC involved in modulation of cellular responses. The phosphorylated ITIM
CC motif can bind the SH2 domain of several SH2-containing phosphatases.
CC {ECO:0000269|PubMed:17562706, ECO:0000269|PubMed:34310951}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:34310951}.
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DR EMBL; DQ368812; ABC96323.1; -; mRNA.
DR EMBL; AY358810; AAQ89170.1; -; mRNA.
DR EMBL; AK128243; BAC87350.1; -; mRNA.
DR EMBL; CH471094; EAW96136.1; -; Genomic_DNA.
DR CCDS; CCDS44830.1; -. [Q2HXU8-1]
DR CCDS; CCDS8610.1; -. [Q2HXU8-2]
DR RefSeq; NP_001123470.1; NM_001129998.2. [Q2HXU8-1]
DR RefSeq; NP_995324.2; NM_205852.3. [Q2HXU8-2]
DR AlphaFoldDB; Q2HXU8; -.
DR SMR; Q2HXU8; -.
DR BioGRID; 132463; 217.
DR IntAct; Q2HXU8; 11.
DR STRING; 9606.ENSP00000344563; -.
DR GlyGen; Q2HXU8; 3 sites.
DR iPTMnet; Q2HXU8; -.
DR PhosphoSitePlus; Q2HXU8; -.
DR BioMuta; CLEC12B; -.
DR DMDM; 121941174; -.
DR MassIVE; Q2HXU8; -.
DR MaxQB; Q2HXU8; -.
DR PaxDb; Q2HXU8; -.
DR PeptideAtlas; Q2HXU8; -.
DR PRIDE; Q2HXU8; -.
DR Antibodypedia; 57539; 69 antibodies from 18 providers.
DR DNASU; 387837; -.
DR Ensembl; ENST00000338896.11; ENSP00000344563.5; ENSG00000256660.7. [Q2HXU8-1]
DR Ensembl; ENST00000396502.5; ENSP00000379759.1; ENSG00000256660.7. [Q2HXU8-2]
DR Ensembl; ENST00000544853.5; ENSP00000439561.1; ENSG00000256660.7. [Q2HXU8-2]
DR GeneID; 387837; -.
DR KEGG; hsa:387837; -.
DR MANE-Select; ENST00000338896.11; ENSP00000344563.5; NM_001129998.3; NP_001123470.1.
DR UCSC; uc001qwx.3; human. [Q2HXU8-1]
DR CTD; 387837; -.
DR DisGeNET; 387837; -.
DR GeneCards; CLEC12B; -.
DR HGNC; HGNC:31966; CLEC12B.
DR HPA; ENSG00000256660; Group enriched (bone marrow, skin, testis).
DR MIM; 617573; gene.
DR neXtProt; NX_Q2HXU8; -.
DR OpenTargets; ENSG00000256660; -.
DR PharmGKB; PA162382325; -.
DR VEuPathDB; HostDB:ENSG00000256660; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000162751; -.
DR HOGENOM; CLU_049894_5_1_1; -.
DR InParanoid; Q2HXU8; -.
DR OMA; IMFLQMS; -.
DR PhylomeDB; Q2HXU8; -.
DR TreeFam; TF336674; -.
DR PathwayCommons; Q2HXU8; -.
DR SignaLink; Q2HXU8; -.
DR BioGRID-ORCS; 387837; 11 hits in 1064 CRISPR screens.
DR ChiTaRS; CLEC12B; human.
DR GenomeRNAi; 387837; -.
DR Pharos; Q2HXU8; Tbio.
DR PRO; PR:Q2HXU8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q2HXU8; protein.
DR Bgee; ENSG00000256660; Expressed in monocyte and 84 other tissues.
DR ExpressionAtlas; Q2HXU8; baseline and differential.
DR Genevisible; Q2HXU8; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IMP:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0019903; F:protein phosphatase binding; IDA:UniProtKB.
DR GO; GO:0030547; F:signaling receptor inhibitor activity; IMP:UniProtKB.
DR GO; GO:0097325; P:melanocyte proliferation; IDA:UniProtKB.
DR GO; GO:0002769; P:natural killer cell inhibitory signaling pathway; IMP:UniProtKB.
DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; IMP:UniProtKB.
DR GO; GO:1904893; P:negative regulation of receptor signaling pathway via STAT; IDA:UniProtKB.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; IMP:UniProtKB.
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; IPR042916; CLEC12A/B.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR013600; Ly49_N.
DR InterPro; IPR033992; NKR-like_CTLD.
DR PANTHER; PTHR47647; PTHR47647; 1.
DR Pfam; PF00059; Lectin_C; 1.
DR Pfam; PF08391; Ly49; 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 Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein; Lectin;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..276
FT /note="C-type lectin domain family 12 member B"
FT /id="PRO_0000313581"
FT TOPO_DOM 1..43
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 44..64
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 65..276
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 150..264
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT MOTIF 5..10
FT /note="ITIM motif"
FT /evidence="ECO:0000303|PubMed:17562706"
FT MOD_RES 7
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:17562706"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 237
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 172..263
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 242..255
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT VAR_SEQ 228..232
FT /note="FSTKE -> YVSNY (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_030034"
FT VAR_SEQ 233..276
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_030035"
FT VARIANT 6
FT /note="T -> N (in dbSNP:rs1359082)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_037670"
FT VARIANT 116
FT /note="V -> L (in dbSNP:rs637790)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_037671"
FT MUTAGEN 7
FT /note="Y->F: Abolishes tyrosine phosphorylation and
FT inhibitory receptor activity. Abolishes interaction with
FT PTPN6 and PTPN11. Abolishes protection against natural
FT killer cell-mediated cytotoxicity."
FT /evidence="ECO:0000269|PubMed:17562706,
FT ECO:0000269|PubMed:34310951"
SQ SEQUENCE 276 AA; 31616 MW; 3FD95A30C5C1BAC4 CRC64;
MSEEVTYATL TFQDSAGARN NRDGNNLRKR GHPAPSPIWR HAALGLVTLC LMLLIGLVTL
GMMFLQISND INSDSEKLSQ LQKTIQQQQD NLSQQLGNSN NLSMEEEFLK SQISSVLKRQ
EQMAIKLCQE LIIHTSDHRC NPCPKMWQWY QNSCYYFTTN EEKTWANSRK DCIDKNSTLV
KIDSLEEKDF LMSQPLLMFS FFWLGLSWDS SGRSWFWEDG SVPSPSLFST KELDQINGSK
GCAYFQKGNI YISRCSAEIF WICEKTAAPV KTEDLD
