PD1L2_HUMAN
ID PD1L2_HUMAN Reviewed; 273 AA.
AC Q9BQ51; Q14CN8; Q5T7Z6; Q6JXL8; Q6JXL9;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 164.
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, CD273, PDCD1L2, PDL2;
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), INDUCTION, AND VARIANT SER-229.
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION, AND
RP VARIANT SER-229.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), SUBCELLULAR LOCATION
RP (ISOFORMS 1; 2 AND 3), AND VARIANT SER-229.
RX PubMed=15253154; DOI=10.1093/abbs/36.4.284;
RA He X.-H., Liu Y., Xu L.-H., Zeng Y.-Y.;
RT "Cloning and identification of two novel splice variants of human PD-L2.";
RL Acta Biochim. Biophys. Sin. 36:284-289(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-229.
RC TISSUE=Brain, and Lung;
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 PROTEIN SEQUENCE OF 20-34.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PDCD1. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9BQ51; P27449: ATP6V0C; NbExp=3; IntAct=EBI-16427978, EBI-721179;
CC Q9BQ51; Q7Z2K6: ERMP1; NbExp=3; IntAct=EBI-16427978, EBI-10976398;
CC Q9BQ51; Q8N3T1: GALNT15; NbExp=3; IntAct=EBI-16427978, EBI-3925203;
CC Q9BQ51; O60883: GPR37L1; NbExp=3; IntAct=EBI-16427978, EBI-2927498;
CC Q9BQ51; Q86UP2-3: KTN1; NbExp=3; IntAct=EBI-16427978, EBI-12007212;
CC Q9BQ51; Q7Z4F1: LRP10; NbExp=3; IntAct=EBI-16427978, EBI-2830349;
CC Q9BQ51; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-16427978, EBI-2858252;
CC Q9BQ51; Q15116: PDCD1; NbExp=14; IntAct=EBI-16427978, EBI-4314328;
CC Q9BQ51; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-16427978, EBI-8636004;
CC Q9BQ51; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-16427978, EBI-17295964;
CC Q9BQ51; Q9H2H9: SLC38A1; NbExp=3; IntAct=EBI-16427978, EBI-9978441;
CC Q9BQ51; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-16427978, EBI-10314552;
CC Q9BQ51; Q96JW4: SLC41A2; NbExp=3; IntAct=EBI-16427978, EBI-10290130;
CC Q9BQ51; P30825: SLC7A1; NbExp=3; IntAct=EBI-16427978, EBI-4289564;
CC Q9BQ51; Q9BZL3: SMIM3; NbExp=3; IntAct=EBI-16427978, EBI-741850;
CC Q9BQ51; Q9NYW0: TAS2R10; NbExp=3; IntAct=EBI-16427978, EBI-12963900;
CC Q9BQ51; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-16427978, EBI-348587;
CC Q9BQ51; A2RU14: TMEM218; NbExp=3; IntAct=EBI-16427978, EBI-10173151;
CC Q9BQ51; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-16427978, EBI-11528917;
CC Q9BQ51; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-16427978, EBI-12111910;
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted
CC {ECO:0000305|PubMed:15253154}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endomembrane system
CC {ECO:0000269|PubMed:15253154}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:15253154}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q9WUL5, ECO:0000305|PubMed:15340161}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=PD-L2I, Type I;
CC IsoId=Q9BQ51-1; Sequence=Displayed;
CC Name=2; Synonyms=PD-L2II, Type II;
CC IsoId=Q9BQ51-2; Sequence=VSP_013740;
CC Name=3; Synonyms=PD-L2III, Type III;
CC IsoId=Q9BQ51-3; Sequence=VSP_013738, VSP_013739;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, placenta, pancreas, lung
CC and liver and weakly expressed in spleen, lymph nodes and thymus.
CC {ECO:0000269|PubMed:11224527}.
CC -!- INDUCTION: Up-regulated by IFNG/IFN-gamma stimulation in monocytes and
CC induced on dendritic cells grown from peripheral blood mononuclear
CC cells with CSF2 and IL4/interleukin-4. {ECO:0000269|PubMed:11224527,
CC ECO:0000269|PubMed:11283156}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. BTN/MOG family.
CC {ECO:0000305}.
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DR EMBL; AF329193; AAK31105.1; -; mRNA.
DR EMBL; AF344424; AAK15370.1; -; mRNA.
DR EMBL; AY254343; AAP13471.1; -; mRNA.
DR EMBL; AY271901; AAP49000.1; -; mRNA.
DR EMBL; AY271902; AAP49001.1; -; mRNA.
DR EMBL; AL162253; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074766; AAH74766.1; -; mRNA.
DR EMBL; BC113678; AAI13679.1; -; mRNA.
DR EMBL; BC113680; AAI13681.1; -; mRNA.
DR CCDS; CCDS6465.1; -. [Q9BQ51-1]
DR RefSeq; NP_079515.2; NM_025239.3. [Q9BQ51-1]
DR PDB; 6UMT; X-ray; 1.99 A; B=1-123.
DR PDBsum; 6UMT; -.
DR AlphaFoldDB; Q9BQ51; -.
DR SMR; Q9BQ51; -.
DR BioGRID; 123259; 34.
DR IntAct; Q9BQ51; 21.
DR STRING; 9606.ENSP00000380855; -.
DR BindingDB; Q9BQ51; -.
DR ChEMBL; CHEMBL3713006; -.
DR GlyGen; Q9BQ51; 5 sites.
DR iPTMnet; Q9BQ51; -.
DR PhosphoSitePlus; Q9BQ51; -.
DR SwissPalm; Q9BQ51; -.
DR BioMuta; PDCD1LG2; -.
DR DMDM; 73917618; -.
DR EPD; Q9BQ51; -.
DR jPOST; Q9BQ51; -.
DR MassIVE; Q9BQ51; -.
DR MaxQB; Q9BQ51; -.
DR PaxDb; Q9BQ51; -.
DR PeptideAtlas; Q9BQ51; -.
DR PRIDE; Q9BQ51; -.
DR ProteomicsDB; 78624; -. [Q9BQ51-1]
DR ProteomicsDB; 78625; -. [Q9BQ51-2]
DR ProteomicsDB; 78626; -. [Q9BQ51-3]
DR ABCD; Q9BQ51; 8 sequenced antibodies.
DR Antibodypedia; 2736; 1104 antibodies from 42 providers.
DR CPTC; Q9BQ51; 1 antibody.
DR DNASU; 80380; -.
DR Ensembl; ENST00000397747.5; ENSP00000380855.3; ENSG00000197646.8. [Q9BQ51-1]
DR GeneID; 80380; -.
DR KEGG; hsa:80380; -.
DR MANE-Select; ENST00000397747.5; ENSP00000380855.3; NM_025239.4; NP_079515.2.
DR UCSC; uc003zjg.5; human. [Q9BQ51-1]
DR CTD; 80380; -.
DR DisGeNET; 80380; -.
DR GeneCards; PDCD1LG2; -.
DR HGNC; HGNC:18731; PDCD1LG2.
DR HPA; ENSG00000197646; Tissue enhanced (lymphoid).
DR MIM; 605723; gene.
DR neXtProt; NX_Q9BQ51; -.
DR OpenTargets; ENSG00000197646; -.
DR PharmGKB; PA134891547; -.
DR VEuPathDB; HostDB:ENSG00000197646; -.
DR eggNOG; ENOG502S1Y9; Eukaryota.
DR GeneTree; ENSGT00940000161373; -.
DR HOGENOM; CLU_013137_8_3_1; -.
DR InParanoid; Q9BQ51; -.
DR OMA; YKKINTH; -.
DR OrthoDB; 892262at2759; -.
DR PhylomeDB; Q9BQ51; -.
DR TreeFam; TF331083; -.
DR PathwayCommons; Q9BQ51; -.
DR Reactome; R-HSA-389948; PD-1 signaling.
DR SignaLink; Q9BQ51; -.
DR BioGRID-ORCS; 80380; 10 hits in 1063 CRISPR screens.
DR ChiTaRS; PDCD1LG2; human.
DR GeneWiki; PDCD1LG2; -.
DR GenomeRNAi; 80380; -.
DR Pharos; Q9BQ51; Tchem.
DR PRO; PR:Q9BQ51; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9BQ51; protein.
DR Bgee; ENSG00000197646; Expressed in stromal cell of endometrium and 89 other tissues.
DR Genevisible; Q9BQ51; HS.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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; IMP:UniProtKB.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IMP:UniProtKB.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IMP:UniProtKB.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IBA:GO_Central.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IBA:GO_Central.
DR GO; GO:0031295; P:T cell costimulation; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 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 Pfam; PF08205; C2-set_2; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Membrane; Receptor; Reference proteome; Repeat;
KW Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 20..273
FT /note="Programmed cell death 1 ligand 2"
FT /id="PRO_0000014555"
FT TOPO_DOM 20..220
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 221..241
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 242..273
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 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 VAR_SEQ 121..211
FT /note="ASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPEG
FT LYQVTSVLRLKPPPGRNFSCVFWNTHVRELTLASIDLQS -> G (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15253154"
FT /id="VSP_013740"
FT VAR_SEQ 121..182
FT /note="ASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPEG
FT LYQVTSVLRL -> DGTQDPSNLAASHFHPLLHHCFHFHSHSDSPKKTTLSKAVFFKRH
FT NKKTCHHNKEGSEQCYL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15253154"
FT /id="VSP_013738"
FT VAR_SEQ 183..273
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15253154"
FT /id="VSP_013739"
FT VARIANT 58
FT /note="S -> T (in dbSNP:rs12339171)"
FT /id="VAR_049842"
FT VARIANT 229
FT /note="F -> S (in dbSNP:rs7854303)"
FT /evidence="ECO:0000269|PubMed:11224527,
FT ECO:0000269|PubMed:11283156, ECO:0000269|PubMed:15253154,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_022449"
FT VARIANT 241
FT /note="I -> T (in dbSNP:rs7854413)"
FT /id="VAR_049843"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:6UMT"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:6UMT"
FT STRAND 38..45
FT /evidence="ECO:0007829|PDB:6UMT"
FT STRAND 53..62
FT /evidence="ECO:0007829|PDB:6UMT"
FT HELIX 77..82
FT /evidence="ECO:0007829|PDB:6UMT"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:6UMT"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:6UMT"
FT STRAND 98..106
FT /evidence="ECO:0007829|PDB:6UMT"
FT STRAND 109..120
FT /evidence="ECO:0007829|PDB:6UMT"
SQ SEQUENCE 273 AA; 30957 MW; 8B7E963C9BA26ED9 CRC64;
MIFLLLMLSL ELQLHQIAAL FTVTVPKELY IIEHGSNVTL ECNFDTGSHV NLGAITASLQ
KVENDTSPHR ERATLLEEQL PLGKASFHIP QVQVRDEGQY QCIIIYGVAW DYKYLTLKVK
ASYRKINTHI LKVPETDEVE LTCQATGYPL AEVSWPNVSV PANTSHSRTP EGLYQVTSVL
RLKPPPGRNF SCVFWNTHVR ELTLASIDLQ SQMEPRTHPT WLLHIFIPFC IIAFIFIATV
IALRKQLCQK LYSSKDTTKR PVTTTKREVN SAI
