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fredag 3 januari 2020

Rintasyöpä , C16- cer ja S1P keskiössä, mahdollisesti uusia terapiakohteita .

https://www.ncbi.nlm.nih.gov/pubmed/30226616

2018 Nov;40(5):2977-2987. doi: 10.3892/or.2018.6689. Epub 2018 Sep 7.

C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation.

Abstract

Recently, sphingolipid derivatives, such as ceramide and sphingosine‑1‑phosphate (S1P), have emerged as key modulators in apoptotic cell death and cell proliferation. This study aimed to clarify the underlying signaling pathways of ceramide and S1P involved in breast cancer cell proliferation. Ceramide acyl chain length is determined by six mammalian ceramide synthases (CerS). We overexpressed CerS1 to 6 in MCF‑7 cells to examine whether ceramide signaling propagation varies as a function of acyl chain length. Among the six CerS, only CerS6 overexpression reduced phosphorylation of Akt, S6 kinase (S6K), and extracellular signal‑regulated kinases (ERK) as shown by western blotting. In addition, CerS6 overexpression reduced MCF‑7 cell proliferation. This effect was partially reversed by co‑treatment with MHY1485, an activator of mammalian target of rapamycin (mTOR), demonstrating an important role for the mTOR pathway in the CerS6‑mediated decrease in MCF‑7 cell proliferation. ERK inhibition, but not Akt inhibition, along with mTOR inhibition synergistically reduced MCF‑7 cell proliferation as measured by MTT assay. Notably, the expression of CerS6 and S1P receptor 2 (S1PR2), or CerS6 and sphingosine kinase 1 (SphK1), were negatively correlated according to the invasive breast carcinoma patient cohort in The Cancer Genome Atlas database. In addition, both SphK1 overexpression and S1P addition increased mTOR phosphorylation as shown by ELISA, while S1PR2 inhibition had the inverse effect. These data suggest that CerS6 and SphK1 regulate mTOR signaling in breast cancer cell proliferation. Moreover, mTOR activity can be regulated by the balance between S1P and C16‑ceramide, which is generated by CerS6

Keramidisyntaasit ja sfingolipidien keramidien rasvahappopituuksien (N-acyl chain length) määrytyminen

https://www.ncbi.nlm.nih.gov/pubmed/29632068/
  2018 Jun 22;293(25):9912-9921. doi: 10.1074/jbc.RA118.001936. Epub 2018 Apr 9.

Eleven residues determine the acyl chain specificity of ceramide synthases.

Tidhar R1, Zelnik ID1 et al. Abstract

Lipids display large structural complexity, with ∼40,000 different lipids identified to date, ∼4000 of which are sphingolipids. A critical factor determining the biological activities of the sphingolipid, ceramide, and of more complex sphingolipids is their N-acyl chain length, which in mammals is determined by a family of six ceramide synthases (CerS). Little information is available about the CerS regions that determine specificity toward different acyl-CoA substrates. We previously demonstrated that substrate specificity resides in a region of ∼150 residues in the Tram-Lag-CLN8 domain. Using site-directed mutagenesis and biochemical analyses, we now narrow specificity down to an 11-residue sequence in a loop located between the last two putative transmembrane domains (TMDs) of the CerS.
The specificity of a chimeric protein, CerS5(299-309→CerS2), based on the backbone of CerS5 (which generates C16-ceramide), but containing 11 residues from CerS2 (which generates C22-C24-ceramides), was altered such that it generated C22-C24 and other ceramides.
 Moreover, a chimeric protein, CerS4(291-301→CerS2), based on CerS4 (which normally generates C18-C22 ceramides) displayed significant activity toward C24:1-CoA.
Additional data supported the notion that substitutions of these 11 residues alter the specificities of the CerS toward their cognate acyl-CoAs.

KEYWORDS:ceramide; ceramide synthase; lipid; membrane; sphingolipid

Free PMC Article

keramidien rasvahappopituuksien määräytyminen keramidisyntaasilla on kartoitettu 2018 aikoihin. On kuusi keramidisyntaasia. Israelissa ollaan tästä kiinnostuneita. 

Suomennosta artikkelista 3.1. 2019: 

LIPIDEILLA on laaja rakenteellinen kompleksisuutensa . Näihin mennessä on tunnistettu noin 40 000 erilaista lipidiä ja niistä kuuluu sfingolipidien luokkaan noin 4000 .
Kriittisenä tekijänä sfingolipidien, keramidien ja monimutkaisempien sfingolipidien biologisessa aktiivisuudessa on niiden aktivoituneiden  N-rasvahappojen (N-Acyl CoA) pituus;  imettäväisissä se määräytyy keramidisyntaasientsyymien avulla (CERS-perhe) Ihmisellä on kuusi CERS- entsyymiä CERS1- CERS6.
On olemassa vain vähän informaatiota siitä, mitkä CERS- entsyymin kohdat  määrittävät spesifisyyden eri rasvahappo-CoA- substraatteja kohtaan.
Aiemmin tämä tutkijaryhmä on osoittanut, että substraattispesifisyys on Tram- Lag-CLN8 domaanin 150:n aminohapon kohdalla.
 Käyttämällä kohdennettua mutageneesiä ja biokemiallisia analyysejä he nyt kaventavat spesifisyyden 11 aminohapon sekvenssiin eräässä silmukassa, joka sijaitsee kahden transmembraanisen domeenin (TMD) välissä keramidisyntaasissa (CERS) .

C16-keramidikokoa tuottavan CERS5 runkoon perustuva kimeerinen CerS5( 299-309 jakso-CerS2::sta). jossa on myös 11 aminohappoa CERS2 entsyymistä (joka taas tuottaa C22- C24 keramideja), aiheutti sellaisen muuntumisen CERS-spesifisyyteen, että tuottui C22- C24 - ja muita keramideja.

Lisäksi sellainen CERS4- perusteinen keramidisyntaasi ( jotka tuottaa normaalisti C18-C22 keramideja) muutettuna kimeeriseksi proteiiniksi CERS(291-301 jakso CERS2:sta) , osoittaa merkitsevää spesifisyyttä aktiivoitua C24:1- rasvahappoa (C24:1-CoA) kohtaan.

Lisätiedot tukevat havaintoa niden 11 aminohapon kyvystä muuntaa CERS entsyymien spesifisyyksiä niille tyypillisiä aktivoituja rasvahappoja kohtaan. Tutkijoiden havainnot viittanevat siihen, että tämä lyhyt silmukka rajoittanee toisiaan lähellä olevia transmembraanisia domaaneja (TMD) johtaen kalvon avoimempaan konfrontaatioon ja ne CERS entsyymit, jotka vaikuttavat lyhyehköihin aktivoituneisiin rasvahappoihin saattavat omata pidempiä, taipuvaisempia silmukoita sallien transmembraanidomaaneille joustoa. Yhteenvetona tutkijat ovat tunnistaneet 11 aminohapon alueen, joka määrittää CERS entsyymin spesifisyyden aktiivia rasvahappoa kohtaan.

Keramidisyntaasit 1-6 , CERS1- CERS6

CERS1(19p13.11) , EPM8, GDF1, LAG1, UOG1, GDF-1, LASS1.

Tämä  entsyymi tuottaa C18-keramideja  aivojen neuroneissa. Jos  geenin ilmentymä on koholla se merkitse  neuronin  pitkäikäisyyttä, kuntaas  alentunut ilmenemä assosioituu  myoklooniseen epilepsiaan.  ja dementiaan ihmisessä.

https://www.ncbi.nlm.nih.gov/gene/10715
Official Symbol
CERS1
Official Full Name
ceramide synthase 1
Also known as
EPM8; GDF1; LAG1; UOG1; GDF-1; LASS1
Summary
This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]
Expression
Biased expression in brain (RPKM 22.5) and testis (RPKM 5.1).
Preferred Names
ceramide synthase 1
Names
Embryonic growth/differentiation factor 1; (EPM8)
longevity assurance (LAG1, S. cerevisiae) homolog 1
longevity assurance gene 1 protein homolog 1 (LASS1)
protein UOG-1
upstream of GDF1; (UOG1)

CERS2  (1q21.3), TMSG1 (  Tuumormetastasis-suppressor gene 1 protein )

https://www.ncbi.nlm.nih.gov/gene/29956
Also known as
L3; LASS2; SP260; TMSG1
Summary
This gene encodes a protein that has sequence similarity to yeast longevity assurance gene 1. Mutation or overexpression of the related gene in yeast has been shown to alter yeast lifespan. The human protein may play a role in the regulation of cell growth. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in liver (RPKM 113.9), adrenal (RPKM 85.4) and 25 other tissues See more
Preferred Names
ceramide synthase 2
Names
LAG1 homolog, ceramide synthase 2
LAG1 longevity assurance 2
longevity assurance (LAG1, S. cerevisiae) homolog 2
sphingosine N-acyltransferase CERS2
tumor metastasis-suppressor gene 1 protein

( 299-309 aminohapot : FFGYYFFNSMM

ff
      301 gyyffnsmm) 

CERS3 (5q21.3), 

 https://www.ncbi.nlm.nih.gov/gene/204219
Also known as
ARCI9; LASS3
Summary
This gene is a member of the ceramide synthase family of genes. The ceramide synthase enzymes regulate sphingolipid synthesis by catalyzing the formation of ceramides from sphingoid base and acyl-coA substrates. This family member is involved in the synthesis of ceramides with ultra-long-chain acyl moieties (ULC-Cers), important to the epidermis in its role in creating a protective barrier from the environment. The protein encoded by this gene has also been implicated in modification of the lipid structures required for spermatogenesis. Mutations in this gene have been associated with male fertility defects, and epidermal defects, including ichthyosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
Expression
Biased expression in skin (RPKM 15.5), esophagus (RPKM 13.5) and 1 other tissue See more
Preferred Names
ceramide synthase 3
Names
LAG1 homolog, ceramide synthase 3
LAG1 longevity assurance homolog 3
dihydroceramide synthase 3
sphingosine N-acyltransferase CERS3
NM_001290341.2NP_001277270.1  ceramide synthase 3 isoform 1

CERS4 (19p13.2),

 https://www.ncbi.nlm.nih.gov/gene/79603
Also known as
Trh1; LASS4
Expression
Ubiquitous expression in thyroid (RPKM 13.9), prostate (RPKM 10.3) and 24 other tissues See more
Orthologs


CERS5 (12q13.12),

 https://www.ncbi.nlm.nih.gov/gene/91012
Also known as
Trh4; LASS5
Summary
This gene encodes a protein that belongs to the TLC (TRAM, LAG1 and CLN8 homology domains) family of proteins. The encoded protein functions in the synthesis of ceramide, a lipid molecule that is involved in a several cellular signaling pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Expression
Ubiquitous expression in endometrium (RPKM 6.0), placenta (RPKM 5.6) and 25 other tissues See more
Preferred Names
ceramide synthase 5
Names
LAG1 homolog, ceramide synthase 5
LAG1 longevity assurance homolog 5
TRAM homolog 4
sphingosine N-acyltransferase CERS5
 NM_001281731.1NP_001268660.1  ceramide synthase 5 isoform 2
2008 Sep 26;283(39):26509-17. doi: 10.1074/jbc.M801597200. Epub 2008 Aug 1.
Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells.
Jin J1, Hou Q, Mullen TD,et al.

CERS6 (2q24.3),

 https://www.ncbi.nlm.nih.gov/gene/253782
Also known as
CERS5; LASS6
Expression
Ubiquitous expression in colon (RPKM 18.1), thyroid (RPKM 16.4) and 25 other tissues See more
Preferred Names
ceramide synthase 6
Names
LAG1 homolog, ceramide synthase 6
longevity assurance homolog 6
NM_001256126.2NP_001243055.1  ceramide synthase 6 isoform 1.
The human CERS6 gene promoter harbors a large CpG island (94 CpGs) and multiple transcription factor binding sites (TFBS), which support precise transcriptional regulation and signaling functions
Additional regulation is conferred by 15 microRNA
            (miRNA) target sites identified in the CERS6 3'-UTR region
            Publication Status: Online-Only

onsdag 17 juli 2019

ihmisen sytosolisesta AcetylCoa syntetaasista ACSS2 (20q11.22)

 (Mainitsen että aiemmin sain eräästä lähteestä tietää, että vain sirtuiini SIRT1 pystyy deasetyloimaan tätä sytosolista asetyyliCoA-syntaasia, kun taas mitokondriaalista deasetyloi SIRT3. )


 ACSS2 ( 20q11.22), sytosolinen asetyyliCoA syntetaasi, etikkahapon aktivoija.
https://www.ncbi.nlm.nih.gov/gene/55902
Tämä geeni koodaa sytosolista etnsyymiä, joka  katalysoi etikkahapon aktivoitumista   ja  tämä aktivoitunut etikkahappo  voi käyttyä lipidisynteesiin tai energian generoimiseen. Proteiini toimii monomeerina ja  tuottaa asetyyli-CoA:n etikkahaposta reaktiossa, joka vaatii ATP:tä.
 Tämän geenin ilmentymää säätelee SREB- proteiinit, transkriptiotekijät, jotka aktivoivat geenejä, mitä vaaditaan  kolesterolin ja tyydyttymättömien rasvahappojen synteesin. Vaihtoehtoispleissauksista tulee useita  transkriptivariantteja. Geeniä ilmentyy laajasti rasvakudoksessa, pohjukaissuolesas ja 24 muussa kudoksessa. 
Official Symbol ACSS2
Official Full Name acyl-CoA synthetase short chain family member 2
Also known as ACS; ACSA; ACAS2; ACECS; dJ1161H23.1
Summary: This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP.
 Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]
Expression: Broad expression in fat (RPKM 49.2), duodenum (RPKM 47.1) and 24 other tissues See more. Orthologs. mouse all.
Preferred Names
acetyl-coenzyme A synthetase, cytoplasmic

Names
acetate thiokinase
acetate-CoA ligase
acetyl-Coenzyme A synthetase 2 (ADP forming)
acyl-activating enzyme
cytoplasmic acetyl-coenzyme A synthetase
 
( Millä tavalla sytosolinen ja mitokondriaalinen ACSS eroavat  toisistaan rakenteellisesti? Mm. vaikuttaa olevan kuusi seriinifosforylaatiota ja vain yksi N-lysiiniasetylaatio tässä sytosolisessa. Tämä geeni sijaitsee saman kromosomin q päädyssä, kun mitokondrinen  ACSS taas sijaitsee p-päädyssä).
  
Features
NM_001076552.2NP_001070020.2  acetyl-coenzyme A synthetase, cytoplasmic isoform 2
 
FEATURES             Location/Qualifiers
     source          1..714
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20q11.22"
     Protein         1..714
                     /product="acetyl-coenzyme A synthetase, cytoplasmic
                     isoform 2"
                     /EC_number="6.2.1.1"
                     /note="acetyl-Coenzyme A synthetase 2 (ADP forming);
                     cytoplasmic acetyl-coenzyme A synthetase; acetate-CoA
                     ligase; acyl-activating enzyme; acetate thiokinase;
                     acetyl-coenzyme A synthetase, cytoplasmic"
                     /calculated_mol_wt=79957
     Site            28
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163,
                     ECO:0000244|PubMed:24275569}; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            30
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:23186163, ECO:0000244|PubMed:24275569};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Region          31..705
                     /region_name="PRK00174"
                     /note="acetyl-CoA synthetase; Provisional"
                     /db_xref="CDD:234677"
     Site            36
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:24275569};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Region          51..698
                     /region_name="ACS"
                     /note="Acetyl-CoA synthetase (also known as acetate-CoA
                     ligase and acetyl-activating enzyme); cd05966"
                     /db_xref="CDD:213313"
     Site            order(191..193,219,222,224,370,375..376,398..400,424..425,
                     428,451..454,476..481,565,577,580,588..591,649,654..655)
                     /site_type="active"
                     /db_xref="CDD:213313"
     Site            order(191..193,219,222,224,370,376,398..400,424..425,428,
                     588..590,649,654)
                     /site_type="other"
                     /note="CoA binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Region          219..222
                     /region_name="Coenzyme A binding. {ECO:0000250}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            263
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q9QXG4};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            265
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q9QXG4};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            267
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:23186163,
                     ECO:0000244|PubMed:24275569}; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            order(326,329..334,336..337)
                     /site_type="other"
                     /note="acyl-activating enzyme (AAE) consensus motif"
                     /db_xref="CDD:213313"
     Site            order(375..376,451..454,476..481,565,577,580,591)
                     /site_type="other"
                     /note="AMP binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Site            order(375..376,451..452,479)
                     /site_type="other"
                     /note="acetate binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Site            431
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000244|PubMed:19608861};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     CDS             1..714
                     /gene="ACSS2"
                     /gene_synonym="ACAS2; ACECS; ACS; ACSA; dJ1161H23.1"
                     /coded_by="NM_001076552.2:122..2266"
                     /note="isoform 2 is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS42868.2"
                     /db_xref="GeneID:55902"
                     /db_xref="HGNC:HGNC:15814"
                     /db_xref="MIM:605832"
ORIGIN      
        1 mglpeervrs gsgsrgqeea gaggrarsws pppevsrsah vpslqryrel hrrsveepre
       61 fwgdiakefy wktpcpgpfl rynfdvtkgk ifiewmkgat tnicynvldr nvhekklgdk
      121 vafywegnep gettqityhq llvqvcqfsn vlrkqgiqkg drvaiympmi pelvvamlac
      181 arigalhsiv fagfsseslc erildsscsl littdafyrg eklvnlkela dealqkcqek
      241 gfpvrccivv khlgraelgm gdstsqsppi krscpdvqgk lkekskrvqp qiswnqgidl
      301 wwhelmqeag decepewcda edplfilyts gstgkpkgvv htvggymlyv attfkyvfdf
      361 haedvfwcta digwitghsy vtygplanga tsvlfegipt ypdvnrlwsi vdkykvtkfy
      421 taptairllm Kfgdepvtkh sraslqvlgt vgepinpeaw lwyhrvvgaq rcpivdtfwq
      481 tetgghmltp lpgatpmkpg satfpffgva pailnesgee legeaegylv fkqpwpgimr
      541 tvygnherfe ttyfkkfpgy yvtgdgcqrd qdgyywitgr iddmlnvsgh llstaevesa
      601 lveheavaea avvghphpvk geclycfvtl cdghtfspkl teelkkqire kigpiatpdy
      661 iqnapglpkt rsgkimrrvl rkiaqndhdl gdmstvadps vishlfshrc ltiq
//
(Mitä tietoja on tästä proteiinista saatu tähän mennessä?)
 
GeneRIFs: Gene References Into Functions
Submit: New GeneRIF Correction See all GeneRIFs (21)

https://www.ncbi.nlm.nih.gov/pubmed/?term=ACSS2%2C+Sirtuins 
https://www.ncbi.nlm.nih.gov/pubmed/?term=ACSS2%2C++hypercholesterolemia 
(Joku toinenkin on kiinnittänyt huomion ACSS- geenien  sijaintiin ja ominaisuuksiin ja  ei koodaavan pitkän RNA:n mahdolliseen  osuuteen. Otan aivan  tuoreen artikkelin pohdittavaksi. ACSS1 ja ACSS2  pitävät lyhyistä ja keskipitkistä rasvahapoista C2-C5  ensisijaisena kohteena C2 etikkahappoa.)  
https://www.ncbi.nlm.nih.gov/pubmed/31281828 
2019 Jun 2;2019:5070975. doi: 10.1155/2019/5070975. eCollection 2019.
Identification of lncRNAs and Genes Responsible for Fatness and Fatty Acid Composition Traits between the Tibetan and Yorkshire Pigs.
Shang P1, Li W2, Liu G3, Zhang J1, Li M1, Wu L1, Wang K2, Chamba Y1.

Abstract

Tibetan pigs from the Tibetan Plateau are characterized with a significant phenotypic difference relative to lowland pigs. In this study, a significant difference of the fatness and fatty acid composition traits was observed between the Tibetan and Yorkshire pigs. To uncover the involved mechanism, the expression profile of long noncoding RNAs (lncRNAs) and genes was compared between them. After serial filtered steps, 1,964 lncRNAs were obtained through our computational pipeline. In total, 63 and 715 lncRNAs and genes were identified to be differentially expressed. Evidence from cis- and trans-targeting analysis of lncRNAs demonstrated that some lncRNAs, such as MSTRG.14097 and MSTRG.8034, played important roles in the fatness and fatty acid composition traits. Bioinformatics analysis revealed that many candidate genes were responsible for the two traits. Of these, FASN, ACACA, SCD, ME3, PDHB, ACSS1, ACSS2, and ACLY were identified, which functioned in regulating the level of hexadecanoic acid, hexadecenoic acid, octadecenoic acid, and monounsaturated fatty acid. And LPGAT1, PDK4, ACAA1, and ADIPOQ were associated with the content of stearic acid, octadecadienoic acid, and polyunsaturated fatty acid. Candidate genes, which were responsible for fatness trait, consisted of FGF2, PLAG1, ADIPOQ, IRX3, MIF, IL-34, ADAM8, HMOX1, Vav1, and TLR8. In addition, association analysis also revealed that 34 and 57 genes significantly correlated to the fatness and fatty acid composition trait, respectively. Working out the mechanism caused by these lncRNAs and candidate genes is proven to be complicated but is invaluable to our understanding of fatness and fatty acid composition traits.


Aktivoidusta etikkahaposta ihmisen solussa ja mitokondriassa. Mitokondriaalinen ACSS1( 20p11.21)

AceSC1 ja AceC2
https://www.ncbi.nlm.nih.gov/pubmed/11150295
Näillä on nykyisin toiset  nimetm joissa numero on päinvastoin siis  ACSS2 sytosolinen  (AceCS1 ennen) ja  ACSS1 mitokondriaalinen ( AceCS2 ennen). Mitokondriaalista on eniten sydämessä ja maksasta se puuttuu.

AseCS1 on mitokondriaalinen asetyyli-CoA-syntetaasi. (Asetaatti-CoA ligaasi;  etikkahapon CoA-ligaasi) ,  Sillä on ainakin hiirissä - (joilla ei liikuntafaktoristaole puutetta)    tärkeä osuus sitruunahapposyklissä (CSC, TCA) , jossa se katalysoi asetaatit eli etikkahapon konversiota aktiiviksi etikkahapoksi , asetyyli CoA:ksi.( AsetyyliCoA taas on se perustava molekyyli, jolla on heti käyttöä monenmoisiin  metabolisiin teihin! Pelkkä etikkahappo taas tuottaa  harmia, jos se ei  kykene aktivoitumaan).  Geenistä pleissautuu  vaihtoehtoisia transkriptejä, jotka koodaavat  monia isoformeja. Tätä geeniä ilmentyy istukassa, pohjukaisisuolessa ja 24 muussa kudoksessa.
Geenin virallinen symboli nykyään on ACSS1, muita nimiä ovat ACAS2L, ACECS1, AceCS2L

ACSS1 (20p11.21) . acyl-CoA synthetase short chain family member 1 [ Homo sapiens (human) ]
https://www.ncbi.nlm.nih.gov/gene/84532
Official Symbol ACSS1
Official Full Name acyl-CoA synthetase short chain family member 1
Also known as ACAS2L; ACECS1; AceCS2L
Summary:  This gene encodes a mitochondrial acetyl-CoA synthetase enzyme. A similar protein in mice plays an important role in the tricarboxylic acid cycle by catalyzing the conversion of acetate to acetyl CoA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
Expression Broad expression in placenta (RPKM 70.4), duodenum (RPKM 23.0) and 24 other tissues See more Orthologs mouse all
Preferred Names: acetyl-coenzyme A synthetase 2-like, mitochondrial
Names: acetate--CoA ligase 2
Features: NM_001252675.1NP_001239604.1  acetyl-coenzyme A synthetase 2-like, mitochondrial isoform 2 precursor   ( Plenty of  isoforms!)
 
 
FEATURES             Location/Qualifiers
     source          1..687
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20p11.21"
     Protein         1..687
                     /product="acetyl-coenzyme A synthetase 2-like,
                     mitochondrial isoform 2 precursor"
                     /EC_number="6.2.1.1"
                     /note="acetyl-coenzyme A synthetase 2-like, mitochondrial;
                     acetate--CoA ligase 2"
                     /calculated_mol_wt=70901
     transit_peptide 1..37
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Mitochondrion. {ECO:0000269|PubMed:16788062};
                     propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)"
                     /calculated_mol_wt=3743
     Region          54..674
                     /region_name="Ac_CoA_lig_AcsA"
                     /note="acetate--CoA ligase; TIGR02188"
                     /db_xref="CDD:274022"
     Region          64..665
                     /region_name="ACS"
                     /note="Acetyl-CoA synthetase (also known as acetate-CoA
                     ligase and acetyl-activating enzyme); cd05966"
                     /db_xref="CDD:213313"
Acetyl-CoA synthetase (also known as acetate-CoA ligase and acetyl-activating enzyme)
Acetyl-CoA synthetase (ACS) catalyzes the formation of acetyl-CoA from acetate, CoA, and ATP. Synthesis of acetyl-CoA is carried out in a two-step reaction. In the first step, the enzyme catalyzes the synthesis of acetyl-AMP intermediate from acetate and ATP. In the second step, acetyl-AMP reacts with CoA to produce acetyl-CoA. This enzyme is widely present in all living organisms. The activity of this enzyme is crucial for maintaining the required levels of acetyl-CoA, a key intermediate in many important biosynthetic and catabolic processes. Acetyl-CoA is used in the biosynthesis of glucose, fatty acids, and cholesterol. It can also be used in the production of energy in the citric acid cycle. Eukaryotes typically have two isoforms of acetyl-CoA synthetase, a cytosolic form involved in biosynthetic processes and a mitochondrial form primarily involved in energy generation.
Site order(196..198,224,227,229,335,340..341,363..365,389..390, 393,416..419,441..446,531,543,546,554..557,615,620..621) /site_type="active" /db_xref="CDD:213313" Site order(196..198,224,227,229,335,341,363..365,389..390,393, 554..556,615,620) /site_type="other" /note="CoA binding site [chemical binding]" /db_xref="CDD:213313" Region 224..227 (RGGR) /region_name="Coenzyme A binding. {ECO:0000250}" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)" Site order(291,294..299,301..302) /site_type="other" /note="acyl-activating enzyme (AAE) consensus motif" /db_xref="CDD:213313" Site order(340..341,416..419,441..446,531,543,546,557) /site_type="other" /note="AMP binding site [chemical binding]" /db_xref="CDD:213313" Site order(340..341,416..417,444) /site_type="other" /note="acetate binding site [chemical binding]" /db_xref="CDD:213313" Site 396 K /site_type="acetylation" /experiment="experimental evidence, no additional details recorded" /note="N6-acetyllysine. {ECO:0000244|PubMed:19608861}; propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)" Site 640 K /site_type="acetylation" /experiment="experimental evidence, no additional details recorded" /note="N6-acetyllysine. {ECO:0000269|PubMed:16788062}; propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)" CDS 1..687 /gene="ACSS1" /gene_synonym="ACAS2L; ACECS1; AceCS2L" /coded_by="NM_001252675.1:81..2144" /note="isoform 2 precursor is encoded by transcript variant 2" /db_xref="GeneID:84532" /db_xref="HGNC:HGNC:16091" /db_xref="MIM:614355" ORIGIN 1 maartlgrgv grllgslrgl sgqparppcg vsaprraasg psgsapavaa aaaqpgsypa 61 lsaqaarepa afwgplardt lvwdtpyhtv wdcdfstgki gwflggqlnv svncldqhvr 121 kspesvaliw erdepgtevr ityrellett crlantlkrh gvhrgdrvai ympvsplava 181 amlacariga vhtvifagfs aeslagrind akckvvitfn qglrggrvve lkkivdeavk 241 hcptvqhvlv ahrtdnkvhm gdldvpleqe makedpvcap esmgsedmlf mlytsgstgm 301 pkgivhtqag yllyaalthk lvfdhqpgdi fgcvadigwi tghsyvvygp lcngatsvlf 361 estpvypnag rywetverlk inqfygapta vrlllKygda wvkkydrssl rtlgsvgepi 421 nceawewlhr vvgdsrctlv dtwwqtggic iaprpseega eilpamamrp ffgivpvlmd 481 ekgsvvegsn vsgalcisqa wpgmartiyg dhqrfvdayf kaypgyyftg dgayrteggy 541 yqitgrmddv inisghrlgt aeiedaiadh pavpesavig yphdikgeaa fafivvkdsa 601 gdsdvvvqel ksmvatkiak yavpdeilvv krlpktrsgK vmrrllrkii tseaqelgdt 661 ttledpsiia eilsvyqkck dkqaaak //
 
 
 
 
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Article | Open | Published:
Constructing a synthetic pathway for acetyl-coenzyme A from one-carbon through enzyme design