Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, Gentaur another in time delivery
GARE1_HUMAN Reviewed; 876 AA.
Q9H706; Q0VAG3; Q0VAG4; Q8ND03; Q9BSF5;
06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
06-FEB-2007, sequence version 2.
16-OCT-2019, entry version 138.
RecName: Full=GRB2-associated and regulator of MAPK protein 1;
AltName: Full=GRB2-associated and regulator of MAPK1;
Name=GAREM1; Synonyms=C18orf11, FAM59A, GAREM;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
TISSUE=Colon;
PubMed=14702039; DOI=10.1038/ng1285;
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.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Testis;
PubMed=17974005; DOI=10.1186/1471-2164-8-399;
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
"The full-ORF clone resource of the German cDNA consortium.";
BMC Genomics 8:399-399(2007).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
TISSUE=Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
FUNCTION, INTERACTION WITH EGFR; GRB2 AND PTPN11, ALTERNATIVE SPLICING
(ISOFORMS 1 AND 2), PHOSPHORYLATION AT TYR-453 AND TYR-105,
MUTAGENESIS OF TYR-105 AND TYR-453, AND TISSUE SPECIFICITY.
PubMed=19509291; DOI=10.1074/jbc.m109.021139;
Tashiro K., Tsunematsu T., Okubo H., Ohta T., Sano E., Yamauchi E.,
Taniguchi H., Konishi H.;
"GAREM, a novel adaptor protein for growth factor receptor-bound
protein 2, contributes to cellular transformation through the
activation of extracellular signal-regulated kinase signaling.";
J. Biol. Chem. 284:20206-20214(2009).
[5]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-610 AND SER-614, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[6]
STRUCTURE BY NMR OF 2-165.
RIKEN structural genomics initiative (RSGI);
"Solution structure of the SAM_PNT-domain of the hypothetical protein
LOC64762.";
Submitted (OCT-2006) to the PDB data bank.
-!- FUNCTION: Isoform 1: Acts as an adapter protein that plays a role
in intracellular signaling cascades triggered either by the cell
surface activated epidermal growth factor receptor and/or
cytoplasmic protein tyrosine kinases. Promotes activation of the
MAPK/ERK signaling pathway. Plays a role in the regulation of cell
proliferation. {ECO:0000269|PubMed:19509291}.
-!- SUBUNIT: Isoform 1 interacts with EGFR. Isoform 1 interacts (via
proline-rich domain and phosphorylated at Tyr-105 and Tyr-453)
with GRB2 (via SH3 domains); the interaction occurs upon EGF
stimulation. Isoform 1 interacts (phosphorylated at Tyr-453) with
PTPN11; the interaction increases MAPK/ERK activity and does not
affect the GRB2/SOS complex formation. Isoform 2 does not interact
with GRB2. {ECO:0000269|PubMed:19509291}.
-!- INTERACTION:
O75791:GRAP2; NbExp=3; IntAct=EBI-3440103, EBI-740418;
P62993:GRB2; NbExp=8; IntAct=EBI-3440103, EBI-401755;
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=Q9H706-1; Sequence=Displayed;
Name=2; Synonyms=GAREM(S);
IsoId=Q9H706-2; Sequence=VSP_023047;
Name=3;
IsoId=Q9H706-3; Sequence=VSP_023048;
-!- TISSUE SPECIFICITY: Isoform 1 is ubiquitously expressed.
{ECO:0000269|PubMed:19509291}.
-!- PTM: On EGF stimulation, phosphorylated on Tyr-105 and Tyr-453.
{ECO:0000269|PubMed:19509291}.
-!- SIMILARITY: Belongs to the GAREM family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=CAD39149.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; AK025263; BAB15094.1; -; mRNA.
EMBL; AL834491; CAD39149.1; ALT_INIT; mRNA.
EMBL; BC005074; AAH05074.1; -; mRNA.
EMBL; BC121067; AAI21068.1; -; mRNA.
EMBL; BC121068; AAI21069.1; -; mRNA.
CCDS; CCDS11905.1; -. [Q9H706-3]
CCDS; CCDS56057.1; -. [Q9H706-1]
RefSeq; NP_001229338.1; NM_001242409.1. [Q9H706-1]
RefSeq; NP_073588.1; NM_022751.2. [Q9H706-3]
PDB; 2DKZ; NMR; -; A=801-871.
PDBsum; 2DKZ; -.
SMR; Q9H706; -.
BioGrid; 122275; 9.
IntAct; Q9H706; 10.
STRING; 9606.ENSP00000269209; -.
iPTMnet; Q9H706; -.
PhosphoSitePlus; Q9H706; -.
BioMuta; GAREM1; -.
DMDM; 125991851; -.
jPOST; Q9H706; -.
MassIVE; Q9H706; -.
MaxQB; Q9H706; -.
PaxDb; Q9H706; -.
PeptideAtlas; Q9H706; -.
PRIDE; Q9H706; -.
ProteomicsDB; 81068; -. [Q9H706-1]
ProteomicsDB; 81069; -. [Q9H706-2]
ProteomicsDB; 81070; -. [Q9H706-3]
Ensembl; ENST00000269209; ENSP00000269209; ENSG00000141441. [Q9H706-1]
Ensembl; ENST00000399218; ENSP00000382165; ENSG00000141441. [Q9H706-3]
GeneID; 64762; -.
KEGG; hsa:64762; -.
UCSC; uc002kxk.3; human. [Q9H706-1]
CTD; 64762; -.
DisGeNET; 64762; -.
GeneCards; GAREM1; -.
HGNC; HGNC:26136; GAREM1.
HPA; HPA040709; -.
HPA; HPA042046; -.
MIM; 617998; gene.
neXtProt; NX_Q9H706; -.
OpenTargets; ENSG00000141441; -.
PharmGKB; PA134888032; -.
eggNOG; ENOG410II0U; Eukaryota.
eggNOG; ENOG410XSPW; LUCA.
GeneTree; ENSGT00530000063834; -.
HOGENOM; HOG000074085; -.
InParanoid; Q9H706; -.
OMA; HMAMPRF; -.
OrthoDB; 288834at2759; -.
PhylomeDB; Q9H706; -.
TreeFam; TF329726; -.
ChiTaRS; GAREM1; human.
EvolutionaryTrace; Q9H706; -.
GenomeRNAi; 64762; -.
Pharos; Q9H706; -.
PRO; PR:Q9H706; -.
Proteomes; UP000005640; Chromosome 18.
Bgee; ENSG00000141441; Expressed in 218 organ(s), highest expression level in frontal cortex.
ExpressionAtlas; Q9H706; baseline and differential.
Genevisible; Q9H706; HS.
GO; GO:0005886; C:plasma membrane; NAS:UniProtKB.
GO; GO:0070064; F:proline-rich region binding; IDA:UniProtKB.
GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:UniProtKB.
GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
Gene3D; 1.10.150.50; -; 1.
InterPro; IPR025946; CABIT_dom.
InterPro; IPR013761; SAM/pointed_sf.
Pfam; PF12736; CABIT; 1.
SUPFAM; SSF47769; SSF47769; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome; Mitogen;
Phosphoprotein; Polymorphism; Reference proteome.
CHAIN 1 876 GRB2-associated and regulator of MAPK
protein 1.
/FTId=PRO_0000277647.
DOMAIN 811 876 SAM.
REGION 12 320 CABIT.
REGION 498 550 Necessary for interaction with GRB2.
{ECO:0000269|PubMed:19509291}.
COMPBIAS 512 566 Pro-rich.
MOD_RES 105 105 Phosphotyrosine.
{ECO:0000269|PubMed:19509291}.
MOD_RES 453 453 Phosphotyrosine.
{ECO:0000269|PubMed:19509291}.
MOD_RES 610 610 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 614 614 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
VAR_SEQ 495 563 Missing (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_023047.
VAR_SEQ 579 579 Missing (in isoform 3).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_023048.
VARIANT 243 243 T -> N (in dbSNP:rs671138).
/FTId=VAR_030580.
VARIANT 291 291 K -> R (in dbSNP:rs3744921).
/FTId=VAR_030581.
VARIANT 490 490 A -> V (in dbSNP:rs16962974).
/FTId=VAR_030582.
VARIANT 580 580 V -> I (in dbSNP:rs3891458).
/FTId=VAR_030583.
VARIANT 720 720 T -> M (in dbSNP:rs2276374).
/FTId=VAR_030584.
MUTAGEN 105 105 Y->F: Does not abolish phosphorylation
upon EGF stimulation. Reduces interaction
with GRB2. Abolishes phosphorylation,
interaction with GRB2 and ERK activation
upon EGF stimulation; when associated
with F-453.
{ECO:0000269|PubMed:19509291}.
MUTAGEN 453 453 Y->F: Does not abolish phosphorylation
upon EGF stimulation. Abolishes
interaction with PTPN11. Abolishes
phosphorylation upon EGF stimulation;
when associated with F-105.
{ECO:0000269|PubMed:19509291}.
HELIX 813 819 {ECO:0000244|PDB:2DKZ}.
HELIX 820 822 {ECO:0000244|PDB:2DKZ}.
HELIX 827 834 {ECO:0000244|PDB:2DKZ}.
TURN 835 837 {ECO:0000244|PDB:2DKZ}.
HELIX 840 845 {ECO:0000244|PDB:2DKZ}.
HELIX 848 853 {ECO:0000244|PDB:2DKZ}.
HELIX 859 870 {ECO:0000244|PDB:2DKZ}.
SEQUENCE 876 AA; 97186 MW; 668EBABC9CDE4CDF CRC64;
MDPAPSLGCS LKDVKWSSVA VPLDLLVSTY RLPQIARLDN GECVEGLREN DYLLIHSCRQ
WTTITAHSLE EGHYVIGPKI EIPVHYAGQF KLLEQDRDIK EPVQYFNSVE EVAKAFPERV
YVMEDITFNV KVASGECNED TEVYNITLCT GDELTLMGQA EILYAKTFKE KSRLNTIFKK
IGKLNSISKL GKGKMPCLIC MNHRTNESIS LPFQCKGRFS TRSPLELQMQ EGEHTIRNIV
EKTRLPVNVT VPSPPPRNPY DLHFIREGHR YKFVNIQTKT VVVCCVLRNN KILPMHFPLH
LTVPKFSLPE HLVKGESWPE TLVHHWLGIC QEQFDIDEYS RAVRDVKTDW NEECKSPKKG
RCSGHNHVPN SLSYARDELT QSFHRLSVCV YGNNLHGNSE VNLHGCRDLG GDWAPFPHDI
LPYQDSGDSG SDYLFPEASE ESAGIPGKSE LPYEELWLEE GKPSHQPLTR SLSEKNRCDQ
FRGSVRSKCA TSPLPIPGTL GAAVKSSDTA LPPPPVPPKS EAVREECRLL NAPPVPPRSA
KPLSTSPSIP PRTVKPARQQ TRSPSPTLSY YSSGLHNISV TKTDTNPSES TPVSCYPCNR
VKTDSVDLKS PFGSPSAEAV SSRLSWPNHY SGASESQTRS DFLLDPSRSY SYPRQKTPGT
PKRNCPAPFD FDGCELLASP TSPVTAEFSS SVSGCPKSAS YSLESTDVKS LAAGVTKQST
SCPALPPRAP KLVEEKVASE TSPLPLKIDG AEEDPKSGSP DLSEDQYFVK KGMQDIFSAS
YPFSSPLHLQ LAPRSCGDGS PWQPPADLSG LSIEEVSKSL RFIGLSEDVI SFFVTEKIDG
NLLVQLTEEI LSEDFKLSKL QVKKIMQFIN GWRPKI