ID PD1L2_MOUSE Reviewed; 247 AA.
AC Q9WUL5;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 27-MAR-2024, entry version 157.
DE RecName: Full=Programmed cell death 1 ligand 2;
DE Short=PD-1 ligand 2;
DE Short=PD-L2;
DE Short=PDCD1 ligand 2;
DE Short=Programmed death ligand 2;
DE AltName: Full=Butyrophilin B7-DC;
DE Short=B7-DC;
DE AltName: CD_antigen=CD273;
DE Flags: Precursor;
GN Name=Pdcd1lg2; Synonyms=B7dc, Btdc, Cd273, Pdl2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH PDCD1, AND TISSUE
RP SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=11283156; DOI=10.1084/jem.193.7.839;
RA Tseng S.-Y., Otsuji M., Gorski K., Huang X., Slansky J.E., Pai S.I.,
RA Shalabi A., Shin T., Pardoll D.M., Tsuchiya H.;
RT "B7-DC, a new dendritic cell molecule with potent costimulatory properties
RT for T cells.";
RL J. Exp. Med. 193:839-846(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11224527; DOI=10.1038/85330;
RA Latchman Y., Wood C.R., Chernova T., Chaudhary D., Borde M., Chernova I.,
RA Iwai Y., Long A.J., Brown J.A., Nunes R., Greenfield E.A., Bourque K.,
RA Boussiotis V.A., Carter L.L., Carreno B.M., Malenkovich N., Nishimura H.,
RA Okazaki T., Honjo T., Sharpe A.H., Freeman G.J.;
RT "PD-L2 is a second ligand for PD-1 and inhibits T cell activation.";
RL Nat. Immunol. 2:261-268(2001).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF ASP-33; SER-39; GLU-41; ARG-56; SER-58;
RP ASP-65; SER-67; GLU-71; ARG-72; LYS-84; HIS-88; ARG-101; LEU-103; ILE-105;
RP ASP-111; LYS-113 AND THR-116.
RX PubMed=12719480; DOI=10.1084/jem.20021752;
RA Wang S., Bajorath J., Flies D.B., Dong H., Honjo T., Chen L.;
RT "Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple
RT costimulatory function from PD-1 interaction.";
RL J. Exp. Med. 197:1083-1091(2003).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-220 IN COMPLEX WITH PDCD1, AND
RP DISULFIDE BOND.
RX PubMed=18641123; DOI=10.1073/pnas.0804453105;
RA Lazar-Molnar E., Yan Q., Cao E., Ramagopal U., Nathenson S.G., Almo S.C.;
RT "Crystal structure of the complex between programmed death-1 (PD-1) and its
RT ligand PD-L2.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10483-10488(2008).
CC -!- FUNCTION: Involved in the costimulatory signal essential for T-cell
CC proliferation and IFNG production in a PDCD1-independent manner.
CC Interaction with PDCD1 inhibits T-cell proliferation by blocking cell
CC cycle progression and cytokine production.
CC {ECO:0000269|PubMed:11224527, ECO:0000269|PubMed:11283156,
CC ECO:0000269|PubMed:12719480}.
CC -!- SUBUNIT: Interacts with PDCD1. {ECO:0000269|PubMed:11283156,
CC ECO:0000269|PubMed:18641123}.
CC -!- INTERACTION:
CC Q9WUL5; Q02242: Pdcd1; NbExp=2; IntAct=EBI-15716794, EBI-5258903;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9BQ51};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q9BQ51,
CC ECO:0000305|PubMed:18641123}.
CC -!- TISSUE SPECIFICITY: Expressed in immature and mature bone marrow-
CC derived dendritic cells and splenic dendritic cells. Highly expressed
CC in placenta, liver and weakly expressed in heart, spleen, lymph nodes
CC and thymus. Also expressed in some tumor cell lines of lymphoid origin.
CC {ECO:0000269|PubMed:11224527, ECO:0000269|PubMed:11283156}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. BTN/MOG family.
CC {ECO:0000305}.
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DR EMBL; AF142780; AAD33892.1; -; mRNA.
DR EMBL; AK089369; BAC40858.1; -; mRNA.
DR CCDS; CCDS29736.1; -.
DR RefSeq; NP_067371.1; NM_021396.2.
DR PDB; 3BOV; X-ray; 1.77 A; A=20-123.
DR PDB; 3BP5; X-ray; 1.80 A; B=20-220.
DR PDB; 3BP6; X-ray; 1.60 A; B=20-220.
DR PDB; 3RNK; X-ray; 1.74 A; B=20-123.
DR PDB; 3RNQ; X-ray; 1.60 A; B=20-220.
DR PDBsum; 3BOV; -.
DR PDBsum; 3BP5; -.
DR PDBsum; 3BP6; -.
DR PDBsum; 3RNK; -.
DR PDBsum; 3RNQ; -.
DR AlphaFoldDB; Q9WUL5; -.
DR SMR; Q9WUL5; -.
DR BioGRID; 208388; 1.
DR DIP; DIP-46166N; -.
DR IntAct; Q9WUL5; 1.
DR STRING; 10090.ENSMUSP00000158422; -.
DR BindingDB; Q9WUL5; -.
DR ChEMBL; CHEMBL4523499; -.
DR GlyCosmos; Q9WUL5; 4 sites, No reported glycans.
DR GlyGen; Q9WUL5; 4 sites.
DR PhosphoSitePlus; Q9WUL5; -.
DR PaxDb; 10090-ENSMUSP00000108195; -.
DR ProteomicsDB; 294037; -.
DR ABCD; Q9WUL5; 27 sequenced antibodies.
DR Antibodypedia; 2736; 1253 antibodies from 43 providers.
DR DNASU; 58205; -.
DR Ensembl; ENSMUST00000112576.4; ENSMUSP00000108195.3; ENSMUSG00000016498.11.
DR Ensembl; ENSMUST00000235164.2; ENSMUSP00000158422.2; ENSMUSG00000016498.11.
DR GeneID; 58205; -.
DR KEGG; mmu:58205; -.
DR UCSC; uc008hdk.2; mouse.
DR AGR; MGI:1930125; -.
DR CTD; 80380; -.
DR MGI; MGI:1930125; Pdcd1lg2.
DR VEuPathDB; HostDB:ENSMUSG00000016498; -.
DR eggNOG; ENOG502S1Y9; Eukaryota.
DR GeneTree; ENSGT00940000161373; -.
DR HOGENOM; CLU_013137_8_3_1; -.
DR InParanoid; Q9WUL5; -.
DR OMA; ELYIVEH; -.
DR OrthoDB; 5315576at2759; -.
DR PhylomeDB; Q9WUL5; -.
DR TreeFam; TF331083; -.
DR Reactome; R-MMU-389948; PD-1 signaling.
DR BioGRID-ORCS; 58205; 1 hit in 81 CRISPR screens.
DR ChiTaRS; Pdcd1lg2; mouse.
DR EvolutionaryTrace; Q9WUL5; -.
DR PRO; PR:Q9WUL5; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9WUL5; Protein.
DR Bgee; ENSMUSG00000016498; Expressed in gastrula and 25 other cell types or tissues.
DR ExpressionAtlas; Q9WUL5; baseline and differential.
DR Genevisible; Q9WUL5; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISO:MGI.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:MGI.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IDA:MGI.
DR GO; GO:0032689; P:negative regulation of type II interferon production; ISO:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:MGI.
DR GO; GO:0031295; P:T cell costimulation; IBA:GO_Central.
DR CDD; cd20986; IgC1_PD-L2; 1.
DR CDD; cd20983; IgV_PD-L2; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR InterPro; IPR013162; CD80_C2-set.
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 PANTHER; PTHR25466:SF1; PROGRAMMED CELL DEATH 1 LIGAND 2; 1.
DR PANTHER; PTHR25466; T-LYMPHOCYTE ACTIVATION ANTIGEN; 1.
DR Pfam; PF08205; C2-set_2; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000250|UniProtKB:Q9BQ51"
FT CHAIN 20..247
FT /note="Programmed cell death 1 ligand 2"
FT /id="PRO_0000014556"
FT TOPO_DOM 20..221
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..247
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..118
FT /note="Ig-like V-type"
FT DOMAIN 122..203
FT /note="Ig-like C2-type"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 42..102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 143..192
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:18641123"
FT MUTAGEN 33
FT /note="D->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 39
FT /note="S->Y: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 41
FT /note="E->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 56
FT /note="R->S: Significantly reduces the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 58
FT /note="S->Y: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 65
FT /note="D->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 67
FT /note="S->Y: Significantly reduces the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 71
FT /note="E->S: Significantly reduces the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 72
FT /note="R->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 84
FT /note="K->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 88
FT /note="H->A: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 101
FT /note="R->S: Significantly reduces the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 103
FT /note="L->A: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 105
FT /note="I->A: Abolishes the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 111
FT /note="D->S: Abolishes the binding to PDCD1. Costimulates
FT proliferation and IFNG production of T-cells."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 113
FT /note="K->S: Abolishes the binding to PDCD1. Costimulates
FT proliferation and IFNG production of T-cells."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 116
FT /note="T->Y: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT STRAND 28..33
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 38..44
FT /evidence="ECO:0007829|PDB:3BP6"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:3RNQ"
FT HELIX 52..54
FT /evidence="ECO:0007829|PDB:3RNQ"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:3RNK"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:3RNQ"
FT HELIX 77..82
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:3BP6"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 98..106
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 109..121
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 126..132
FT /evidence="ECO:0007829|PDB:3BP6"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 139..149
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 163..168
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 174..182
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:3BP6"
FT TURN 197..200
FT /evidence="ECO:0007829|PDB:3BP6"
FT STRAND 201..207
FT /evidence="ECO:0007829|PDB:3BP6"
SQ SEQUENCE 247 AA; 27820 MW; 9BFDDE14F3EC138F CRC64;
MLLLLPILNL SLQLHPVAAL FTVTAPKEVY TVDVGSSVSL ECDFDRRECT ELEGIRASLQ
KVENDTSLQS ERATLLEEQL PLGKALFHIP SVQVRDSGQY RCLVICGAAW DYKYLTVKVK
ASYMRIDTRI LEVPGTGEVQ LTCQARGYPL AEVSWQNVSV PANTSHIRTP EGLYQVTSVL
RLKPQPSRNF SCMFWNAHMK ELTSAIIDPL SRMEPKVPRT WPLHVFIPAC TIALIFLAIV
IIQRKRI
//
