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 27-MAR-2024, entry version 198. 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7WSL; X-ray; 1.53 A; D=29-150. DR PDB; 7WVM; X-ray; 3.40 A; E/F=31-147. DR PDB; 8AS0; X-ray; 3.50 A; A/F/I/L/O/R/X/Y=24-170. DR PDB; 8EQ6; X-ray; 1.65 A; A=25-148. DR PDB; 8GY5; X-ray; 1.98 A; P/Q=26-150. 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 PDBsum; 7WSL; -. DR PDBsum; 7WVM; -. DR PDBsum; 8AS0; -. DR PDBsum; 8EQ6; -. DR PDBsum; 8GY5; -. DR AlphaFoldDB; Q15116; -. DR BMRB; Q15116; -. DR SMR; Q15116; -. DR BioGRID; 111160; 118. 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; DB11595; Atezolizumab. DR DrugBank; DB11945; Avelumab. DR DrugBank; DB16668; Budigalimab. DR DrugBank; DB14776; Camrelizumab. DR DrugBank; DB14707; Cemiplimab. DR DrugBank; DB05916; CT-011. DR DrugBank; DB15627; Dostarlimab. DR DrugBank; DB11714; Durvalumab. DR DrugBank; DB16417; Geptanolimab. 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 GlyCosmos; Q15116; 4 sites, No reported glycans. DR GlyGen; Q15116; 4 sites. DR iPTMnet; Q15116; -. DR PhosphoSitePlus; Q15116; -. DR BioMuta; PDCD1; -. DR DMDM; 145559515; -. DR MassIVE; Q15116; -. DR PaxDb; 9606-ENSP00000335062; -. DR PeptideAtlas; Q15116; -. DR ProteomicsDB; 60443; -. DR ABCD; Q15116; 130 sequenced antibodies. DR Antibodypedia; 20331; 3564 antibodies from 53 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 AGR; HGNC:8760; -. DR CTD; 5133; -. DR DisGeNET; 5133; -. DR GeneCards; PDCD1; -. DR HGNC; HGNC:8760; PDCD1. DR HPA; ENSG00000188389; Tissue enhanced (heart muscle, lymphoid tissue). 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; 5314254at2759; -. 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 1153 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 cell types or tissues. DR ExpressionAtlas; Q15116; baseline and differential. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. 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 CDD; cd16088; IgV_PD1; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 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; PROGRAMMED CELL DEATH PROTEIN 1; 1. DR PANTHER; PTHR15264:SF2; PROGRAMMED CELL DEATH PROTEIN 1; 1. DR Pfam; PF07686; V-set; 1. DR SMART; SM00409; IG; 1. DR SMART; SM00406; IGv; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR Genevisible; Q15116; HS. 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:7WSL" 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 //