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   27-MAR-2024, entry version 161.
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. Ubiquitinated by MARCHF8; leading
CC       to 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   BioGRID; 208602; 16.
DR   DIP; DIP-46167N; -.
DR   IntAct; Q9EP73; 2.
DR   STRING; 10090.ENSMUSP00000016640; -.
DR   BindingDB; Q9EP73; -.
DR   ChEMBL; CHEMBL4523448; -.
DR   GlyCosmos; Q9EP73; 5 sites, No reported glycans.
DR   GlyGen; Q9EP73; 5 sites.
DR   iPTMnet; Q9EP73; -.
DR   PhosphoSitePlus; Q9EP73; -.
DR   SwissPalm; Q9EP73; -.
DR   MaxQB; Q9EP73; -.
DR   PaxDb; 10090-ENSMUSP00000016640; -.
DR   ProteomicsDB; 289330; -.
DR   ABCD; Q9EP73; 66 sequenced antibodies.
DR   Antibodypedia; 24139; 2629 antibodies from 55 providers.
DR   DNASU; 60533; -.
DR   Ensembl; ENSMUST00000016640.8; ENSMUSP00000016640.8; ENSMUSG00000016496.8.
DR   GeneID; 60533; -.
DR   KEGG; mmu:60533; -.
DR   UCSC; uc008hdi.2; mouse.
DR   AGR; MGI:1926446; -.
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; YCCMISY; -.
DR   OrthoDB; 5315576at2759; -.
DR   PhylomeDB; Q9EP73; -.
DR   TreeFam; TF331083; -.
DR   Reactome; R-MMU-389948; PD-1 signaling.
DR   BioGRID-ORCS; 60533; 7 hits in 86 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 102 other cell types or tissues.
DR   ExpressionAtlas; Q9EP73; baseline and differential.
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: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:0003713; F:transcription coactivator activity; ISO:MGI.
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: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:0032689; P:negative regulation of type II interferon 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:0035666; P:TRIF-dependent toll-like receptor signaling pathway; IEA:Ensembl.
DR   CDD; cd20947; IgV_PDl1; 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   InterPro; IPR013106; Ig_V-set.
DR   PANTHER; PTHR25466:SF3; PROGRAMMED CELL DEATH 1 LIGAND 1; 1.
DR   PANTHER; PTHR25466; T-LYMPHOCYTE ACTIVATION ANTIGEN; 1.
DR   Pfam; PF08205; C2-set_2; 1.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00409; IG; 2.
DR   SUPFAM; SSF48726; Immunoglobulin; 2.
DR   PROSITE; PS50835; IG_LIKE; 2.
DR   Genevisible; Q9EP73; MM.
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
//