UniProtKB - Q15116 (PDCD1_HUMAN)
Programmed cell death protein 1
PDCD1
Functioni
Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005).
Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:21276005).
Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity).
Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (By similarity).
By similarity1 PublicationThe PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:28951311).
The interaction with CD274/PDCD1L1 inhibits cytotoxic T lymphocytes (CTLs) effector function (PubMed:28951311).
The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (PubMed:22658127, PubMed:25034862, PubMed:25399552).
1 Publication3 PublicationsActivity regulationi
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- apoptotic process Source: ProtInc
- humoral immune response Source: ProtInc
- multicellular organism development Source: ProtInc
- negative regulation of apoptotic process Source: Ensembl
- negative regulation of immune response Source: UniProtKB
- negative regulation of tolerance induction Source: Ensembl
- positive regulation of T cell apoptotic process Source: UniProtKB
- regulation of immune response Source: GO_Central
Keywordsi
Biological process | Adaptive immunity, Apoptosis, Immunity |
Enzyme and pathway databases
PathwayCommonsi | Q15116 |
Reactomei | R-HSA-389948, PD-1 signaling R-HSA-9679191, Potential therapeutics for SARS |
SignaLinki | Q15116 |
SIGNORi | Q15116 |
Protein family/group databases
TCDBi | 8.A.17.4.1, the na(+) channel auxiliary subunit Beta1-Beta4 (sca-Beta) family |
Names & Taxonomyi
Protein namesi | Recommended name: Programmed cell death protein 11 PublicationShort name: Protein PD-11 Publication Short name: hPD-12 Publications Alternative name(s): CD_antigen: CD279 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:8760, PDCD1 |
MIMi | 600244, gene |
neXtProti | NX_Q15116 |
VEuPathDBi | HostDB:ENSG00000188389 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein
Plasma Membrane
- external side of plasma membrane Source: GO_Central
- plasma membrane Source: Reactome
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 24 – 170 | ExtracellularSequence analysisAdd BLAST | 147 | |
Transmembranei | 171 – 191 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 192 – 288 | CytoplasmicSequence analysisAdd BLAST | 97 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Systemic lupus erythematosus 2 (SLEB2)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 49 | N → A: Decreased N-glycosylation without affecting binding to binding to nivolumab drug. 1 Publication | 1 | |
Mutagenesisi | 58 | N → A: Decreased N-glycosylation without affecting binding to binding to nivolumab drug. 1 Publication | 1 | |
Mutagenesisi | 74 | N → A: Decreased N-glycosylation without affecting binding to binding to nivolumab drug. 1 Publication | 1 | |
Mutagenesisi | 116 | N → A: Decreased N-glycosylation without affecting binding to binding to nivolumab drug. 1 Publication | 1 | |
Mutagenesisi | 210 | K → R: Does not affect ubiquitination by the SCF(FBXO38) complex. 1 Publication | 1 | |
Mutagenesisi | 233 | K → R: Abolishes ubiquitination by the SCF(FBXO38) complex. 1 Publication | 1 |
Keywords - Diseasei
Systemic lupus erythematosusOrganism-specific databases
DisGeNETi | 5133 |
MalaCardsi | PDCD1 |
MIMi | 605218, phenotype |
OpenTargetsi | ENSG00000188389 |
Orphaneti | 802, NON RARE IN EUROPE: Multiple sclerosis 536, Systemic lupus erythematosus |
PharmGKBi | PA33110 |
Miscellaneous databases
Pharosi | Q15116, Tclin |
Chemistry databases
ChEMBLi | CHEMBL3307223 |
DrugBanki | DB15767, AMP-224 DB14776, Camrelizumab DB14707, Cemiplimab DB05916, CT-011 DB15627, Dostarlimab DB15768, MEDI0680 DB09035, Nivolumab DB09037, Pembrolizumab DB15766, Retifanlimab DB15765, Sintilimab DB14892, Spartalizumab DB14922, Tislelizumab DB15043, Toripalimab |
DrugCentrali | Q15116 |
GuidetoPHARMACOLOGYi | 2760 |
Genetic variation databases
BioMutai | PDCD1 |
DMDMi | 145559515 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 23 | Sequence analysisAdd BLAST | 23 | |
ChainiPRO_0000014892 | 24 – 288 | Programmed cell death protein 1Add BLAST | 265 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 49 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 54 ↔ 123 | PROSITE-ProRule annotationCombined sources4 Publications | ||
Glycosylationi | 58 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 74 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 116 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Modified residuei | 223 | PhosphotyrosineBy similarity | 1 | |
Cross-linki | 233 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Modified residuei | 248 | PhosphotyrosineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
MassIVEi | Q15116 |
PaxDbi | Q15116 |
PeptideAtlasi | Q15116 |
PRIDEi | Q15116 |
ProteomicsDBi | 60443 |
PTM databases
GlyGeni | Q15116, 4 sites |
iPTMneti | Q15116 |
PhosphoSitePlusi | Q15116 |
Expressioni
Developmental stagei
Gene expression databases
Bgeei | ENSG00000188389, Expressed in lymph node and 99 other tissues |
ExpressionAtlasi | Q15116, baseline and differential |
Genevisiblei | Q15116, HS |
Organism-specific databases
HPAi | ENSG00000188389, Tissue enhanced (lymphoid) |
Interactioni
Subunit structurei
Binary interactionsi
Q15116
With | #Exp. | IntAct |
---|---|---|
CD274 [Q9NZQ7] | 17 | EBI-4314328,EBI-4314282 |
CD274 - isoform 1 [Q9NZQ7-1] | 2 | EBI-4314328,EBI-15686469 |
PDCD1LG2 [Q9BQ51] | 14 | EBI-4314328,EBI-16427978 |
PTPN11 [Q06124] | 3 | EBI-4314328,EBI-297779 |
Protein-protein interaction databases
BioGRIDi | 111160, 65 interactors |
DIPi | DIP-44126N |
IntActi | Q15116, 53 interactors |
MINTi | Q15116 |
STRINGi | 9606.ENSP00000335062 |
Chemistry databases
BindingDBi | Q15116 |
Miscellaneous databases
RNActi | Q15116, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | Q15116 |
SMRi | Q15116 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 35 – 145 | Ig-like V-typePROSITE-ProRule annotationAdd BLAST | 111 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 25 – 34 | Nivolumab bindingCombined sources1 Publication | 10 | |
Regioni | 70 – 77 | Interaction with CD274/PDCD1L11 Publication | 8 | |
Regioni | 74 – 99 | Pembrolizumab bindingCombined sources2 PublicationsAdd BLAST | 26 | |
Regioni | 254 – 288 | DisorderedSequence analysisAdd BLAST | 35 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 221 – 226 | ITIM motifBy similarity | 6 | |
Motifi | 247 – 251 | ITSM motifBy similarity | 5 |
Keywords - Domaini
Immunoglobulin domain, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502SUIW, Eukaryota |
GeneTreei | ENSGT00390000013662 |
HOGENOMi | CLU_1075828_0_0_1 |
InParanoidi | Q15116 |
OMAi | QDGHCSW |
OrthoDBi | 1437063at2759 |
PhylomeDBi | Q15116 |
TreeFami | TF336181 |
Family and domain databases
Gene3Di | 2.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003599, Ig_sub IPR013106, Ig_V-set IPR042379, PDCD1 |
PANTHERi | PTHR15264, PTHR15264, 1 hit |
Pfami | View protein in Pfam PF07686, V-set, 1 hit |
SMARTi | View protein in SMART SM00409, IG, 1 hit SM00406, IGv, 1 hit |
SUPFAMi | SSF48726, SSF48726, 1 hit |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MQIPQAPWPV VWAVLQLGWR PGWFLDSPDR PWNPPTFSPA LLVVTEGDNA
60 70 80 90 100
TFTCSFSNTS ESFVLNWYRM SPSNQTDKLA AFPEDRSQPG QDCRFRVTQL
110 120 130 140 150
PNGRDFHMSV VRARRNDSGT YLCGAISLAP KAQIKESLRA ELRVTERRAE
160 170 180 190 200
VPTAHPSPSP RPAGQFQTLV VGVVGGLLGS LVLLVWVLAV ICSRAARGTI
210 220 230 240 250
GARRTGQPLK EDPSAVPVFS VDYGELDFQW REKTPEPPVP CVPEQTEYAT
260 270 280
IVFPSGMGTS SPARRGSADG PRSAQPLRPE DGHCSWPL
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0Y2W6 | H0Y2W6_HUMAN | Programmed cell death protein 1 | PDCD1 | 122 | Annotation score: | ||
E7ER21 | E7ER21_HUMAN | Programmed cell death protein 1 | PDCD1 | 66 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 38 | S → F in AAC51773 (PubMed:9332365).Curated | 1 | |
Sequence conflicti | 162 | P → S in AAC41700 (PubMed:7851902).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_031685 | 215 | A → V. Corresponds to variant dbSNP:rs2227982Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L27440 Genomic DNA Translation: AAC41700.1 U64863 mRNA Translation: AAC51773.1 AF363458 Genomic DNA Translation: AAN64003.1 AY238517 mRNA Translation: AAO63583.1 EF064716 Genomic DNA Translation: ABK41899.1 AK313848 mRNA Translation: BAG36577.1 CH471063 Genomic DNA Translation: EAW71298.1 BC074740 mRNA Translation: AAH74740.1 |
CCDSi | CCDS33428.1 |
PIRi | A55737 |
RefSeqi | NP_005009.2, NM_005018.2 |
Genome annotation databases
Ensembli | ENST00000334409; ENSP00000335062; ENSG00000188389 ENST00000618185; ENSP00000480684; ENSG00000276977 |
GeneIDi | 5133 |
KEGGi | hsa:5133 |
MANE-Selecti | ENST00000334409.10; ENSP00000335062.5; NM_005018.3; NP_005009.2 |
UCSCi | uc002wcq.5, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L27440 Genomic DNA Translation: AAC41700.1 U64863 mRNA Translation: AAC51773.1 AF363458 Genomic DNA Translation: AAN64003.1 AY238517 mRNA Translation: AAO63583.1 EF064716 Genomic DNA Translation: ABK41899.1 AK313848 mRNA Translation: BAG36577.1 CH471063 Genomic DNA Translation: EAW71298.1 BC074740 mRNA Translation: AAH74740.1 |
CCDSi | CCDS33428.1 |
PIRi | A55737 |
RefSeqi | NP_005009.2, NM_005018.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2M2D | NMR | - | A | 34-150 | [»] | |
3RRQ | X-ray | 2.10 | A | 32-160 | [»] | |
4ZQK | X-ray | 2.45 | B | 33-150 | [»] | |
5B8C | X-ray | 2.15 | C/F/I/L | 32-160 | [»] | |
5GGR | X-ray | 3.30 | Y/Z | 26-150 | [»] | |
5GGS | X-ray | 2.00 | Y/Z | 26-148 | [»] | |
5IUS | X-ray | 2.89 | A/B | 26-146 | [»] | |
5JXE | X-ray | 2.90 | A/B | 33-146 | [»] | |
5WT9 | X-ray | 2.40 | G | 1-167 | [»] | |
6HIG | X-ray | 2.20 | B | 33-150 | [»] | |
6J14 | X-ray | 1.40 | G | 33-147 | [»] | |
6J15 | X-ray | 2.60 | C/D | 32-147 | [»] | |
6JBT | X-ray | 2.47 | F | 21-170 | [»] | |
6JJP | X-ray | 2.90 | C/F | 21-167 | [»] | |
6K0Y | X-ray | 1.70 | C | 25-167 | [»] | |
6R5G | NMR | - | B | 244-254 | [»] | |
6ROY | X-ray | 2.10 | C/D | 219-229 | [»] | |
6ROZ | X-ray | 2.89 | B/D | 244-254 | [»] | |
6UMT | X-ray | 1.99 | A | 33-150 | [»] | |
6UMU | X-ray | 1.18 | A | 33-150 | [»] | |
6UMV | X-ray | 1.42 | A | 33-150 | [»] | |
6XKR | X-ray | 2.59 | P | 32-160 | [»] | |
7BXA | X-ray | 3.32 | A/P | 29-150 | [»] | |
7CGW | X-ray | 3.20 | C/P | 25-169 | [»] | |
7CU5 | X-ray | 2.81 | E/Q | 30-147 | [»] | |
7E9B | X-ray | 1.78 | C | 32-146 | [»] | |
BMRBi | Q15116 | |||||
SMRi | Q15116 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111160, 65 interactors |
DIPi | DIP-44126N |
IntActi | Q15116, 53 interactors |
MINTi | Q15116 |
STRINGi | 9606.ENSP00000335062 |
Chemistry databases
BindingDBi | Q15116 |
ChEMBLi | CHEMBL3307223 |
DrugBanki | DB15767, AMP-224 DB14776, Camrelizumab DB14707, Cemiplimab DB05916, CT-011 DB15627, Dostarlimab DB15768, MEDI0680 DB09035, Nivolumab DB09037, Pembrolizumab DB15766, Retifanlimab DB15765, Sintilimab DB14892, Spartalizumab DB14922, Tislelizumab DB15043, Toripalimab |
DrugCentrali | Q15116 |
GuidetoPHARMACOLOGYi | 2760 |
Protein family/group databases
TCDBi | 8.A.17.4.1, the na(+) channel auxiliary subunit Beta1-Beta4 (sca-Beta) family |
PTM databases
GlyGeni | Q15116, 4 sites |
iPTMneti | Q15116 |
PhosphoSitePlusi | Q15116 |
Genetic variation databases
BioMutai | PDCD1 |
DMDMi | 145559515 |
Proteomic databases
MassIVEi | Q15116 |
PaxDbi | Q15116 |
PeptideAtlasi | Q15116 |
PRIDEi | Q15116 |
ProteomicsDBi | 60443 |
Protocols and materials databases
ABCDi | Q15116, 125 sequenced antibodies |
Antibodypediai | 20331, 2939 antibodies from 51 providers |
CPTCi | Q15116, 1 antibody |
DNASUi | 5133 |
Genome annotation databases
Ensembli | ENST00000334409; ENSP00000335062; ENSG00000188389 ENST00000618185; ENSP00000480684; ENSG00000276977 |
GeneIDi | 5133 |
KEGGi | hsa:5133 |
MANE-Selecti | ENST00000334409.10; ENSP00000335062.5; NM_005018.3; NP_005009.2 |
UCSCi | uc002wcq.5, human |
Organism-specific databases
CTDi | 5133 |
DisGeNETi | 5133 |
GeneCardsi | PDCD1 |
HGNCi | HGNC:8760, PDCD1 |
HPAi | ENSG00000188389, Tissue enhanced (lymphoid) |
MalaCardsi | PDCD1 |
MIMi | 600244, gene 605218, phenotype |
neXtProti | NX_Q15116 |
OpenTargetsi | ENSG00000188389 |
Orphaneti | 802, NON RARE IN EUROPE: Multiple sclerosis 536, Systemic lupus erythematosus |
PharmGKBi | PA33110 |
VEuPathDBi | HostDB:ENSG00000188389 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502SUIW, Eukaryota |
GeneTreei | ENSGT00390000013662 |
HOGENOMi | CLU_1075828_0_0_1 |
InParanoidi | Q15116 |
OMAi | QDGHCSW |
OrthoDBi | 1437063at2759 |
PhylomeDBi | Q15116 |
TreeFami | TF336181 |
Enzyme and pathway databases
PathwayCommonsi | Q15116 |
Reactomei | R-HSA-389948, PD-1 signaling R-HSA-9679191, Potential therapeutics for SARS |
SignaLinki | Q15116 |
SIGNORi | Q15116 |
Miscellaneous databases
BioGRID-ORCSi | 5133, 7 hits in 1037 CRISPR screens |
ChiTaRSi | PDCD1, human |
GeneWikii | Programmed_cell_death_1 |
GenomeRNAii | 5133 |
Pharosi | Q15116, Tclin |
PROi | PR:Q15116 |
RNActi | Q15116, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000188389, Expressed in lymph node and 99 other tissues |
ExpressionAtlasi | Q15116, baseline and differential |
Genevisiblei | Q15116, HS |
Family and domain databases
Gene3Di | 2.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003599, Ig_sub IPR013106, Ig_V-set IPR042379, PDCD1 |
PANTHERi | PTHR15264, PTHR15264, 1 hit |
Pfami | View protein in Pfam PF07686, V-set, 1 hit |
SMARTi | View protein in SMART SM00409, IG, 1 hit SM00406, IGv, 1 hit |
SUPFAMi | SSF48726, SSF48726, 1 hit |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PDCD1_HUMAN | |
Accessioni | Q15116Primary (citable) accession number: Q15116 Secondary accession number(s): O00517, Q8IX89 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | April 17, 2007 | |
Last modified: | February 23, 2022 | |
This is version 187 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references