Q9NZQ7 (PD1L1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Programmed cell death 1 ligand 1
Short name=PD-L1
Short name=PDCD1 ligand 1
Short name=Programmed death ligand 1

Alternative name(s):
B7 homolog 1
Short name=B7-H1
CD_antigen=CD274

Gene names

Name:	CD274
Synonyms:	B7H1, PDCD1L1, PDCD1LG1, PDL1

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	290 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	Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production. Ref.1 Ref.2
Subunit structure	Interacts with PDCD1. Ref.2
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.3. Isoform 2: Endomembrane system; Single-pass type I membrane protein Ref.3.
Tissue specificity	Highly expressed in the heart, skeletal muscle, placenta and lung. Weakly expressed in the thymus, spleen, kidney and liver. Expressed on activated T- and B-cells, dendritic cells, keratinocytes and monocytes. Ref.1 Ref.2
Induction	Up-regulated on T- and B-cells, dendritic cells, keratinocytes and monocytes after LPS and IFNG activation. Up-regulated in B-cells activated by surface Ig cross-linking. Ref.1 Ref.2
Sequence similarities	Belongs to the immunoglobulin superfamily. BTN/MOG family. Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 1 Ig-like V-type (immunoglobulin-like) domain.
Sequence caution	The sequence BAA91966.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Inferred from direct assay Ref.1. Source: UniProtKB cell surface receptor signaling pathway Inferred from direct assay Ref.1. Source: UniProtKB immune response Inferred from direct assay Ref.1. Source: UniProtKB negative regulation of T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of T cell proliferation Traceable author statement Ref.1. Source: UniProtKB positive regulation of interleukin-10 secretion Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular vesicular exosome Inferred from direct assay PubMed 17076679. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD80	P33681	2	EBI-4314282,EBI-1031024
PDCD1	Q15116	2	EBI-4314282,EBI-4314328

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NZQ7-1)

Also known as: PD-L1I;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NZQ7-2)

Also known as: PD-L1II;

The sequence of this isoform differs from the canonical sequence as follows:
     17-130: Missing.

Isoform 3 (identifier: Q9NZQ7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     178-178: K → D
     179-290: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 290

272

Programmed cell death 1 ligand 1

PRO_0000014553

Regions

Topological domain

19 – 238

220

Extracellular Potential

Transmembrane

239 – 259

21

Helical; Potential

Topological domain

260 – 290

31

Cytoplasmic Potential

Domain

19 – 127

109

Ig-like V-type

Domain

133 – 225

93

Ig-like C2-type

Amino acid modifications

Glycosylation

35

1

N-linked (GlcNAc...) Potential

Glycosylation

192

1

N-linked (GlcNAc...) Ref.9

Glycosylation

200

1

N-linked (GlcNAc...) Potential

Glycosylation

219

1

N-linked (GlcNAc...) Potential

Disulfide bond

40 ↔ 114

Ref.10

Disulfide bond

155 ↔ 209

Ref.10

Natural variations

Alternative sequence

17 – 130

114

Missing in isoform 2.

VSP_013735

Alternative sequence

178

1

K → D in isoform 3.

VSP_013736

Alternative sequence

179 – 290

112

Missing in isoform 3.

VSP_013737

Secondary structure

1

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290

Helix Strand Turn

Details...

Beta strand

26 – 31

6

Beta strand

36 – 41

6

Turn

50 – 52

3

Beta strand

54 – 59

6

Beta strand

62 – 68

7

Beta strand

74 – 77

4

Helix

79 – 81

3

Beta strand

82 – 87

6

Helix

89 – 92

4

Turn

93 – 95

3

Beta strand

96 – 103

8

Helix

106 – 108

3

Beta strand

110 – 132

23

Beta strand

138 – 145

8

Turn

146 – 149

4

Beta strand

150 – 161

12

Beta strand

164 – 169

6

Beta strand

178 – 183

6

Beta strand

185 – 187

3

Beta strand

191 – 200

10

Beta strand

206 – 213

8

Turn

214 – 217

4

Beta strand

218 – 225

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PD-L1I) [UniParc]. Last modified October 1, 2000. Version 1. Checksum: FE957086E62A31A8	FASTA	290	33,275
	10 20 30 40 50 60 MRIFAVFIFM TYWHLLNAFT VTVPKDLYVV EYGSNMTIEC KFPVEKQLDL AALIVYWEME 70 80 90 100 110 120 DKNIIQFVHG EEDLKVQHSS YRQRARLLKD QLSLGNAALQ ITDVKLQDAG VYRCMISYGG 130 140 150 160 170 180 ADYKRITVKV NAPYNKINQR ILVVDPVTSE HELTCQAEGY PKAEVIWTSS DHQVLSGKTT 190 200 210 220 230 240 TTNSKREEKL FNVTSTLRIN TTTNEIFYCT FRRLDPEENH TAELVIPELP LAHPPNERTH 250 260 270 280 290 LVILGAILLC LGVALTFIFR LRKGRMMDVK KCGIQDTNSK KQSDTHLEET
	Isoform 2 (PD-L1II) [UniParc]. Checksum: B8BD0CFF9DEA722F	FASTA	176	20,246
	10 20 30 40 50 60 MRIFAVFIFM TYWHLLNAPY NKINQRILVV DPVTSEHELT CQAEGYPKAE VIWTSSDHQV 70 80 90 100 110 120 LSGKTTTTNS KREEKLFNVT STLRINTTTN EIFYCTFRRL DPEENHTAEL VIPELPLAHP 130 140 150 160 170 PNERTHLVIL GAILLCLGVA LTFIFRLRKG RMMDVKKCGI QDTNSKKQSD THLEET
	Isoform 3 [UniParc]. Checksum: A306BF2018885F0B	FASTA	178	20,454
	10 20 30 40 50 60 MRIFAVFIFM TYWHLLNAFT VTVPKDLYVV EYGSNMTIEC KFPVEKQLDL AALIVYWEME 70 80 90 100 110 120 DKNIIQFVHG EEDLKVQHSS YRQRARLLKD QLSLGNAALQ ITDVKLQDAG VYRCMISYGG 130 140 150 160 170 ADYKRITVKV NAPYNKINQR ILVVDPVTSE HELTCQAEGY PKAEVIWTSS DHQVLSGD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion." Dong H., Zhu G., Tamada K., Chen L. Nat. Med. 5:1365-1369(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[2]	"Engagement of the PD-1 immunoinhibitory receptor by a novel B7-family member leads to negative regulation of lymphocyte activation." Freeman G.J., Long A.J., Iwai Y., Bourque K., Chernova T., Nishimura H., Fitz L.J., Malenkovich N., Okazaki T., Byrne M.C., Horton H.F., Fouser L., Carter L., Ling V., Bowman M.R., Carreno B.M., Collins M., Wood C.R., Honjo T. J. Exp. Med. 192:1027-1034(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH PDCD1, TISSUE SPECIFICITY, INDUCTION. Tissue: Placenta.
[3]	"Identification of a novel splice variant of human PD-L1 mRNA encoding an isoform-lacking Igv-like domain." He X.-H., Xu L.-H., Liu Y. Acta Pharmacol. Sin. 26:462-468(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION.
[4]	"Identification of a novel splice variant of human PD-L1 in the peripheral blood mononuclear cells." Xu L.-H., Liu Y., He X.-H. Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[5]	"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] (ISOFORMS 1 AND 3). Tissue: Placenta.
[6]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORM 1). Tissue: Lung.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-192, MASS SPECTROMETRY. Tissue: Liver.
[10]	"The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors." Lin D.Y., Tanaka Y., Iwasaki M., Gittis A.G., Su H.P., Mikami B., Okazaki T., Honjo T., Minato N., Garboczi D.N. Proc. Natl. Acad. Sci. U.S.A. 105:3011-3016(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 18-239 IN COMPLEX WITH MOUSE PDCD1, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF177937 mRNA. Translation: AAF25807.1.
AF233516 mRNA. Translation: AAG18508.1.
AY254342 mRNA. Translation: AAP13470.1.
AY291313 mRNA. Translation: AAP42144.1.
AY714881 mRNA. Translation: AAU09634.1.
AK001894 mRNA. Translation: BAA91966.1. Different initiation.
AK300470 mRNA. Translation: BAG62189.1.
AK314567 mRNA. Translation: BAG37149.1.
AL162253 Genomic DNA. Translation: CAI15983.1.
CH471071 Genomic DNA. Translation: EAW58763.1.
BC069381 mRNA. Translation: AAH69381.1.
BC074984 mRNA. Translation: AAH74984.1.
BC113734 mRNA. Translation: AAI13735.1.
BC113736 mRNA. Translation: AAI13737.1.

IPI

IPI00023021.
IPI00446867.
IPI00556058.

RefSeq

NP_001254635.1. NM_001267706.1.
NP_054862.1. NM_014143.3.

UniGene

Hs.521989.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BIK	X-ray	2.65	A	18-239	[»]
3BIS	X-ray	2.64	A/B	18-239	[»]
3FN3	X-ray	2.70	A/B	19-238	[»]
3SBW	X-ray	2.28	C	19-239	[»]

ProteinModelPortal

Q9NZQ7.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29731N.

IntAct

Q9NZQ7. 2 interactions.

STRING

9606.ENSP00000370989.

PTM databases

PhosphoSite

Q9NZQ7.

Polymorphism databases

DMDM

83287884.

Proteomic databases

PaxDb

Q9NZQ7.

PRIDE

Q9NZQ7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000381573; ENSP00000370985; ENSG00000120217.
ENST00000381577; ENSP00000370989; ENSG00000120217.

GeneID

29126.

KEGG

hsa:29126.

UCSC

uc003zje.3. human.
uc011lmb.2. human.

Organism-specific databases

CTD

29126.

GeneCards

GC09P005444.

HGNC

HGNC:17635. CD274.

HPA

CAB030018.

MIM

605402. gene.

neXtProt

NX_Q9NZQ7.

PharmGKB

PA134915280.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG43849.

HOGENOM

HOG000059625.

HOVERGEN

HBG082112.

InParanoid

Q9NZQ7.

KO

K06745.

OMA

AEVIWTS.

OrthoDB

EOG4DFPPP.

PhylomeDB

Q9NZQ7.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9NZQ7.

Bgee

Q9NZQ7.

CleanEx

HS_CD274.

Genevestigator

Q9NZQ7.

GermOnline

ENSG00000120217. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 2 hits.

InterPro

IPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]

Pfam

PF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00409. IG. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9NZQ7.

GenomeRNAi

29126.

NextBio

52236.

SOURCE

Search...

Entry information

Entry name

PD1L1_HUMAN

Accession

Primary (citable) accession number: Q9NZQ7
Secondary accession number(s): B2RBA2 , B4DU27, Q14CJ2, Q66RK1, Q6WEX4, Q9NUZ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 110 of the entry and version 1 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.