PD1L1_MOUSE
ID PD1L1_MOUSE Reviewed; 290 AA.
AC Q9EP73;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Programmed cell death 1 ligand 1;
DE Short=PD-L1;
DE Short=PDCD1 ligand 1;
DE Short=Programmed death ligand 1;
DE AltName: Full=B7 homolog 1;
DE Short=B7-H1;
DE AltName: CD_antigen=CD274;
DE Flags: Precursor;
GN Name=Cd274; Synonyms=B7h1, Pdcd1l1, Pdcd1lg1, Pdl1;
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, TISSUE
RP SPECIFICITY, AND INDUCTION.
RC TISSUE=Spleen;
RX PubMed=11015443; DOI=10.1084/jem.192.7.1027;
RA Freeman G.J., Long A.J., Iwai Y., Bourque K., Chernova T., Nishimura H.,
RA Fitz L.J., Malenkovich N., Okazaki T., Byrne M.C., Horton H.F., Fouser L.,
RA Carter L., Ling V., Bowman M.R., Carreno B.M., Collins M., Wood C.R.,
RA Honjo T.;
RT "Engagement of the PD-1 immunoinhibitory receptor by a novel B7-family
RT member leads to negative regulation of lymphocyte activation.";
RL J. Exp. Med. 192:1027-1034(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=C57BL/6J;
RX PubMed=11238124; DOI=10.1182/blood.v97.6.1809;
RA Tamura H., Dong H., Zhu G., Sica G.L., Flies D.B., Tamada K., Chen L.;
RT "B7-H1 costimulation preferentially enhances CD28-independent T-helper cell
RT function.";
RL Blood 97:1809-1816(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CD-1; TISSUE=Neural stem cell;
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 [4]
RP 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 [5]
RP FUNCTION.
RX PubMed=12218188; DOI=10.1073/pnas.192461099;
RA Iwai Y., Ishida M., Tanaka Y., Okazaki T., Honjo T., Minato N.;
RT "Involvement of PD-L1 on tumor cells in the escape from host immune system
RT and tumor immunotherapy by PD-L1 blockade.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:12293-12297(2002).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF LEU-27; GLU-31; SER-34; THR-37; ASP-49;
RP TYR-56; GLU-58; GLU-62; PHE-67; ALA-69; GLU-72; LYS-75; LYS-89; ALA-98;
RP CYS-113; ILE-115; SER-117; LYS-124; ILE-126 AND LYS-129.
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 [7]
RP FUNCTION.
RX PubMed=27281199; DOI=10.1038/nature18294;
RA Kataoka K., Shiraishi Y., Takeda Y., Sakata S., Matsumoto M., Nagano S.,
RA Maeda T., Nagata Y., Kitanaka A., Mizuno S., Tanaka H., Chiba K., Ito S.,
RA Watatani Y., Kakiuchi N., Suzuki H., Yoshizato T., Yoshida K., Sanada M.,
RA Itonaga H., Imaizumi Y., Totoki Y., Munakata W., Nakamura H., Hama N.,
RA Shide K., Kubuki Y., Hidaka T., Kameda T., Masuda K., Minato N.,
RA Kashiwase K., Izutsu K., Takaori-Kondo A., Miyazaki Y., Takahashi S.,
RA Shibata T., Kawamoto H., Akatsuka Y., Shimoda K., Takeuchi K., Seya T.,
RA Miyano S., Ogawa S.;
RT "Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers.";
RL Nature 534:402-406(2016).
CC -!- FUNCTION: Plays a critical role in induction and maintenance of immune
CC tolerance to self (PubMed:11238124). As a ligand for the inhibitory
CC receptor PDCD1/PD-1, modulates the activation threshold of T-cells and
CC limits T-cell effector response (PubMed:11238124). Through a yet
CC unknown activating receptor, may costimulate T-cell subsets that
CC predominantly produce interleukin-10 (IL10) (PubMed:11015443,
CC PubMed:12719480). {ECO:0000269|PubMed:11015443,
CC ECO:0000269|PubMed:11238124, ECO:0000269|PubMed:12719480}.
CC -!- FUNCTION: The PDCD1-mediated inhibitory pathway is exploited by tumors
CC to attenuate anti-tumor immunity and escape destruction by the immune
CC system, thereby facilitating tumor survival (PubMed:12218188,
CC PubMed:27281199). The interaction with PDCD1/PD-1 inhibits cytotoxic T
CC lymphocytes (CTLs) effector function (PubMed:12218188). The blockage of
CC the PDCD1-mediated pathway results in the reversal of the exhausted T-
CC cell phenotype and the normalization of the anti-tumor response,
CC providing a rationale for cancer immunotherapy (PubMed:12218188).
CC {ECO:0000269|PubMed:12218188, ECO:0000269|PubMed:27281199}.
CC -!- SUBUNIT: Interacts with PDCD1 (PubMed:11015443). Interacts with CMTM4
CC and CMTM6 (By similarity). {ECO:0000250|UniProtKB:Q9NZQ7,
CC ECO:0000269|PubMed:11015443}.
CC -!- INTERACTION:
CC Q9EP73; Q00609: Cd80; NbExp=7; IntAct=EBI-5258879, EBI-5258929;
CC Q9EP73; Q02242: Pdcd1; NbExp=3; IntAct=EBI-5258879, EBI-5258903;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9NZQ7};
CC Single-pass type I membrane protein {ECO:0000255}. Early endosome
CC membrane {ECO:0000250|UniProtKB:Q9NZQ7}; Single-pass type I membrane
CC protein {ECO:0000255}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:Q9NZQ7}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the heart, thymus, skeletal
CC muscle, and lung. Weakly expressed in the kidney, spleen, thyroid, and
CC liver. Expressed on activated dendritic cells, B-cells and macrophages.
CC Expressed in numerous tumor cells lines of lymphoid origin.
CC {ECO:0000269|PubMed:11015443, ECO:0000269|PubMed:11224527,
CC ECO:0000269|PubMed:11238124}.
CC -!- INDUCTION: Up-regulated by IFNG treatment in monocytes. Up-regulated on
CC dendritic cells, B-cells and macrophages after activation by LPS and
CC IFNG. {ECO:0000269|PubMed:11015443, ECO:0000269|PubMed:11238124}.
CC -!- PTM: Ubiquitinated; STUB1 likely mediates polyubiquitination of PD-
CC L1/CD274 triggering its degradation. {ECO:0000250|UniProtKB:Q9NZQ7}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. BTN/MOG family.
CC {ECO:0000305}.
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DR EMBL; AF233517; AAG18509.1; -; mRNA.
DR EMBL; AF317088; AAG31810.1; -; mRNA.
DR EMBL; BC066841; AAH66841.1; -; mRNA.
DR CCDS; CCDS29735.1; -.
DR RefSeq; NP_068693.1; NM_021893.3.
DR PDB; 6SRU; X-ray; 2.53 A; A/B/C/D/E/F/G/H/I/J=19-134.
DR PDBsum; 6SRU; -.
DR AlphaFoldDB; Q9EP73; -.
DR SMR; Q9EP73; -.
DR DIP; DIP-46167N; -.
DR IntAct; Q9EP73; 2.
DR STRING; 10090.ENSMUSP00000016640; -.
DR BindingDB; Q9EP73; -.
DR ChEMBL; CHEMBL4523448; -.
DR GlyGen; Q9EP73; 5 sites.
DR iPTMnet; Q9EP73; -.
DR PhosphoSitePlus; Q9EP73; -.
DR SwissPalm; Q9EP73; -.
DR MaxQB; Q9EP73; -.
DR PaxDb; Q9EP73; -.
DR PRIDE; Q9EP73; -.
DR ProteomicsDB; 289330; -.
DR ABCD; Q9EP73; 66 sequenced antibodies.
DR Antibodypedia; 24139; 1926 antibodies from 54 providers.
DR DNASU; 60533; -.
DR Ensembl; ENSMUST00000016640; ENSMUSP00000016640; ENSMUSG00000016496.
DR GeneID; 60533; -.
DR KEGG; mmu:60533; -.
DR UCSC; uc008hdi.2; mouse.
DR CTD; 29126; -.
DR MGI; MGI:1926446; Cd274.
DR VEuPathDB; HostDB:ENSMUSG00000016496; -.
DR eggNOG; ENOG502S1Y9; Eukaryota.
DR GeneTree; ENSGT00940000161430; -.
DR HOGENOM; CLU_013137_8_3_1; -.
DR InParanoid; Q9EP73; -.
DR OMA; AGVYCCM; -.
DR OrthoDB; 892262at2759; -.
DR PhylomeDB; Q9EP73; -.
DR TreeFam; TF331083; -.
DR Reactome; R-MMU-389948; PD-1 signaling.
DR BioGRID-ORCS; 60533; 7 hits in 81 CRISPR screens.
DR ChiTaRS; Cd274; mouse.
DR PRO; PR:Q9EP73; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9EP73; protein.
DR Bgee; ENSMUSG00000016496; Expressed in mesenteric lymph node and 101 other tissues.
DR ExpressionAtlas; Q9EP73; baseline and differential.
DR Genevisible; Q9EP73; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; ISO:MGI.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISO:MGI.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; ISO:MGI.
DR GO; GO:2001186; P:negative regulation of CD8-positive, alpha-beta T cell activation; ISS:UniProtKB.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; 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:1903556; P:negative regulation of tumor necrosis factor superfamily cytokine production; ISO:MGI.
DR GO; GO:1905404; P:positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:MGI.
DR GO; GO:0002845; P:positive regulation of tolerance induction to tumor cell; ISS:UniProtKB.
DR GO; GO:0034097; P:response to cytokine; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0031295; P:T cell costimulation; ISO:MGI.
DR GO; GO:1901998; P:toxin transport; IMP:MGI.
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 InterPro; IPR013106; Ig_V-set.
DR Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 2.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond; Endosome;
KW Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..290
FT /note="Programmed cell death 1 ligand 1"
FT /id="PRO_0000014554"
FT TOPO_DOM 19..239
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..290
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 19..127
FT /note="Ig-like V-type"
FT DOMAIN 133..224
FT /note="Ig-like C2-type"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 154..208
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT MUTAGEN 27
FT /note="L->A: PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 31
FT /note="E->S: Significantly reduces the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 34
FT /note="S->Y: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 37
FT /note="T->Y: Significantly reduces the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 49
FT /note="D->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 56
FT /note="Y->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 58
FT /note="E->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 62
FT /note="E->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 67
FT /note="F->A: Abolishes the binding to PDCD1. Costimulates
FT proliferation and IFNG production of T-cells."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 69
FT /note="A->F: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 72
FT /note="E->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 75
FT /note="K->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 89
FT /note="K->S: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 98
FT /note="A->F: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 100
FT /note="Q->S: No effect on PDCD1 binding."
FT MUTAGEN 113
FT /note="C->Y: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 115
FT /note="I->A: Abolishes the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 117
FT /note="S->Y: No effect on PDCD1 binding."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 124
FT /note="K->A: Abolishes the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 126
FT /note="I->A: Abolishes the binding to PDCD1. Costimulates
FT proliferation and IFNG production of T-cells."
FT /evidence="ECO:0000269|PubMed:12719480"
FT MUTAGEN 129
FT /note="K->S: Abolishes the binding to PDCD1."
FT /evidence="ECO:0000269|PubMed:12719480"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:6SRU"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:6SRU"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:6SRU"
FT STRAND 54..61
FT /evidence="ECO:0007829|PDB:6SRU"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:6SRU"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:6SRU"
FT TURN 80..84
FT /evidence="ECO:0007829|PDB:6SRU"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:6SRU"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:6SRU"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:6SRU"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:6SRU"
FT STRAND 110..131
FT /evidence="ECO:0007829|PDB:6SRU"
SQ SEQUENCE 290 AA; 32780 MW; AB7C46CF853EBB02 CRC64;
MRIFAGIIFT ACCHLLRAFT ITAPKDLYVV EYGSNVTMEC RFPVERELDL LALVVYWEKE
DEQVIQFVAG EEDLKPQHSN FRGRASLPKD QLLKGNAALQ ITDVKLQDAG VYCCIISYGG
ADYKRITLKV NAPYRKINQR ISVDPATSEH ELICQAEGYP EAEVIWTNSD HQPVSGKRSV
TTSRTEGMLL NVTSSLRVNA TANDVFYCTF WRSQPGQNHT AELIIPELPA THPPQNRTHW
VLLGSILLFL IVVSTVLLFL RKQVRMLDVE KCGVEDTSSK NRNDTQFEET
