RUFY3_RAT
ID RUFY3_RAT Reviewed; 469 AA.
AC Q5FVJ0; A5HLX7; A5JUR6;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Protein RUFY3 {ECO:0000305};
DE AltName: Full=RUN and FYVE domain-containing protein 3 {ECO:0000312|RGD:1565242};
DE AltName: Full=Rap2-interacting protein x {ECO:0000250|UniProtKB:Q9D394};
DE Short=RIPx {ECO:0000250|UniProtKB:Q9D394};
DE AltName: Full=Single axon-regulated protein {ECO:0000303|PubMed:17439943};
DE Short=Singar {ECO:0000303|PubMed:17439943};
GN Name=Rufy3 {ECO:0000312|RGD:1565242};
GN Synonyms=Ripx {ECO:0000250|UniProtKB:Q9D394};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 82-92;
RP 139-151; 265-284; 306-328; 348-356 AND 403-411, FUNCTION, SUBCELLULAR
RP LOCATION, PHOSPHORYLATION (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, INTERACTION WITH PIK3CA AND PIK3R1, INDUCTION, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=17439943; DOI=10.1074/jbc.m700770200;
RA Mori T., Wada T., Suzuki T., Kubota Y., Inagaki N.;
RT "Singar1, a novel RUN domain-containing protein, suppresses formation of
RT surplus axons for neuronal polarity.";
RL J. Biol. Chem. 282:19884-19893(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5; THR-12; SER-49 AND THR-51,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Plays a role in the generation of neuronal polarity formation
CC and axon growth (PubMed:17439943). Implicated in the formation of a
CC single axon by developing neurons (PubMed:17439943). May inhibit the
CC formation of additional axons by inhibition of PI3K in minor neuronal
CC processes (PubMed:17439943). Plays a role in the formation of F-actin-
CC enriched protrusive structures at the cell periphery (By similarity).
CC Plays a role in cytoskeletal organization by regulating the subcellular
CC localization of FSCN1 and DBN1 at axonal growth cones (By similarity).
CC Promotes gastric cancer cell migration and invasion in a PAK1-dependent
CC manner (By similarity). {ECO:0000250|UniProtKB:Q7L099,
CC ECO:0000250|UniProtKB:Q9D394, ECO:0000269|PubMed:17439943}.
CC -!- SUBUNIT: Interacts with PIK3CA and PIK3R1 (PubMed:17439943). Interacts
CC with PAK1 (By similarity). Interacts (via C-terminus) with Ras-related
CC Rab-5 proteins (By similarity). Interacts (via C-terminus) with Ras-
CC related Rap-2 proteins (By similarity). Interacts (via N-terminus) with
CC FSCN1; this interaction induces neuron axon development (By
CC similarity). Interacts with DBN1 (By similarity).
CC {ECO:0000250|UniProtKB:Q7L099, ECO:0000250|UniProtKB:Q9D394,
CC ECO:0000269|PubMed:17439943}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q7L099}.
CC Endomembrane system {ECO:0000250|UniProtKB:Q7L099}. Cell projection,
CC invadopodium {ECO:0000250|UniProtKB:Q7L099}. Perikaryon
CC {ECO:0000269|PubMed:17439943}. Cell projection
CC {ECO:0000269|PubMed:17439943}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q9D394}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:Q9D394}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q9D394}. Note=Localized in F-actin-enriched
CC filopodia and lamellipodia at axonal growth cones (PubMed:17439943).
CC Colocalizes with PAK1, F-actin, myosins and integrins in invadopodia at
CC the cell periphery (By similarity). Colocalized with Ras-related Rab-5
CC proteins in cytoplasmic vesicles (By similarity). Accumulates in axon
CC growth cones in a F-actin-dependent manner (By similarity). Colocalized
CC with FSCN1 and F-actin at filipodia and lamellipodia of axonal growth
CC cones (By similarity). Colocalized with DBN1 and F-actin at
CC transitional domain of the axonal growth cone (By similarity).
CC {ECO:0000250|UniProtKB:Q7L099, ECO:0000250|UniProtKB:Q9D394,
CC ECO:0000269|PubMed:17439943}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Singar1 {ECO:0000303|PubMed:17439943};
CC IsoId=Q5FVJ0-1; Sequence=Displayed;
CC Name=2; Synonyms=Singar2 {ECO:0000303|PubMed:17439943};
CC IsoId=Q5FVJ0-2; Sequence=VSP_026950;
CC -!- TISSUE SPECIFICITY: Expressed in brain (at protein level)
CC (PubMed:17439943). {ECO:0000269|PubMed:17439943}.
CC -!- DEVELOPMENTAL STAGE: Low level expression in brain up to E15, higher
CC level expression from E18 to P14 with highest level around P4
CC (PubMed:17439943). Low level expression in adult brain
CC (PubMed:17439943). Low level expression in hippocampal neurons up to
CC stage 2 in culture (PubMed:17439943). Higher level from stage 3 with
CC highest level of isoform 1 on day 7 in vitro (DIV7) (PubMed:17439943).
CC Phosphorylated isoform 1 from DIV7 with high level up to DIV28, isoform
CC 2 detectable from stage 3 to DIV7 (PubMed:17439943).
CC {ECO:0000269|PubMed:17439943}.
CC -!- INDUCTION: Up-regulated during neuronal polarization (PubMed:17439943).
CC {ECO:0000269|PubMed:17439943}.
CC -!- PTM: Isoform 1 is partially phosphorylated (PubMed:17439943).
CC Phosphorylated by PAK1 (By similarity). {ECO:0000250|UniProtKB:Q7L099,
CC ECO:0000269|PubMed:17439943}.
CC -!- MISCELLANEOUS: Hippocampal neurons with reduced levels of RUFY3 show an
CC increase in formation of additional axons (PubMed:17439943). This
CC effect is suppressed in the presence of the PI3K inhibitor LY294002 and
CC enhanced by overexpression of SHTN1 (PubMed:17439943). Overexpression
CC of RUFY3 suppresses additional axons formed upon overexpression of
CC SHTN1 (PubMed:17439943). {ECO:0000269|PubMed:17439943}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EF538802; ABP99060.1; -; mRNA.
DR EMBL; EF577045; ABQ45403.1; -; mRNA.
DR EMBL; BC089952; AAH89952.1; -; mRNA.
DR RefSeq; NP_001020298.1; NM_001025127.1. [Q5FVJ0-1]
DR RefSeq; XP_008768270.1; XM_008770048.2. [Q5FVJ0-2]
DR AlphaFoldDB; Q5FVJ0; -.
DR SMR; Q5FVJ0; -.
DR BioGRID; 262306; 2.
DR STRING; 10116.ENSRNOP00000020608; -.
DR iPTMnet; Q5FVJ0; -.
DR PhosphoSitePlus; Q5FVJ0; -.
DR PaxDb; Q5FVJ0; -.
DR PRIDE; Q5FVJ0; -.
DR ABCD; Q5FVJ0; 3 sequenced antibodies.
DR GeneID; 360921; -.
DR KEGG; rno:360921; -.
DR UCSC; RGD:1565242; rat. [Q5FVJ0-1]
DR CTD; 22902; -.
DR RGD; 1565242; Rufy3.
DR VEuPathDB; HostDB:ENSRNOG00000003428; -.
DR eggNOG; KOG4381; Eukaryota.
DR HOGENOM; CLU_014576_0_0_1; -.
DR InParanoid; Q5FVJ0; -.
DR OrthoDB; 753155at2759; -.
DR PRO; PR:Q5FVJ0; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000003428; Expressed in cerebellum and 20 other tissues.
DR ExpressionAtlas; Q5FVJ0; baseline and differential.
DR Genevisible; Q5FVJ0; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0030175; C:filopodium; IDA:HGNC-UCL.
DR GO; GO:0030426; C:growth cone; IDA:HGNC-UCL.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0050771; P:negative regulation of axonogenesis; IDA:HGNC-UCL.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0045773; P:positive regulation of axon extension; ISS:UniProtKB.
DR GO; GO:0050772; P:positive regulation of axonogenesis; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0090316; P:positive regulation of intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; ISO:RGD.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; ISS:UniProtKB.
DR Gene3D; 1.20.58.900; -; 1.
DR InterPro; IPR004012; Run_dom.
DR InterPro; IPR037213; Run_dom_sf.
DR Pfam; PF02759; RUN; 1.
DR SMART; SM00593; RUN; 1.
DR SUPFAM; SSF140741; SSF140741; 1.
DR PROSITE; PS50826; RUN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell projection; Coiled coil;
KW Cytoplasm; Developmental protein; Differentiation;
KW Direct protein sequencing; Membrane; Neurogenesis; Oncogene;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..469
FT /note="Protein RUFY3"
FT /id="PRO_0000245836"
FT DOMAIN 95..227
FT /note="RUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00178"
FT COILED 267..464
FT /evidence="ECO:0000255"
FT MOD_RES 5
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 12
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D394"
FT MOD_RES 49
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 51
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 60
FT /note="D -> DSWEDLTDLVEQVRADPED (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17439943"
FT /id="VSP_026950"
SQ SEQUENCE 469 AA; 52907 MW; 98580BE52F52BC04 CRC64;
MSALTPPTDM PTPTTDKITQ AAMETIYLCK FRVSMDGEWL CLRELDDISL TPDPEPTHED
PNYLMANERM NLMNMAKLSI KGLIESALNL GRTLDSDYAP LQQFFVVMEH CLKHGLKAKK
TFLGQNKSFW GPLELVEKLV PEAAEITASV KDLPGLKTPV GRGRAWLRLA LMQKKLSEYM
KALINKKELL SEFYEANALM MEEEGAIIAG LLVGLNVIDA NFCMKGEDLD SQVGVIDFSM
YLKDGNSSKG SEGDGQITAI LDQKNYVEEL NRHLNATVNN LQAKVDALEK SNTKLTEELA
VANNRIITLQ EEMERVKEES SYLLESNRKG PKQDRTAEGQ ALSEARKHLK EETQLRLDVE
KELELQISMR QEMELAMKML EKDVCEKQDA LVSLRQQLDD LRALKHELAF KLQSSDLGVK
QKSELNSRLE EKTNQMAATI KQLEQSEKDL VKQAKTLNSA ANKLIPKHH
