RPH3A (12q24.13) , RABPHILIN 3A , exofiliini-1, ( 133 artikkelia)

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rabphilin+3A

Haku: Geeni Rabphilin 3A  ( Huom.  luin tmän proteiinin olemassaolosta vasta eilen 16.12.2019)

Official Symbol

RPH3Aprovided by HGNC

Official Full Name

rabphilin 3Aprovided by HGNC

Summary

The protein encoded by this gene is thought to be an effector for RAB3A, which is a small G protein that acts in the late stages of neurotransmitter exocytosis. The encoded protein may be involved in neurotransmitter release and synaptic vesicle traffic. [provided by RefSeq, Dec 2016]

Expression

Biased expression in brain (RPKM 30.1) and adrenal (RPKM 1.7) See more

Orthologs

mouse all

Preferred Names

rabphilin-3A

Names

exophilin-1

rabphilin 3A homolog

Genomic context

See RPH3A in Genome Data Viewer

Location:

12q24.13

Exon count:

27
https://www.ncbi.nlm.nih.gov/protein/NP_001137326.1

Conserved Domains (3) summary

cd04035
Location:393 → 516

C2A_Rabphilin_Doc2; C2 domain first repeat present in Rabphilin and Double C2 domain ( Ca2++ binding  domain)

cd08384
Location:553 → 685

C2B_Rabphilin_Doc2; C2 domain second repeat present in Rabphilin and Double C2 domain

(C2 domain second repeat present in Rabphilin and Double C2 domain

Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

cd15762
Location:92 → 171

FYVE_RP3A; FYVE-related domain found in rabphilin-3A and similar proteins

FYVE-related domain found in rabphilin-3A and similar proteins

Rabphilin-3A, also termed exophilin-1, is an effector protein that binds to the GTP-bound form of Rab3A, which is one of the most abundant Rab proteins in neurons and predominantly localized to synaptic vesicles. Rabphilin-3A is homologous to alpha-Rab3-interacting molecules (RIMs). It is a multi-domain protein containing an N-terminal Rab3A effector domain, a proline-rich linker region, and two tandem C2 domains. The effector domain binds specifically to the activated GTP-bound state of Rab3A and harbors a conserved FYVE zinc finger. The C2 domains are responsible for the binding of phosphatidylinositol-4,5-bisphosphate (PIP2) , a key player in the neurotransmitter release process. Thus, Rabphilin-3A has also been implicated in vesicle trafficking. The FYVE domain of Rabphilin-3A resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.

Feature 1: Zn binding site [ion binding site], 8 residue positions

Conserved feature residue pattern:C C C C C C C C

Evidence:

• Structure:1ZBD; Rattus norvegicus Rabphilin-3A binds two Zn2+ through its effector domain.
  - View structure with Cn3D
• Citation:PMID 10025402

ite            order(98,101,115,118,123,126,140,143)
                     /site_type="other"
                     /note="Zn binding site [ion binding]"
                     /db_xref="CDD:277301"

ORIGIN      
        1 mtdtvfsnss nrwmypsdrp lqsndkeqlq agwsvhpggq pdrqrkqeel tdeekeiinr
       61 viaraekmee meqerigrlv drlenmrknv agdgvnrCil Cgeqlgmlgs acvvCedCkk
      121 nvCtkCgvet nnrlhsvwlC kiCieqrevw krsgawffkg fpkqvlpqpm pikktkpqqp
      181 vsepaapeqp apepkhpara pargdsedrr gpgqktgpdp asapgrgnyg ppvrrasear
      241 mssssrdses wdhsggagds srspaglrra nsvqasrpap gsvqspappq pgqpgtpggs
      301 rpgpgpagrf pdqkpevaps dpgttappre ertggvggyp avgaredrms hpsgpysqas
      361 aaapqpaaar qppppeeeee eansydsdea ttlgalefsl lydqdnsslq ctiikakglk
      421 pmdsngladp yvklhllpga sksnklrtkt lrntrnpiwn etlvyhgitd edmqrktlri
      481 svcdedkfgh nefigetrfs lkklkpnqrk nfniclervi pmkragttgs argmalyeee
      541 qvervgdiee rgkilvslmy stqqgglivg iircvhlaam dangysdpfv klwlkpdmgk
      601 kakhktqikk ktlnpefnee ffydikhsdl akksldisvw dydigksndy iggcqlgisa
      661 kgerlkhwye clknkdkkie rwhqlqnenh vssd
//

Select item 314011964.

NMDA receptor modulation of glutamate release in activated neutrophils.

Del Arroyo AG, Hadjihambi A, Sanchez J, Turovsky E, Kasymov V, Cain D, Nightingale TD, Lambden S, Grant SGN, Gourine AV, Ackland GL.

EBioMedicine. 2019 Sep;47:457-469. doi: 10.1016/j.ebiom.2019.08.004. Epub 2019 Aug 8.

NMDA receptor (NMDAR) subunit composition plays a pivotal role in synaptic plasticity at excitatory synapses. Still, the mechanisms responsible for the synaptic retention of NMDARs following induction of plasticity need to be fully elucidated. Rabphilin3A (Rph3A) is involved in the stabilization of NMDARs at synapses through the formation of a complex with GluN2A and PSD-95. Here we used different protocols to induce synaptic plasticity in the presence or absence of agents modulating Rph3A function. The use of Forskolin/Rolipram/Picrotoxin cocktail to induce chemical LTP led to synaptic accumulation of Rph3A and formation of synaptic GluN2A/Rph3A complex. Notably, Rph3A silencing or use of peptides interfering with the GluN2A/Rph3A complex blocked LTP induction. Moreover, in vivo disruption of GluN2A/Rph3A complex led to a profound alteration of spatial memory. Overall, our results demonstrate a molecular mechanism needed for NMDAR stabilization at synapses after plasticity induction and to trigger downstream signaling events necessary for cognitive behavior.Free PMC Article

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Decreased rabphilin 3A immunoreactivity in Alzheimer's disease is associated with Aβ burden.

Tan MG¹, Lee C², Lee JH², Francis PT³, Williams RJ⁴, Ramírez MJ⁵, Chen CP⁶, Wong PT⁶, Lai MK⁷.

Abstract
Synaptic dysfunction, together with neuritic plaques, neurofibrillary tangles and cholinergic neuron loss is an established finding in the Alzheimer's disease (AD) neocortex. The synaptopathology of AD is known to involve both pre- and postsynaptic components. However, the status of rabphilin 3A (RPH3A), which interacts with the SNARE complex and regulates synaptic vesicle exocytosis and Ca(2+)-triggered neurotransmitter release, is at present unclear. In this study, we measured RPH3A and its ligand Rab3A as well as several SNARE proteins in postmortem neocortex of patients with AD, and found specific reductions of RPH3A immunoreactivity compared with aged controls. RPH3A loss correlated with dementia severity, cholinergic deafferentation, and increased β-amyloid (Aβ) concentrations. Furthermore, RPH3A expression is selectively downregulated in cultured neurons treated with Aβ25-35 peptides. Our data suggest that presynaptic SNARE dysfunction forms part of the synaptopathology of AD.