ARHG2_PIG
ID ARHG2_PIG Reviewed; 961 AA.
AC B2DCZ9;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 25-MAY-2022, entry version 91.
DE RecName: Full=Rho guanine nucleotide exchange factor 2;
DE AltName: Full=Guanine nucleotide exchange factor H1;
DE Short=GEF-H1;
GN Name=ARHGEF2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Suzuki S.;
RT "Identification of down-regulated genes in pig mesenteric adipocyte
RT differentiation.";
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP REVIEW ON FUNCTION.
RX PubMed=18394899; DOI=10.1016/j.tcb.2008.02.006;
RA Birkenfeld J., Nalbant P., Yoon S.-H., Bokoch G.M.;
RT "Cellular functions of GEF-H1, a microtubule-regulated Rho-GEF: is altered
RT GEF-H1 activity a crucial determinant of disease pathogenesis?";
RL Trends Cell Biol. 18:210-219(2008).
CC -!- FUNCTION: Activates Rho-GTPases by promoting the exchange of GDP for
CC GTP. May be involved in epithelial barrier permeability, cell motility
CC and polarization, dendritic spine morphology, antigen presentation,
CC leukemic cell differentiation, cell cycle regulation, innate immune
CC response, and cancer. Binds Rac-GTPases, but does not seem to promote
CC nucleotide exchange activity toward Rac-GTPases. May stimulate instead
CC the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-
CC GTPases. Forms an intracellular sensing system along with NOD1 for the
CC detection of microbial effectors during cell invasion by pathogens.
CC Involved in innate immune signaling transduction pathway promoting
CC cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon
CC stimulation by bacterial peptidoglycans; acts as a signaling
CC intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the
CC tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading
CC to NF-kappaB activation by NOD2. Overexpression activates Rho-, but not
CC Rac-GTPases, and increases paracellular permeability. Involved in
CC neuronal progenitor cell division and differentiation. Involved in the
CC migration of precerebellar neurons. {ECO:0000250|UniProtKB:Q60875,
CC ECO:0000250|UniProtKB:Q865S3}.
CC -!- SUBUNIT: Found in a complex composed at least of ARHGEF2, NOD2 and
CC RIPK2. Interacts with RIPK2; the interaction mediates tyrosine
CC phosphorylation of RIPK2 by Src kinase CSK. Interacts with RIPK1 and
CC RIPK3. Interacts with YWHAZ/14-3-3 zeta; when phosphorylated at Ser-
CC 860. Interacts with the kinases PAK4, AURKA and MAPK1. Interacts with
CC RHOA and RAC1. Interacts with NOD1 (By similarity). Interacts (via the
CC N- terminal zinc finger) with CAPN6 (via domain II). Interacts with
CC DYNLT1 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q865S3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q865S3, ECO:0000250|UniProtKB:Q92974}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q865S3, ECO:0000250|UniProtKB:Q92974}. Cell
CC junction, tight junction {ECO:0000250|UniProtKB:Q865S3,
CC ECO:0000250|UniProtKB:Q92974}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q92974}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:Q865S3, ECO:0000250|UniProtKB:Q92974}.
CC Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q92974}. Note=Localizes to
CC the tips of cortical microtubules of the mitotic spindle during cell
CC division, and is further released upon microtubule depolymerization.
CC Colocalized with NOD2 and RIPK2 in vesicles and with the cytoskeleton.
CC {ECO:0000250|UniProtKB:Q92974}.
CC -!- DOMAIN: The DH (DBL-homology) domain promotes tyrosine phosphorylation
CC of RIPK2 (By similarity). The DH (DBL-homology) domain interacts with
CC and promotes loading of GTP on RhoA. {ECO:0000250}.
CC -!- DOMAIN: The PH domain has no affinity for phosphoinositides suggesting
CC that it does not interact directly with membranes.
CC {ECO:0000250|UniProtKB:Q92974}.
CC -!- DOMAIN: The phorbol-ester/DAG-type zinc-finger and the C-terminal
CC coiled-coil domains (606-986) are both important for association with
CC microtubules. {ECO:0000250|UniProtKB:Q92974}.
CC -!- PTM: Phosphorylation of Ser-860 by PAK1 induces binding to protein
CC YWHAZ, promoting its relocation to microtubules and the inhibition of
CC its activity. Phosphorylated by AURKA and CDK1 during mitosis, which
CC negatively regulates its activity. Phosphorylation by MAPK1 or MAPK3
CC increases nucleotide exchange activity. Phosphorylation by PAK4
CC releases GEF-H1 from the microtubules. Phosphorylated on serine,
CC threonine and tyrosine residues in a RIPK2-dependent manner (By
CC similarity). {ECO:0000250}.
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DR EMBL; AB364503; BAG24505.1; -; mRNA.
DR RefSeq; NP_001121935.1; NM_001128463.1.
DR AlphaFoldDB; B2DCZ9; -.
DR SMR; B2DCZ9; -.
DR STRING; 9823.ENSSSCP00000006929; -.
DR iPTMnet; B2DCZ9; -.
DR PaxDb; B2DCZ9; -.
DR PeptideAtlas; B2DCZ9; -.
DR PRIDE; B2DCZ9; -.
DR GeneID; 100145887; -.
DR KEGG; ssc:100145887; -.
DR CTD; 9181; -.
DR eggNOG; KOG3520; Eukaryota.
DR InParanoid; B2DCZ9; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0031982; C:vesicle; ISS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:AgBase.
DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR GO; GO:0055059; P:asymmetric neuroblast division; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0000902; P:cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; ISS:UniProtKB.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IMP:AgBase.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:AgBase.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:1904685; P:positive regulation of metalloendopeptidase activity; IMP:AgBase.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IMP:AgBase.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IMP:AgBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0090303; P:positive regulation of wound healing; IMP:AgBase.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:AgBase.
DR CDD; cd00029; C1; 1.
DR CDD; cd13393; PH_ARHGEF2; 1.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR037806; ARHGEF2_PH.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041020; PH_16.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF17838; PH_16; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cell cycle; Cell division; Cell junction; Coiled coil;
KW Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Developmental protein;
KW Differentiation; Golgi apparatus; Guanine-nucleotide releasing factor;
KW Immunity; Innate immunity; Metal-binding; Microtubule; Mitosis;
KW Neurogenesis; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Tight junction; Zinc; Zinc-finger.
FT CHAIN 1..961
FT /note="Rho guanine nucleotide exchange factor 2"
FT /id="PRO_0000345623"
FT DOMAIN 209..406
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 446..545
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 12..59
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 104..134
FT /note="Interaction with DYNLT1"
FT /evidence="ECO:0000250|UniProtKB:Q865S3"
FT REGION 659..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 742..770
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 867..961
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 561..588
FT /evidence="ECO:0000255"
FT COILED 772..841
FT /evidence="ECO:0000255"
FT COMPBIAS 663..679
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 742..757
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 883..917
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 940..961
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 102
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 327
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 622
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 653
FT /note="Phosphothreonine; by MAPK1 or MAPK3"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 665
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 670
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 756
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60875"
FT MOD_RES 860
FT /note="Phosphoserine; by PAK1 and AURKA"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 868
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 870
FT /note="Phosphoserine; by PAK4"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 906
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 914
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 915
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 919
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 921
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 927
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60875"
FT MOD_RES 928
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 931
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 935
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
SQ SEQUENCE 961 AA; 108483 MW; 279B9EA9C2AACC90 CRC64;
MKEAKDARYT NGHLFTTISV SGMTMCYACN KSITAKEALI CPTCNVTIHN RCKDTLANCT
KVKQKQQKAA LLKNNTALQS VSLRSKTTTR ERPSSAIYPS DSFRQSLLGS RRGRSPLSLA
KSVSTTNIAG HFNDESPLGL RRILSQSTDS LNMRNRTLSV ESLIDEGAEV IYNELMSDFE
MGEKDFAADS WSLAVDSSFL QQHKKEVMKQ QDVIYELIQT ELHHVRTLKI MTRLFRTGML
EELQLEPGVV QGLFPCVDEL SDIHTRFLSQ LLERRRQALC PGSPRNFVIH RLGDLLITQF
SGPSADQMRK TYSEFCSRHT KALKLYKELY ARDKRFQQFI RKVTRSAVLK RHGVQECILL
VTQRITKYPV LISRILQHTH GIEEERQDLT TALGLVKELL SNVDQDVHEL EKGARLQEIY
NRMDPRAQTP VPGKGPFGRE ELLRRKLIHD GCLLWKTAAG RFKDVLMLLM TDVLVFLQEK
DQKYIFPALD KPSVVSLQNL IVRDIANQEK GMFLISAAPP EMYEVHTASR DDRSTWIRVI
QQSVRVCPSR EDFPLIETED EAYLRRIKME LQQKDRALVE LLQEKVGLFA EMTHFQVEED
GGGGMPLPTL PRGLFRSESL ESPRGERLLQ DAIREVEGLK DLLVGPGVEL LLTSREPALP
VETDSGGNTS PGVTANGEAR TFNGSIELCR ADSDSSQKDR NGNQLRSPQE EALQRLVNLY
GLLHGLQAAV AQQDTLMEAR FPEGPERREK LTRANSRDGE AGRAGAAPVA PEKQATELAL
LQRQHALLQE ELRRCRRLGE ERATEAGSLE ARLRESEQAR ALLEREVEEA RRQLAALGHT
EPLPAEAPWA RRPLDPRRRS LPAGDALYLS FTPPQPSRGH DRLDLPVTIR SVHRPFEDRE
RQELGSPDER LQDSSDPDTG SEEEGSSSRL SPPHSPRDFT RMQDIPEETE SRDGEPVASE
S
