Muistiin omalle tietokoneelle 23.12.2019
Nämä proteiinit pitää käydä yksityiskohtaisesti läpi, koska ne tekevät interaktiota fosfoinositidilipidien (PI) kanssa.
En voi kopioida niitä suoraan tähän.
FYVE domeenin merkityksestä (2015) :
https://www.ncbi.nlm.nih.gov/pubmed/25985087
FYVE DOMEENIN MERKITYKSESTÄ:
Elife. 2015 May 18;4.
doi: 10.7554/eLife.06041
FYVE-domeeni
linkkii spesifisesti mRNA-kuljetuksen endosomaaliseen liikenteeseen
A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking.
Pohlmann T1, Baumann S1, Haag C1, Albrecht M2, Feldbrügge M1.
TIIVISTELMÄ. Abstract
Solussa tapahtuvasta kuljetustoiminnasta on kertyvää aihepiiriä mRNA:n ja kalvokuljetuksen välisestä läheisestä yhteydestä. Näkyvä esimerkki on mikrotubuluksista riippuvan lähettiRNA:n ja siihen assosioituvien ribosomien kuljetus endosomeissa. Tämä koordinoitu prosessi on ratkaiseva septiinifilamentoitumisen asianmukaisuudelle ja polarisoituneiden solujen tehokkaalle kasvulle. kuten esim sienirihmoissa ( fungal hyphae).
- An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae.
Vaikka on olemassa yksityiskohtaista tietoa avainasemassa olevista RNA:ta sitovista proteiineista ja prosessiin osallistuvista molekulaarisista moottoreista, on ollut kuitenkin epäselvää, millä tavalla mRNA- proteiinit ovat kalvoihin liittyneinä kuljetuksen aikana. Tässä työssään tutkijat identifioivat erään uuden FYVE-sinkkisormidomeenin sisältävän tekijän, joka tekee interaktiota endosomaalisiin lipideihin ja erään uuden PAM2-kaltaisen domeenin, jota vaatii interaktio RNA:ta sitovan avainproteiinin MLLE-domeenin kanssa.
- Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein.
Johdonmukaisesti tämän FYVE-domeeninomaavan proteiinin puuttuminen johtaa sepsifisiin puutoksiin mRNA-. ribosomi- ja septiinikuljetuksissa, muta ei vaikuta endosomien yleisfunktioihin eikä niiden liikkumisiin.
- Consistently, loss of this FYVE domain protein leads to specific defects in mRNA, ribosome, and septin transport without affecting general functions of endosomes or their movement.
Täten tämä on ensimmäinen endosomaalinen komponentti, joka on spesifinen mRNP:n kuljetukselle
mikä tuo valoon erään uuden mekanimsin, joka kytkee mRNP:n endosomeihin.
Hence, this is the first endosomal component specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to endosomes.
KEYWORDS:
FYVE;
PAM2;
RRM;
Ustilago maydis;
cell biology;
endosome;
infectious disease;
mRNA transport;
microbiology
INTRODUCTION
Trafficking of membranes is essential for intracellular logistics.
Important membranous carriers are endosomes that transport lipids,
proteins, and mRNAs. These large vesicular structures are well-known for
their function in endocytosis, transporting plasma membrane proteins to
their site of degradation in the lysosome/vacuole system (
Huotari and Helenius, 2011;
Rusten et al., 2012).
However, they also carry out other functions, such as receptor
recycling or cytoplasmic signalling, and are therefore considered to be
multipurpose platforms (
Gould and Lippincott-Schwartz, 2009).
Early endosomes (EE) are characterised by the presence of Rab5-like small G
proteins and their special lipid composition consisting of
PI3P lipids (phosphatidylinositol 3-phosphate;
Stenmark et al., 2002;
Kutateladze, 2006).
These lipids are recognised by distinct protein domains, such as the FYVE zinc finger (
Stenmark et al., 1996).
Endosomes are actively transported along the microtubule cytoskeleton,
which is particularly critical in highly polarised cells, such as
neurons and fungal hyphae. In the latter, microtubule-dependent
transport supports apical tip growth and secretion of hydrolytic
enzymes. This process is streamlined for efficiency and defects in
transport result in impaired polar growth and reduced fitness (
Peñalva et al., 2012;
Riquelme and Sánchez-León, 2014).
..
Key factors are RNA-binding proteins that recognise specific
localisation sequences within target mRNAs. Together with accessory
factors, such as the poly(A)-binding protein, they form large
macromolecular complexes called
mRNPs (messenger ribonucleoprotein
particles,
Bullock, 2011;
Eliscovich et al., 2013;
..
The best fungal model system to study co-trafficking of endosomes and mRNAs is the corn pathogen
Ustilago maydis (
Jansen et al., 2014).
Here, the switch from yeast-like to hyphal growth is essential for the
infection of its host, and defects in this polar growth correlate with
reduced fungal virulence (
Brefort et al., 2009;
Vollmeister et al., 2012a). In hyphae, endosomes shuttle extensively along the microtubule cytoskeleton throughout the entire length of the hyphae (
Steinberg, 2014). Transport is mediated by a c
ytoplasmic dynein complex (
Straube et al., 2001)
transporting Rab5a-positive endosomes towards the microtubule
minus-ends and the
kinesin-3 type motor
Kin3 transports in the opposite
direction (plus-ends) (
Schuster et al., 2011). Since endosomes carry the SNARE Yup1 (soluble N-ethylmaleimide-sensitive-factor attachment receptor;
Wedlich-Söldner et al., 2000)
and are positive for Rab5a, they were classified as
early endosomes,
which have initially been proposed to mainly function in endocytosis and
signalling (
Steinberg, 2012;
Bielska et al., 2014).
..
Recently, we discovered a novel function for these endosomes, namely
mRNA transport throughout the hyphae (
Baumann et al., 2012), a process that is critical for polar growth and unconventional secretion of the endochitinase Cts1 (
Becht et al., 2006;
Koepke et al., 2011).
The key factor is the RNA-binding protein Rrm4 containing three
N-terminal RRMs (
RNA recognition motifs) for RNA-binding and two
C-terminal PABC/MLLE domains (
Figure 1A;
Becht et al., 2005;
Zarnack and Feldbrügge, 2010;
Baumann et al., 2012;
Vollmeister et al., 2012b).
The latter is known from the cytoplasmic
poly(A)-binding protein and
functions as a binding pocket for peptides containing a PAM2 motif
(PABP-interacting motif 2;
Albrecht and Lengauer, 2004;
Kozlov et al., 2004;
Jinek et al., 2010;
Xie et al., 2014).
Rrm4 specifically associates with shuttling Rab5a-positive endosomes (
Baumann et al., 2012) and binds a specific set of mRNAs encoding, for example, the small G protein Rho3 or the
septin Cdc3 (
König et al., 2009).
Studying Cdc3 in more detail revealed that not only its mRNA but also
the protein is transported on endosomes in an Rrm4-dependent manner
suggesting that endosome-coupled translation is
crucial for septin
localisation on these membranous carriers and needed for
septin
filamentation (
Baumann et al., 2014). This was verified by demonstrating that translationally active ribosomes are transported on endosomes (
Higuchi et al., 2014).
..
In addition to the PAM2 motif (
Figure 1B) and the FYVE domain, it contained five ankyrin repeats known to be protein–protein interaction interfaces (
Al-Khodor et al., 2010), and a RING domain involved in ubiquitination (
Figure 1A). The protein was designated Upa1 for the
U. maydis PAM2 protein.
..
A novel FYVE domain protein containing PAM2 and PAM2L motifs for interaction with different MLLE proteins
Aiming at the identification of endosomal
components involved in mRNP transport, the PAM2 protein Upa1 caught our
attention because of its FYVE and RING domains. This domain organisation
is similar to Pib1p in
S. cerevisiae and
mammalian Rififylin,
two proteins which appear to function i
n endosomal protein sorting.
Although their precise roles are still unclear (
Shin et al., 2001;
Coumailleau et al., 2004),
they might function in ubiquitination during protein sorting due to the
presence of the
RING domain found in RNF-type E3 ubiquitin ligases (
Nikko and Pelham, 2009).
RFFL (17q12) RIFIFYLIINI
- Official
Symbol
- RFFLprovided by HGNC
- Official
Full Name
- ring finger and FYVE like domain containing E3 ubiquitin protein ligase
- Also known as
- CARP2; FRING; CARP-2; RNF189; RNF34L; RIFIFYLIN
- Expression
- Ubiquitous expression in thyroid (RPKM 18.0), esophagus (RPKM 12.3) and 25 other tissues See more
LISÄYKSENI:
Huomaan aiemmasta RNF- luettelosta jostain syystä samaan funktionaaliseen ryhmään merkattujani:
(a) RNF34,( kr.12q24.31) , CARP-1. RIF, RIFF , "MOMO"
https://www.ncbi.nlm.nih.gov/gene/80196 Preferred Names
- E3 ubiquitin-protein ligase RNF34
- Names
- FYVE-RING finger protein MOMO ( Expr. Brain Grey matter)
- RING finger protein RIFF
- RING-type E3 ubiquitin transferase RNF34
- caspase regulator CARP1
- caspases-8 and -10-associated RING finger protein 1
- human RING finger homologous to inhibitor of apoptosis protein
- ring finger protein 34, E3 ubiquitin protein ligase
Esim: Termogeneesin säätely: RNF34 säätää negatiivisesti kylmän aktivoimaa ruskean rasvan uncoupling factor proteiinia.
https://www.ncbi.nlm.nih.gov/pubmed/22064484/
(b) RNF45, AMFR, (16q13) Autocrine motility factor receptor gp78. Tumour motility stimulating protein. h
ttps://www.ncbi.nlm.nih.gov/gene/267
- Conserved Domains (3) summary
-
- cd14421
Location:458 → 498
- CUE_AMFR; CUE domain found in autocrine motility factor receptor (AMFR) and similar proteins
- cd16455
Location:339 → 382
- RING-H2_AMFR; RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins
- cl26329
Location:86 → 382
- zf-rbx1; RING-H2 zinc finger domain
(c) RNF145,( 5q33.3). Hajoittaa HMGCR yhdessä ubikitiinilig. gp78 kanssa)
https://www.ncbi.nlm.nih.gov/gene/153830
Ring finger protein 145 (RNF145) is a ubiquitin ligase for sterol-induced degradation of HMG-CoA reductase.
Jiang LY, et al. J Biol Chem, 2018 Mar 16. PMID 29374057, Free PMC Article
- Conserved Domains (3) summary
-
- pfam12678
Location:564 → 605
- zf-rbx1; RING-H2 zinc finger
- pfam13639
Location:565 → 605
- zf-RING_2; Ring finger domain
- pfam13705
Location:38 → 536
- TRC8_N; TRC8 N-terminal domain
TRC8 N-terminal domain
This region is
found at the N-terminus of the TRC8 protein. TRC8 is an E3
ubiquitin-protein ligase also known as RNF139. This region contains 12
transmembrane domains. This region has been suggested to contain a
sterol sensing domain. It has been found that TRC8 protein levels are
sterol responsive and that it binds and stimulates ubiquitylation of the
endoplasmic reticulum anchor protein INSIG.
(d) RNF189, RFFL, Rififylin, CARP-2, FRING, 17q12. "SAKURA"
Sydämen repolarisaatiossa merkitsevä.
https://www.ncbi.nlm.nih.gov/gene/117584 (QT)
- Preferred Names
- E3 ubiquitin-protein ligase rififylin
- Names
- FYVE-RING finger protein SAKURA ( Expr. Brain White matter and periph. organs)
- RING finger and FYVE-like domain-containing protein 1
- RING finger protein 189
- RING-type E3 ubiquitin transferase rififylin
- caspase 8 and 10 associated RING protein-2
- caspase regulator CARP2
- caspases-8 and -10-associated RING finger protein 2
- ring finger and FYVE-like domain containing 1
NP_001017368.1 E3 ubiquitin-protein ligase rififylin
- Conserved Domains (3) summary
-
- cd15770
Location:44 → 92
- FYVE_CARP2; FYVE-like domain found in caspase regulator CARP2 and similar proteins
- pfam13920
Location:312 → 356
- zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
- pfam15439
Location:149 → 232
- NYAP_N; Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter
https://www.ncbi.nlm.nih.gov/pubmed/28827789/
-
RFFL
is an important regulator of voltage-gated hERG potassium channel
activity and therefore cardiac repolarization and that this
ubiquitination-mediated regulation requires parts of the ERAD pathway.
-
it
is interesting to note that a human lncRNA does exist within the 5'-UTR
intronic region of the human RFFL gene . Given the rat data, our study
may serve as a translational foundation for considering this human
lncRNA as a candidate regulator for cardiovascular diseases.
https://www.ncbi.nlm.nih.gov/pubmed/12859687
Katson FYVE - Znf finger proteiinista SAKURA nimeltään tietoa:
https://www.ncbi.nlm.nih.gov/pubmed/12859687
A palmitoylated RING
finger ubiquitin ligase and its homologue in the brain membranes.
Araki K1,
Kawamura M,
Suzuki T,
Matsuda N,
Kanbe D,
Ishii K,
Ichikawa T,
Kumanishi T,
Chiba T,
Tanaka K,
Nawa H.
Ubiquitin (Ub) ligation is implicated in active protein
metabolism and subcellular trafficking and its impairment is involved
in various neurologic diseases. In rat brain, we identified two novel Ub
ligases, Momo and Sakura, carrying double zinc finger motif and RING finger domain. Momo expression is enriched in the brain gray matter and testis, and Sakura expression is more widely detected in the brain white matter as well as in many peripheral organs. Both proteins
associate with the cell membranes of neuronal and/or glial cells. We
examined their Ub ligase activity in vivo and in vitro using viral
expression vectors carrying myc-tagged Momo and Sakura. Overexpression of either Momo or Sakura
in mixed cortical cultures increased total polyubiquitination levels.
In vitro ubiquitination assay revealed that the combination of Momo and
UbcH4 and H5c, or of Sakura and UbcH4, H5c and H6 is required for the reaction. Deletion mutagenesis suggested that the E3 Ub ligase activity of Momo and Sakura depended on their C-terminal domains containing RING finger structure, while their N-terminal domains influenced their membrane association. In agreement, Sakura
associating with the membrane was specifically palmitoylated. Although
the molecular targets of their Ub ligation remain to be identified,
these findings imply a novel function of the palmitoylated E3 Ub
ligase(s).
Siirsin Veri ja hyytyminen blogiin viitteen 27.12. 2019.
