Geeni PDCD1, 2q37.3, Cell death 1, proteiini PD-1 ( Löytäjä T. Honjo 1991, 1992)

Koska  en ole tiedostanut tätä proteiinia ennen ja nyt siitä annetaan tämän vuoden Nobelin palkinto proteiinin löytäjälle T. Hontolle, niin otan  geenin ja proteiinin rakenteesta PubMed tiedot tähän:
Pitkä  sitaatti:

PDCD1, 2q37.3, Cell death1

https://www.ncbi.nlm.nih.gov/gene/5133

PD1; PD-1; CD279; SLEB2; hPD-1; hPD-l; hSLE1

Summary

This gene encodes a cell surface membrane protein of the immunoglobulin superfamily. This protein is expressed in pro-B-cells and is thought to play a role in their differentiation. In mice, expression of this gene is induced in the thymus when anti-CD3 antibodies are injected and large numbers of thymocytes undergo apoptosis. Mice deficient for this gene bred on a BALB/c background developed dilated cardiomyopathy and died from congestive heart failure. These studies suggest that this gene product may also be important in T cell function and contribute to the prevention of autoimmune diseases. [provided by RefSeq, Jul 2008]

Expression

Biased expression in lymph node (RPKM 8.8), spleen (RPKM 2.6) and 7 other tissues See

Bibliography

Related articles in PubMed

1. Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer. Drakes ML, et al. J Ovarian Res, 2018 May 30. PMID 29843813, Free PMC Article
2. Rs2227982 and rs2227981 in PDCD1 gene are functional SNPs associated with T1D risk in East Asian. Gu Y, et al. Acta Diabetol, 2018 Aug. PMID 29774466
3. [Association of programmed cell death 1 (PDCD1) gene polymorphisms with colorectal cancer among Han Chinese population]. Zhao Y, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2018 Apr 10. PMID 29652996
4. Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression. Guo Y, et al. PLoS One, 2018. PMID 29489833, Free PMC Article
5. [Role of programmed death-1 in viral infectious diseases]. Lu FC, et al. Zhongguo Dang Dai Er Ke Za Zhi, 2018 Jan. PMID 29335088
   

See all (642) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling
2. Both rs2227982 and rs2227981 polymorphisms were associated with T1 Diabetes (T1D) risk in East Asians, and rs2227982 also had a significant association with glycemic traits, which suggested PDCD1 gene polymorphisms might participate in facilitating T1D risk. [meta-analysis]
3. PD.1 (-538G/A) gene polymorphism is associated with Colon Cancer Risk.
4. The high-affinity PD-1 mutant could compete with the binding of antibodies specific to PD-L1 or PD-L2 on cancer cells.
5. The G allele of rs36084323 of PDCD1 is associated with increased risk of advanced TNM staging of colorectal cancer.
6. promoter methylation of CTLA4, PD-L1, PD-L2, and PD-1 in diffuse lower-grade gliomas (LGG) harboring isocitrate dehydrogenase (IDH) mutation, is reported.
7. Unlike other multiple autoimmune disease associated genetic variants, there was no association between PDCD1 variants and Juvenile Idiopathic Arthritis
8. Alteration of the PD-1/PD-L1 pathway can modulate Treg/Th17 balance in asthmatic children.
9. The expression of PD1 on T cells was elevated in patients with rheumatoid arthritis and was correlated with the disease activity.
10. High expression of programmed death-1 in sentinel lymph nodes is associated with breast cancer.
    

Submit: New GeneRIF Correction See all GeneRIFs (602)

PD-1 signaling
The Programmed cell death protein 1 (PD-1) is one of the negative regulators of TCR signaling. PD-1 may exert its effects on cell differentiation and survival directly by inhibiting early activation events that are positively regulated by CD28 or indirectly through IL-2. PD-1 ligation inhibits the induction of the cell survival factor Bcl-xL and the expression of transcription factors associated with effector cell function, including GATA-3, Tbet, and Eomes. PD-1 exerts its inhibitory effects by bringing phosphatases SHP-1 and SHP-2 into the immune synapse, leading to dephosphorylation of CD3-zeta chain, PI3K and AKT. … from REACTOME source record: R-HSA-389948

Sequence:

https://www.ncbi.nlm.nih.gov/protein/NP_005009.2

programmed cell death protein 1 precursor [Homo sapiens]

NCBI Reference Sequence: NP_005009.2
Identical Proteins FASTA Graphics

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LOCUS       NP_005009                288 aa            linear   PRI 30-SEP-2018
DEFINITION  programmed cell death protein 1 precursor [Homo sapiens].
ACCESSION   NP_005009
VERSION     NP_005009.2
DBSOURCE    REFSEQ: accession NM_005018.2
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 288)
  AUTHORS   Li Y, Liang Z, Tian Y, Cai W, Weng Z, Chen L, Zhang H, Bao Y, Zheng
            H, Zeng S, Bei C and Li Y.
  TITLE     High-affinity PD-1 molecules deliver improved interaction with
            PD-L1 and PD-L2
  JOURNAL   Cancer Sci. 109 (8), 2435-2445 (2018)
   PUBMED   29890018
  REMARK    GeneRIF: The high-affinity PD-1 mutant could compete with the
            binding of antibodies specific to PD-L1 or PD-L2 on cancer cells.
REFERENCE   2  (residues 1 to 288)
  AUTHORS   Gu Y, Xiao L, Gu W, Chen S, Feng Y, Wang J, Wang Z, Cai Y, Chen H,
            Xu X, Shi Y, Zhang M, Xu K and Yang T.
  TITLE     Rs2227982 and rs2227981 in PDCD1 gene are functional SNPs
            associated with T1D risk in East Asian
  JOURNAL   Acta Diabetol 55 (8), 813-819 (2018)
   PUBMED   29774466
  REMARK    GeneRIF: Both rs2227982 and rs2227981 polymorphisms were associated
            with T1 Diabetes (T1D) risk in East Asians, and rs2227982 also had
            a significant association with glycemic traits, which suggested
            PDCD1 gene polymorphisms might participate in facilitating T1D
            risk. [meta-analysis]
REFERENCE   3  (residues 1 to 288)
  AUTHORS   Enkhbat T, Nishi M, Takasu C, Yoshikawa K, Jun H, Tokunaga T,
            Kashihara H, Ishikawa D and Shimada M.
  TITLE     Programmed Cell Death Ligand 1 Expression Is an Independent
            Prognostic Factor in Colorectal Cancer
  JOURNAL   Anticancer Res. 38 (6), 3367-3373 (2018)
   PUBMED   29848685
  REMARK    GeneRIF: High expressions of programmed cell death protein 1 (PD-1)
            and programmed cell death 1 ligand 1 (PD-L1) were associated with
            poor prognosis after surgery.
REFERENCE   4  (residues 1 to 288)
  AUTHORS   Drakes ML, Mehrotra S, Aldulescu M, Potkul RK, Liu Y, Grisoli A,
            Joyce C, O'Brien TE, Stack MS and Stiff PJ.
  TITLE     Stratification of ovarian tumor pathology by expression of
            programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian
            cancer
  JOURNAL   J Ovarian Res 11 (1), 43 (2018)
   PUBMED   29843813
  REMARK    GeneRIF: We conclude that a subgroup of advanced disease ovarian
            cancer patients with high grade tumors, expressing PD-L1, may be
            prime candidates for immunotherapy targeting PD-1 signaling
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 288)
  AUTHORS   Xi X, Liu JM and Guo JY.
  TITLE     Correlation of PD-1/PD-L1 Signaling Pathway with Treg/Th17
            Imbalance from Asthmatic Children
  JOURNAL   Int. Arch. Allergy Immunol. 176 (3-4), 255-267 (2018)
   PUBMED   29874664
  REMARK    GeneRIF: Alteration of the PD-1/PD-L1 pathway can modulate
            Treg/Th17 balance in asthmatic children.
REFERENCE   6  (residues 1 to 288)
  AUTHORS   Moser KL, Neas BR, Salmon JE, Yu H, Gray-McGuire C, Asundi N,
            Bruner GR, Fox J, Kelly J, Henshall S, Bacino D, Dietz M, Hogue R,
            Koelsch G, Nightingale L, Shaver T, Abdou NI, Albert DA, Carson C,
            Petri M, Treadwell EL, James JA and Harley JB.
  TITLE     Genome scan of human systemic lupus erythematosus: evidence for
            linkage on chromosome 1q in African-American pedigrees
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 95 (25), 14869-14874 (1998)
   PUBMED   9843982
REFERENCE   7  (residues 1 to 288)
  AUTHORS   Finger LR, Pu J, Wasserman R, Vibhakar R, Louie E, Hardy RR,
            Burrows PD and Billips LG.
  TITLE     The human PD-1 gene: complete cDNA, genomic organization, and
            developmentally regulated expression in B cell progenitors
  JOURNAL   Gene 197 (1-2), 177-187 (1997)
   PUBMED   9332365
  REMARK    Erratum:[Gene 1997 Dec 12;203(2):253]
REFERENCE   8  (residues 1 to 288)
  AUTHORS   Vibhakar R, Juan G, Traganos F, Darzynkiewicz Z and Finger LR.
  TITLE     Activation-induced expression of human programmed death-1 gene in
            T-lymphocytes
  JOURNAL   Exp. Cell Res. 232 (1), 25-28 (1997)
   PUBMED   9141617
REFERENCE   9  (residues 1 to 288)
  AUTHORS   Shinohara T, Taniwaki M, Ishida Y, Kawaichi M and Honjo T.
  TITLE     Structure and chromosomal localization of the human PD-1 gene
            (PDCD1)
  JOURNAL   Genomics 23 (3), 704-706 (1994)
   PUBMED   7851902
REFERENCE   10 (residues 1 to 288)
  AUTHORS   Ishida Y, Agata Y, Shibahara K and Honjo T.
  TITLE     Induced expression of PD-1, a novel member of the immunoglobulin
            gene superfamily, upon programmed cell death
  JOURNAL   EMBO J. 11 (11), 3887-3895 (1992)
   PUBMED   1396582
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from U64863.1, AY238517.1,
            CR988122.1 and AI928135.1.
            This sequence is a reference standard in the RefSeqGene project.
            On Feb 14, 2008 this sequence version replaced NP_005009.1.
            
            Summary: This gene encodes a cell surface membrane protein of the
            immunoglobulin superfamily. This protein is expressed in
            pro-B-cells and is thought to play a role in their differentiation.
            In mice, expression of this gene is induced in the thymus when
            anti-CD3 antibodies are injected and large numbers of thymocytes
            undergo apoptosis. Mice deficient for this gene bred on a BALB/c
            background developed dilated cardiomyopathy and died from
            congestive heart failure. These studies suggest that this gene
            product may also be important in T cell function and contribute to
            the prevention of autoimmune diseases. [provided by RefSeq, Jul
            2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: U64863.1, SRR1163657.270333.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2158800 [ECO:0000348]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..288
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q37.3"
     Protein         1..288
                     /product="programmed cell death protein 1 precursor"
                     /note="programmed cell death protein 1; protein PD-1;
                     systemic lupus erythematosus susceptibility 2; programmed
                     cell death 1 protein"
                     /calculated_mol_wt=29289
     sig_peptide     1..20
                     /calculated_mol_wt=2376
     mat_peptide     21..288
                     /product="programmed cell death protein 1"
                     /calculated_mol_wt=29289
     Region          35..144
                     /region_name="IgV_PD1"
                     /note="Immunoglobulin (Ig)-like domain of Programmed cell
                     Death 1 (PD1); cd16088"
                     /db_xref="CDD:319337"
     Site            order(64,66,68,73..76,78,83..84,86,88,90,122,124,128,
                     130..132,134,136)
                     /site_type="other"
                     /note="PD-1/PD-L1 complex [polypeptide binding]"
                     /db_xref="CDD:319337"
     Site            order(64,66,68,75..78,83..84,88..90,122,124..126,128..129,
                     132..134,136)
                     /site_type="other"
                     /note="PD-1/PD-L2 complex [polypeptide binding]"
                     /db_xref="CDD:319337"
     Site            171..191
                     /site_type="transmembrane region"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q15116.3)"
     CDS             1..288
                     /gene="PDCD1"
                     /gene_synonym="CD279; hPD-1; hPD-l; hSLE1; PD-1; PD1;
                     SLEB2"
                     /coded_by="NM_005018.2:69..935"
                     /db_xref="CCDS:CCDS33428.1"
                     /db_xref="GeneID:5133"
                     /db_xref="HGNC:HGNC:8760"
                     /db_xref="MIM:600244"
ORIGIN      
        1 mqipqapwpv vwavlqlgwr pgwfldspdr pwnpptfspa llvvtegdna tftcsfsnts
       61 esfvlnwyrm spsnqtdkla afpedrsqpg qdcrfrvtql pngrdfhmsv vrarrndsgt
      121 ylcgaislap kaqikeslra elrvterrae vptahpspsp rpagqfqtlv vgvvggllgs
      181 lvllvwvlav icsraargti garrtgqplk edpsavpvfs vdygeldfqw rektpeppvp
      241 cvpeqteyat ivfpsgmgts sparrgsadg prsaqplrpe dghcswpl
//

Muistiin 2.10.2018 . Tämän vuoden lääketieteen ja fysiologian Nobelin palkinnon yhteydessä: Professori  T. Honjo työryhmineen mainitaan  sekvenssin löytymisen yhteydessä 1992 ja geenin sekä geeniproduktin jatkotutkimuksissa myös.