Leta i den här bloggen

tisdag 3 mars 2020

PHB2(12p13.31) Prohibitiini 2 on ilmeisesti viruksille sopiva kaapattava isäntäproteiini . COVID-19 nsp2 näkökohta

 COVID-1 työkaluissa nsp2 mainitaan mahdollisena  isäntäsolun PHB ja PHB2-proteiinien  suosijana. PHB2 suosinta   olisikin loogista, jos  COVID-19 nsp1 hävittää osan  ribosomeista  isäntäsolun mRNAn ohella. Samalla  viruksella on tarvetta tehostaa ribosomitoimintaa, mutta ei  kuitenkaan DNA-synteesiä, jolloin  PHB2:n  suosiminen on ilmeisen loogista.  Mainitaan,  että  COVID-19 nsp2 on keskittynyt  tässä asiassa  PHB ja PHB2  interaktioon ja  mitokondrian suojaamiseen  tietyisti viruksen replikaation eduksi.  Myöhäisemmässä vaiheesshan  eräät muut virustekijät tuhoavat mitokondrian.

Myös  HIV-1 viruksesta mainitaan, että se ottaa tätä proteiinia  PHB2  ( molempiakin PHB1/PHB2)  komplekseihinsa mukaan.  Nämä  kuuluvat  ihmisen mitokondriaalisiin SPFH- superperheen proteiineihin (stomatiini, prohibitiini, flotilliini ja Hflm/c). Tämä  PHB2 esiintyy nukleolissa ja säätelee ribosomaalisen RNA:n transkriptiota ja suojaa esim  ribosomien 45S ja 18S synteesiä. Samalla sen vaikutus liittyy DNA-synteesin estoon.   Tämä  mitokondriaalinen SPFH- proteiiniperhe säätelee replikatiivisen   soluelämän pituutta. Prohibitiini 2:n muita nimiä ovat B-soluun assosioitunut proteiini (BAP), p22, D-prohibitiini, B-solureseptoriin assosioitunut proteiini BAP37, PNAS-141, estrogeenireseptoriaktiivisuuden repressori. Sillä on  vaikutusta myös inflammasomi NLRP3:n säätelyyn.  Sitä sijaitsee mitokondrian sisäkalvossa ja se auttaa pitämään yllä mitokondrian funktiota.

  • (Myös: PubMed tieto PHB1 proteiinista (17q21.33)  PHB1; HEL-215; HEL-S-54e SummaryThis gene is evolutionarily conserved, and its product is proposed to play a role in human cellular senescence and tumor suppression. Antiproliferative activity is reported to be localized to the 3' UTR, which is proposed to function as a trans-acting regulatory RNA.
  • https://www.ncbi.nlm.nih.gov/pubmed/29324904/  
  •  https://www.ncbi.nlm.nih.gov/gene/5245)
  • Jokin neurotrooppinen virus voi käyttä tätä isäntäproteiinia hyödyksi . HIV-1 lataa myös tätä komplekseihinsa) 

Prohibitin-2 isoform 1 [Homo sapiens]

NCBI Reference Sequence: NP_001138303.1

LOCUS       NP_001138303             299 aa            linear   PRI 04-DEC-2019
DEFINITION  prohibitin-2 isoform 1 [Homo sapiens].
ACCESSION   NP_001138303 NP_009204
VERSION     NP_001138303.1
DBSOURCE    REFSEQ: accession NM_001144831.2
KEYWORDS    RefSeq; MANE Select.
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 299)
  AUTHORS   Xu Y, Wang J, Xu W, Ding F and Ding W.
  TITLE     Prohibitin 2-mediated mitophagy attenuates renal tubular epithelial
            cells injury by regulating mitochondrial dysfunction and NLRP3
            inflammasome activation
  JOURNAL   Am. J. Physiol. Renal Physiol. 316 (2), F396-F407 (2019)
   PUBMED   30539655
  REMARK    GeneRIF: Prohibitin 2-mediated mitophagy attenuates renal tubular
            epithelial cells injury by regulating mitochondrial dysfunction and
            NLRP3 inflammasome activation.
REFERENCE   2  (residues 1 to 299)
  AUTHORS   Zhang Y, Wang LN, Lin YN, Xing YX, Shi Y, Zhao J, Chen WW and Han
            B.
  TITLE     The novel long noncoding RNA LOC283070 is involved in the
            transition of LNCaP cells into androgen-independent cells via its
            interaction with PHB2
  JOURNAL   Asian J. Androl. 20 (5), 511-517 (2018)
   PUBMED   29956684
  REMARK    GeneRIF: we found that LOC283070 can bind to PHB2 located in the
            nucleus and inhibit its effect, and this is one of the mechanisms
            by which LOC283070 is involved in the transition of LNCaP cells
            into androgen-independent cells
REFERENCE   3  (residues 1 to 299)
  AUTHORS   Xiao Y, Zhou Y, Lu Y, Zhou K and Cai W.
  TITLE     PHB2 interacts with LC3 and SQSTM1 is required for bile
            acids-induced mitophagy in cholestatic liver
  JOURNAL   Cell Death Dis 9 (2), 160 (2018)
   PUBMED   29416008
  REMARK    GeneRIF: PHB2 forms a ternary protein complex with sequestosome 1
            (SQSTM1) and LC3, leading to loading of LC3 onto the damaged
            mitochondria.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 299)
  AUTHORS   Taniguchi K, Matsumura K, Kageyama S, Ii H, Ashihara E, Chano T,
            Kawauchi A, Yoshiki T and Nakata S.
  TITLE     Prohibitin-2 is a novel regulator of p21(WAF1/CIP1) induced by
            depletion of gamma-glutamylcyclotransferase
  JOURNAL   Biochem. Biophys. Res. Commun. 496 (1), 218-224 (2018)
   PUBMED   29307834
  REMARK    GeneRIF: Taken together, the results indicate that PHB2 plays a
            central role in p21 upregulation following GGCT knockdown and as
            such may promote deregulated proliferation of cancer cells by
            suppressing p21.
REFERENCE   5  (residues 1 to 299)
  AUTHORS   Zhou Z, Ai H, Li K, Yao X, Zhu W, Liu L, Yu C, Song Z, Bao Y, Huang
            Y, Wu Y, Zheng L, Sun Y, Wang G, Ma K, Sun L and Li Y.
  TITLE     Prohibitin 2 localizes in nucleolus to regulate ribosomal RNA
            transcription and facilitate cell proliferation in RD cells
  JOURNAL   Sci Rep 8 (1), 1479 (2018)
   PUBMED   29367618
  REMARK    GeneRIF: High PHB2 expression is associated with high ribosomal RNA
            transcription and facilitation of cell proliferation in
            rhabdomyosarcoma.
            Publication Status: Online-Only
REFERENCE   6  (residues 1 to 299)
  AUTHORS   Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH,
            Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong
            R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM,
            Huang GY, Chen Z, Chen MD and Chen JL.
  TITLE     Gene expression profiling in the human
            hypothalamus-pituitary-adrenal axis and full-length cDNA cloning
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 97 (17), 9543-9548 (2000)
   PUBMED   10931946
REFERENCE   7  (residues 1 to 299)
  AUTHORS   Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P and
            Katzenellenbogen BS.
  TITLE     An estrogen receptor-selective coregulator that potentiates the
            effectiveness of antiestrogens and represses the activity of
            estrogens
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 96 (12), 6947-6952 (1999)
   PUBMED   10359819
REFERENCE   8  (residues 1 to 299)
  AUTHORS   Coates PJ, Jamieson DJ, Smart K, Prescott AR and Hall PA.
  TITLE     The prohibitin family of mitochondrial proteins regulate
            replicative lifespan
  JOURNAL   Curr. Biol. 7 (8), 607-610 (1997)
   PUBMED   9259555
REFERENCE   9  (residues 1 to 299)
  AUTHORS   Ansari-Lari MA, Shen Y, Muzny DM, Lee W and Gibbs RA.
  TITLE     Large-scale sequencing in human chromosome 12p13: experimental and
            computational gene structure determination
  JOURNAL   Genome Res. 7 (3), 268-280 (1997)
   PUBMED   9074930
REFERENCE   10 (residues 1 to 299)
  AUTHORS   Ansari-Lari MA, Muzny DM, Lu J, Lu F, Lilley CE, Spanos S, Malley T
            and Gibbs RA.
  TITLE     A gene-rich cluster between the CD4 and triosephosphate isomerase
            genes at human chromosome 12p13
  JOURNAL   Genome Res. 6 (4), 314-326 (1996)
   PUBMED   8723724
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BC110322.1 and U47924.1.
            On Jun 12, 2012 this sequence version replaced NP_009204.1.
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: SRR7410570.496782.1,
                                           SRR7410570.496788.1 [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000350]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000535923.6/ ENSP00000441875.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..299
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12p13.31"
     Protein         1..299
                     /product="prohibitin-2 isoform 1"
                     /note="B-cell associated protein; repressor of estrogen
                     receptor activity; D-prohibitin; B-cell
                     receptor-associated protein BAP37"
                     /calculated_mol_wt=33165
     Site            2
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N-acetylalanine. {ECO:0000244|PubMed:22814378,
                     ECO:0000269|Ref.8}; propagated from UniProtKB/Swiss-Prot
                     (Q99623.2)"
     Region          19..49
                     /region_name="Necessary for transcriptional repression.
                     {ECO:0000269|PubMed:10359819}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99623.2)"
     Region          40..235
                     /region_name="SPFH_prohibitin"
                     /note="Prohibitin family; SPFH (stomatin, prohibitin,
                     flotillin, and HflK/C) superfamily; cd03401"
                     /db_xref="CDD:259799"
     Site            128
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphotyrosine. {ECO:0000244|PubMed:15592455};
                     propagated from UniProtKB/Swiss-Prot (Q99623.2)"
     Site            147
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000250|UniProtKB:O35129};
                     propagated from UniProtKB/Swiss-Prot (Q99623.2)"
     Region          150..174
                     /region_name="Necessary for transcriptional repression.
                     {ECO:0000269|PubMed:10359819}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99623.2)"
     Site            151
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (Q99623.2)"
     Site            200
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000250|UniProtKB:O35129};
                     propagated from UniProtKB/Swiss-Prot (Q99623.2)"
     Site            236
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000250|UniProtKB:O35129};
                     propagated from UniProtKB/Swiss-Prot (Q99623.2)"
     Site            250
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000244|PubMed:19608861};
                     propagated from UniProtKB/Swiss-Prot (Q99623.2)"
     Site            262
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000250|UniProtKB:O35129};
                     propagated from UniProtKB/Swiss-Prot (Q99623.2)"
     CDS             1..299
                     /gene="PHB2"
                     /gene_synonym="BAP; Bap37; BCAP37; hBAP; p22; PNAS-141;
                     REA"
                     /coded_by="NM_001144831.2:122..1021"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS53741.1"
                     /db_xref="GeneID:11331"
                     /db_xref="HGNC:HGNC:30306"
                     /db_xref="MIM:610704"
ORIGIN      
        1 maqnlkdlag rlpagprgmg talklllgag avaygvresv ftvegghrai ffnriggvqq
       61 dtilaeglhf ripwfqypii ydirarprki ssptgskdlq mvnislrvls rpnaqelpsm
      121 yqrlgldyee rvlpsivnev lksvvakfna sqlitqraqv sllirrelte rakdfslild
      181 dvaitelsfs reytaaveak qvaqqeaqra qflvekakqe qrqkivqaeg eaeaakmlge
      241 alsknpgyik lrkiraaqni sktiatsqnr iyltadnlvl nlqdesftrg sdslikgkk
//

Inga kommentarer:

Skicka en kommentar