RP3A_BOVIN
ID RP3A_BOVIN Reviewed; 704 AA.
AC Q06846;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Rabphilin-3A;
DE AltName: Full=Exophilin-1;
GN Name=RPH3A;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Brain;
RX PubMed=8384302; DOI=10.1128/mcb.13.4.2061-2068.1993;
RA Shirataki H., Kaibuchi K., Sakoda T., Kishida S., Yamaguchi T., Wada K.,
RA Miyazaki M., Takai Y.;
RT "Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-
RT binding protein related to synaptotagmin.";
RL Mol. Cell. Biol. 13:2061-2068(1993).
RN [2]
RP DOMAINS.
RX PubMed=8262955; DOI=10.1016/s0021-9258(19)74232-x;
RA Yamaguchi T., Shirataki H., Kishida S., Miyazaki M., Nishikawa J., Wada K.,
RA Numata S., Kaibuchi K., Takai Y.;
RT "Two functionally different domains of rabphilin-3A, Rab3A p25/smg p25A-
RT binding and phospholipid- and Ca(2+)-binding domains.";
RL J. Biol. Chem. 268:27164-27170(1993).
RN [3]
RP FUNCTION.
RX PubMed=9450942; DOI=10.1085/jgp.111.2.243;
RA Burns M.E., Sasaki T., Takai Y., Augustine G.J.;
RT "Rabphilin-3A: a multifunctional regulator of synaptic vesicle traffic.";
RL J. Gen. Physiol. 111:243-255(1998).
CC -!- FUNCTION: Plays an essential role in docking and fusion steps of
CC regulated exocytosis (By similarity). At the presynaptic level, RPH3A
CC is recruited by RAB3A to the synaptic vesicle membrane in a GTP-
CC dependent manner where it modulates synaptic vesicle trafficking and
CC calcium-triggered neurotransmitter release (PubMed:9450942). In the
CC post-synaptic compartment, forms a ternary complex with GRIN2A and DLG4
CC and regulates NMDA receptor stability. Also plays a role in the
CC exocytosis of arginine vasopressin hormone (By similarity).
CC {ECO:0000250|UniProtKB:P47709, ECO:0000269|PubMed:9450942}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with RAB3B, RAB3C, RAB3D, RAB8A, RAB27A and RAB27B
CC (By similarity). Interacts with RAB3A; this interaction recruits RPH3A
CC to synaptic vesicules (By similarity). Interacts (via C2B domain) with
CC SNAP25 (By similarity). Interacts with deubiquitinating enzyme CAND1;
CC this interaction results in the deubiquitination of RPH3A (By
CC similarity). Interacts with GRIN2A and DLG4; this ternary complex
CC regulates NMDA receptor composition at postsynaptic membranes (By
CC similarity). Interacts with SNCA (By similarity).
CC {ECO:0000250|UniProtKB:P47708, ECO:0000250|UniProtKB:P47709,
CC ECO:0000250|UniProtKB:Q9Y2J0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250|UniProtKB:P47709}. Cell projection,
CC dendritic spine {ECO:0000250|UniProtKB:P47709}. Postsynaptic cell
CC membrane {ECO:0000250|UniProtKB:P47709}. Membrane
CC {ECO:0000250|UniProtKB:P47709}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P47709}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in brain.
CC -!- DOMAIN: Binds calcium via the C2 domains. The calcium-bound C2 domains
CC mediate interactions with phospholipid bilayers (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Deubiquitinated by CAND1 to prevent its
CC degradation. {ECO:0000250|UniProtKB:P47709}.
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DR EMBL; D13613; BAA02780.1; -; mRNA.
DR PIR; A48097; A48097.
DR RefSeq; NP_776879.1; NM_174454.3.
DR AlphaFoldDB; Q06846; -.
DR SMR; Q06846; -.
DR STRING; 9913.ENSBTAP00000005564; -.
DR PaxDb; Q06846; -.
DR PRIDE; Q06846; -.
DR GeneID; 282044; -.
DR KEGG; bta:282044; -.
DR CTD; 22895; -.
DR eggNOG; KOG1013; Eukaryota.
DR InParanoid; Q06846; -.
DR OrthoDB; 374694at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0098850; C:extrinsic component of synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0006887; P:exocytosis; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IBA:GO_Central.
DR GO; GO:0061669; P:spontaneous neurotransmitter secretion; IBA:GO_Central.
DR Gene3D; 2.60.40.150; -; 2.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR041282; FYVE_2.
DR InterPro; IPR010911; Rab_BD.
DR InterPro; IPR043566; Rabphilin/DOC2/Noc2.
DR InterPro; IPR028698; RPH3A.
DR InterPro; IPR001565; Synaptotagmin.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR45729; PTHR45729; 1.
DR PANTHER; PTHR45729:SF3; PTHR45729:SF3; 1.
DR Pfam; PF00168; C2; 2.
DR Pfam; PF02318; FYVE_2; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR PRINTS; PR00399; SYNAPTOTAGMN.
DR SMART; SM00239; C2; 2.
DR SUPFAM; SSF49562; SSF49562; 2.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50004; C2; 2.
DR PROSITE; PS50916; RABBD; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Direct protein sequencing; Lipid-binding; Membrane; Metal-binding;
KW Methylation; Phosphoprotein; Postsynaptic cell membrane; Protein transport;
KW Reference proteome; Repeat; Synapse; Transport; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..704
FT /note="Rabphilin-3A"
FT /id="PRO_0000190226"
FT DOMAIN 44..161
FT /note="RabBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00234"
FT DOMAIN 402..524
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 560..693
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT ZN_FING 92..149
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 1..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 167..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..40
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 183..199
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 201..217
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..286
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 287..309
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 123
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 432
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 439
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 494
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 494
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 495
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 496
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 496
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 502
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT BINDING 549
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT BINDING 591
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT BINDING 591
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT BINDING 597
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT BINDING 651
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT BINDING 651
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT BINDING 652
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT BINDING 653
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT BINDING 653
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT BINDING 659
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT MOD_RES 229
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47708"
FT MOD_RES 702
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47709"
FT MOD_RES 703
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47709"
SQ SEQUENCE 704 AA; 77978 MW; 1324D048F5F8FFD4 CRC64;
MTDTVFSSSS SRWMCPSDRP LQSNDKEQLQ TGWSVHPSGQ PDRQRKQEEL TDEEKEIINR
VIARAEKMEE MEQERIGRLV DRLENMRKNV AGDGVNRCIL CGEQLGMLGS ACVVCEDCKK
NVCTKCGVET SNNRPHPVWL CKICIEQREV WKRSGAWFFK GFPKQVLPQP MPIKKNKPQQ
PVSEPVPAAP EPATPEPKHP ARAPTRGDTE DRRGPGQKTG PDMTSAPGRG SYGPPVRRAS
EARMSSSGRD SDSWDQGHGM AAGDPSQSPA GLRRANSVQA SRPAPASMQS PAPPQPGQPG
PPGGSRPSPG PTGRFPDQRP EVAPSDPDYT GAAAQPREER TGGIGGYSAA GTREDRAGHP
PGSYTQASAA APQPVVASAR QPPPPEEDEE EANSYDSDEA TTLGALEFSL LYDQDNSSLH
CTIIKAKGLK PMDSNGLADP YVKLHLLPGA SKSNKLRTKT LRNTRNPIWN ETLVYHGITD
EDMQRKTLRI SVCDEDKFGH NEFIGETRFS LKKLKPNQRK NFNICLERVI PMKRAGTTGS
ARGMALYEEE QVERIGDIEE RGKILVSLMY STQQGGLIVG IIRCVHLAAM DANGYSDPFV
KLWLKPDMGK KAKHKTQIKK KTLNPEFNEE FFYDIKHSDL AKKSLDISVW DYDIGKSNDY
IGGCQLGISA KGERLKHWYE CLKNKDKKIE RWHQLQNENH VSSD
