Kiinnostava FYVE-domeeni_ mitä siitä tiedetään? Harmaan aivosolun EEA1 reseptoriproteiini omaa myös FYVE domaanin

Kerään jotain lähdetietoa.
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fyve-domain 
SITEERAAN tästä linkistä seuraavia  tietoja.

 Löytö on tuo EEA1, joka on tärkeä harmaassa aivokuoressa excitatorisen aminohapon glutamaatin järjestelmässä  toimiva reseptori.  Myös koko  fosfoinositidien ja inositolifosfaattien  PI-aineenvaihdunta-alue on aivoissa tärkeä.  Siihen järjestelmäänkin kuuluu inositolijohdannaisia kai  yli 35 erilaista.  kehon  tapa hyödyntää  FYVE-domeenia on proteiinien tapa seuloa  esiin ja  integroida  PI(3)P  muista  kymmenistä   inositolifosfateista ja  fosfoinositideistä  erilleen. Samoin on  neuroneille  tärkeä saada kehkeytettyä endogeenistä yksittäistä glutamiinihappoa (Glu9  ja pitää yllä sen integroitua aineenvaihduntaa, johon taas on  monta erilaista reseptoria  erottamassa  vaikutusteitä.
 (Lisäksi FYVE- domeenin N-terminaalissa omaa TP53  (Kr.17p13.1) . Otan sen rakenteen erikseen EAA1:n jälkeen )

FYVE domain

The FYVE domain is the only phosphoinositide-binding domain found so far to only bind a single phosphoinositide (namely, PtdIns3P) (De Matteis & Godi, 2004).

From: Methods in Enzymology, 2014

Volume 2

Roger L. Williams, in Handbook of Cell Signaling (Second Edition), 2010

FYVE Domains

The FYVE domains are found in many proteins involved in membrane transport [33].

The FYVE domains from Vps27 [34], Hrs [35], and EEA1 [36,37] consist of two small β-sheets stabilized by two Zn²⁺ ions and a C-terminal α-helix.

The PtdIns(3)P forms hydrogen bonds with the protein by using the 1- and 3-phosphates and the 4-, 5-, and 6-OH groups [37]. The close approach of these hydrogen-bonding partners precludes polyphosphorylated phosphoinositides from binding (Figure 135.3).

 The 3-phosphate forms a hydrogen bond with the last arginine in the (R/K) (R/K)HHCR signature motif characteristic of the FYVE domains. The 1-phosphate interacts with the protein via the first Arg of this motif. Like the PH domains, the FYVE domain buries only one face of the bound phosphoinositide.

 For EEA1, the face with the axial 2-OH is exposed to solution. The presence of the coiled-coil region preceding the EEA1 FYVE domain helps to unambiguously define the mode of membrane interaction and suggests that a loop flanking the PtdIns(3)P pocket, the “turret” loop, penetrates into the lipid bilayer (Figure 135.3). Biophysical measurements indicate that this partial membrane penetration follows rather than precedes specific PtdIns(3)P binding [38].

• LISÄTIETO PubMed Gene EEA1 

 EAA1 gene, (Kr.11q23.3), KA1, GRIK, GluK4

Preferred Names

glutamate receptor ionotropic, kainate 4

Names

excitatory amino acid receptor 1

glutamate receptor KA1

glutamate receptor, ionotropic, kainate 4

Conserved Domains (4) summary

cd06394
Location:26 → 400

PBP1_iGluR_Kainate_KA1_2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the KA1 and KA2 subunits of Kainate receptor

cd13724
Location:415 → 785

PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily

pfam00060
Location:547 → 816

Lig_chan; Ligand-gated ion channel

pfam01094
Location:43 → 382

ANF_receptor; Receptor family ligand binding region

 FYVE- ei ole merkitty konservoituneisiin domaaneihin mutta näkee tuosta peptidirakenteesta jotain, asetan tummalla FYVE jaksoja  muutaman pätkän sekvenssitä. niitä on kai enemmän kuin kaksi, itseasiassa N-terminaalista  päin  on paljon FYVE- jaksoja.  C-terminaali on toista  sorttia. Tietysti vasta käytännöstä näkee, mikä  FYVE jakso kiinnittää PI3P.  Tiedemiehet eivät ole kirjoitaneet tähän, minkä jakson he kutsuvat FYVE-domeeniksi, poimin vain jaksot jossa on  yksittäinen F Y V E järjestys havaittavissa.

https://www.ncbi.nlm.nih.gov/protein/NP_001269399.1

ORIGIN      
        1 mprvsaplvl lpawlvmvac sphslriaai lddpmecsrg erlsitlakn rinraperlg
       61 kakvevdife llrdseyeta etmcqilpkg vvavlgpsss passsiisni cgekevphfk
      121 vapeefvkfq fqrfttlnlh psntdisvav agilnffnct taclicakae cllnlekllr
      181 qfliskdtls vrmlddtrdp tpllkeirdd ktatiiihan asmshtillk aaelgmvsay
      241 ytyiftnlef slqrmdslvd drvnilgfsi fnqshaffqe faqslnqswq encdhvpftg
      301 palssallfd avyavvtavq elnrsqeigv kplscgsaqi wqhgtslmny lrmveleglt
      361 ghiefnskgq rsnyalkilq ftrngfrqig qwhvaeglsm dshlyasnis dtlfnttlvv
      421 ttilenpylm lkgnhqemeg ndryegfcvd mlkelaeilr fnykirlvgd gvygvpeang
      481 twtgmvgeli arkadlavag ltitaerekv idfskpfmtl gisilyrvhm grkpgyfsfl
      541 dpfspgvwlf mllaylavsc vlflvarltp yewysphpca qgrcnllvnq yslgnslwfp
      601 vggfmqqgst iapralstrc vsgvwwaftl iiissytanl aafltvqrmd vpiesvddla
      661 dqtaieygti hggssmtffq nsryqtyqrm wnymyskqps vfvksteegi arvlnsnyaf
      721 llestmneyy rqrncnltqi gglldtkgyg igmpvgsvfr defdlailql qennrleilk
      781 rkwweggkcp keedhrakgl gmeniggifv vlicglivai fmamleflwt lrhseatevs
      841 vcqemvtelr siilcqdsih prrrraavpp prppipeerr prgtatlsng klcgagepdq
      901 laqrlaqeaa lvargcthir vcpecrrfqg lrarpspars eeslewektt nssepe

VPS15 (Kr.3q22.1) PIK3R4, p150 , (VPS-associated ESCRT-0)

PI3P synteesi , VPS 15 ja VPS34 , mitä ne tekevät vakuolaaristen proteiinien lajitelujärjstlmään assosioituneina?

Vacuolar Protein Sorting Associated protein 15

VPS15 (Kr. 3q22.3), PIK3R4, Phosphoinositide-3-kinase regulatory subunit 4.

Also known as p150; VPS15

Expression Ubiquitous expression in thyroid (RPKM 9.2), testis (RPKM 8.7) and 25 other tissues See moreOrthologs mouse all

Preferred Names

phosphoinositide 3-kinase regulatory subunit 4

Names

PI3-kinase p150 subunit

PI3-kinase regulatory subunit 4

phosphatidylinositol 3-kinase-associated p150

phosphoinositide 3-kinase adaptor protein

phosphoinositide-3-kinase, regulatory subunit 4, p150

NP_055417.1

• EC 2.7.11.1

Peptidirakenne:

Conserved Domains (8) summary

smart00320
Location:1327 → 1358

WD40; WD40 repeats

smart00220
Location:26 → 309

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG2319
Location:991 → 1358

WD40; WD40 repeat [General function prediction only]

cd13980
Location:25 → 320

STKc_Vps15; Catalytic domain of the Serine/Threonine kinase, Vacuolar protein sorting-associated protein 15

pfam07539
Location:352 → 448

DRIM; Down-regulated in metastasis

sd00044
Location:539 → 566

HEAT; HEAT repeat [structural motif]

sd00039
Location:997 → 1040

7WD40; WD40 repeat [structural motif]

cl02567
Location:985 → 1269

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

Related articles in PubMed

1. Autophagy dysregulation in Danon disease. Nascimbeni AC, et al. Cell Death Dis, 2017 Jan 19. PMID 28102838, Free PMC Article
2. High expression of PI3K core complex genes is associated with poor prognosis in chronic lymphocytic leukemia. Kristensen L, et al. Leuk Res, 2015 Jun. PMID 25840748
3. hVps15, but not Ca2+/CaM, is required for the activity and regulation of hVps34 in mammalian cells. Yan Y, et al. Biochem J, 2009 Feb 1. PMID 18957027, Free PMC Article
4. The microtubule plus-end proteins EB1 and dynactin have differential effects on microtubule polymerization. Ligon LA, et al. Mol Biol Cell, 2003 Apr. PMID 12686597, Free PMC Article
5. Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9. Takeshita F, et al. Semin Immunol, 2004 Feb. PMID 14751759
   

See all (37) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Both Danon Disease and glycogen storage disease type II show accumulation and altered localization of VPS15 in autophagy-incompetent fibers. However, TFEB displays a different pattern between these two lysosomal storage diseases
2. High expression of PI3K core complex genes is associated with poor prognosis in chronic lymphocytic leukemia.
3. A specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates both receptor degradation and cytokinesis, whereas ATG14L, a PI3K-III subunit involved in autophagy, is not required.
4. hVps15, but not Ca2+/CaM, is required for the activity and regulation of hVps34 in mammalian cells
   

Rakenne ja historia

phosphoinositide 3-kinase regulatory subunit 4 [Homo sapiens]

NCBI Reference Sequence: NP_055417.1
Identical Proteins FASTA Graphics

Go to:

LOCUS       NP_055417               1358 aa            linear   PRI 01-APR-2018
DEFINITION  phosphoinositide 3-kinase regulatory subunit 4 [Homo sapiens].
ACCESSION   NP_055417
VERSION     NP_055417.1
DBSOURCE    REFSEQ: accession NM_014602.2
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 1358)
  AUTHORS   Nascimbeni AC, Fanin M, Angelini C and Sandri M.
  TITLE     Autophagy dysregulation in Danon disease
  JOURNAL   Cell Death Dis 8 (1), e2565 (2017)
   PUBMED   28102838
  REMARK    GeneRIF: Both Danon Disease and glycogen storage disease type II
            show accumulation and altered localization of VPS15 in
            autophagy-incompetent fibers. However, TFEB displays a different
            pattern between these two lysosomal storage diseases
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 1358)
  AUTHORS   Kristensen L, Kristensen T, Abildgaard N, Thomassen M, Frederiksen
            M, Mour
phosphoinositide 3-kinase regulatory subunit 4 [Homo sapiens]

NCBI Reference Sequence: NP_055417.1

Identical Proteins FASTA Graphics
Go to:

LOCUS       NP_055417               1358 aa            linear   PRI 01-APR-2018
DEFINITION  phosphoinositide 3-kinase regulatory subunit 4 [Homo sapiens].
ACCESSION   NP_055417
VERSION     NP_055417.1
DBSOURCE    REFSEQ: accession NM_014602.2
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 1358)
  AUTHORS   Nascimbeni AC, Fanin M, Angelini C and Sandri M.
  TITLE     Autophagy dysregulation in Danon disease
  JOURNAL   Cell Death Dis 8 (1), e2565 (2017)
   PUBMED   28102838
  REMARK    GeneRIF: Both Danon Disease and glycogen storage disease type II
            show accumulation and altered localization of VPS15 in
            autophagy-incompetent fibers. However, TFEB displays a different
            pattern between these two lysosomal storage diseases
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 1358)
  AUTHORS   Kristensen L, Kristensen T, Abildgaard N, Thomassen M, Frederiksen
            M, Mourits-Andersen T and Moller MB.
  TITLE     High expression of PI3K core complex genes is associated with poor
            prognosis in chronic lymphocytic leukemia
  JOURNAL   Leuk. Res. 39 (6), 555-560 (2015)
   PUBMED   25840748
  REMARK    GeneRIF: High expression of PI3K core complex genes is associated
            with poor prognosis in chronic lymphocytic leukemia.
REFERENCE   3  (residues 1 to 1358)
  AUTHORS   Cao Y, Wang Y, Abi Saab WF, Yang F, Pessin JE and Backer JM.
  TITLE     NRBF2 regulates macroautophagy as a component of Vps34 Complex I
  JOURNAL   Biochem. J. 461 (2), 315-322 (2014)
   PUBMED   24785657
REFERENCE   4  (residues 1 to 1358)
  AUTHORS   Lu J, He L, Behrends C, Araki M, Araki K, Jun Wang Q, Catanzaro JM,
            Friedman SL, Zong WX, Fiel MI, Li M and Yue Z.
  TITLE     NRBF2 regulates autophagy and prevents liver injury by modulating
            Atg14L-linked phosphatidylinositol-3 kinase III activity
  JOURNAL   Nat Commun 5, 3920 (2014)
   PUBMED   24849286
  REMARK    Publication Status: Online-Only
REFERENCE   5  (residues 1 to 1358)
  AUTHORS   Fogel AI, Dlouhy BJ, Wang C, Ryu SW, Neutzner A, Hasson SA, Sideris
            DP, Abeliovich H and Youle RJ.
  TITLE     Role of membrane association and Atg14-dependent phosphorylation in
            beclin-1-mediated autophagy
  JOURNAL   Mol. Cell. Biol. 33 (18), 3675-3688 (2013)
   PUBMED   23878393
REFERENCE   6  (residues 1 to 1358)
  AUTHORS   Stein MP, Feng Y, Cooper KL, Welford AM and Wandinger-Ness A.
  TITLE     Human VPS34 and p150 are Rab7 interacting partners
  JOURNAL   Traffic 4 (11), 754-771 (2003)
   PUBMED   14617358
REFERENCE   7  (residues 1 to 1358)
  AUTHORS   Ligon LA, Shelly SS, Tokito M and Holzbaur EL.
  TITLE     The microtubule plus-end proteins EB1 and dynactin have
            differential effects on microtubule polymerization
  JOURNAL   Mol. Biol. Cell 14 (4), 1405-1417 (2003)
   PUBMED   12686597
REFERENCE   8  (residues 1 to 1358)
  AUTHORS   Koyasu S.
  TITLE     The role of PI3K in immune cells
  JOURNAL   Nat. Immunol. 4 (4), 313-319 (2003)
   PUBMED   12660731
  REMARK    Review article
REFERENCE   9  (residues 1 to 1358)
  AUTHORS   Askham JM, Vaughan KT, Goodson HV and Morrison EE.
  TITLE     Evidence that an interaction between EB1 and p150(Glued) is
            required for the formation and maintenance of a radial microtubule
            array anchored at the centrosome
  JOURNAL   Mol. Biol. Cell 13 (10), 3627-3645 (2002)
   PUBMED   12388762
REFERENCE   10 (residues 1 to 1358)
  AUTHORS   Panaretou C, Domin J, Cockcroft S and Waterfield MD.
  TITLE     Characterization of p150, an adaptor protein for the human
            phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by
            phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase
            complex
  JOURNAL   J. Biol. Chem. 272 (4), 2477-2485 (1997)
   PUBMED   8999962
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BP359657.1 and Y08991.1.
            
            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 :: Y08991.1, SRR1803616.271117.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000350]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..1358
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q22.1"
     Protein         1..1358
                     /product="phosphoinositide 3-kinase regulatory subunit 4"
                     /EC_number="2.7.11.1"
                     /note="phosphatidylinositol 3-kinase-associated p150;
                     phosphoinositide-3-kinase, regulatory subunit 4, p150;
                     PI3-kinase regulatory subunit 4; PI3-kinase p150 subunit;
                     phosphoinositide 3-kinase adaptor protein"
                     /calculated_mol_wt=152973
     Region          25..320
                     /region_name="STKc_Vps15"
                     /note="Catalytic domain of the Serine/Threonine kinase,
                     Vacuolar protein sorting-associated protein 15; cd13980"
                     /db_xref="CDD:270882"
     Region          26..309
                     /region_name="S_TKc"
                     /note="Serine/Threonine protein kinases, catalytic domain;
                     smart00220"
                     /db_xref="CDD:214567"
     Site            order(32..36,40,51,53,85,103..106,109,111,148,150,
                     152..153,155,166,169,192..195)
                     /site_type="active"
                     /db_xref="CDD:270882"
     Site            order(32..36,40,51,53,85,103..106,109,148,150,152..153,
                     155,166)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:270882"
     Site            order(36,109,111,148,150,152,169,192..195)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:270882"
     Site            order(165..187,192..195)
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:270882"
     Region          <352 ..="">448
                     /region_name="DRIM"
                     /note="Down-regulated in metastasis; pfam07539"
                     /db_xref="CDD:284870"
     Region          377..408
                     /region_name="HEAT repeat"
                     /note="HEAT repeat [structural motif]"
                     /db_xref="CDD:293787"
     Region          413..450
                     /region_name="HEAT 1"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          417..443
                     /region_name="HEAT repeat"
                     /note="HEAT repeat [structural motif]"
                     /db_xref="CDD:293787"
     Region          458..495
                     /region_name="HEAT 2"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          460..489
                     /region_name="HEAT repeat"
                     /note="HEAT repeat [structural motif]"
                     /db_xref="CDD:293787"
     Region          539..566
                     /region_name="HEAT repeat"
                     /note="HEAT repeat [structural motif]"
                     /db_xref="CDD:293787"
     Site            order(554..555,558,562..563,566,595..596,599,602..603,606,
                     633..634,637,640..641,673..674,677,680..681)
                     /site_type="other"
                     /note="putative peptide binding site [polypeptide
                     binding]"
                     /db_xref="CDD:293787"
     Region          572..610
                     /region_name="HEAT 3"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          576..607
                     /region_name="HEAT repeat"
                     /note="HEAT repeat [structural motif]"
                     /db_xref="CDD:293787"
     Region          614..641
                     /region_name="HEAT repeat"
                     /note="HEAT repeat [structural motif]"
                     /db_xref="CDD:293787"
     Region          652..682
                     /region_name="HEAT repeat"
                     /note="HEAT repeat [structural motif]"
                     /db_xref="CDD:293787"
     Site            808
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:19369195};
                     propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Site            813
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Site            853
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:19369195};
                     propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Site            865
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:19369195};
                     propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          985..1269
                     /region_name="WD40"
                     /note="WD40 domain, found in a number of eukaryotic
                     proteins that cover a wide variety of functions including
                     adaptor/regulatory modules in signal transduction,
                     pre-mRNA processing and cytoskeleton assembly; typically
                     contains a GH dipeptide 11-24 residues from...; cl02567"
                     /db_xref="CDD:295369"
     Region          991..1358
                     /region_name="WD40"
                     /note="WD40 repeat [General function prediction only];
                     COG2319"
                     /db_xref="CDD:225201"
     Region          991..1030
                     /region_name="WD 1"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Site            order(992,1010,1014,1020..1021,1039..1040,1059,1063,
                     1069..1070,1090..1091,1104,1113,1118,1124..1125,1137,1158,
                     1162,1168..1169,1182..1183,1201,1206,1213..1214,
                     1226..1227,1258,1262,1268..1269)
                     /site_type="other"
                     /note="structural tetrad"
                     /db_xref="CDD:238121"
     Region          997..1040
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Region          1040..1079
                     /region_name="WD 2"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          1045..1091
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Region          1093..1134
                     /region_name="WD 3"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          1099..1136
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Region          1139..1178
                     /region_name="WD 4"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          1144..1179
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Region          1182..1223
                     /region_name="WD 5"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          1187..1236
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Region          1237..1278
                     /region_name="WD 6"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          1242..1268
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Site            1316
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphothreonine. {ECO:0000244|PubMed:18691976};
                     propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          1327..1358
                     /region_name="WD 7"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)"
     Region          <1327 ..1358="" 1..1358="" 1021="" 1081="" 1141="" 1201="" 121="" 1261="" 1321="" 1332..1357="" 181="" 1="" 241="" 301="" 361="" 39="" 421="" 481="" 541="" 555-560="" 601="" 61="" 661="" 721="" 781="" 841="" 901="" 961="" a="" adfnyffdts="" akqmmenaew="" and="" apflchpnlw="" aqddativrl="" aqnclpfqka="" arakhreglv="" associated="" ayaenialla="" aypersyvva="" cds="" chronic="" cmcqlgllqk="" coded_by="NM_014602.2:582..4658" complex="" core="" cqgshylaia="" csndgtvkiw="" db_xref="MIM:602610" ddkrarkhvk="" dgivkvwk="" dgnpilltag="" dlpekaegep="" dqkedgcvvd="" eeeedkllal="" ehksavnrir="" eleymrdpst="" erilvirkdl="" erklvllsvl="" eskppppgwr="" etalrflelv="" expression="" eyilpgiahl="" faketflsad="" gene="PIK3R4" gene_synonym="p150; VPS15" genes="" gniihnlcgh="" gpsddtprrg="" gstsspsvsy="" hdssqkgvid="" hffpeqvlnk="" high="" hpngnydtel="" hpsrarirrl="" href="https://www.ncbi.nlm.nih.gov/pubmed/25840748" iaavqgnnev="" ieasklpksp="" iedhsirelv="" ifsagcviae="" iggrvktltf="" ihqcwlcigt="" iitdvatfqt="" in="" ipvlsstilp="" irygavgfit="" is="" itrlcvffgr="" its-andersen="" ivgvaayvgw="" ivkqtlmeng="" journal="" kanivdqshl="" kdfmmksnka="" kenglvilvs="" kepvsrsifd="" kihplqsril="" kptylpednp="" kreqcnaeri="" krngslpdcp="" ksgvrhgdik="" ktelqqliqq="" laalgitgrq="" leelkirlns="" leuk.="" leukemia="" lfrhlhmrqk="" lfrqyvrdnl="" lftegvplfd="" lilhlaprls="" lkkllsqgmt="" lsqllayrng="" ltkvlalvke="" lvgwdlrsss="" lymphocytic="" mb.="" mgnqlagiap="" mhhfnsgaqs="" mitflndknd="" moller="" mpqalpkgsd="" nawtlkhdlk="" nniekrwiaf="" note="WD40 repeat [structural motif]" nsqkmegktt="" of="" origin="" peslpvghhd="" phvyefasdi="" pi3k="" pkgllvahlh="" plselqpsph="" plstssqvpe="" plvdlnsnqr="" pnneeidevt="" poor="" ppedpaiaql="" prognosis="" prvraealrt="" pubmed="" pyitqpiiqi="" qalhemvqqk="" qdsnvneewk="" qeviqtgkpp="" qiltavdqah="" qkandvllsh="" qlknlnmend="" qqglsdaeef="" qrgnafpeif="" qsssilkpll="" region="" region_name="WD40 repeat" res.="" rfqlpisshc="" rftlwassap="" rfvdggmfat="" rleaedylkq="" rrrtcyiape="" rsessagicv="" sdihdfeydk="" sdmkirfwdl="" sdngavqllg="" sekasekaam="" sglitsfavd="" slgstrffkv="" smfgsldppn="" smhplyqswv="" smwdmetgdr="" sqilsvesyf="" ssgtmacwdm="" styqirittc="" svhgiycspa="" t="" tenvmvtswn="" title="" tlpltsykqe="" tqgfivtasr="" tqmihrepdk="" trgelkramd="" ttrsiltysr="" vdlvktkqep="" veilldritp="" vitsclqtlk="" vivkalyalt="" vlayatvngs="" vprndiniyp="" vqeiqnkqkv="" vsdehslfat="" vttvqnkkpv="" vvarqistad="" vvkvfaiqdp="" vvtllsdpen="" vycklmpyld="" whlrgaffds="" with="" wvlltdfasf="" yalrskdits="" ycdsklaale="" ydristrpfl="" yllhfsndsv="" yrkiiegtev="" ytflqpymaq="">25840748

REMARK GeneRIF: High expression of PI3K core complex genes is associated with poor prognosis in chronic lymphocytic leukemia. REFERENCE 3 (residues 1 to 1358) AUTHORS Cao Y, Wang Y, Abi Saab WF, Yang F, Pessin JE and Backer JM. TITLE NRBF2 regulates macroautophagy as a component of Vps34 Complex I JOURNAL Biochem. J. 461 (2), 315-322 (2014) PUBMED 24785657 REFERENCE 4 (residues 1 to 1358) AUTHORS Lu J, He L, Behrends C, Araki M, Araki K, Jun Wang Q, Catanzaro JM, Friedman SL, Zong WX, Fiel MI, Li M and Yue Z. TITLE NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity JOURNAL Nat Commun 5, 3920 (2014) PUBMED 24849286 REMARK Publication Status: Online-Only REFERENCE 5 (residues 1 to 1358) AUTHORS Fogel AI, Dlouhy BJ, Wang C, Ryu SW, Neutzner A, Hasson SA, Sideris DP, Abeliovich H and Youle RJ. TITLE Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy JOURNAL Mol. Cell. Biol. 33 (18), 3675-3688 (2013) PUBMED 23878393 REFERENCE 6 (residues 1 to 1358) AUTHORS Stein MP, Feng Y, Cooper KL, Welford AM and Wandinger-Ness A. TITLE Human VPS34 and p150 are Rab7 interacting partners JOURNAL Traffic 4 (11), 754-771 (2003) PUBMED 14617358 REFERENCE 7 (residues 1 to 1358) AUTHORS Ligon LA, Shelly SS, Tokito M and Holzbaur EL. TITLE The microtubule plus-end proteins EB1 and dynactin have differential effects on microtubule polymerization JOURNAL Mol. Biol. Cell 14 (4), 1405-1417 (2003) PUBMED 12686597 REFERENCE 8 (residues 1 to 1358) AUTHORS Koyasu S. TITLE The role of PI3K in immune cells JOURNAL Nat. Immunol. 4 (4), 313-319 (2003) PUBMED 12660731 REMARK Review article REFERENCE 9 (residues 1 to 1358) AUTHORS Askham JM, Vaughan KT, Goodson HV and Morrison EE. TITLE Evidence that an interaction between EB1 and p150(Glued) is required for the formation and maintenance of a radial microtubule array anchored at the centrosome JOURNAL Mol. Biol. Cell 13 (10), 3627-3645 (2002) PUBMED 12388762 REFERENCE 10 (residues 1 to 1358) AUTHORS Panaretou C, Domin J, Cockcroft S and Waterfield MD. TITLE Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex JOURNAL J. Biol. Chem. 272 (4), 2477-2485 (1997) PUBMED 8999962 COMMENT VALIDATED REFSEQ: This record has undergone validation or preliminary review. The reference sequence was derived from BP359657.1 and Y08991.1. 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 :: Y08991.1, SRR1803616.271117.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## FEATURES Location/Qualifiers source 1..1358 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="3" /map="3q22.1" Protein 1..1358 /product="phosphoinositide 3-kinase regulatory subunit 4" /EC_number="2.7.11.1" /note="phosphatidylinositol 3-kinase-associated p150; phosphoinositide-3-kinase, regulatory subunit 4, p150; PI3-kinase regulatory subunit 4; PI3-kinase p150 subunit; phosphoinositide 3-kinase adaptor protein" /calculated_mol_wt=152973 Region 25..320 /region_name="STKc_Vps15" /note="Catalytic domain of the Serine/Threonine kinase, Vacuolar protein sorting-associated protein 15; cd13980" /db_xref="CDD:270882" Region 26..309 /region_name="S_TKc" /note="Serine/Threonine protein kinases, catalytic domain; smart00220" /db_xref="CDD:214567" Site order(32..36,40,51,53,85,103..106,109,111,148,150, 152..153,155,166,169,192..195) /site_type="active" /db_xref="CDD:270882" Site order(32..36,40,51,53,85,103..106,109,148,150,152..153, 155,166) /site_type="other" /note="ATP binding site [chemical binding]" /db_xref="CDD:270882" Site order(36,109,111,148,150,152,169,192..195) /site_type="other" /note="polypeptide substrate binding site [polypeptide binding]" /db_xref="CDD:270882" Site order(165..187,192..195) /site_type="other" /note="activation loop (A-loop)" /db_xref="CDD:270882" Region <352 ..="">448 /region_name="DRIM" /note="Down-regulated in metastasis; pfam07539" /db_xref="CDD:284870" Region 377..408 /region_name="HEAT repeat" /note="HEAT repeat [structural motif]" /db_xref="CDD:293787" Region 413..450 /region_name="HEAT 1" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 417..443 /region_name="HEAT repeat" /note="HEAT repeat [structural motif]" /db_xref="CDD:293787" Region 458..495 /region_name="HEAT 2" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 460..489 /region_name="HEAT repeat" /note="HEAT repeat [structural motif]" /db_xref="CDD:293787" Region 539..566 /region_name="HEAT repeat" /note="HEAT repeat [structural motif]" /db_xref="CDD:293787" Site order(554..555,558,562..563,566,595..596,599,602..603,606, 633..634,637,640..641,673..674,677,680..681) /site_type="other" /note="putative peptide binding site [polypeptide binding]" /db_xref="CDD:293787" Region 572..610 /region_name="HEAT 3" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 576..607 /region_name="HEAT repeat" /note="HEAT repeat [structural motif]" /db_xref="CDD:293787" Region 614..641 /region_name="HEAT repeat" /note="HEAT repeat [structural motif]" /db_xref="CDD:293787" Region 652..682 /region_name="HEAT repeat" /note="HEAT repeat [structural motif]" /db_xref="CDD:293787" Site 808 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphoserine. {ECO:0000244|PubMed:19369195}; propagated from UniProtKB/Swiss-Prot (Q99570.3)" Site 813 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphoserine. {ECO:0000244|PubMed:23186163}; propagated from UniProtKB/Swiss-Prot (Q99570.3)" Site 853 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphoserine. {ECO:0000244|PubMed:19369195}; propagated from UniProtKB/Swiss-Prot (Q99570.3)" Site 865 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphoserine. {ECO:0000244|PubMed:19369195}; propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 985..1269 /region_name="WD40" /note="WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from...; cl02567" /db_xref="CDD:295369" Region 991..1358 /region_name="WD40" /note="WD40 repeat [General function prediction only]; COG2319" /db_xref="CDD:225201" Region 991..1030 /region_name="WD 1" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Site order(992,1010,1014,1020..1021,1039..1040,1059,1063, 1069..1070,1090..1091,1104,1113,1118,1124..1125,1137,1158, 1162,1168..1169,1182..1183,1201,1206,1213..1214, 1226..1227,1258,1262,1268..1269) /site_type="other" /note="structural tetrad" /db_xref="CDD:238121" Region 997..1040 /region_name="WD40 repeat" /note="WD40 repeat [structural motif]" /db_xref="CDD:293791" Region 1040..1079 /region_name="WD 2" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 1045..1091 /region_name="WD40 repeat" /note="WD40 repeat [structural motif]" /db_xref="CDD:293791" Region 1093..1134 /region_name="WD 3" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 1099..1136 /region_name="WD40 repeat" /note="WD40 repeat [structural motif]" /db_xref="CDD:293791" Region 1139..1178 /region_name="WD 4" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 1144..1179 /region_name="WD40 repeat" /note="WD40 repeat [structural motif]" /db_xref="CDD:293791" Region 1182..1223 /region_name="WD 5" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 1187..1236 /region_name="WD40 repeat" /note="WD40 repeat [structural motif]" /db_xref="CDD:293791" Region 1237..1278 /region_name="WD 6" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 1242..1268 /region_name="WD40 repeat" /note="WD40 repeat [structural motif]" /db_xref="CDD:293791" Site 1316 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphothreonine. {ECO:0000244|PubMed:18691976}; propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region 1327..1358 /region_name="WD 7" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q99570.3)" Region <1327 ..1358="" cdd="" cddsrv.cgi="" db_xref="CDD:<a href=" https:="" note="WD40 repeats; smart00320" region_name="WD40" tructure="" uid="197651" www.ncbi.nlm.nih.gov="">197651" Region 1332..1357 /region_name="WD40 repeat" /note="WD40 repeat [structural motif]" /db_xref="CDD:293791" CDS 1..1358 /gene="PIK3R4" /gene_synonym="p150; VPS15" /coded_by="NM_014602.2:582..4658" /db_xref="CCDS:CCDS3067.1" /db_xref="GeneID:30849" /db_xref="HGNC:HGNC:8982" /db_xref="MIM:602610" ORIGIN 1 mgnqlagiap sqilsvesyf sdihdfeydk slgstrffkv arakhreglv vvkvfaiqdp 61 tlpltsykqe leelkirlns aqnclpfqka sekasekaam lfrqyvrdnl ydristrpfl 121 nniekrwiaf qiltavdqah ksgvrhgdik tenvmvtswn wvlltdfasf kptylpednp 181 adfnyffdts rrrtcyiape rfvdggmfat eleymrdpst plvdlnsnqr trgelkramd 241 ifsagcviae lftegvplfd lsqllayrng hffpeqvlnk iedhsirelv tqmihrepdk 301 rleaedylkq qrgnafpeif ytflqpymaq faketflsad erilvirkdl gniihnlcgh 361 dlpekaegep kenglvilvs vitsclqtlk ycdsklaale lilhlaprls veilldritp 421 yllhfsndsv prvraealrt ltkvlalvke vprndiniyp eyilpgiahl aqddativrl 481 ayaenialla etalrflelv qlknlnmend pnneeidevt hpngnydtel qalhemvqqk 541 vvtllsdpen ivkqtlmeng itrlcvffgr qkandvllsh mitflndknd whlrgaffds 601 ivgvaayvgw qsssilkpll qqglsdaeef vivkalyalt cmcqlgllqk phvyefasdi 661 apflchpnlw irygavgfit vvarqistad vycklmpyld pyitqpiiqi erklvllsvl 721 kepvsrsifd yalrskdits lfrhlhmrqk krngslpdcp ppedpaiaql lkkllsqgmt 781 eeeedkllal kdfmmksnka kanivdqshl hdssqkgvid laalgitgrq vdlvktkqep 841 ddkrarkhvk qdsnvneewk smfgsldppn mpqalpkgsd qeviqtgkpp rsessagicv 901 plstssqvpe vttvqnkkpv ipvlsstilp styqirittc ktelqqliqq kreqcnaeri 961 akqmmenaew eskppppgwr pkgllvahlh ehksavnrir vsdehslfat csndgtvkiw 1021 nsqkmegktt ttrsiltysr iggrvktltf cqgshylaia sdngavqllg ieasklpksp 1081 kihplqsril dqkedgcvvd mhhfnsgaqs vlayatvngs lvgwdlrsss nawtlkhdlk 1141 sglitsfavd ihqcwlcigt ssgtmacwdm rfqlpisshc hpsrarirrl smhplyqswv 1201 iaavqgnnev smwdmetgdr rftlwassap plselqpsph svhgiycspa dgnpilltag 1261 sdmkirfwdl aypersyvva gstsspsvsy yrkiiegtev vqeiqnkqkv gpsddtprrg 1321 peslpvghhd iitdvatfqt tqgfivtasr dgivkvwk //

ESCRT koneisto ja PI

Fosfoinositidein (PI) osuus ESCRT-kompleksien funktiossa

LÄHDE: https://www.ncbi.nlm.nih.gov/pubmed/17233579

Format: Abstract

Rakenteellisia tutkimuksia 3-fosfoinositidien merkityksestä multivesikulaarisiin kappaleitten liikenteessä (MVB) .

Biochem Soc Symp. 2007;(74):47-57. Structural studies of phosphoinositide 3-kinase-dependent traffic to multivesicular bodies. Gill DJ¹, Teo H, Sun J, Perisic O, Veprintsev DB, Vallis Y, Emr SD, Williams RL. Abstract

SUOMENNOSTA: Kolme isoa proteiinikompleksia ESCRT-I, -II ja -III vaikuttaa ubikitinoitujen kalvoaineskuorman etenemisen varhaisista endosomeista lysosomeille. Moni vaihe tässä prosessissa on riippuvainen PI3P-fosfatidyyli-inositidilajista, jota muodostuu luokan III fosfoinositidi-3-kinaasin (PI3K) avulla. (Tunnettu kinaasi harmillisissa asioissa). Tässä työssä on saatu oivalluksia ESCRT-koneiston arkkitehtuurista, kalvorekrytoinneista ja funktionaalisista interaktioista.

Viuhkamainen ESCRT-I ydin ja kolmilohkoinen ESCRT-II ydin ovat välttämättömät stabiilin, rigidin telineen muodostamisella, josta on tukea muille, joustavasti linkkiytyneille domeeneille, jotka toimivat tarttuvina työkaluina tunnistaen multivesikulaaristen kappaleiden tien aineksia: kuorman proteiineja, kalvomateriaalia tai muita multivesikulaarisia proteiineja.

 Ydinosaansa kuulumattomilla lisäproteiineilla ESCRT-I tarttuu monoubikitinoituihin kalvoproteiineihin ja VPS36-alayksikköön (EAP45) , joka kuuluu alavirran ESCRT- II kompleksin.

ESCRT-II- kompleksin EAP45 (VPS36) omaa GLUE-domeenin, joka ulottuu ESCRT-II-ytimen ulkopuolelle ja tunnistaa PI3P-sisältäviä kalvoja, monoubikitinoitunutta kuormaa ja ESCRT-I:n.

(GLUE domeeni tarkoittaa:  GRAM-kaltainen, ubikitiiniä sisältävä EAP45:n kohta)

Tämän GLUE- domeenin tarkempi rakenne sisältää PH - eli plekstriinihomologia - pirstoisen poimun, jossa on epätyypillinen fosfoinositidiä sitova tasku. Hiivatutkimuksissa havaittiin, että mutaatiot tässä ESCRT-II -GLUE-domeenin lipidiä sitovassa taskussa aiheuttivat vahvan vian vakuolaaristen proteiinien lajitteluun. 

 https://www.cell.com/cms/attachment/2119039383/2088388025/gr2.jpg

• Three large protein complexes known as ESCRT I, ESCRT II and ESCRT III drive the progression of ubiquitinated membrane cargo from early endosomes to lysosomes. Several steps in this process critically depend on PtdIns3P, the product of the class III phosphoinositide 3-kinase. Our work has provided insights into the architecture, membrane recruitment and functional interactions of the ESCRT machinery. The fan-shaped ESCRT I core and the trilobal ESCRT II core are essential to forming stable, rigid scaffolds that support additional, flexibly-linked domains, which serve as gripping tools for recognizing elements of the MVB (multivesicular body) pathway: cargo protein, membranes and other MVB proteins. With these additional (non-core) domains, ESCRT I grasps monoubiquitinated membrane proteins and the Vps36 subunit of the downstream ESCRT II complex. The GLUE (GRAM-like, ubiquitin-binding on Eap45) domain extending beyond the core of the ESCRT II complex recognizes PtdIns3P-containing membranes, monoubiquitinated cargo and ESCRT I. The structure of this GLUE domain demonstrates that it has a split PH (pleckstrin homology) domain fold, with a non-typical phosphoinositide-binding pocket. Mutations in the lipid-binding pocket of the ESCRT II GLUE domain cause a strong defect in vacuolar protein sorting in yeast. PMID: 17233579 DOI: 10.1042/BSS0740047 [Indexed for MEDLINE]

Muistiin 17.5. 2018

ESCRT-II on kolmilohkoisen näköinen oranssilla värillä,  alapuolella on GLUE-domeeni ja siihen on liittynyt ubikitiinillä jokin kuorma ja sen vieressä vasemmalla näkyy PI3P, fosfoinositidi-3-fosfaatti 
Vihreällä on  väritetty ylävirran puoella  ESCRT-I ja sinisellä ESCRT-III alavirran puolella.
 

ESCRT-II jäsenet  kirjoitan erikseen Solusykli-blogiin.
EAP20, VPS25,DERP9, FAP20, Kr.17q21.2.
EAP30, SNF8, Dot3, VPS22, Kr.17q21.32.
EAP45, VPS36, CGI-148, C13orf9, Kr.13q14.3.

Inositolitekijä ja dimyristylaatio , DMPC

http://www.jbc.org/content/281/32/22773

Inositol Induces a Profound Alteration in the Pattern and Rate of Synthesis and Turnover of Membrane Lipids in Saccharomyces cerevisiae^*

1. Maria L. Gaspar,
2. Manuel A. Aregullin,
3. Stephen A. Jesch and
4. Susan A. Henry¹

1. Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853

1. ↵1 To whom correspondence should be addressed: College of Agriculture and Life Sciences, Cornell University, 260 Roberts Hall, Ithaca, NY 14853. Tel.: 607-255-2241; Fax:

   Abstract

   The addition of inositol to actively growing yeast cultures causes a rapid increase in the rate of synthesis of phosphatidylinositol and, simultaneously, triggers changes in the expression of hundreds of genes. We now demonstrate that the addition of inositol to yeast cells growing in the presence of choline leads to a dramatic reprogramming of cellular lipid synthesis and turnover. The response to inositol includes a 5-6-fold increase in cellular phosphatidylinositol content within a period of 30 min. The increase in phosphatidylinositol content appears to be dependent upon fatty acid synthesis. Phosphatidylcholine turnover increased rapidly following inositol addition, a response that requires the participation of Nte1p, an endoplasmic reticulum-localized phospholipase B. Mass spectrometry revealed that the acyl species composition of phosphatidylinositol is relatively constant regardless of supplementation with inositol or choline, whereas phosphatidylcholine acyl species composition is influenced by both inositol and choline. In medium containing inositol, but lacking choline, high levels of dimyristoylphosphatidylcholine (DMPC) were detected. Within 60 min following the addition of inositol, dimyristoylphosphatidylcholine levels had decreased from ∼40% of total phosphatidylcholine to a basal level of less than 5%. nte1Δ cells grown in the absence of inositol and in the presence of choline exhibited lower levels of dimyristoylphosphatidylcholine than wild type cells grown under these same conditions, but these levels remained largely constant after the addition of inositol. These results are discussed in relationship to transcriptional regulation known to be linked to lipid metabolism in yeast.
2. Received April 25, 2006.
3. Revision received June 7, 2006.
4. 607-255-3803; E-mail: sah42{at}cornell.edu. 

ESCRT kompleksissa fosfoinositidit tärkeitä

• https://www.ncbi.nlm.nih.gov/pubmed/26929449

J Cell Biol. 2016 Feb 29;212(5):499-513. doi: 10.1083/jcb.201507009.

ALIX and ESCRT-I/II function as parallel ESCRT-III recruiters in cytokinetic abscission.

Christ L¹, Wenzel EM¹, Liestøl K², Raiborg C¹, Campsteijn C³, Stenmark H³.

Abstract

Cytokinetic abscission, the final stage of cell division where the two daughter cells are separated, is mediated by the endosomal sorting complex required for transport (ESCRT) machinery. The ESCRT-III subunit CHMP4B is a key effector in abscission, whereas its paralogue, CHMP4C, is a component in the abscission checkpoint that delays abscission until chromatin is cleared from the intercellular bridge. How recruitment of these components is mediated during cytokinesis remains poorly understood, although the ESCRT-binding protein ALIX has been implicated. Here, we show that ESCRT-II and the ESCRT-II-binding ESCRT-III subunit CHMP6 cooperate with ESCRT-I to recruit CHMP4B, with ALIX providing a parallel recruitment arm. In contrast to CHMP4B, we find that recruitment of CHMP4C relies predominantly on ALIX. Accordingly, ALIX depletion leads to furrow regression in cells with chromosome bridges, a phenotype associated with abscission checkpoint signaling failure. Collectively, our work reveals a two-pronged recruitment of ESCRT-III to the cytokinetic bridge and implicates ALIX in abscission checkpoint signaling.

Comment in

• Burning cellular bridges: Two pathways to the big breakup. [J Cell Biol. 2016]

 Huom. Geeni ALIX on muilta nimiltä
 DRIP4, Dopamine Receptor Interacting Protein 4;
PDCD6IP , Programmed Cell death 6 Interacting protein
AIP1 ,
ALG-2 interacting protein 1  (or X)
Apoptosis Linked Gene 2 interacting protein X
HP95,
(Hiiren vastaava geeni on Bro1)

https://www.nature.com/articles/s41598-017-09467-9

• https://www.ncbi.nlm.nih.gov/pubmed/28419521

J Cell Biochem. 2017 Nov;118(11):3561-3568. doi: 10.1002/jcb.26066. Epub 2017 May 30.

Cytokinetic Abscission: Phosphoinositides and ESCRTs Direct the Final Cut.

Gulluni F¹, Martini M¹, Hirsch E¹.

Abstract

Cytokinetic abscission involves the fine and regulated recruitment of membrane remodeling proteins that participate in the abscission of the intracellular bridge that connects the two dividing cells. This essential process is mediated by the concomitant activity of the endosomal sorting complex required for transport (ESCRT) and the vesicular trafficking directed to the midbody. Phosphoinositides (PtdIns), produced at plasma membrane, and endosomes, act as molecular intermediates by recruiting effector proteins involved in multiple cellular processes, such as intracellular signaling, endo- and exo-cytosis, and membrane remodeling events. Emerging evidences suggest that PtdIns have an active role in recruiting key elements that control the stability and the remodeling of the cytoskeleton from the furrow ingression to the abscission, at the end of cytokinesis. Accordingly, a possible concomitant and coordinated activity between PtdIns production and ESCRT machinery assembly could also exist and recent findings are pointing the attention on poorly understood ESCRT subunits potentially able to associate with PtdIns rich membranes. Although further studies are required to link PtdIns to ESCRT machinery during abscission, this might represent a promising field of study. J. Cell. Biochem. 118: 3561-3568, 2017.

© 2017 Wiley Periodicals, Inc.

KEYWORDS:

CYTOKINESIS; ESCRT; PHOSPHOINOSITIDES

TRIM23 pohdittavaksi:TRIM, jossa on fuusioituneena ARF1-funktio (ARFD1)

https://www.wikigenes.org/e/gene/e/375.html

Tämä EC2.3.2.27  osallistuu inositoliperheen proteiinien metaboliakarttaan.

https://www.wikigenes.org/e/gene/e/375.html

https://www.wikigenes.org/e/ref/e/9003363.html

https://www.wikigenes.org/e/ref/e/10377261.html

Vertailu eri TRIM proteiinien rakenteesta:

Huomaa että TRIM23 omaa ARF. Huomasin tämän kun etsin hakusanalla  sellaisia trimejä joissa on ARF-domeeni  ja niitä olikin vain tämä yksi. Sensijaan ARF perhettä on paljon ja tämä TRIM23 on ARFD1.Tässä tapauksessa  kannattaa katsoa  ARF-perheen funktionaalista karttaa, koska se alkaa olla aika keskeinen solumetaboliassa.

http://embomolmed.embopress.org/content/3/9/513.figures-only
 Figure 1.

Schematic representation of human TRIM family proteins. The TRIM family proteins are classified into 11 subgroups (C‐I to C‐XI) as defined by Short & Cox, 2006, Ozato et al, 2008 and Carthagena et al, 20

. COS, C‐terminal subgroup one signature;
FN3, fibronectin type 3;
 PHD, plant homeodomain;
FIL, filamin‐type Ig;
NHL, NCL‐1, HT2A and LIN‐41;
MATH, meprin and TRAF homology;
ARF, ADP ribosylation factor‐like;
TM, transmembrane;
 UN, unclassified.

Ps.89:15,16

6.2.2018,11:03.Sana psalmista 86:15,16.

(A Maskil of Ethan the Ezrahite) Blessed are the people who know the festal shout, who walk , o Lord, in the light of thy countenance; who exult in thy name all the day, and extol thy righteousness.