RHG44_RAT
ID RHG44_RAT Reviewed; 814 AA.
AC F1LQX4; F1LST2; M0RAT0;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Rho GTPase-activating protein 44 {ECO:0000305};
DE AltName: Full=Rho-type GTPase-activating protein RICH2;
DE AltName: Full=RhoGAP interacting with CIP4 homologs protein 2;
DE Short=RICH-2;
GN Name=Arhgap44 {ECO:0000312|RGD:1305664}; Synonyms=Rich2;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-805, AND IDENTIFICATION BY
RP 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).
RN [3]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=23739967; DOI=10.1523/jneurosci.2725-12.2013;
RA Raynaud F., Janossy A., Dahl J., Bertaso F., Perroy J., Varrault A.,
RA Vidal M., Worley P.F., Boeckers T.M., Bockaert J., Marin P., Fagni L.,
RA Homburger V.;
RT "Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic
RT long-term potentiation.";
RL J. Neurosci. 33:9699-9715(2013).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, AND MUTAGENESIS
RP OF ARG-291.
RX PubMed=25498153; DOI=10.7554/elife.03116;
RA Galic M., Tsai F.C., Collins S.R., Matis M., Bandara S., Meyer T.;
RT "Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to
RT nanoscale membrane deformations limits exploratory filopodia initiation in
RT neurons.";
RL Elife 3:E03116-E03116(2014).
CC -!- FUNCTION: GTPase-activating protein (GAP) that stimulates the GTPase
CC activity of Rho-type GTPases. Thereby, controls Rho-type GTPases
CC cycling between their active GTP-bound and inactive GDP-bound states.
CC Acts as a GAP at least for CDC42 and RAC1 (PubMed:25498153). In
CC neurons, is involved in dendritic spine formation and synaptic
CC plasticity in a specific RAC1-GAP activity (PubMed:25498153). Limits
CC the initiation of exploratory dendritic filopodia. Recruited to actin-
CC patches that seed filopodia, binds specifically to plasma membrane
CC sections that are deformed inward by acto-myosin mediated contractile
CC forces. Acts through GAP activity on RAC1 to reduce actin
CC polymerization necessary for filopodia formation (PubMed:25498153). In
CC association with SHANK3, promotes GRIA1 exocytosis from recycling
CC endosomes and spine morphological changes associated to long-term
CC potentiation (By similarity). {ECO:0000250|UniProtKB:Q5SSM3,
CC ECO:0000269|PubMed:25498153}.
CC -!- SUBUNIT: Interacts with BST2 (via cytoplasmic domain). Interacts
CC (probably via PDZ-binding motif) with SHANK3 (via PDZ domain); the
CC interaction takes place in dendritic spines and promotes GRIA1
CC exocytosis (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell projection, dendritic spine
CC {ECO:0000269|PubMed:23739967, ECO:0000269|PubMed:25498153}. Recycling
CC endosome {ECO:0000250|UniProtKB:Q5SSM3}. Presynapse
CC {ECO:0000269|PubMed:23739967}. Cell projection, dendrite
CC {ECO:0000269|PubMed:25498153}. Note=In CA1 hippocampal synapses,
CC detected at both presynaptic and postsynaptic sites (By similarity).
CC Located in convoluted dendritic plasma membrane sections enriched in
CC polymerized actin and myosin (patches) along dendrites where often
CC emerge filopodia (PubMed:25498153). {ECO:0000250|UniProtKB:Q5SSM3,
CC ECO:0000269|PubMed:25498153}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=F1LQX4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=F1LQX4-2; Sequence=VSP_053619;
CC Name=3;
CC IsoId=F1LQX4-3; Sequence=VSP_053620, VSP_053621;
CC -!- TISSUE SPECIFICITY: Expressed in brain, detected at high levels in
CC hippocampal CA1 (at protein level). {ECO:0000269|PubMed:23739967,
CC ECO:0000269|PubMed:25498153}.
CC -!- DEVELOPMENTAL STAGE: Expression increases in prefrontal cortex from 6
CC months to, at least, 39 months. {ECO:0000269|PubMed:25498153}.
CC -!- DOMAIN: Rho-GAP domain is required to promote GRIA1 exocytosis from
CC recycling endosomes. Rho-GAP and BAR domains are necessary for the
CC control of long-term potentiation in hippocampal neurons (By
CC similarity). In dendrites, BAR domain mediates the recruitment to
CC patches where plasma membrane is deformed by acto-myosin mediated
CC contractile forces (PubMed:25498153). {ECO:0000250|UniProtKB:Q5SSM3,
CC ECO:0000269|PubMed:25498153}.
CC -!- MISCELLANEOUS: [Isoform 2]: Contains a PDZ-binding motif at positions
CC 767-770. {ECO:0000305}.
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DR EMBL; AABR06064261; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06064262; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06064263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06064264; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06064265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_006220759.1; XM_006220697.3. [F1LQX4-1]
DR RefSeq; XP_006220760.1; XM_006220698.3. [F1LQX4-2]
DR RefSeq; XP_006246896.1; XM_006246834.3. [F1LQX4-1]
DR RefSeq; XP_006246897.1; XM_006246835.3. [F1LQX4-2]
DR RefSeq; XP_008766117.1; XM_008767895.2. [F1LQX4-3]
DR RefSeq; XP_008773220.1; XM_008774998.2. [F1LQX4-3]
DR AlphaFoldDB; F1LQX4; -.
DR SMR; F1LQX4; -.
DR BioGRID; 257451; 1.
DR STRING; 10116.ENSRNOP00000004829; -.
DR iPTMnet; F1LQX4; -.
DR PhosphoSitePlus; F1LQX4; -.
DR PaxDb; F1LQX4; -.
DR PRIDE; F1LQX4; -.
DR Ensembl; ENSRNOT00000004829; ENSRNOP00000004829; ENSRNOG00000003603. [F1LQX4-2]
DR Ensembl; ENSRNOT00000101528; ENSRNOP00000096546; ENSRNOG00000003603. [F1LQX4-1]
DR GeneID; 303222; -.
DR KEGG; rno:303222; -.
DR CTD; 9912; -.
DR RGD; 1305664; Arhgap44.
DR eggNOG; KOG4270; Eukaryota.
DR GeneTree; ENSGT00940000157296; -.
DR HOGENOM; CLU_013806_0_0_1; -.
DR InParanoid; F1LQX4; -.
DR OrthoDB; 821331at2759; -.
DR TreeFam; TF316514; -.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR PRO; PR:F1LQX4; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000003603; Expressed in frontal cortex and 18 other tissues.
DR ExpressionAtlas; F1LQX4; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0031256; C:leading edge membrane; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0048786; C:presynaptic active zone; IDA:SynGO.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0098886; P:modification of dendritic spine; ISO:RGD.
DR GO; GO:0099010; P:modification of postsynaptic structure; ISO:RGD.
DR GO; GO:0051490; P:negative regulation of filopodium assembly; IDA:UniProtKB.
DR GO; GO:0035021; P:negative regulation of Rac protein signal transduction; ISO:RGD.
DR GO; GO:0098887; P:neurotransmitter receptor transport, endosome to postsynaptic membrane; ISO:RGD.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISO:RGD.
DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0099152; P:regulation of neurotransmitter receptor transport, endosome to postsynaptic membrane; ISO:RGD.
DR GO; GO:0035020; P:regulation of Rac protein signal transduction; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR004148; BAR_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR Pfam; PF03114; BAR; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR SMART; SM00721; BAR; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS51021; BAR; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Coiled coil; Endosome; Exocytosis;
KW GTPase activation; Phosphoprotein; Reference proteome; Synapse.
FT CHAIN 1..814
FT /note="Rho GTPase-activating protein 44"
FT /id="PRO_0000425252"
FT DOMAIN 14..249
FT /note="BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00361"
FT DOMAIN 255..445
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 467..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 531..768
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 727..814
FT /note="Interaction with BST2"
FT /evidence="ECO:0000250"
FT REGION 784..814
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 811..814
FT /note="PDZ-binding"
FT /evidence="ECO:0000305"
FT COMPBIAS 541..572
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 574..637
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 672..687
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 695..724
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 728..743
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 790..814
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 493
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5SSM3"
FT MOD_RES 805
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 509..514
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053619"
FT VAR_SEQ 769..770
FT /note="DL -> AV (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_053620"
FT VAR_SEQ 771..814
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_053621"
FT MUTAGEN 291
FT /note="R->M: Reduces GAP activity. Decreases inhibition of
FT filopodia formation."
FT /evidence="ECO:0000269|PubMed:25498153"
SQ SEQUENCE 814 AA; 89115 MW; 11D4B1F0F16BC76C CRC64;
MKKQFNRMRQ LANQTVGRAE KTEVLSEDLL QVEKRLELVK QVSHSTHKKL TACLQGQQGA
EADKRSKKLP LTTLAQCLME GSAILGDDTL LGKMLKLCGE TEDELAQELI HFELRVERDV
IEPLFLLAEV EIPNIQKQRK HLAKLVLDMD SSRTRWQQTS KSSGLSSSLQ PAGAKADALR
EEMEEAANRV EICRDQLSAD MYSFVAKEID YANYFQTLIE VQAEYHRKSL TLLQAVLPQI
KAQQEAWVEK PSFGKPLEEH LMISGREIAF PIEACVTMLL ECGMQEEGLF RVAPSASKLK
KLKAALDCCV VDVQEYSADP HAIAGALKSY LRELPEPLMT FELYDEWIQA SNIQEQDKRL
QALWNACEKL PKANHNNIRY LIKFLSKLSE YQDVNKMTPS NMAIVLGPNL LWPQSEGNIT
EMMTTVSLQI VGIIEPIIQH ADWFFPGEIE FNITGSYGSP VHVNHNANYS SMPSPDMDPA
DRRQPEQARR PLSVATDNMM LEFYKKDGLR KIQSMGVRVM DTSWVARRGS SAGRKAACAP
PSMQPPAPPS ELAAPLPSPL PEQVPDSPAT PAPALSPSGA SLQPTPERPS VSKSKELSPG
SGQKGSPGSI QGTTCPGTQL GPQPAASPSQ LPADQSPHTL RKVSKKLAPI PPKVPFVQPG
TVSDQPTGQP SPVSLSPTPP STPSPYGLSY PPGYSMASGQ LSPASAPPLA SPSVFTSTLA
KSRPTPKPRQ RPTLPPPQPP SVSLSASSPQ STEHPMLDGM SPGESMSTDL VHFDVPSIHI
ELGSTLRLSP LEHARRHSVT DKRDSEEESE STAL
