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Protein

GRB2-associated and regulator of MAPK protein 1

Gene

GAREM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • proline-rich region binding Source: UniProtKB

GO - Biological processi

  • cellular response to epidermal growth factor stimulus Source: UniProtKB
  • epidermal growth factor receptor signaling pathway Source: UniProtKB
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Mitogen

Names & Taxonomyi

Protein namesi
Recommended name:
GRB2-associated and regulator of MAPK protein 1
Alternative name(s):
GRB2-associated and regulator of MAPK1
Gene namesi
Name:GAREM1
Synonyms:C18orf11, FAM59A, GAREM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:26136. GAREM1.

Subcellular locationi

GO - Cellular componenti

  • plasma membrane Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi105 – 1051Y → 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. 1 Publication
Mutagenesisi453 – 4531Y → F: Does not abolish phosphorylation upon EGF stimulation. Abolishes interaction with PTPN11. Abolishes phosphorylation upon EGF stimulation; when associated with F-105. 1 Publication

Organism-specific databases

PharmGKBiPA134888032.

Polymorphism and mutation databases

BioMutaiGAREM.
DMDMi125991851.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 876876GRB2-associated and regulator of MAPK protein 1PRO_0000277647Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei105 – 1051Phosphotyrosine1 Publication
Modified residuei453 – 4531Phosphotyrosine1 Publication
Modified residuei610 – 6101PhosphoserineBy similarity
Modified residuei614 – 6141PhosphoserineBy similarity

Post-translational modificationi

On EGF stimulation, phosphorylated on Tyr-105 and Tyr-453.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9H706.
MaxQBiQ9H706.
PaxDbiQ9H706.
PRIDEiQ9H706.

PTM databases

iPTMnetiQ9H706.
PhosphoSiteiQ9H706.

Expressioni

Tissue specificityi

Isoform 1 is ubiquitously expressed.1 Publication

Gene expression databases

BgeeiQ9H706.
CleanExiHS_FAM59A.
ExpressionAtlasiQ9H706. baseline and differential.
GenevisibleiQ9H706. HS.

Organism-specific databases

HPAiHPA040709.
HPA042046.

Interactioni

Subunit structurei

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 GRB2.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GRB2P629936EBI-3440103,EBI-401755

GO - Molecular functioni

  • proline-rich region binding Source: UniProtKB

Protein-protein interaction databases

BioGridi122275. 9 interactions.
IntActiQ9H706. 6 interactions.
STRINGi9606.ENSP00000269209.

Structurei

Secondary structure

1
876
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi813 – 8197Combined sources
Helixi820 – 8223Combined sources
Helixi827 – 8348Combined sources
Turni835 – 8373Combined sources
Helixi840 – 8456Combined sources
Helixi848 – 8536Combined sources
Helixi859 – 87012Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DKZNMR-A801-871[»]
ProteinModelPortaliQ9H706.
SMRiQ9H706. Positions 795-874.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H706.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini811 – 87666SAMAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni12 – 320309CABITAdd
BLAST
Regioni498 – 55053Necessary for interaction with GRB2Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi512 – 56655Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the GAREM family.Curated

Phylogenomic databases

eggNOGiENOG410II0U. Eukaryota.
ENOG410XSPW. LUCA.
GeneTreeiENSGT00530000063834.
HOGENOMiHOG000074085.
HOVERGENiHBG060860.
InParanoidiQ9H706.
OMAiEVNLQGC.
OrthoDBiEOG7BKCSW.
PhylomeDBiQ9H706.
TreeFamiTF329726.

Family and domain databases

InterProiIPR025946. CABIT_dom.
IPR013761. SAM/pointed.
[Graphical view]
PfamiPF12736. CABIT. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H706-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDPAPSLGCS LKDVKWSSVA VPLDLLVSTY RLPQIARLDN GECVEGLREN
60 70 80 90 100
DYLLIHSCRQ WTTITAHSLE EGHYVIGPKI EIPVHYAGQF KLLEQDRDIK
110 120 130 140 150
EPVQYFNSVE EVAKAFPERV YVMEDITFNV KVASGECNED TEVYNITLCT
160 170 180 190 200
GDELTLMGQA EILYAKTFKE KSRLNTIFKK IGKLNSISKL GKGKMPCLIC
210 220 230 240 250
MNHRTNESIS LPFQCKGRFS TRSPLELQMQ EGEHTIRNIV EKTRLPVNVT
260 270 280 290 300
VPSPPPRNPY DLHFIREGHR YKFVNIQTKT VVVCCVLRNN KILPMHFPLH
310 320 330 340 350
LTVPKFSLPE HLVKGESWPE TLVHHWLGIC QEQFDIDEYS RAVRDVKTDW
360 370 380 390 400
NEECKSPKKG RCSGHNHVPN SLSYARDELT QSFHRLSVCV YGNNLHGNSE
410 420 430 440 450
VNLHGCRDLG GDWAPFPHDI LPYQDSGDSG SDYLFPEASE ESAGIPGKSE
460 470 480 490 500
LPYEELWLEE GKPSHQPLTR SLSEKNRCDQ FRGSVRSKCA TSPLPIPGTL
510 520 530 540 550
GAAVKSSDTA LPPPPVPPKS EAVREECRLL NAPPVPPRSA KPLSTSPSIP
560 570 580 590 600
PRTVKPARQQ TRSPSPTLSY YSSGLHNISV TKTDTNPSES TPVSCYPCNR
610 620 630 640 650
VKTDSVDLKS PFGSPSAEAV SSRLSWPNHY SGASESQTRS DFLLDPSRSY
660 670 680 690 700
SYPRQKTPGT PKRNCPAPFD FDGCELLASP TSPVTAEFSS SVSGCPKSAS
710 720 730 740 750
YSLESTDVKS LAAGVTKQST SCPALPPRAP KLVEEKVASE TSPLPLKIDG
760 770 780 790 800
AEEDPKSGSP DLSEDQYFVK KGMQDIFSAS YPFSSPLHLQ LAPRSCGDGS
810 820 830 840 850
PWQPPADLSG LSIEEVSKSL RFIGLSEDVI SFFVTEKIDG NLLVQLTEEI
860 870
LSEDFKLSKL QVKKIMQFIN GWRPKI
Length:876
Mass (Da):97,186
Last modified:February 6, 2007 - v2
Checksum:i668EBABC9CDE4CDF
GO
Isoform 2 (identifier: Q9H706-2) [UniParc]FASTAAdd to basket

Also known as: GAREM(S)

The sequence of this isoform differs from the canonical sequence as follows:
     495-563: Missing.

Show »
Length:807
Mass (Da):90,008
Checksum:i5C5DF3BFC90F1717
GO
Isoform 3 (identifier: Q9H706-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     579-579: Missing.

Show »
Length:875
Mass (Da):97,099
Checksum:i10A0E9147A9BFCB1
GO

Sequence cautioni

The sequence CAD39149.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti243 – 2431T → N.
Corresponds to variant rs671138 [ dbSNP | Ensembl ].
VAR_030580
Natural varianti291 – 2911K → R.
Corresponds to variant rs3744921 [ dbSNP | Ensembl ].
VAR_030581
Natural varianti490 – 4901A → V.
Corresponds to variant rs16962974 [ dbSNP | Ensembl ].
VAR_030582
Natural varianti580 – 5801V → I.
Corresponds to variant rs3891458 [ dbSNP | Ensembl ].
VAR_030583
Natural varianti720 – 7201T → M.
Corresponds to variant rs2276374 [ dbSNP | Ensembl ].
VAR_030584

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei495 – 56369Missing in isoform 2. 1 PublicationVSP_023047Add
BLAST
Alternative sequencei579 – 5791Missing in isoform 3. 1 PublicationVSP_023048

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK025263 mRNA. Translation: BAB15094.1.
AL834491 mRNA. Translation: CAD39149.1. Different initiation.
BC005074 mRNA. Translation: AAH05074.1.
BC121067 mRNA. Translation: AAI21068.1.
BC121068 mRNA. Translation: AAI21069.1.
CCDSiCCDS11905.1. [Q9H706-3]
CCDS56057.1. [Q9H706-1]
RefSeqiNP_001229338.1. NM_001242409.1. [Q9H706-1]
NP_073588.1. NM_022751.2. [Q9H706-3]
UniGeneiHs.444314.

Genome annotation databases

EnsembliENST00000269209; ENSP00000269209; ENSG00000141441. [Q9H706-1]
ENST00000399218; ENSP00000382165; ENSG00000141441. [Q9H706-3]
GeneIDi64762.
KEGGihsa:64762.
UCSCiuc002kxk.3. human. [Q9H706-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK025263 mRNA. Translation: BAB15094.1.
AL834491 mRNA. Translation: CAD39149.1. Different initiation.
BC005074 mRNA. Translation: AAH05074.1.
BC121067 mRNA. Translation: AAI21068.1.
BC121068 mRNA. Translation: AAI21069.1.
CCDSiCCDS11905.1. [Q9H706-3]
CCDS56057.1. [Q9H706-1]
RefSeqiNP_001229338.1. NM_001242409.1. [Q9H706-1]
NP_073588.1. NM_022751.2. [Q9H706-3]
UniGeneiHs.444314.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DKZNMR-A801-871[»]
ProteinModelPortaliQ9H706.
SMRiQ9H706. Positions 795-874.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122275. 9 interactions.
IntActiQ9H706. 6 interactions.
STRINGi9606.ENSP00000269209.

PTM databases

iPTMnetiQ9H706.
PhosphoSiteiQ9H706.

Polymorphism and mutation databases

BioMutaiGAREM.
DMDMi125991851.

Proteomic databases

EPDiQ9H706.
MaxQBiQ9H706.
PaxDbiQ9H706.
PRIDEiQ9H706.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269209; ENSP00000269209; ENSG00000141441. [Q9H706-1]
ENST00000399218; ENSP00000382165; ENSG00000141441. [Q9H706-3]
GeneIDi64762.
KEGGihsa:64762.
UCSCiuc002kxk.3. human. [Q9H706-1]

Organism-specific databases

CTDi64762.
GeneCardsiGAREM.
HGNCiHGNC:26136. GAREM1.
HPAiHPA040709.
HPA042046.
neXtProtiNX_Q9H706.
PharmGKBiPA134888032.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410II0U. Eukaryota.
ENOG410XSPW. LUCA.
GeneTreeiENSGT00530000063834.
HOGENOMiHOG000074085.
HOVERGENiHBG060860.
InParanoidiQ9H706.
OMAiEVNLQGC.
OrthoDBiEOG7BKCSW.
PhylomeDBiQ9H706.
TreeFamiTF329726.

Miscellaneous databases

EvolutionaryTraceiQ9H706.
GenomeRNAii64762.
PROiQ9H706.

Gene expression databases

BgeeiQ9H706.
CleanExiHS_FAM59A.
ExpressionAtlasiQ9H706. baseline and differential.
GenevisibleiQ9H706. HS.

Family and domain databases

InterProiIPR025946. CABIT_dom.
IPR013761. SAM/pointed.
[Graphical view]
PfamiPF12736. CABIT. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    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.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Colon.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Testis.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Lung.
  4. "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."
    Tashiro K., Tsunematsu T., Okubo H., Ohta T., Sano E., Yamauchi E., Taniguchi H., Konishi H.
    J. Biol. Chem. 284:20206-20214(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: 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, TISSUE SPECIFICITY.
  5. "Solution structure of the SAM_PNT-domain of the hypothetical protein LOC64762."
    RIKEN structural genomics initiative (RSGI)
    Submitted (OCT-2006) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 2-165.

Entry informationi

Entry nameiGARE1_HUMAN
AccessioniPrimary (citable) accession number: Q9H706
Secondary accession number(s): Q0VAG3
, Q0VAG4, Q8ND03, Q9BSF5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: June 8, 2016
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.