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Protein

Rho guanine nucleotide exchange factor 15

Gene

ARHGEF15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Specific GEF for RhoA activation. Does not activate RAC1 or CDC42. Regulates vascular smooth muscle contractility. Negatively regulates excitatory synapse development by suppressing the synapse-promoting activity of EPHB2.1 Publication

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB-KW
  • Rho guanyl-nucleotide exchange factor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

GTPase activation, Guanine-nucleotide releasing factor

Enzyme and pathway databases

SignaLinkiO94989.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 15
Alternative name(s):
Ephexin-5
Short name:
E5
Vsm-RhoGEF
Gene namesi
Name:ARHGEF15
Synonyms:KIAA0915
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:15590. ARHGEF15.

Subcellular locationi

  • Cell projectiondendrite By similarity

  • Note: Expressed exclusively in dendrites of the developing hippocampus.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell projection

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24970.

Polymorphism and mutation databases

BioMutaiARHGEF15.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 841841Rho guanine nucleotide exchange factor 15PRO_0000080932Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei107 – 1071PhosphoserineBy similarity
Modified residuei109 – 1091PhosphoserineBy similarity
Modified residuei353 – 3531Phosphotyrosine; by EPHB2By similarity

Post-translational modificationi

Phosphorylated on tyrosine residues upon EFNA1 stimulation. EPHB2-dependent phosphorylation at Tyr-353 triggers UBE3A-mediated ubiquitination (By similarity).By similarity
Ubiquitinated; UBE3A-mediated ubiquitination and degradation by the proteasome promotes EFNB1-dependent synapse formation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO94989.
PeptideAtlasiO94989.
PRIDEiO94989.

PTM databases

iPTMnetiO94989.
PhosphoSiteiO94989.

Expressioni

Tissue specificityi

Expressed in the vascular smooth muscle of coronary artery.1 Publication

Gene expression databases

BgeeiO94989.
CleanExiHS_ARHGEF15.
ExpressionAtlasiO94989. baseline and differential.
GenevisibleiO94989. HS.

Organism-specific databases

HPAiHPA044443.

Interactioni

Subunit structurei

Interacts with EPHB2 (By similarity). Interacts with EPHA4.By similarity1 Publication

Protein-protein interaction databases

BioGridi116563. 8 interactions.
IntActiO94989. 2 interactions.
MINTiMINT-1454033.
STRINGi9606.ENSP00000355026.

Structurei

3D structure databases

ProteinModelPortaliO94989.
SMRiO94989. Positions 388-739.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini417 – 601185DHPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi7 – 133127Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3523. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00550000074493.
HOGENOMiHOG000034047.
HOVERGENiHBG103361.
InParanoidiO94989.
OMAiPPTFRLS.
OrthoDBiEOG7XWPN0.
PhylomeDBiO94989.
TreeFamiTF316357.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
[Graphical view]
PfamiPF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O94989-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAQSLPAAT PPTQKPPRII RPRPPSRSRA AQSPGPPHNG SSPQELPRNS
60 70 80 90 100
NDAPTPMCTP IFWEPPAASL KPPALLPPSA SRASLDSQTS PDSPSSTPTP
110 120 130 140 150
SPVSRRSASP EPAPRSPVPP PKPSGSPCTP LLPMAGVLAQ NGSASAPGTV
160 170 180 190 200
RRLAGRFEGG AEGRAQDADA PEPGLQARAD VNGEREAPLT GSGSQENGAP
210 220 230 240 250
DAGLACPPCC PCVCHTTRPG LELRWVPVGG YEEVPRVPRR ASPLRTSRSR
260 270 280 290 300
PHPPSIGHPA VVLTSYRSTA ERKLLPLLKP PKPTRVRQDA TIFGDPPQPD
310 320 330 340 350
LDLLSEDGIQ TGDSPDEAPQ NTPPATVEGR EEEGLEVLKE QNWELPLQDE
360 370 380 390 400
PLYQTYRAAV LSEELWGVGE DGSPSPANAG DAPTFPRPPG PRNTLWQELP
410 420 430 440 450
AVQASGLLDT LSPQERRMQE SLFEVVTSEA SYLRSLRLLT DTFVLSQALR
460 470 480 490 500
DTLTPRDHHT LFSNVQRVQG VSERFLATLL SRVRSSPHIS DLCDVVHAHA
510 520 530 540 550
VGPFSVYVDY VRNQQYQEET YSRLMDTNVR FSAELRRLQS LPKCERLPLP
560 570 580 590 600
SFLLLPFQRI TRLRMLLQNI LRQTEEGSSR QENAQKALGA VSKIIERCSA
610 620 630 640 650
EVGRMKQTEE LIRLTQRLRF HKVKALPLVS WSRRLEFQGE LTELGCRRGG
660 670 680 690 700
VLFASRPRFT PLCLLLFSDL LLITQPKSGQ RLQVLDYAHR SLVQAQQVPD
710 720 730 740 750
PSGPPTFRLS LLSNHQGRPT HRLLQASSLS DMQRWLGAFP TPGPLPCSPD
760 770 780 790 800
TIYEDCDCSQ ELCSESSAPA KTEGRSLESR AAPKHLHKTP EGWLKGLPGA
810 820 830 840
FPAQLVCEVT GEHERRRHLR QNQRLLEAVG SSSGTPNAPP P
Length:841
Mass (Da):91,940
Last modified:January 20, 2009 - v4
Checksum:i40D430ACF777002F
GO

Sequence cautioni

The sequence BAA74938.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti73 – 731P → S.
Corresponds to variant rs9890841 [ dbSNP | Ensembl ].
VAR_057189
Natural varianti155 – 1551G → V.1 Publication
Corresponds to variant rs17857129 [ dbSNP | Ensembl ].
VAR_054215
Natural varianti277 – 2771L → P.3 Publications
Corresponds to variant rs871841 [ dbSNP | Ensembl ].
VAR_054216
Natural varianti831 – 8311S → P.4 Publications
Corresponds to variant rs3744647 [ dbSNP | Ensembl ].
VAR_054217

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020722 mRNA. Translation: BAA74938.2. Different initiation.
AK291626 mRNA. Translation: BAF84315.1.
AC135178 Genomic DNA. No translation available.
CH471108 Genomic DNA. Translation: EAW90060.1.
BC036749 mRNA. Translation: AAH36749.1.
CCDSiCCDS11139.1.
RefSeqiNP_079290.1. NM_025014.1.
NP_776089.2. NM_173728.3.
UniGeneiHs.443109.

Genome annotation databases

EnsembliENST00000361926; ENSP00000355026; ENSG00000198844.
ENST00000421050; ENSP00000412505; ENSG00000198844.
GeneIDi22899.
KEGGihsa:22899.
UCSCiuc002glc.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020722 mRNA. Translation: BAA74938.2. Different initiation.
AK291626 mRNA. Translation: BAF84315.1.
AC135178 Genomic DNA. No translation available.
CH471108 Genomic DNA. Translation: EAW90060.1.
BC036749 mRNA. Translation: AAH36749.1.
CCDSiCCDS11139.1.
RefSeqiNP_079290.1. NM_025014.1.
NP_776089.2. NM_173728.3.
UniGeneiHs.443109.

3D structure databases

ProteinModelPortaliO94989.
SMRiO94989. Positions 388-739.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116563. 8 interactions.
IntActiO94989. 2 interactions.
MINTiMINT-1454033.
STRINGi9606.ENSP00000355026.

PTM databases

iPTMnetiO94989.
PhosphoSiteiO94989.

Polymorphism and mutation databases

BioMutaiARHGEF15.

Proteomic databases

PaxDbiO94989.
PeptideAtlasiO94989.
PRIDEiO94989.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361926; ENSP00000355026; ENSG00000198844.
ENST00000421050; ENSP00000412505; ENSG00000198844.
GeneIDi22899.
KEGGihsa:22899.
UCSCiuc002glc.4. human.

Organism-specific databases

CTDi22899.
GeneCardsiARHGEF15.
H-InvDBHIX0013523.
HGNCiHGNC:15590. ARHGEF15.
HPAiHPA044443.
MIMi608504. gene.
neXtProtiNX_O94989.
PharmGKBiPA24970.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3523. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00550000074493.
HOGENOMiHOG000034047.
HOVERGENiHBG103361.
InParanoidiO94989.
OMAiPPTFRLS.
OrthoDBiEOG7XWPN0.
PhylomeDBiO94989.
TreeFamiTF316357.

Enzyme and pathway databases

SignaLinkiO94989.

Miscellaneous databases

ChiTaRSiARHGEF15. human.
GenomeRNAii22899.
PROiO94989.
SOURCEiSearch...

Gene expression databases

BgeeiO94989.
CleanExiHS_ARHGEF15.
ExpressionAtlasiO94989. baseline and differential.
GenevisibleiO94989. HS.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
[Graphical view]
PfamiPF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
    Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-831.
    Tissue: Brain.
  2. "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
    Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
    DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SEQUENCE REVISION.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS PRO-277 AND PRO-831.
    Tissue: Placenta.
  4. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS PRO-277 AND PRO-831.
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS VAL-155; PRO-277 AND PRO-831.
    Tissue: Lung.
  7. "EphA4-mediated Rho activation via Vsm-RhoGEF expressed specifically in vascular smooth muscle cells."
    Ogita H., Kunimoto S., Kamioka Y., Sawa H., Masuda M., Mochizuki N.
    Circ. Res. 93:23-31(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH EPHA4, REGULATION.

Entry informationi

Entry nameiARHGF_HUMAN
AccessioniPrimary (citable) accession number: O94989
Secondary accession number(s): A8K6G1, Q8N449, Q9H8B4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: January 20, 2009
Last modified: July 6, 2016
This is version 124 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.