ID GARE1_MOUSE Reviewed; 876 AA.
AC Q3UFT3; G5E8B7; Q3TSA2; Q5DTF6; Q80V96;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 24-JAN-2024, entry version 121.
DE RecName: Full=GRB2-associated and regulator of MAPK protein;
DE AltName: Full=GRB2-associated and regulator of MAPK1;
GN Name=Garem1; Synonyms=Fam59a, Garem, Gm944, Kiaa4238;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 219-876 (ISOFORM 1).
RC TISSUE=Mammary gland;
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-609 AND SER-613, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Acts as an adapter protein that plays a role in intracellular
CC signaling cascades triggered either by the cell surface activated
CC epidermal growth factor receptor and/or cytoplasmic protein tyrosine
CC kinases. Promotes activation of the MAPK/ERK signaling pathway. Plays a
CC role in the regulation of cell proliferation (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with EGFR. Interacts (via proline-rich domain and
CC phosphorylated at Tyr-105 and Tyr-453) with GRB2 (via SH3 domains); the
CC interaction occurs upon EGF stimulation. Interacts (phosphorylated at
CC Tyr-453) with PTPN11; the interaction increases MAPK/ERK activity and
CC does not affect the GRB2/SOS complex formation (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UFT3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UFT3-2; Sequence=VSP_023049, VSP_023050;
CC -!- PTM: On EGF stimulation, phosphorylated on Tyr-105 and Tyr-453.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GAREM family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD90542.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK148318; BAE28477.1; -; mRNA.
DR EMBL; AK162177; BAE36773.1; -; mRNA.
DR EMBL; AK220564; BAD90542.1; ALT_INIT; mRNA.
DR EMBL; AC127570; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC158774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466557; EDK96964.1; -; Genomic_DNA.
DR EMBL; BC049983; AAH49983.1; -; mRNA.
DR CCDS; CCDS29091.1; -. [Q3UFT3-1]
DR RefSeq; NP_001028617.2; NM_001033445.2. [Q3UFT3-1]
DR AlphaFoldDB; Q3UFT3; -.
DR SMR; Q3UFT3; -.
DR IntAct; Q3UFT3; 1.
DR STRING; 10090.ENSMUSP00000048914; -.
DR iPTMnet; Q3UFT3; -.
DR PhosphoSitePlus; Q3UFT3; -.
DR MaxQB; Q3UFT3; -.
DR PaxDb; 10090-ENSMUSP00000048914; -.
DR ProteomicsDB; 271669; -. [Q3UFT3-1]
DR ProteomicsDB; 271670; -. [Q3UFT3-2]
DR Pumba; Q3UFT3; -.
DR Antibodypedia; 41891; 120 antibodies from 23 providers.
DR Ensembl; ENSMUST00000049260.7; ENSMUSP00000048914.7; ENSMUSG00000042680.9. [Q3UFT3-1]
DR Ensembl; ENSMUST00000234115.2; ENSMUSP00000157254.2; ENSMUSG00000042680.9. [Q3UFT3-2]
DR GeneID; 381126; -.
DR KEGG; mmu:381126; -.
DR UCSC; uc008efg.1; mouse. [Q3UFT3-1]
DR UCSC; uc008efh.1; mouse. [Q3UFT3-2]
DR AGR; MGI:2685790; -.
DR CTD; 64762; -.
DR MGI; MGI:2685790; Garem1.
DR VEuPathDB; HostDB:ENSMUSG00000042680; -.
DR eggNOG; ENOG502QRDN; Eukaryota.
DR GeneTree; ENSGT00530000063834; -.
DR HOGENOM; CLU_014784_0_0_1; -.
DR InParanoid; Q3UFT3; -.
DR OMA; HNISGAC; -.
DR OrthoDB; 2952379at2759; -.
DR PhylomeDB; Q3UFT3; -.
DR TreeFam; TF329726; -.
DR BioGRID-ORCS; 381126; 4 hits in 79 CRISPR screens.
DR ChiTaRS; Garem; mouse.
DR PRO; PR:Q3UFT3; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q3UFT3; Protein.
DR Bgee; ENSMUSG00000042680; Expressed in caudate-putamen and 228 other cell types or tissues.
DR Genevisible; Q3UFT3; MM.
DR GO; GO:0070064; F:proline-rich region binding; ISS:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR CDD; cd09525; SAM_GAREM; 1.
DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1.
DR InterPro; IPR025946; CABIT_dom.
DR InterPro; IPR013761; SAM/pointed_sf.
DR PANTHER; PTHR14454:SF6; GRB2-ASSOCIATED AND REGULATOR OF MAPK PROTEIN 1; 1.
DR PANTHER; PTHR14454; GRB2-ASSOCIATED AND REGULATOR OF MAPK PROTEIN FAMILY MEMBER; 1.
DR Pfam; PF12736; CABIT; 1.
DR SUPFAM; SSF47769; SAM/Pointed domain; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Mitogen; Phosphoprotein; Reference proteome.
FT CHAIN 1..876
FT /note="GRB2-associated and regulator of MAPK protein"
FT /id="PRO_0000277648"
FT DOMAIN 811..876
FT /note="SAM"
FT REGION 12..320
FT /note="CABIT"
FT REGION 427..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 460..501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 498..550
FT /note="Necessary for interaction with GRB2"
FT /evidence="ECO:0000250"
FT REGION 530..572
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 630..664
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 722..759
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 482..501
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 558..572
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 630..657
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 105
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9H706"
FT MOD_RES 453
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9H706"
FT MOD_RES 609
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 578
FT /note="I -> M (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_023049"
FT VAR_SEQ 579..876
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_023050"
FT CONFLICT 324
FT /note="H -> N (in Ref. 1; BAE28477)"
FT /evidence="ECO:0000305"
FT CONFLICT 652
FT /note="P -> H (in Ref. 1; BAE28477)"
FT /evidence="ECO:0000305"
FT CONFLICT 857
FT /note="L -> Q (in Ref. 1; BAE36773)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 876 AA; 97250 MW; 8CC941A2A072DE0A CRC64;
MDPAPSLGCS LKDVKWSPVA MPLDLLVSTY RLPQIARLDS GECVEGLREN DFLLIHSCRQ
WTTITAHSLE EGHYVIGPKI EIPVHYAGQF KLLEQDRDIK EPVQYFNSVE EVAKAFPERV
YVMEEITFNV KVASGECNED TEVYNITLCT GDELTLMGQA EILYAKTFKE KSRLNTIFKK
IGKLNSISKL GKGKMPCLIC MNHRTNESIS LPFQCKGRFS TRSPLELQMQ EGEHTIRNIV
EKTRLPVNVT VPSPPPRNPY DLHFIREGHR YKFVNIQTKT VVVCCVLRNN KILPMHFPLH
LTVPKFSLPE HQVKGDMWPE TLVHHWLGIC QEQFDIDEYS RAVRDVKTDW NEDCKSPKKG
RCSGHNHLPN SLSYARDELT QSFHRLSVCV YGNNLHGNSE VNLHGCRDLG GEWAPFPHDI
LPYQDSGDSG SDYLFPEANE ESAGIPGKTE VPYEELWLEE GKPSRQPLTR SLSEKSRCDT
LRGSTRSTCA PSSPPTPATL GATIKSSEIA LPPPPVPPKS EAVREECRLL NAPPVPPRSA
KPLSTSPSIP PRTVKPVRPQ TRSPSPTLSY YSSGLHNIIT QSDTSPPNSA PVSCYPCTRV
KSDSVDPKSP FGSPSAEALS SRLSWPNHYS GASENQTRSD FLLDPSRSYS YPRQKTPGTP
KRTCPAPFDF EGCELLGSPP STTSAEFSSS GVPSCPKSAS YCLENSEDNS FAAGMTKQSV
SCPALPPRAP KPVEQKATPE TSPLPLKIDG AEEDPTAGSL DLSEDQYFVR KGMQDIFSVS
YPFSSPLHLQ LAPRSCGDGS PWQPPADLSG LSIEEVSKSL RFIGLSEDVI AFFVTEKIDG
NLLVQLTEEI LSEDFKLSKL QVKKILQFIN GWRPKI
//
