ARHGF_HUMAN
ID ARHGF_HUMAN Reviewed; 841 AA.
AC O94989; A8K6G1; Q8N449; Q9H8B4;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2009, sequence version 4.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Rho guanine nucleotide exchange factor 15;
DE AltName: Full=Ephexin-5;
DE Short=E5;
DE AltName: Full=Vsm-RhoGEF;
GN Name=ARHGEF15; Synonyms=KIAA0915;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-831.
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PRO-277 AND PRO-831.
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS PRO-277 AND
RP PRO-831.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-155; PRO-277 AND
RP PRO-831.
RC TISSUE=Lung;
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 [7]
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH EPHA4, AND
RP REGULATION.
RX PubMed=12775584; DOI=10.1161/01.res.0000079310.81429.c8;
RA Ogita H., Kunimoto S., Kamioka Y., Sawa H., Masuda M., Mochizuki N.;
RT "EphA4-mediated Rho activation via Vsm-RhoGEF expressed specifically in
RT vascular smooth muscle cells.";
RL Circ. Res. 93:23-31(2003).
RN [8]
RP VARIANT CYS-604.
RX PubMed=23647072; DOI=10.1111/epi.12201;
RA Veeramah K.R., Johnstone L., Karafet T.M., Wolf D., Sprissler R.,
RA Salogiannis J., Barth-Maron A., Greenberg M.E., Stuhlmann T., Weinert S.,
RA Jentsch T.J., Pazzi M., Restifo L.L., Talwar D., Erickson R.P.,
RA Hammer M.F.;
RT "Exome sequencing reveals new causal mutations in children with epileptic
RT encephalopathies.";
RL Epilepsia 54:1270-1281(2013).
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:12775584}.
CC -!- SUBUNIT: Interacts with EPHB2 (By similarity). Interacts with EPHA4.
CC {ECO:0000250, ECO:0000269|PubMed:12775584}.
CC -!- INTERACTION:
CC O94989; Q53EZ4: CEP55; NbExp=6; IntAct=EBI-740691, EBI-747776;
CC O94989; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-740691, EBI-739467;
CC O94989; Q13976-2: PRKG1; NbExp=3; IntAct=EBI-740691, EBI-4280187;
CC -!- SUBCELLULAR LOCATION: Cell projection, dendrite {ECO:0000250}.
CC Note=Expressed exclusively in dendrites of the developing hippocampus.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the vascular smooth muscle of coronary
CC artery. {ECO:0000269|PubMed:12775584}.
CC -!- PTM: Phosphorylated on tyrosine residues upon EFNA1 stimulation. EPHB2-
CC dependent phosphorylation at Tyr-353 triggers UBE3A-mediated
CC ubiquitination (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated; UBE3A-mediated ubiquitination and degradation by
CC the proteasome promotes EFNB1-dependent synapse formation.
CC {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74938.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB020722; BAA74938.2; ALT_INIT; mRNA.
DR EMBL; AK291626; BAF84315.1; -; mRNA.
DR EMBL; AC135178; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90060.1; -; Genomic_DNA.
DR EMBL; BC036749; AAH36749.1; -; mRNA.
DR CCDS; CCDS11139.1; -.
DR RefSeq; NP_079290.1; NM_025014.1.
DR RefSeq; NP_776089.2; NM_173728.3.
DR AlphaFoldDB; O94989; -.
DR SMR; O94989; -.
DR BioGRID; 116563; 44.
DR IntAct; O94989; 8.
DR STRING; 9606.ENSP00000355026; -.
DR CarbonylDB; O94989; -.
DR iPTMnet; O94989; -.
DR PhosphoSitePlus; O94989; -.
DR BioMuta; ARHGEF15; -.
DR MassIVE; O94989; -.
DR PaxDb; O94989; -.
DR PeptideAtlas; O94989; -.
DR PRIDE; O94989; -.
DR ProteomicsDB; 50618; -.
DR Antibodypedia; 24648; 33 antibodies from 14 providers.
DR DNASU; 22899; -.
DR Ensembl; ENST00000361926.8; ENSP00000355026.3; ENSG00000198844.12.
DR Ensembl; ENST00000421050.2; ENSP00000412505.1; ENSG00000198844.12.
DR GeneID; 22899; -.
DR KEGG; hsa:22899; -.
DR MANE-Select; ENST00000361926.8; ENSP00000355026.3; NM_173728.4; NP_776089.2.
DR UCSC; uc002glc.4; human.
DR CTD; 22899; -.
DR DisGeNET; 22899; -.
DR GeneCards; ARHGEF15; -.
DR HGNC; HGNC:15590; ARHGEF15.
DR HPA; ENSG00000198844; Tissue enhanced (adipose tissue, breast).
DR MIM; 608504; gene.
DR neXtProt; NX_O94989; -.
DR OpenTargets; ENSG00000198844; -.
DR PharmGKB; PA24970; -.
DR VEuPathDB; HostDB:ENSG00000198844; -.
DR eggNOG; KOG3523; Eukaryota.
DR GeneTree; ENSGT01030000234571; -.
DR HOGENOM; CLU_012820_3_0_1; -.
DR InParanoid; O94989; -.
DR OMA; FEWGAED; -.
DR OrthoDB; 1176939at2759; -.
DR PhylomeDB; O94989; -.
DR TreeFam; TF316357; -.
DR PathwayCommons; O94989; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR SignaLink; O94989; -.
DR SIGNOR; O94989; -.
DR BioGRID-ORCS; 22899; 19 hits in 1066 CRISPR screens.
DR ChiTaRS; ARHGEF15; human.
DR GenomeRNAi; 22899; -.
DR Pharos; O94989; Tbio.
DR PRO; PR:O94989; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O94989; protein.
DR Bgee; ENSG00000198844; Expressed in apex of heart and 125 other tissues.
DR ExpressionAtlas; O94989; baseline and differential.
DR Genevisible; O94989; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; ISS: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; ISS:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISS:UniProtKB.
DR GO; GO:0050790; P:regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0061299; P:retina vasculature morphogenesis in camera-type eye; IEA:Ensembl.
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 Cell projection; GTPase activation; Guanine-nucleotide releasing factor;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..841
FT /note="Rho guanine nucleotide exchange factor 15"
FT /id="PRO_0000080932"
FT DOMAIN 417..601
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT REGION 1..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 239..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 279..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 765..793
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..128
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 777..791
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5FWH6"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5FWH6"
FT MOD_RES 353
FT /note="Phosphotyrosine; by EPHB2"
FT /evidence="ECO:0000250|UniProtKB:Q5FWH6"
FT VARIANT 73
FT /note="P -> S (in dbSNP:rs9890841)"
FT /id="VAR_057189"
FT VARIANT 155
FT /note="G -> V (in dbSNP:rs17857129)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_054215"
FT VARIANT 277
FT /note="L -> P (in dbSNP:rs871841)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5"
FT /id="VAR_054216"
FT VARIANT 604
FT /note="R -> C (found in a child with sporadic epilepsy;
FT unknown pathological significance; dbSNP:rs587777166)"
FT /evidence="ECO:0000269|PubMed:23647072"
FT /id="VAR_077835"
FT VARIANT 831
FT /note="S -> P (in dbSNP:rs3744647)"
FT /evidence="ECO:0000269|PubMed:10048485,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.5"
FT /id="VAR_054217"
SQ SEQUENCE 841 AA; 91940 MW; 40D430ACF777002F CRC64;
MSAQSLPAAT PPTQKPPRII RPRPPSRSRA AQSPGPPHNG SSPQELPRNS NDAPTPMCTP
IFWEPPAASL KPPALLPPSA SRASLDSQTS PDSPSSTPTP SPVSRRSASP EPAPRSPVPP
PKPSGSPCTP LLPMAGVLAQ NGSASAPGTV RRLAGRFEGG AEGRAQDADA PEPGLQARAD
VNGEREAPLT GSGSQENGAP DAGLACPPCC PCVCHTTRPG LELRWVPVGG YEEVPRVPRR
ASPLRTSRSR PHPPSIGHPA VVLTSYRSTA ERKLLPLLKP PKPTRVRQDA TIFGDPPQPD
LDLLSEDGIQ TGDSPDEAPQ NTPPATVEGR EEEGLEVLKE QNWELPLQDE PLYQTYRAAV
LSEELWGVGE DGSPSPANAG DAPTFPRPPG PRNTLWQELP AVQASGLLDT LSPQERRMQE
SLFEVVTSEA SYLRSLRLLT DTFVLSQALR DTLTPRDHHT LFSNVQRVQG VSERFLATLL
SRVRSSPHIS DLCDVVHAHA VGPFSVYVDY VRNQQYQEET YSRLMDTNVR FSAELRRLQS
LPKCERLPLP SFLLLPFQRI TRLRMLLQNI LRQTEEGSSR QENAQKALGA VSKIIERCSA
EVGRMKQTEE LIRLTQRLRF HKVKALPLVS WSRRLEFQGE LTELGCRRGG VLFASRPRFT
PLCLLLFSDL LLITQPKSGQ RLQVLDYAHR SLVQAQQVPD PSGPPTFRLS LLSNHQGRPT
HRLLQASSLS DMQRWLGAFP TPGPLPCSPD TIYEDCDCSQ ELCSESSAPA KTEGRSLESR
AAPKHLHKTP EGWLKGLPGA FPAQLVCEVT GEHERRRHLR QNQRLLEAVG SSSGTPNAPP
P
