ABR_RAT
ID ABR_RAT Reviewed; 859 AA.
AC A0A0G2JTR4;
DT 03-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2019, sequence version 2.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=Active breakpoint cluster region-related protein {ECO:0000305};
GN Name=Abr {ECO:0000312|RGD:1306279};
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] {ECO:0000312|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|Proteomes:UP000002494};
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 INTERACTION WITH DLG4, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=20962234; DOI=10.1523/jneurosci.1711-10.2010;
RA Oh D., Han S., Seo J., Lee J.R., Choi J., Groffen J., Kim K., Cho Y.S.,
RA Choi H.S., Shin H., Woo J., Won H., Park S.K., Kim S.Y., Jo J.,
RA Whitcomb D.J., Cho K., Kim H., Bae Y.C., Heisterkamp N., Choi S.Y., Kim E.;
RT "Regulation of synaptic Rac1 activity, long-term potentiation maintenance,
RT and learning and memory by BCR and ABR Rac GTPase-activating proteins.";
RL J. Neurosci. 30:14134-14144(2010).
RN [3] {ECO:0007744|PubMed:22673903}
RP IDENTIFICATION BY 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).
CC -!- FUNCTION: Protein with a unique structure having two opposing
CC regulatory activities toward small GTP-binding proteins. The C-terminus
CC is a GTPase-activating protein domain which stimulates GTP hydrolysis
CC by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP
CC hydrolysis of RAC1 or CDC42, leading to down-regulation of the active
CC GTP-bound form. The central Dbl homology (DH) domain functions as
CC guanine nucleotide exchange factor (GEF) that modulates the GTPases
CC CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1
CC from the GDP-bound to the GTP-bound form (By similarity). Functions as
CC an important negative regulator of neuronal RAC1 activity (By
CC similarity). Regulates macrophage functions such as CSF-1 directed
CC motility and phagocytosis through the modulation of RAC1 activity (By
CC similarity). {ECO:0000250|UniProtKB:Q12979,
CC ECO:0000250|UniProtKB:Q5SSL4}.
CC -!- SUBUNIT: Interacts with DLG4. {ECO:0000269|PubMed:20962234}.
CC -!- SUBCELLULAR LOCATION: Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:Q5SSL4}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q5SSL4}. Synapse {ECO:0000269|PubMed:20962234}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, including the cortex,
CC hippocampus, cerebellum, and brainstem, as well as the spinal cord (at
CC protein level). {ECO:0000269|PubMed:20962234}.
CC -!- DEVELOPMENTAL STAGE: Expression gradually increases from late embryonic
CC (E18) stage until adulthood. {ECO:0000269|PubMed:20962234}.
CC -!- DOMAIN: The central Dbl homology (DH) domain functions as guanine
CC nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA
CC and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-
CC bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which
CC stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a
CC unique structure having two opposing regulatory activities toward small
CC GTP-binding proteins. {ECO:0000250|UniProtKB:Q12979}.
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DR EMBL; AABR07030047; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07072152; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FQ078152.1; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001099284.1; NM_001105814.2.
DR AlphaFoldDB; A0A0G2JTR4; -.
DR SMR; A0A0G2JTR4; -.
DR STRING; 10116.ENSRNOP00000038889; -.
DR jPOST; A0A0G2JTR4; -.
DR PaxDb; A0A0G2JTR4; -.
DR GeneID; 287537; -.
DR KEGG; rno:287537; -.
DR CTD; 29; -.
DR RGD; 1306279; Abr.
DR eggNOG; KOG4269; Eukaryota.
DR Reactome; R-RNO-193648; NRAGE signals death through JNK.
DR Reactome; R-RNO-416482; G alpha (12/13) signalling events.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR Reactome; R-RNO-9013106; RHOC GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR PRO; PR:A0A0G2JTR4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; IDA:SynGO.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; ISO:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:RGD.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0090630; P:activation of GTPase activity; ISO:RGD.
DR GO; GO:0007420; P:brain development; ISO:RGD.
DR GO; GO:0042472; P:inner ear morphogenesis; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISS:UniProtKB.
DR GO; GO:0060313; P:negative regulation of blood vessel remodeling; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:0002692; P:negative regulation of cellular extravasation; ISO:RGD.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0043314; P:negative regulation of neutrophil degranulation; ISO:RGD.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISO:RGD.
DR GO; GO:0043114; P:regulation of vascular permeability; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR CDD; cd13366; PH_ABR; 1.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR037769; Abr/Bcr.
DR InterPro; IPR037865; ABR_PH.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR PANTHER; PTHR23182; PTHR23182; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW Cell projection; Coiled coil; GTPase activation;
KW Guanine-nucleotide releasing factor; Phosphoprotein; Reference proteome;
KW Synapse.
FT CHAIN 1..859
FT /note="Active breakpoint cluster region-related protein"
FT /id="PRO_0000447438"
FT DOMAIN 91..284
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 301..459
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 484..613
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 647..845
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 31..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..71
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5SSL4"
SQ SEQUENCE 859 AA; 97693 MW; 5B06EC3D6845FD17 CRC64;
MEPLSHRGLP RLSWIDTLYS NFSYGAEDYD AEGHEEQKGP PEGSETMPYI DESPTMSPQL
SARSQGGGES ISPTPPEGLA PGVEAGKGLE MRKLVLSGFL ASEEIYINQL EALLLPMKPL
KATATTSQPV LTIQQIETIF YKIQDIYEIH KEFYDNLCPK VQQWDSQVTM GHLFQKLASQ
LGVYKAFVDN YKVALETAEK CSQSNNQFQK ISEELKVKGP KDSKDSHTSV TMEALLYKPI
DRVTRSTLVL HDLLKHTPVD HPDYPLLQDA LRISQNFLSS INEDIDPRRT AVTTPKGETR
QLVKDGFLVE MSESSRKLRH VFLFTDVLLC AKLKKTSAGK HQQYDCKWYI PLADLVFPSP
EESEASPQVH PFPDHELEDM KVKISALKSE IQKEKANKGQ SRAIERLKKK MFENEFLLLL
NSPTIPFRIH NRNGKSYLFL LSSDYERSEW REAIQKLQKK DLQAFVLSSV ELQVLTGSCF
KLRTVHNIPV TSNKDDDESP GLYGFLHVIV HSAKGFKQSA NLYCTLEVDS FGYFVSKAKT
RVFRDTTEPK WDEEFEIELE GSQSLRILCY EKCYDKTKVN KDNNEIVDKI MGKGQIQLDP
QTVESKNWHT DVIEMNGIKV EFSMKFTSRD MSLKRTPSKK QTGVFGVKIS VVTKRERSKV
PYIVRQCIEE VEKRGIEEVG IYRISGVATD IQALKAVFDA NNKDILLMLS DMDINAIAGT
LKLYFRELPE PLLTDRLYPA FMEGIALSDP AAKENCMMHL LRSLPDPNLI TFLFLLEHLK
RVAEKEPINK MSLHNLATVF GPTLLRPSEV ESKAHLTSAA DIWSHDVMAQ VQVLLYYLQH
PPISFAELKR NTLYFSTDV
