PDCD1_HUMAN
ID PDCD1_HUMAN Reviewed; 288 AA.
AC Q15116; O00517; Q8IX89;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Programmed cell death protein 1 {ECO:0000303|PubMed:7851902};
DE Short=Protein PD-1 {ECO:0000303|PubMed:7851902};
DE Short=hPD-1 {ECO:0000303|PubMed:26602187, ECO:0000303|PubMed:9332365};
DE AltName: CD_antigen=CD279;
DE Flags: Precursor;
GN Name=PDCD1 {ECO:0000303|PubMed:7851902, ECO:0000312|HGNC:HGNC:8760};
GN Synonyms=PD1 {ECO:0000303|PubMed:7851902};
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 [GENOMIC DNA].
RX PubMed=7851902; DOI=10.1006/geno.1994.1562;
RA Shinohara T., Taniwaki M., Ishida Y., Kawaich M., Honjo T.;
RT "Structure and chromosomal localization of the human PD-1 gene (PDCD1).";
RL Genomics 23:704-706(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9332365; DOI=10.1016/s0378-1119(97)00260-6;
RA Finger L.R., Pu J., Wasserman R., Vibhakar R., Louie E., Hardy R.R.,
RA Burrows P.D., Billips L.D.;
RT "The human PD-1 gene: complete cDNA, genomic organization, and
RT developmentally regulated expression in B cell progenitors.";
RL Gene 197:177-187(1997).
RN [3]
RP ERRATUM OF PUBMED:9332365.
RA Finger L.R., Pu J., Wasserman R., Vibhakar R., Louie E., Hardy R.R.,
RA Burrows P.D., Billips L.D.;
RL Gene 203:253-253(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INVOLVEMENT IN SLEB2.
RX PubMed=12402038; DOI=10.1038/ng1020;
RA Prokunina L., Castillejo-Lopez C., Oberg F., Gunnarsson I., Berg L.,
RA Magnusson V., Brookes A.J., Tentler D., Kristjansdottir H., Grondal G.,
RA Bolstad A.I., Svenungsson E., Lundberg I., Sturfelt G., Jonssen A.,
RA Truedsson L., Lima G., Alcocer-Varela J., Jonsson R., Gyllensten U.B.,
RA Harley J.B., Alarcon-Segovia D., Steinsson K., Alarcon-Riquelme M.E.;
RT "A regulatory polymorphism in PDCD1 is associated with susceptibility to
RT systemic lupus erythematosus in humans.";
RL Nat. Genet. 32:666-669(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA He X., Xu L., Liu Y., Zeng Y.;
RT "Cloning of PD-1 cDNA from activated peripheral leukocytes.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA Nickerson D.A.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [10]
RP FUNCTION.
RX PubMed=21276005; DOI=10.1111/j.1749-6632.2010.05919.x;
RA Fife B.T., Pauken K.E.;
RT "The role of the PD-1 pathway in autoimmunity and peripheral tolerance.";
RL Ann. N. Y. Acad. Sci. 1217:45-59(2011).
RN [11]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=22658127; DOI=10.1056/nejmoa1200690;
RA Topalian S.L., Hodi F.S., Brahmer J.R., Gettinger S.N., Smith D.C.,
RA McDermott D.F., Powderly J.D., Carvajal R.D., Sosman J.A., Atkins M.B.,
RA Leming P.D., Spigel D.R., Antonia S.J., Horn L., Drake C.G., Pardoll D.M.,
RA Chen L., Sharfman W.H., Anders R.A., Taube J.M., McMiller T.L., Xu H.,
RA Korman A.J., Jure-Kunkel M., Agrawal S., McDonald D., Kollia G.D.,
RA Gupta A., Wigginton J.M., Sznol M.;
RT "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.";
RL N. Engl. J. Med. 366:2443-2454(2012).
RN [12]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=25034862; DOI=10.1016/s0140-6736(14)60958-2;
RA Robert C., Ribas A., Wolchok J.D., Hodi F.S., Hamid O., Kefford R.,
RA Weber J.S., Joshua A.M., Hwu W.J., Gangadhar T.C., Patnaik A., Dronca R.,
RA Zarour H., Joseph R.W., Boasberg P., Chmielowski B., Mateus C.,
RA Postow M.A., Gergich K., Elassaiss-Schaap J., Li X.N., Iannone R.,
RA Ebbinghaus S.W., Kang S.P., Daud A.;
RT "Anti-programmed-death-receptor-1 treatment with pembrolizumab in
RT ipilimumab-refractory advanced melanoma: a randomised dose-comparison
RT cohort of a phase 1 trial.";
RL Lancet 384:1109-1117(2014).
RN [13]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=25399552; DOI=10.1056/nejmoa1412082;
RA Robert C., Long G.V., Brady B., Dutriaux C., Maio M., Mortier L.,
RA Hassel J.C., Rutkowski P., McNeil C., Kalinka-Warzocha E., Savage K.J.,
RA Hernberg M.M., Lebbe C., Charles J., Mihalcioiu C., Chiarion-Sileni V.,
RA Mauch C., Cognetti F., Arance A., Schmidt H., Schadendorf D., Gogas H.,
RA Lundgren-Eriksson L., Horak C., Sharkey B., Waxman I.M., Atkinson V.,
RA Ascierto P.A.;
RT "Nivolumab in previously untreated melanoma without BRAF mutation.";
RL N. Engl. J. Med. 372:320-330(2015).
RN [14]
RP UBIQUITINATION AT LYS-233, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-210
RP AND LYS-233.
RX PubMed=30487606; DOI=10.1038/s41586-018-0756-0;
RA Meng X., Liu X., Guo X., Jiang S., Chen T., Hu Z., Liu H., Bai Y., Xue M.,
RA Hu R., Sun S.C., Liu X., Zhou P., Huang X., Wei L., Yang W., Xu C.;
RT "FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of
RT T cells.";
RL Nature 564:130-135(2018).
RN [15]
RP REVIEW.
RX PubMed=28951311; DOI=10.1016/j.gene.2017.09.050;
RA Berger K.N., Pu J.J.;
RT "PD-1 pathway and its clinical application: A 20year journey after
RT discovery of the complete human PD-1 gene.";
RL Gene 638:20-25(2018).
RN [16] {ECO:0007744|PDB:2M2D}
RP STRUCTURE BY NMR OF 34-150, AND DISULFIDE BOND.
RX PubMed=23417675; DOI=10.1074/jbc.m112.448126;
RA Cheng X., Veverka V., Radhakrishnan A., Waters L.C., Muskett F.W.,
RA Morgan S.H., Huo J., Yu C., Evans E.J., Leslie A.J., Griffiths M.,
RA Stubberfield C., Griffin R., Henry A.J., Jansson A., Ladbury J.E.,
RA Ikemizu S., Carr M.D., Davis S.J.;
RT "Structure and interactions of the human programmed cell death 1
RT receptor.";
RL J. Biol. Chem. 288:11771-11785(2013).
RN [17] {ECO:0007744|PDB:4ZQK}
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 33-150 IN COMPLEX WITH CD274, AND
RP DISULFIDE BOND.
RX PubMed=26602187; DOI=10.1016/j.str.2015.09.010;
RA Zak K.M., Kitel R., Przetocka S., Golik P., Guzik K., Musielak B.,
RA Domling A., Dubin G., Holak T.A.;
RT "Structure of the complex of human programmed death 1, PD-1, and its ligand
RT PD-L1.";
RL Structure 23:2341-2348(2015).
RN [18] {ECO:0007744|PDB:5B8C}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 32-160 IN COMPLEX WITH
RP PEMBROLIZUMAB, ACTIVITY REGULATION, AND DISULFIDE BOND.
RX PubMed=27734966; DOI=10.1038/srep35297;
RA Horita S., Nomura Y., Sato Y., Shimamura T., Iwata S., Nomura N.;
RT "High-resolution crystal structure of the therapeutic antibody
RT pembrolizumab bound to the human PD-1.";
RL Sci. Rep. 6:35297-35297(2016).
RN [19] {ECO:0007744|PDB:5IUS}
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) OF 26-146.
RX PubMed=27618663; DOI=10.1016/j.str.2016.06.026;
RA Pascolutti R., Sun X., Kao J., Maute R.L., Ring A.M., Bowman G.R.,
RA Kruse A.C.;
RT "Structure and Dynamics of PD-L1 and an Ultra-High-Affinity PD-1 Receptor
RT Mutant.";
RL Structure 24:1719-1728(2016).
RN [20] {ECO:0007744|PDB:5JXE}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 33-146 IN COMPLEX WITH
RP PEMBROLIZUMAB, ACTIVITY REGULATION, AND DISULFIDE BOND.
RX PubMed=27325296; DOI=10.1038/cr.2016.77;
RA Na Z., Yeo S.P., Bharath S.R., Bowler M.W., Balikci E., Wang C.I., Song H.;
RT "Structural basis for blocking PD-1-mediated immune suppression by
RT therapeutic antibody pembrolizumab.";
RL Cell Res. 27:147-150(2017).
RN [21] {ECO:0007744|PDB:5WT9}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-167 IN COMPLEX WITH NIVOLUMAB,
RP GLYCOSYLATION AT ASN-49; ASN-58; ASN-74 AND ASN-116, AND MUTAGENESIS OF
RP ASN-49; ASN-58; ASN-74 AND ASN-116.
RX PubMed=28165004; DOI=10.1038/ncomms14369;
RA Tan S., Zhang H., Chai Y., Song H., Tong Z., Wang Q., Qi J., Wong G.,
RA Zhu X., Liu W.J., Gao S., Wang Z., Shi Y., Yang F., Gao G.F., Yan J.;
RT "An unexpected N-terminal loop in PD-1 dominates binding by nivolumab.";
RL Nat. Commun. 8:14369-14369(2017).
CC -!- FUNCTION: Inhibitory receptor on antigen activated T-cells that plays a
CC critical role in induction and maintenance of immune tolerance to self
CC (PubMed:21276005). Delivers inhibitory signals upon binding to ligands
CC CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:21276005). Following T-cell
CC receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the
CC immunological synapse and directly inhibits T-cell activation (By
CC similarity). Suppresses T-cell activation through the recruitment of
CC PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within
CC the ITSM motif, leading to the recruitment of the protein tyrosine
CC phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR
CC proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and
CC CD247/CD3zeta (By similarity). {ECO:0000250|UniProtKB:Q02242,
CC ECO:0000269|PubMed:21276005}.
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:28951311). The
CC interaction with CD274/PDCD1L1 inhibits cytotoxic T lymphocytes (CTLs)
CC effector function (PubMed:28951311). The blockage of the PDCD1-mediated
CC pathway results in the reversal of the exhausted T-cell phenotype and
CC the normalization of the anti-tumor response, providing a rationale for
CC cancer immunotherapy (PubMed:22658127, PubMed:25034862,
CC PubMed:25399552). {ECO:0000269|PubMed:22658127,
CC ECO:0000269|PubMed:25034862, ECO:0000269|PubMed:25399552,
CC ECO:0000303|PubMed:28951311}.
CC -!- ACTIVITY REGULATION: Inhibited by pembrolizumab (also named MK-3475 or
CC lambrolizumab), a monoclonal antibody that prevents the interaction
CC with CD274/PDCD1L1 (PubMed:27734966, PubMed:27325296). Inhibited by
CC nivolumab (also named ONO-4538, BMS-936558 or Opdivo), a monoclonal
CC antibody that prevents the interaction with CD274/PDCD1L1
CC (PubMed:28165004). The interaction with nivolumab is not dependent on
CC glycosylation and depends on a loop at the N-terminus (N-terminal loop,
CC corresponding to residues 25-34) (PubMed:28165004). Targeting the
CC interaction between PDCD1 and CD274/PDCD1L1 with pembrolizumab and
CC nivolumab antibodies has demonstrated great promise as a strategy for
CC controlling and eradicating cancer (PubMed:22658127, PubMed:25034862,
CC PubMed:25399552). Pembrolizumab and nivolumab are used for treatment of
CC patients with advanced melanoma (PubMed:25034862, PubMed:25399552).
CC These antibodies are also effective against other cancers, such as non-
CC small cell lung cancer, renal cell carcinoma, bladder cancer and
CC Hodgkin's lymphoma (PubMed:25034862). {ECO:0000269|PubMed:22658127,
CC ECO:0000269|PubMed:25034862, ECO:0000269|PubMed:25399552,
CC ECO:0000269|PubMed:27325296, ECO:0000269|PubMed:27734966,
CC ECO:0000269|PubMed:28165004}.
CC -!- SUBUNIT: Monomer (PubMed:26602187). Interacts with CD274/PDCD1L1
CC (PubMed:26602187). Interacts with CD273/PDCD1LG2 (By similarity).
CC Interacts with FBXO38; leading to ubiquitination and degradation of
CC PDCD1 by the proteasome (PubMed:30487606).
CC {ECO:0000250|UniProtKB:Q02242, ECO:0000269|PubMed:26602187,
CC ECO:0000269|PubMed:30487606}.
CC -!- INTERACTION:
CC Q15116; Q9NZQ7: CD274; NbExp=17; IntAct=EBI-4314328, EBI-4314282;
CC Q15116; Q9NZQ7-1: CD274; NbExp=2; IntAct=EBI-4314328, EBI-15686469;
CC Q15116; Q9BQ51: PDCD1LG2; NbExp=14; IntAct=EBI-4314328, EBI-16427978;
CC Q15116; Q06124: PTPN11; NbExp=3; IntAct=EBI-4314328, EBI-297779;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30487606};
CC Single-pass type I membrane protein.
CC -!- DEVELOPMENTAL STAGE: Induced at programmed cell death.
CC {ECO:0000269|PubMed:7851902}.
CC -!- PTM: Ubiquitinated at Lys-233 by the SCF(FBXO38) complex, leading to
CC its proteasomal degradation (PubMed:30487606). Ubiquitinated via 'Lys-
CC 48'-linked polyubiquitin chains (PubMed:30487606).
CC {ECO:0000269|PubMed:30487606}.
CC -!- PTM: Tyrosine phosphorylated at Tyr-223 (within ITIM motif) and Tyr-248
CC (ITSM motif) upon ligand binding. Phosphorylation at Tyr-248 promotes
CC the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that
CC mediates dephosphorylation of key TCR proximal signaling molecules,
CC such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta.
CC {ECO:0000250|UniProtKB:Q02242}.
CC -!- PTM: N-glycosylation at Asn-58 contains at least two N-
CC acetylglucosamine units and one fucose (PubMed:28165004). N-
CC glycosylation does not affect binding to nivolumab drug
CC (PubMed:28165004). {ECO:0000269|PubMed:28165004}.
CC -!- DISEASE: Systemic lupus erythematosus 2 (SLEB2) [MIM:605218]: A
CC chronic, relapsing, inflammatory, and often febrile multisystemic
CC disorder of connective tissue, characterized principally by involvement
CC of the skin, joints, kidneys and serosal membranes. It is of unknown
CC etiology, but is thought to represent a failure of the regulatory
CC mechanisms of the autoimmune system. The disease is marked by a wide
CC range of system dysfunctions, an elevated erythrocyte sedimentation
CC rate, and the formation of LE cells in the blood or bone marrow.
CC {ECO:0000269|PubMed:12402038}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
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DR EMBL; L27440; AAC41700.1; -; Genomic_DNA.
DR EMBL; U64863; AAC51773.1; -; mRNA.
DR EMBL; AF363458; AAN64003.1; -; Genomic_DNA.
DR EMBL; AY238517; AAO63583.1; -; mRNA.
DR EMBL; EF064716; ABK41899.1; -; Genomic_DNA.
DR EMBL; AK313848; BAG36577.1; -; mRNA.
DR EMBL; CH471063; EAW71298.1; -; Genomic_DNA.
DR EMBL; BC074740; AAH74740.1; -; mRNA.
DR CCDS; CCDS33428.1; -.
DR PIR; A55737; A55737.
DR RefSeq; NP_005009.2; NM_005018.2.
DR PDB; 2M2D; NMR; -; A=34-150.
DR PDB; 3RRQ; X-ray; 2.10 A; A=32-160.
DR PDB; 4ZQK; X-ray; 2.45 A; B=33-150.
DR PDB; 5B8C; X-ray; 2.15 A; C/F/I/L=32-160.
DR PDB; 5GGR; X-ray; 3.30 A; Y/Z=26-150.
DR PDB; 5GGS; X-ray; 2.00 A; Y/Z=26-148.
DR PDB; 5IUS; X-ray; 2.89 A; A/B=26-146.
DR PDB; 5JXE; X-ray; 2.90 A; A/B=33-146.
DR PDB; 5WT9; X-ray; 2.40 A; G=1-167.
DR PDB; 6HIG; X-ray; 2.20 A; B=33-150.
DR PDB; 6J14; X-ray; 1.40 A; G=33-147.
DR PDB; 6J15; X-ray; 2.60 A; C/D=32-147.
DR PDB; 6JBT; X-ray; 2.47 A; F=21-170.
DR PDB; 6JJP; X-ray; 2.90 A; C/F=21-167.
DR PDB; 6K0Y; X-ray; 1.70 A; C=25-167.
DR PDB; 6R5G; NMR; -; B=244-254.
DR PDB; 6ROY; X-ray; 2.10 A; C/D=219-229.
DR PDB; 6ROZ; X-ray; 2.89 A; B/D=244-254.
DR PDB; 6UMT; X-ray; 1.99 A; A=33-150.
DR PDB; 6UMU; X-ray; 1.18 A; A=33-150.
DR PDB; 6UMV; X-ray; 1.42 A; A=33-150.
DR PDB; 6XKR; X-ray; 2.59 A; P=32-160.
DR PDB; 7BXA; X-ray; 3.32 A; A/P=29-150.
DR PDB; 7CGW; X-ray; 3.20 A; C/P=25-169.
DR PDB; 7CU5; X-ray; 2.81 A; E/Q=30-147.
DR PDB; 7E9B; X-ray; 1.78 A; C=32-146.
DR PDB; 7VUX; X-ray; 1.64 A; A=32-160.
DR PDBsum; 2M2D; -.
DR PDBsum; 3RRQ; -.
DR PDBsum; 4ZQK; -.
DR PDBsum; 5B8C; -.
DR PDBsum; 5GGR; -.
DR PDBsum; 5GGS; -.
DR PDBsum; 5IUS; -.
DR PDBsum; 5JXE; -.
DR PDBsum; 5WT9; -.
DR PDBsum; 6HIG; -.
DR PDBsum; 6J14; -.
DR PDBsum; 6J15; -.
DR PDBsum; 6JBT; -.
DR PDBsum; 6JJP; -.
DR PDBsum; 6K0Y; -.
DR PDBsum; 6R5G; -.
DR PDBsum; 6ROY; -.
DR PDBsum; 6ROZ; -.
DR PDBsum; 6UMT; -.
DR PDBsum; 6UMU; -.
DR PDBsum; 6UMV; -.
DR PDBsum; 6XKR; -.
DR PDBsum; 7BXA; -.
DR PDBsum; 7CGW; -.
DR PDBsum; 7CU5; -.
DR PDBsum; 7E9B; -.
DR PDBsum; 7VUX; -.
DR AlphaFoldDB; Q15116; -.
DR BMRB; Q15116; -.
DR SMR; Q15116; -.
DR BioGRID; 111160; 117.
DR DIP; DIP-44126N; -.
DR IntAct; Q15116; 54.
DR MINT; Q15116; -.
DR STRING; 9606.ENSP00000335062; -.
DR BindingDB; Q15116; -.
DR ChEMBL; CHEMBL3307223; -.
DR DrugBank; DB15767; AMP-224.
DR DrugBank; DB14776; Camrelizumab.
DR DrugBank; DB14707; Cemiplimab.
DR DrugBank; DB05916; CT-011.
DR DrugBank; DB15627; Dostarlimab.
DR DrugBank; DB15768; MEDI0680.
DR DrugBank; DB09035; Nivolumab.
DR DrugBank; DB09037; Pembrolizumab.
DR DrugBank; DB16740; Prolgolimab.
DR DrugBank; DB15766; Retifanlimab.
DR DrugBank; DB15765; Sintilimab.
DR DrugBank; DB14892; Spartalizumab.
DR DrugBank; DB14922; Tislelizumab.
DR DrugBank; DB15043; Toripalimab.
DR DrugCentral; Q15116; -.
DR GuidetoPHARMACOLOGY; 2760; -.
DR TCDB; 8.A.17.4.1; the na(+) channel auxiliary subunit Beta1-Beta4 (sca-Beta) family.
DR GlyGen; Q15116; 4 sites.
DR iPTMnet; Q15116; -.
DR PhosphoSitePlus; Q15116; -.
DR BioMuta; PDCD1; -.
DR DMDM; 145559515; -.
DR MassIVE; Q15116; -.
DR PaxDb; Q15116; -.
DR PeptideAtlas; Q15116; -.
DR PRIDE; Q15116; -.
DR ProteomicsDB; 60443; -.
DR ABCD; Q15116; 126 sequenced antibodies.
DR Antibodypedia; 20331; 2509 antibodies from 52 providers.
DR CPTC; Q15116; 1 antibody.
DR DNASU; 5133; -.
DR Ensembl; ENST00000334409.10; ENSP00000335062.5; ENSG00000188389.11.
DR Ensembl; ENST00000618185.3; ENSP00000480684.1; ENSG00000276977.3.
DR GeneID; 5133; -.
DR KEGG; hsa:5133; -.
DR MANE-Select; ENST00000334409.10; ENSP00000335062.5; NM_005018.3; NP_005009.2.
DR UCSC; uc002wcq.5; human.
DR CTD; 5133; -.
DR DisGeNET; 5133; -.
DR GeneCards; PDCD1; -.
DR HGNC; HGNC:8760; PDCD1.
DR HPA; ENSG00000188389; Tissue enhanced (lymphoid).
DR MalaCards; PDCD1; -.
DR MIM; 600244; gene.
DR MIM; 605218; phenotype.
DR neXtProt; NX_Q15116; -.
DR OpenTargets; ENSG00000188389; -.
DR Orphanet; 802; NON RARE IN EUROPE: Multiple sclerosis.
DR Orphanet; 536; Systemic lupus erythematosus.
DR PharmGKB; PA33110; -.
DR VEuPathDB; HostDB:ENSG00000188389; -.
DR eggNOG; ENOG502SUIW; Eukaryota.
DR GeneTree; ENSGT00390000013662; -.
DR HOGENOM; CLU_1075828_0_0_1; -.
DR InParanoid; Q15116; -.
DR OMA; HTEYATI; -.
DR OrthoDB; 1437063at2759; -.
DR PhylomeDB; Q15116; -.
DR TreeFam; TF336181; -.
DR PathwayCommons; Q15116; -.
DR Reactome; R-HSA-389948; PD-1 signaling.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; Q15116; -.
DR SIGNOR; Q15116; -.
DR BioGRID-ORCS; 5133; 11 hits in 1067 CRISPR screens.
DR ChiTaRS; PDCD1; human.
DR GeneWiki; Programmed_cell_death_1; -.
DR GenomeRNAi; 5133; -.
DR Pharos; Q15116; Tclin.
DR PRO; PR:Q15116; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q15116; protein.
DR Bgee; ENSG00000188389; Expressed in lymph node and 85 other tissues.
DR ExpressionAtlas; Q15116; baseline and differential.
DR Genevisible; Q15116; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
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:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0006959; P:humoral immune response; TAS:ProtInc.
DR GO; GO:0002903; P:negative regulation of B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0050777; P:negative regulation of immune response; ISS:UniProtKB.
DR GO; GO:0002644; P:negative regulation of tolerance induction; IEA:Ensembl.
DR GO; GO:0070234; P:positive regulation of T cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0050776; P:regulation of immune response; IBA:GO_Central.
DR GO; GO:1902482; P:regulatory T cell apoptotic process; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 1.
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 InterPro; IPR042379; PDCD1.
DR PANTHER; PTHR15264; PTHR15264; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Apoptosis; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Isopeptide bond; Membrane;
KW Phosphoprotein; Reference proteome; Signal; Systemic lupus erythematosus;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..288
FT /note="Programmed cell death protein 1"
FT /id="PRO_0000014892"
FT TOPO_DOM 24..170
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 171..191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 192..288
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 35..145
FT /note="Ig-like V-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 25..34
FT /note="Nivolumab binding"
FT /evidence="ECO:0000269|PubMed:28165004,
FT ECO:0007744|PDB:5WT9"
FT REGION 70..77
FT /note="Interaction with CD274/PDCD1L1"
FT /evidence="ECO:0000269|PubMed:26602187"
FT REGION 74..99
FT /note="Pembrolizumab binding"
FT /evidence="ECO:0000269|PubMed:27325296,
FT ECO:0000269|PubMed:27734966, ECO:0007744|PDB:5B8C,
FT ECO:0007744|PDB:5JXE"
FT REGION 254..288
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 221..226
FT /note="ITIM motif"
FT /evidence="ECO:0000250|UniProtKB:Q02242"
FT MOTIF 247..251
FT /note="ITSM motif"
FT /evidence="ECO:0000250|UniProtKB:Q02242"
FT MOD_RES 223
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q02242"
FT MOD_RES 248
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q02242"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:28165004"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28165004,
FT ECO:0007744|PDB:5WT9"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:28165004"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:28165004"
FT DISULFID 54..123
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:23417675, ECO:0000269|PubMed:26602187,
FT ECO:0000269|PubMed:27325296, ECO:0000269|PubMed:27734966,
FT ECO:0007744|PDB:2M2D, ECO:0007744|PDB:4ZQK,
FT ECO:0007744|PDB:5B8C, ECO:0007744|PDB:5JXE"
FT CROSSLNK 233
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:30487606"
FT VARIANT 215
FT /note="A -> V (in dbSNP:rs2227982)"
FT /id="VAR_031685"
FT MUTAGEN 49
FT /note="N->A: Decreased N-glycosylation without affecting
FT binding to binding to nivolumab drug."
FT /evidence="ECO:0000269|PubMed:28165004"
FT MUTAGEN 58
FT /note="N->A: Decreased N-glycosylation without affecting
FT binding to binding to nivolumab drug."
FT /evidence="ECO:0000269|PubMed:28165004"
FT MUTAGEN 74
FT /note="N->A: Decreased N-glycosylation without affecting
FT binding to binding to nivolumab drug."
FT /evidence="ECO:0000269|PubMed:28165004"
FT MUTAGEN 116
FT /note="N->A: Decreased N-glycosylation without affecting
FT binding to binding to nivolumab drug."
FT /evidence="ECO:0000269|PubMed:28165004"
FT MUTAGEN 210
FT /note="K->R: Does not affect ubiquitination by the
FT SCF(FBXO38) complex."
FT /evidence="ECO:0000269|PubMed:30487606"
FT MUTAGEN 233
FT /note="K->R: Abolishes ubiquitination by the SCF(FBXO38)
FT complex."
FT /evidence="ECO:0000269|PubMed:30487606"
FT CONFLICT 38
FT /note="S -> F (in Ref. 2; AAC51773)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="P -> S (in Ref. 1; AAC41700)"
FT /evidence="ECO:0000305"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:5WT9"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:6UMU"
FT STRAND 40..45
FT /evidence="ECO:0007829|PDB:6UMU"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:6UMU"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:7E9B"
FT STRAND 63..70
FT /evidence="ECO:0007829|PDB:6UMU"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:4ZQK"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:6UMU"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:6K0Y"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:7CGW"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:6UMU"
FT STRAND 103..112
FT /evidence="ECO:0007829|PDB:6UMU"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:6UMU"
FT STRAND 119..127
FT /evidence="ECO:0007829|PDB:6UMU"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:6UMU"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:6UMU"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:6UMU"
SQ SEQUENCE 288 AA; 31647 MW; A5210FD40C304FB7 CRC64;
MQIPQAPWPV VWAVLQLGWR PGWFLDSPDR PWNPPTFSPA LLVVTEGDNA TFTCSFSNTS
ESFVLNWYRM SPSNQTDKLA AFPEDRSQPG QDCRFRVTQL PNGRDFHMSV VRARRNDSGT
YLCGAISLAP KAQIKESLRA ELRVTERRAE VPTAHPSPSP RPAGQFQTLV VGVVGGLLGS
LVLLVWVLAV ICSRAARGTI GARRTGQPLK EDPSAVPVFS VDYGELDFQW REKTPEPPVP
CVPEQTEYAT IVFPSGMGTS SPARRGSADG PRSAQPLRPE DGHCSWPL
