https://covid-19.uniprot.org/uniprotkb/A0A663DJA2
Tässä alla katson artikkelin ORF10 interaktioproteiinit, jotka tässä linkissä mainitaan 332 proteiinin joukosta. https://www.biorxiv.org/content/10.1101/2020.03.22.002386v1.full.pdf
The novel Orf10 of SARS-CoV-2 interacts with a Cullin ubiquitin ligase complex Viruses commonly hijack ubiquitination pathways for replication and pathogenesis66. The novel Orf10 of SARS-CoV-2 interacts with multiple members of a Cullin 2 (CUL2) RING E3 ligase complex (Fig. 4c), specifically the CUL2ZYG11Bcomplex.ZYG11B, a substrate adapter of CUL2 that targets substrates with exposed N-terminal glycines for degradation64, is the highest scoring protein in the Orf10 interactome suggesting its direct interaction with Orf10. Orf10 may bind to the CUL2ZYG11Bcomplex and hijack it for ubiquitination and degradation of restriction factors. The ubiquitin transfer to a substrate requires neddylation of CUL2 via NEDD8-activating enzyme (NAE), a druggable target that can be inhibited by the small molecule Pevonedistat67(Fig. 4c)"
ORF10:
MGYINVFAFPFTIYSLLLCRMNSRNYIAQVDVVNFNLTVahvoja interaktiokandidaatteja (40 kpl) tai sekundäärisiä vahvoja kandidaatteja (12 kpl) ei mainita , vaan ORF10 proteiini-proteiini interaktiot mainitaan niiden " 280 muun proteiinin " joukosta ja käytän sille listalle numeroita (59) - (338) koska datalta saatavan sivun lista käyttää nämä 338 riviä otsikkojen kera tälle asialle.
SARS-2-ORF10 kanssa ei-vahvoja -interaktioita " tekevät seuraavat ihmisproteiinit :(119) ZYG11B1p32.3, Ubkitiiniligaasikompleksin jäsen
CLR2 /ZY11 ubikitiiniligaasi kompleksiin kuuluva tekijä, joka säätelee solusykliä mitoosiohitukseen. Ilmenee aivoissa, kilpirauhasesa ja 25 muussa kudoksessa. Johtaa sykliini B1:n silppuriin. LRR proteiini, useita leusiinipitoisia toistoja.
https://www.ncbi.nlm.nih.gov/gene/79699
zyg-11 family member B, cell cycle regulator.
Also known as ZYG11. Expression . Ubiquitous expression in brain (RPKM 12.1), thyroid (RPKM 8.7) and 25 other tissues.
REFERENCE 2 (residues 1 to 744)
AUTHORS Balachandran RS, Heighington CS, Starostina NG, Anderson JW, Owen
DL, Vasudevan S and Kipreos ET.
TITLE The ubiquitin ligase CRL2ZYG11 targets cyclin B1 for degradation in
a conserved pathway that facilitates mitotic slippage
JOURNAL J. Cell Biol. 215 (2), 151-166 (2016)
PUBMED 27810909
https://www.ncbi.nlm.nih.gov/protein/NP_078922.1Compare this CLR2 complex:
Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex.
https://www.sciencedirect.com/science/article/pii/S0969212617301272
(133) PPT1 (1p34.2), INCL. Palmityyliproteiinitioesteraasi 1.
https://www.ncbi.nlm.nih.gov/gene/5538
palmitoyl-protein thioesterase 1. Also known as PPT; CLN1; INCL
Summary. The protein encoded by this gene is a small glycoprotein involved in the catabolism of lipid-modified proteins during lysosomal degradation. The encoded enzyme removes thioester-linked fatty acyl groups such as palmitate from cysteine residues. Defects in this gene are a cause of infantile neuronal ceroid lipofuscinosis 1 (CLN1, or INCL) and neuronal ceroid lipofuscinosis 4 (CLN4). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2008]. Expression. Ubiquitous expression in spleen (RPKM 86.1), lung (RPKM 62.1) and 25 other tissues.Preferred Names palmitoyl-protein thioesterase 1
Names: ceroid-palmitoyl-palmitoyl-protein thioesterase 1
palmitoyl-protein hydrolase 1.
FEATURE.https://www.ncbi.nlm.nih.gov/protein/NP_000301.1 Conserved domain: Abhydrolase (
alpha/beta hydrolases
A functionally
diverse superfamily containing proteases, lipases, peroxidases,
esterases, epoxide hydrolases and dehalogenases. The catalytic apparatus
typically involves three residues (catalytic triad): a serine, a
glutamate or aspartate and a histidine, and often the mechanism involves
a nucleophilic attack on a carbonyl carbon atom).( Ottaen huomioon että SARS-2 kuten muutkin koronavirukset tarvitsee palmitylaation S-piikkiproteiinilleen ehdottomasti, mutta ei jatka kaappaamaansa autofagosomitietä lysosomiin asti, vaan välttää lysosomin, niin tarvitaan ilmeisesti lisäapua virusproteiinista. Arvelen että ORF-10 estää sitä liukua lysosomiin interaktiolla tähän tärkeään tekijään).
Huom: https://www.ncbi.nlm.nih.gov/pubmed/30442709/
Cancer Discov. 2019 Feb;9(2):220-229. doi: 10.1158/2159-8290.CD-18-0706. Epub 2018 Nov 15.
PPT1 Promotes Tumor Growth and Is the Molecular Target of Chloroquine Derivatives in Cancer.(170) MAP7D1 (1p34.3), Mikrotubuluksiin assosioitunut proteiini 7.
MAP7 domeenin sisältävä 1.
https://www.ncbi.nlm.nih.gov/gene/55700
Preferred Names MAP7 domain-containing protein 1 Also known as RPRC1; PARCC1.Expression Ubiquitous expression in fat (RPKM 43.2), brain (RPKM 39.0) and 24 other tissues.
https://www.ncbi.nlm.nih.gov/pubmed/30770434/
" We propose that MAP7 proteins are microtubule-tethered kinesin-1 activators, with which the motor transiently interacts as it moves along microtubules".
Names
arginine/proline rich coiled-coil 1, (RPRC1)
arginine/proline-rich coiled-coil domain-containing protein 1,
proline arginine rich coiled coil 1, (PARCC)
proline/arginine-rich coiled-coil domain-containing protein 1
Kulliini-2
https://www.ncbi.nlm.nih.gov/pubmed/25326537
Expression Ubiquitous expression in testis (RPKM 12.7), brain (RPKM 7.3) and 25 other tissues See more Preferred Names cullin-2
Names:
CUL2
CUL2
testis secretory sperm-binding protein Li 238E.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285538/figure/F6/
Kommentti Wikipediasta:
The human genome contains eight cullin genes
- CUL1, part of SCF complex
- CUL2, part of ECS complex (Elongin C - CUL2 - SOCS-box)
- CUL3, part of CUL3-BTB complex
- CUL4A
- CUL4B
- CUL5
- CUL7
- CUL9, also known as PARC
"The cullin CUL-2 is a crucial component of a subclass of multisubunit cullin-RING ubiquitin-ligases. The specificity of CUL-2-based complexes is provided by variable substrate-recognition subunits that bind to specific substrates"
(203) ELOC (8q21.11) , Elongiini C, SIII, TCEB1
https://www.ncbi.nlm.nih.gov/gene/6921
Elongin C. Also known as SIII; TCEB1.
Summary. This gene encodes the protein elongin C, which is a subunit of the transcription factor B (SIII) complex. The SIII complex is composed of elongins A/A2, B and C. It activates elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin A functions as the transcriptionally active component of the SIII complex, whereas elongins B and C are regulatory subunits. Elongin A2 is specifically expressed in the testis, and capable of forming a stable complex with elongins B and C. The von Hippel-Lindau (VHL) tumor suppressor protein binds to elongins B and C, and thereby inhibits transcription elongation. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been identified. [provided by RefSeq, Mar 2011. Expression Ubiquitous expression in testis (RPKM 15.6), brain (RPKM 14.4) and 25 other tissues See more
Preferred Names: elongin-C
Names: RNA polymerase II transcription factor SIII subunit C,
SIII p15,
elongin 15 kDa subunit,
transcription elongation factor B (SIII), polypeptide 1 (15kDa, elongin C),
transcription elongation factor B polypeptide 1,(TCEB1)
transcription elongation factor B subunit 1.
Region 18..112 /region_name="BTB_POZ_EloC" /note="BTB (Broad-Complex, Tramtrack and Bric a brac) /POZ (poxvirus and zinc finger) domain found in Elongin-C (EloC) and similar proteins; cd18321" /db_xref="CDD:349630"Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase ComplexBTB (Broad-Complex, Tramtrack and Bric a brac) /POZ (poxvirus and zinc finger) domain found in Elongin-C (EloC) and similar proteinsElongin-C is also called elongin 15 kDa subunit, RNA polymerase II transcription factor SIII subunit C, SIII p15, or transcription elongation factor B polypeptide 1 (TCEB1). It is a component of SIII (also known as elongin), which is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. It forms a regulatory complex with subunit B or elongin-B (BC) that enhances the activity of the transcriptionally active subunit A. The BC complex also functions as an adaptor protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC (VHL) and the suppressors of cytokine signaling (SOCS) box ubiquitin ligase family. Elongin-C belongs to the BTB/POZ domain family; the domain is a common protein-protein interaction motif of about 100 amino acids.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5462531/bin/fx1.gif
https://www.ncbi.nlm.nih.gov/pubmed/25326537
(Huom. Esim. HIV-1 virus pidentää vif- elongiini C- interaktion avulla oman virulenssitekijänsä . Tähän on kehitytetty vastavaikuttaja indoliziinijohdannainen, pieni molekyyli). doi/abs/10.1111/cbdd.12119
Olisiko pieni ORF10 -peptidi tuollainen vif-analogi, pohdin vain. )
(300) THTPA(14q11.2)
Tiamiinitrifosfataasi
https://www.ncbi.nlm.nih.gov/gene/79178
THTPA ,thiamine triphosphatase. Also known as THTP; THTPASE
Summary: This gene encodes an enzyme which catalyzes the biosynthesis of thiamine disphophate (vitamin B1) by hydrolysis of thiamine triphosphate (ThTP). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011] Expression Ubiquitous expression in testis (RPKM 8.5), prostate (RPKM 7.8) and 25 other tissues
FEATURES: https://www.ncbi.nlm.nih.gov/protein/NP_001119811.1
Thiamine Triphosphatase
ThTPase is a
soluble cytosolic enzyme which converts thiamine triphosphate (ThTP) to
thiamine diphosphate. This catalytic activity depends on a divalent
metal cofactor, for example Mg++. ThTPase regulates the intracellular
concentration of ThTP, maintaining it at a low concentration in vivo.
ThTP acts as a messenger in cell signaling in response to cellular
stress, and in addition, can phosphorylate proteins in certain tissues.
There is another class of membrane-associated enzymes in animal tissues
which also convert ThTP to thiamine diphosphate, however they do not
belong to this subgroup. This subgroup belongs to the CYTH/triphosphate
tunnel metalloenzyme (TTM)-like superfamily, whose enzymes have a unique
active site located within an eight-stranded beta barrel.(Huom. Aivoissa on tärkeä Tiamiinitrifosfaattimuoto: https://www.ncbi.nlm.nih.gov/pubmed/24590690 )
(B1 vitamiini Benerva palauttaa tiamiinivajeessa näitä aivolle tärkeitä tiamiinitrifosfaattimuotoja,ThTP, joiden muodostus aivoissa ei vaadi ATP:tä). https://www.annualreviews.org/doi/10.1146/annurev.nu.08.070188.002411
(301) TIMM8B (11.q23.1)
https://www.ncbi.nlm.nih.gov/gene/26521
Translocase of inner mitochondrial membrane 8 homolog B. Also known as DDP2; TIM8B
Summary. This gene encodes a member of a well-conserved family of proteins with similarity to yeast Tim mitochondrial import proteins. This gene is encoded by a nuclear gene and is transported into the intermembrane space of the mitochondrion. When formed into complexes, these proteins guide membrane-spanning proteins across the mitochondrial intermembrane space before they are added into the mitochondrial inner membrane. This gene is adjacent to succinate dehydrogenase, subunit D (SDHD), in which mutations have been found in affected members of families with hereditary paraganglioma.[provided by RefSeq, Aug 2009
Expression. Ubiquitous expression in heart (RPKM 16.7), colon (RPKM 15.7) and 25 other tissues
Preferred Names: mitochondrial import inner membrane translocase subunit Tim8 B.
Names: DDP-like protein, deafness dystonia protein 2.
Tim10/DDP family zinc finger
Putative
zinc binding domain with four conserved cysteine residues. This domain
is found in the human disease protein TIMM8A. Members of this family
such as Tim9 and Tim10 are involved in mitochondrial protein import.
Members of this family seem to be localized to the mitochondrial
intermembrane space.HIV-1 gp41 is identified to have a physical interaction with translocase of inner mitochondrial membrane 8 homolog B (TIMM8B) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses.
(302) RBX1 (22q13.2), RNF75
https://www.ncbi.nlm.nih.gov/gene/9978
Official Symbol RBX1. Official Full Name ring-box 1.
Also known as ROC1; RNF75; BA554C12.1
Summary. This locus encodes a RING finger-like domain-containing protein. The encoded protein interacts with cullin proteins and likely plays a role in ubiquitination processes necessary for cell cycle progression. This protein may also affect protein turnover. Related pseudogenes exist on chromosomes 2 and 5.[provided by RefSeq, Sep 2010] Expression Ubiquitous expression in placenta (RPKM 27.7), bone marrow (RPKM 27.1) and 25 other tissues
Preferred Names. E3 ubiquitin-protein ligase RBX1
Names: E3 ubiquitin-protein transferase RBX1,
RING finger protein 75,
RING-box protein 1,
ZYP protein,
regulator of cullins 1,
ring-box 1, E3 ubiquitin protein ligase.
FEATURES: https://www.ncbi.nlm.nih.gov/protein/NP_055063.1.
Conserved Domains (1) summary
-
- cd16485
Location:40 → 101 - mRING-H2-C3H2C2D_RBX1; modified RING finger, H2 subclass (C3H2C2D-type), found in RING-box protein 1 (RBX1) and similar proteins
- cd16485
(303) ELOB (16b13.3), SIII
Elongiini B, RNApolymeraasiII transkriptiofaktori SIII p18 alayksikkö
https://www.ncbi.nlm.nih.gov/gene/6923
Official Symbol ELOB. Official Full Name elongin B. Also known as SIII; TCEB2
Summary This gene encodes the protein elongin B, which is a subunit of the transcription factor B (SIII) complex. The SIII complex is composed of elongins A/A2, B and C. It activates elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin A functions as the transcriptionally active component of the SIII complex, whereas elongins B and C are regulatory subunits. Elongin A2 is specifically expressed in the testis, and capable of forming a stable complex with elongins B and C. The von Hippel-Lindau tumor suppressor protein binds to elongins B and C, and thereby inhibits transcription elongation. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. Pseudogenes have been identified on chromosomes 11 and 13. [provided by RefSeq, Aug 2008]. Expression Ubiquitous expression in testis (RPKM 67.4), adrenal (RPKM 41.2) and 25 other tissues. Preferred Names: elongin-B.
Names: RNA polymerase II transcription factor SIII p18 subunit,
RNA polymerase II transcription factor SIII subunit B.
SIII p18,
elongin 18 kDa subunit,
elongin, 18-kD subunit,
epididymis secretory sperm binding protein,
transcription elongation factor B (SIII), polypeptide 2 (18kDa, elongin B),
transcription elongation factor B polypeptide 2,
transcription elongation factor B subunit 2.
FEATURES:https://www.ncbi.nlm.nih.gov/protein/NP_009039.1
- Conserved Domains (1) summary
-
- cd01788
Location:1 → 118 - ElonginB; Ubiquitin-like domain of Elongin B
Elongin B is part of an E3 ubiquitin ligase complex called VEC that activates ubiquitylation by the E2 ubiquitin-conjugating enzyme Ubc5. VEC is composed of von Hippel-Lindau tumor suppressor protein (pVHL), elongin C, cullin 2, NEDD8, and Rbx1. ElonginB binds elonginC to form the elonginBC complex which is a positive regulator of RNA polymerase II elongation factor Elongin A. The BC complex then binds VHL (von Hippel-Lindau) tumour suppressor protein to form a VCB ternary complex. Elongin B has a ubiquitin-like domain.
- cd01788
Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex.
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