Plektiini - homologi domeenin (PH) sisältävistä proteiineista, joissa on Sars-2 proteiinien interaktioproteiineja

18.11.2021  Otan Wikipediasitaatin  PH-domaanin sisältävistä proteiineista, sillä huomaan eräästä  virus-ihmisproteiini-ointeraktioluettelosta, että 

Sars-2 viruksen nsp12 tekee interaktion erääseen PH-domaanin sisältävään proteiiniin 5A (geeni. PLEKHA5).

Sars-2 ORF8 proteiini tekee interaktion PLEKHF2  proteiiniin, joka on plekstriinihomologi-ja FYVE-domeenin sisältävä  (ZFYVE18).

Sars-2 nsp13 tekee interaktion CIT (citron rho-interacting S/T kinase) entsyymiin. 

Otan näistä kolmesta esimerkistä GeneCard lähteestä sitaatteja esii Exem 1- 3.

 

 

https://en.wikipedia.org/wiki/Pleckstrin_homology_domain

Wikipediasitaatti: 

"Pleckstrin homology domain (PH domain) or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton.^{[1][2][3][4][5][6][7]}

This domain can bind phosphatidylinositol lipids within biological membranes (such as phosphatidylinositol (3,4,5)-trisphosphate and phosphatidylinositol (4,5)-bisphosphate),^[8] and proteins such as the βγ-subunits of heterotrimeric G proteins,^[9] and protein kinase C.^[10] Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways.

Lipid binding specificity

Individual PH domains possess specificities for phosphoinositides phosphorylated at different sites within the inositol ring, e.g., some bind phosphatidylinositol (4,5)-bisphosphate but not phosphatidylinositol (3,4,5)-trisphosphate or phosphatidylinositol (3,4)-bisphosphate, while others may possess the requisite affinity. This is important because it makes the recruitment of different PH domain containing proteins sensitive to the activities of enzymes that either phosphorylate or dephosphorylate these sites on the inositol ring, such as phosphoinositide 3-kinase or PTEN, respectively. Thus, such enzymes exert a part of their effect on cell function by modulating the localization of downstream signaling proteins that possess PH domains that are capable of binding their phospholipid products.

Structure

The 3D structure of several PH domains has been determined.^[11] All known cases have a common structure consisting of two perpendicular anti-parallel beta sheets, followed by a C-terminal amphipathic helix. The loops connecting the beta-strands differ greatly in length, making the PH domain relatively difficult to detect while providing the source of the domain's specificity. The only conserved residue among PH domains is a single tryptophan (W) located within the alpha helix that serves to nucleate the core of the domain.

Proteins containing PH domain

PH domains can be found in many different proteins, such as OSBP or ARF. Recruitment to the Golgi apparatus in this case is dependent on both PtdIns and ARF. A large number of PH domains have poor affinity for phosphoinositides and are hypothesized to function as protein binding domains. A Genome-wide look in Saccharomyces cerevisiae showed that most of the 33 yeast PH domains are indeed promiscuous in binding to phosphoinositides, while only one (Num1-PH) behaved highly specific .^[12] Proteins reported to contain PH domains belong to the following families:

• Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C (PKC)  in platelets. Pleckstrin contains two PH domains. ARAP proteins contain five PH domains.
• Serine/threonine-specific protein kinases such as the Akt/Rac family, protein kinase D1, and the trypanosomal NrkA family.
• Non-receptor tyrosine kinases belonging to the Btk/Itk/Tec subfamily.
• Insulin receptor substrate 1 (IRS-1).
• Regulators of small G-proteins: 64 RhoGEFs of the Dbl-like family.,^[13] and several GTPase activating proteins like ABR, BCR or ARAP proteins.
• Cytoskeletal proteins such as dynamin (see InterPro: IPR001401), Caenorhabditis elegans kinesin-like protein unc-104 (see InterPro: IPR001752), spectrin beta-chain, syntrophin (2 PH domains), and S. cerevisiae nuclear migration protein NUM1.
• Oxysterol-binding proteins OSBP, S. cerevisiae OSH1 and YHR073w.
• Ceramide kinase, a lipid kinase that phosphorylates ceramides to ceramide-1-phosphate.^[14]
• G protein receptor kinases (GRK) of GRK2 subfamily (beta-adrenergic receptor kinases): GRK2 and GRK3.^[15]

Subfamilies

• Spectrin/pleckstrin-like InterPro: IPR001605

Examples

Human genes encoding proteins containing this domain include:

• ABR, ADRBK1, ADRBK2, AFAP, AFAP1, AFAP1L1, AFAP1L2, AKAP13, AKT1, AKT2, AKT3, ANLN, APBB1IP, APPL1, APPL2, ARHGAP10, ARHGAP12, ARHGAP15, ARHGAP21, ARHGAP22, ARHGAP23, ARHGAP24, ARHGAP25, ARHGAP26, ARHGAP27, ARHGAP9, ARHGEF16, ARHGEF18, ARHGEF19, ARHGEF2, ARHGEF3, ARHGEF4, ARHGEF5, ARHGEF6, ARHGEF7, ARHGEF9, ASEF2,
• BMX, BTK,
• C20orf42, C9orf100, CADPS, CADPS2, CDC42BPA, CDC42BPB, CDC42BPG, CENTA1, CENTA2, CENTB1, CENTB2, CENTB5, CENTD1, CENTD2, CENTD3, CENTG1, CENTG2, CENTG3, CERK, CIT, CNKSR1, CNKSR2, COL4A3BP, CTGLF1, CTGLF2, CTGLF3, * CTGLF4, CTGLF5, CTGLF6,
• DAB2IP, DAPP1, DDEF1, DDEF2, DDEFL1, DEF6, DEPDC2, DGKD, DGKH, DGKK, DNM1, DNM2, DNM3, DOCK10, DOCK11, DOCK9, DOK1, DOK2, DOK3, DOK4, DOK5, DOK6, DTGCU2,
• EXOC8,
• FAM109A, FAM109B, FARP1, FARP2, FGD1, FGD2, FGD3, FGD4, FGD5, FGD6,
• GAB1, GAB2, GAB3, GAB4, GRB10, GRB14, GRB7,
• IRS1, IRS2, IRS4, ITK, ITSN1, ITSN2,
• KALRN, KIF1A, KIF1B, KIF1Bbeta,
• MCF2, MCF2L, MCF2L2, MRIP, MYO10,
• NET1, NGEF,
• OBPH1, OBSCN, OPHN1, OSBP, OSBP2, OSBPL10, OSBPL11, OSBPL3, OSBPL5, OSBPL6, OSBPL7, OSBPL8, OSBPL9,
• PHLDA2, PHLDA3, PHLDB1, PHLDB2, PHLPP, PIP3-E, PLCD1, PLCD4, PLCG1, PLCG2, PLCH1, PLCH2, PLCL1, PLCL2, PLD1, PLD2, PLEK, PLEK2, PLEKHA1, PLEKHA2, PLEKHA3, PLEKHA4, PLEKHA5, PLEKHA6, PLEKHA7, PLEKHA8, PLEKHB1, PLEKHB2, PLEKHC1, PLEKHF1, PLEKHF2, PLEKHG1, PLEKHG2, PLEKHG3, PLEKHG4, PLEKHG5, PLEKHG6, PLEKHH1, PLEKHH2, PLEKHH3, PLEKHJ1, PLEKHK1, PLEKHM1, PLEKHM2, PLEKHO1, PLEKHQ1, PREX1, PRKCN, PRKD1, PRKD2, PRKD3, PSCD1, PSCD2, PSCD3, PSCD4, PSD, PSD2, PSD3, PSD4, RALGPS1, RALGPS2, RAPH1,
• RASA1, RASA2, RASA3, RASA4, RASAL1, RASGRF1, RGNEF, ROCK1, ROCK2, RTKN,
• SBF1, SBF2, SCAP2, SGEF, SH2B, SH2B1, SH2B2, SH2B3, SH3BP2, SKAP1, SKAP2, SNTA1, SNTB1, SNTB2, SOS1, SOS2, SPATA13, SPNB4, SPTBN1, SPTBN2, SPTBN4, SPTBN5, STAP1, SWAP70, SYNGAP1,
• TBC1D2, TEC, TIAM1, TRIO, TRIOBP, TYL,
• URP1, URP2,
• VAV1, VAV2, VAV3, VEPH1

See also

 

•  Plexstrin
  
• The unrelated FYVE domain binds Phosphatidylinositol 3-phosphate and has been found in over 60 proteins.

Exem 1. 

Summaries for PLEKHF2 Gene

GeneCards Summary for PLEKHF2 Gene

PLEKHF2 (Pleckstrin Homology And FYVE Domain Containing 2) is a Protein Coding gene. An important paralog of this gene is PLEKHF1.

UniProtKB/Swiss-Prot Summary for PLEKHF2 Gene

• May play a role in early endosome fusion upstream of RAB5, hence regulating receptor trafficking and fluid-phase transport. Enhances cellular sensitivity to TNF-induced apoptosis (PubMed:18288467).

  • PKHF2_HUMAN,Q9H8W4

• ZFYVE18 ^{2 3 4 5}
• PHAFIN2 ^{2 3 5}
• Endoplasmic Reticulum-Associated Apoptosis-Involved Protein Containing PH And FYVE Domains ^{3 4}

 Exem2.

GeneCards Summary for PLEKHA5 Gene

PLEKHA5 (Pleckstrin Homology Domain Containing A5) is a Protein Coding gene. Diseases associated with PLEKHA5 include Cleft Lip With Or Without Cleft Palate and Blepharocheilodontic Syndrome 1. Among its related pathways are PI Metabolism and Glycerophospholipid biosynthesis. Gene Ontology (GO) annotations related to this gene include phosphatidylinositol-3-phosphate binding and phosphatidylinositol-3,5-bisphosphate binding. An important paralog of this gene is PLEKHA7.

Gene Wiki entry for PLEKHA5 Gene

Exem.3

Cit

Entrez Gene Summary for CIT Gene

• This gene encodes a serine/threonine-protein kinase that functions in cell division. Together with the kinesin KIF14, this protein localizes to the central spindle and midbody, and functions to promote efficient cytokinesis. This protein is involved in central nervous system development. Polymorphisms in this gene are associated with bipolar disorder and risk for schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

GeneCards Summary for CIT Gene

CIT (Citron Rho-Interacting Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with CIT include Microcephaly 17, Primary, Autosomal Recessive and Primary Autosomal Recessive Microcephaly. Among its related pathways are Signaling by Rho GTPases and Actin Nucleation by ARP-WASP Complex. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is CDC42BPB.

UniProtKB/Swiss-Prot Summary for CIT Gene

• Plays a role in cytokinesis. Required for KIF14 localization to the central spindle and midbody. Putative RHO/RAC effector that binds to the GTP-bound forms of RHO and RAC1. It probably binds p21 with a tighter specificity in vivo. Displays serine/threonine protein kinase activity. Plays an important role in the regulation of cytokinesis and the development of the central nervous system. Phosphorylates MYL9/MLC2.

  • CTRO_HUMAN,O14578