ARHGF_MOUSE
ID ARHGF_MOUSE Reviewed; 849 AA.
AC Q5FWH6; Q14B44; Q69ZV7;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Rho guanine nucleotide exchange factor 15;
DE AltName: Full=Ephexin-5;
DE Short=E5;
GN Name=Arhgef15; Synonyms=Kiaa0915;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 412-849 (ISOFORM 1).
RC TISSUE=Pancreatic islet;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [4]
RP IDENTIFICATION.
RX PubMed=15848799; DOI=10.1016/j.neuron.2005.01.030;
RA Sahin M., Greer P.L., Lin M.Z., Poucher H., Eberhart J., Schmidt S.,
RA Wright T.M., Shamah S.M., O'connell S., Cowan C.W., Hu L., Goldberg J.L.,
RA Debant A., Corfas G., Krull C.E., Greenberg M.E.;
RT "Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone
RT collapse.";
RL Neuron 46:191-204(2005).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-107 AND SER-109, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, INTERACTION WITH EPHB2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT TYR-361,
RP UBIQUITINATION, AND MUTAGENESIS OF TYR-361; 547-GLU-SER-548;
RP 554-ARG-LEU-555; LEU-562 AND 566-GLU-ARG-567.
RX PubMed=21029865; DOI=10.1016/j.cell.2010.09.038;
RA Margolis S.S., Salogiannis J., Lipton D.M., Mandel-Brehm C., Wills Z.P.,
RA Mardinly A.R., Hu L., Greer P.L., Bikoff J.B., Ho H.Y., Soskis M.J.,
RA Sahin M., Greenberg M.E.;
RT "EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a
RT developmental brake on excitatory synapse formation.";
RL Cell 143:442-455(2010).
CC -!- FUNCTION: Specific GEF for RhoA activation. Does not activate RAC1 or
CC CDC42. Regulates vascular smooth muscle contractility. Negatively
CC regulates excitatory synapse development by suppressing the synapse-
CC promoting activity of EPHB2. {ECO:0000269|PubMed:21029865}.
CC -!- SUBUNIT: Interacts with EPHA4 (By similarity). Interacts with EPHB2.
CC {ECO:0000250, ECO:0000269|PubMed:21029865}.
CC -!- INTERACTION:
CC Q5FWH6-2; P54763: Ephb2; NbExp=3; IntAct=EBI-2943608, EBI-537711;
CC -!- SUBCELLULAR LOCATION: Cell projection, dendrite
CC {ECO:0000269|PubMed:21029865}. Note=Expressed exclusively in dendrites
CC of the developing hippocampus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5FWH6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5FWH6-2; Sequence=VSP_036209, VSP_036210;
CC -!- TISSUE SPECIFICITY: At P12, expressed is detected in the CA1 region and
CC the dentate gyrus of the hippocampus. {ECO:0000269|PubMed:21029865}.
CC -!- DEVELOPMENTAL STAGE: Highest levels in hippocampus are found at
CC postnatal day 3 prior to maximal synapse formation and decrease as
CC synapse formation peaks in the postnatal period (at protein level).
CC {ECO:0000269|PubMed:21029865}.
CC -!- PTM: Phosphorylated on tyrosine residues upon EFNA1 stimulation. EPHB2-
CC dependent phosphorylation at Tyr-361 triggers UBE3A-mediated
CC ubiquitination. {ECO:0000269|PubMed:21029865}.
CC -!- PTM: Ubiquitinated; UBE3A-mediated ubiquitination and degradation by
CC the proteasome promotes EFNB1-dependent synapse formation.
CC {ECO:0000269|PubMed:21029865}.
CC -!- DISRUPTION PHENOTYPE: Significant decrease in RHOA activation in brain
CC extracts. {ECO:0000269|PubMed:21029865}.
CC -!- MISCELLANEOUS: In a mouse model of Angelman syndrome where Ube3a levels
CC are reduced, levels of Arhgef15 are significantly increased and
CC ubiquitination is reduced compared to wild-type litter mates.
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DR EMBL; AL603662; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC089365; AAH89365.1; -; mRNA.
DR EMBL; BC116343; AAI16344.1; -; mRNA.
DR EMBL; BC116344; AAI16345.1; -; mRNA.
DR EMBL; AK173061; BAD32339.1; -; mRNA.
DR CCDS; CCDS24873.1; -. [Q5FWH6-1]
DR RefSeq; NP_808234.2; NM_177566.3. [Q5FWH6-1]
DR RefSeq; XP_006533727.1; XM_006533664.2. [Q5FWH6-1]
DR RefSeq; XP_006533729.1; XM_006533666.2.
DR AlphaFoldDB; Q5FWH6; -.
DR SMR; Q5FWH6; -.
DR BioGRID; 243010; 2.
DR IntAct; Q5FWH6; 1.
DR STRING; 10090.ENSMUSP00000104311; -.
DR iPTMnet; Q5FWH6; -.
DR PhosphoSitePlus; Q5FWH6; -.
DR MaxQB; Q5FWH6; -.
DR PaxDb; Q5FWH6; -.
DR PRIDE; Q5FWH6; -.
DR ProteomicsDB; 273930; -. [Q5FWH6-1]
DR ProteomicsDB; 273931; -. [Q5FWH6-2]
DR Antibodypedia; 24648; 33 antibodies from 14 providers.
DR DNASU; 442801; -.
DR Ensembl; ENSMUST00000065040; ENSMUSP00000067684; ENSMUSG00000052921. [Q5FWH6-1]
DR Ensembl; ENSMUST00000108671; ENSMUSP00000104311; ENSMUSG00000052921. [Q5FWH6-1]
DR GeneID; 442801; -.
DR KEGG; mmu:442801; -.
DR UCSC; uc007jol.1; mouse. [Q5FWH6-1]
DR UCSC; uc007jom.1; mouse. [Q5FWH6-2]
DR CTD; 22899; -.
DR MGI; MGI:3045246; Arhgef15.
DR VEuPathDB; HostDB:ENSMUSG00000052921; -.
DR eggNOG; KOG3523; Eukaryota.
DR GeneTree; ENSGT01030000234571; -.
DR HOGENOM; CLU_012820_3_0_1; -.
DR InParanoid; Q5FWH6; -.
DR OMA; FEWGAED; -.
DR OrthoDB; 1176939at2759; -.
DR PhylomeDB; Q5FWH6; -.
DR TreeFam; TF316357; -.
DR Reactome; R-MMU-193648; NRAGE signals death through JNK.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR BioGRID-ORCS; 442801; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Arhgef15; mouse.
DR PRO; PR:Q5FWH6; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q5FWH6; protein.
DR Bgee; ENSMUSG00000052921; Expressed in superior cervical ganglion and 185 other tissues.
DR Genevisible; Q5FWH6; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:2000297; P:negative regulation of synapse maturation; IMP:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISS:UniProtKB.
DR GO; GO:0050790; P:regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0061299; P:retina vasculature morphogenesis in camera-type eye; IMP:MGI.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR PROSITE; PS50010; DH_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; GTPase activation;
KW Guanine-nucleotide releasing factor; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..849
FT /note="Rho guanine nucleotide exchange factor 15"
FT /id="PRO_0000360997"
FT DOMAIN 425..609
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT REGION 1..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 158..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 771..803
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 819..849
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 80..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..130
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 167..182
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 785..799
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 361
FT /note="Phosphotyrosine; by EPHB2"
FT /evidence="ECO:0000305|PubMed:21029865"
FT VAR_SEQ 800..803
FT /note="GWLK -> EAEG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036209"
FT VAR_SEQ 804..849
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036210"
FT MUTAGEN 361
FT /note="Y->A: Abolishes phosphorylation by EPHB2."
FT /evidence="ECO:0000269|PubMed:21029865"
FT MUTAGEN 547..548
FT /note="QS->AA: No effect on RHOA activation; when
FT associated with 554-A-A-555."
FT /evidence="ECO:0000269|PubMed:21029865"
FT MUTAGEN 554..555
FT /note="RL->AA: No effect on RHOA activation; when
FT associated with 547-A-A-548."
FT /evidence="ECO:0000269|PubMed:21029865"
FT MUTAGEN 562
FT /note="L->A: Impairs RHOA activation; when associated with
FT 566-A-A-567."
FT /evidence="ECO:0000269|PubMed:21029865"
FT MUTAGEN 566..567
FT /note="QR->AA: Impairs RHOA activation; when associated
FT with A-562."
FT /evidence="ECO:0000269|PubMed:21029865"
SQ SEQUENCE 849 AA; 92946 MW; 3AA41B3BCD401CFE CRC64;
MSAQSLPAAT PPTLKPPRII RPRPPSRHRA PHSPGPLHNG SSPKALPQIS NDASASVCTS
IFWEPPTASL KPPALLPPSV SRTSLDSQTS PDSPSSTPSP SPVSRRSISP EPAPCSPVPP
PKPSGSSRTP LPSGPTPLQD GSASAPGTVR RLAGKFEWGA EGKAQSSDSL ERCSQGSTEV
NGEKETPEAA LSGNGSQENG TPDAALACPP CCPCVCHVAK PGLELRWVPV GSSEDILRIP
CRASPLRASR SRINPPVISH PPVVLTSYRS TAERKLLPPL KPPKPTKVRQ DISTSEELPQ
PDLKLPSEDG IQTATKAWEG DRPEGAPLNA PPVALEGREE EGLDGLKGLQ WELPLQDEPL
YQTYRAAVLS EELWGVGEDG GPSPANPGEA PTFSRLPGPR NTLWQELPAV RGSGLLESLS
PQERRMQESL FEVVTSEASY LRSLRLLTDT FVLSQALRDT LTPRDHHTLF SNVQRVQSVS
ERFLGTLLSR VRSSPHITDL CDVVHAHAVG PFFVYVDYVR NQQYQEETYS RLMDTNVRFS
AELRRLQSLP KCERLPLPSF LLLPFQRITR LRMLLQNILS QTEEGSSRQE NAQKALGAVS
KIIERCSAEV GRMKQTEELI RLTQRLRFHK VKALPLVSWS RRLELQGELT ELGCRRGGVL
FTSRPRFTPL CLLLFSDLLL ITQPKSGQRL QVLDYAHRSL VQAQQVPDPS GPPTFRLSLL
SNHQGRPTHR LLQAASLSDM QRWLGAFPTP GPLPCSPDTI YEDCECSQEL CSEPSTPSKT
EGQSLESKAP RKHLHKNPEG WLKGLPGAFP AQLVCEVTGE HERRKHLRQH QKLLEAVGPS
SGTPDTPQP
