Q15116 (PDCD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Programmed cell death protein 1
Short name=Protein PD-1
Short name=hPD-1

Alternative name(s):
CD_antigen=CD279

Gene names

Name:	PDCD1
Synonyms:	PD1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	288 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. Possible cell death inducer, in association with other factors. Ref.10
Subunit structure	Monomer By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Developmental stage	Induced at programmed cell death.
Involvement in disease	Systemic lupus erythematosus 2 (SLEB2) [MIM:605218]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.4
Sequence similarities	Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Apoptosis Immunity
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Systemic lupus erythematosus
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Traceable author statement. Source: Reactome apoptotic process Traceable author statement PubMed 1396582. Source: ProtInc humoral immune response Traceable author statement Ref.2. Source: ProtInc multicellular organismal development Traceable author statement Ref.2. Source: ProtInc
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	signal transducer activity Traceable author statement PubMed 1396582. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD274	Q9NZQ7	2	EBI-4314328,EBI-4314282

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Chain

21 – 288

268

Programmed cell death protein 1

PRO_0000014892

Regions

Topological domain

21 – 170

150

Extracellular Potential

Transmembrane

171 – 191

21

Helical; Potential

Topological domain

192 – 288

97

Cytoplasmic Potential

Domain

35 – 145

111

Ig-like V-type

Amino acid modifications

Glycosylation

49

1

N-linked (GlcNAc...) Potential

Glycosylation

58

1

N-linked (GlcNAc...) Potential

Glycosylation

74

1

N-linked (GlcNAc...) Potential

Glycosylation

116

1

N-linked (GlcNAc...) Potential

Disulfide bond

54 ↔ 123

By similarity

Natural variations

Natural variant

215

1

A → V.
Corresponds to variant rs2227982 [ dbSNP | Ensembl ].

VAR_031685

Experimental info

Sequence conflict

38

1

S → F in AAC51773. Ref.2

Sequence conflict

162

1

P → S in AAC41700. Ref.1

Secondary structure

1

.

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288

Helix Strand Turn

Details...

Beta strand

36 – 38

3

Beta strand

40 – 45

6

Beta strand

50 – 55

6

Beta strand

63 – 72

10

Beta strand

77 – 82

6

Beta strand

95 – 99

5

Beta strand

103 – 112

10

Helix

115 – 117

3

Beta strand

119 – 127

9

Helix

129 – 131

3

Beta strand

133 – 136

4

Beta strand

140 – 145

6

Sequences

	Sequence		Length	Mass (Da)
	Q15116 [UniParc]. Last modified April 17, 2007. Version 3. Checksum: A5210FD40C304FB7	FASTA	288	31,647
	10 20 30 40 50 60 MQIPQAPWPV VWAVLQLGWR PGWFLDSPDR PWNPPTFSPA LLVVTEGDNA TFTCSFSNTS 70 80 90 100 110 120 ESFVLNWYRM SPSNQTDKLA AFPEDRSQPG QDCRFRVTQL PNGRDFHMSV VRARRNDSGT 130 140 150 160 170 180 YLCGAISLAP KAQIKESLRA ELRVTERRAE VPTAHPSPSP RPAGQFQTLV VGVVGGLLGS 190 200 210 220 230 240 LVLLVWVLAV ICSRAARGTI GARRTGQPLK EDPSAVPVFS VDYGELDFQW REKTPEPPVP 250 260 270 280 CVPEQTEYAT IVFPSGMGTS SPARRGSADG PRSAQPLRPE DGHCSWPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and chromosomal localization of the human PD-1 gene (PDCD1)." Shinohara T., Taniwaki M., Ishida Y., Kawaich M., Honjo T. Genomics 23:704-706(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The human PD-1 gene: complete cDNA, genomic organization, and developmentally regulated expression in B cell progenitors." Finger L.R., Pu J., Wasserman R., Vibhakar R., Louie E., Hardy R.R., Burrows P.D., Billips L.D. Gene 197:177-187(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Erratum Finger L.R., Pu J., Wasserman R., Vibhakar R., Louie E., Hardy R.R., Burrows P.D., Billips L.D. Gene 203:253-253(1997)
[4]	"A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans." Prokunina L., Castillejo-Lopez C., Oberg F., Gunnarsson I., Berg L., Magnusson V., Brookes A.J., Tentler D., Kristjansdottir H., Grondal G., Bolstad A.I., Svenungsson E., Lundberg I., Sturfelt G., Jonssen A., Truedsson L., Lima G., Alcocer-Varela J. , Jonsson R., Gyllensten U.B., Harley J.B., Alarcon-Segovia D., Steinsson K., Alarcon-Riquelme M.E. Nat. Genet. 32:666-669(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INVOLVEMENT IN SLEB2.
[5]	"Cloning of PD-1 cDNA from activated peripheral leukocytes." He X., Xu L., Liu Y., Zeng Y. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"The role of the PD-1 pathway in autoimmunity and peripheral tolerance." Fife B.T., Pauken K.E. Ann. N. Y. Acad. Sci. 1217:45-59(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00014830.

PIR

A55737.

RefSeq

NP_005009.2. NM_005018.2.

UniGene

Hs.158297.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2M2D	NMR	-	A	34-150	[»]
3RRQ	X-ray	2.10	A	32-160	[»]

ProteinModelPortal

Q15116.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15116. 1 interaction.

STRING

9606.ENSP00000335062.

PTM databases

PhosphoSite

Q15116.

Polymorphism databases

DMDM

145559515.

Proteomic databases

PaxDb

Q15116.

PRIDE

Q15116.

Protocols and materials databases

DNASU

5133.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000334409; ENSP00000335062; ENSG00000188389.

GeneID

5133.

KEGG

hsa:5133.

UCSC

uc002wcq.4. human.

Organism-specific databases

CTD

5133.

GeneCards

GC02M242792.

H-InvDB

HIX0030684.

HGNC

HGNC:8760. PDCD1.

HPA

HPA035981.

MIM

109100. phenotype.
600244. gene.
605218. phenotype.

neXtProt

NX_Q15116.

Orphanet

802. Multiple sclerosis.
536. Systemic lupus erythematosus.

PharmGKB

PA33110.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46047.

HOGENOM

HOG000253959.

HOVERGEN

HBG053534.

InParanoid

Q15116.

KO

K06744.

OMA

DFQWREK.

OrthoDB

EOG4Z8XX4.

PhylomeDB

Q15116.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q15116.

Bgee

Q15116.

CleanEx

HS_PDCD1.

Genevestigator

Q15116.

GermOnline

ENSG00000188389. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
IPR003596. Ig_V-set_subgr.
[Graphical view]

Pfam

PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00406. IGv. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

5133.

NextBio

19792.

SOURCE

Search...

Entry information

Entry name

PDCD1_HUMAN

Accession

Primary (citable) accession number: Q15116
Secondary accession number(s): O00517, Q8IX89

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	April 17, 2007
Last modified:	May 1, 2013
This is version 118 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.