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Protein

GRB2-associated and regulator of MAPK protein 1

Gene

GAREM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionMitogen

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

EuPathDBiHostDB:ENSG00000141441.15
HGNCiHGNC:26136 GAREM1
MIMi617998 gene
neXtProtiNX_Q9H706

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi105Y → 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 Publication1
Mutagenesisi453Y → F: Does not abolish phosphorylation upon EGF stimulation. Abolishes interaction with PTPN11. Abolishes phosphorylation upon EGF stimulation; when associated with F-105. 1 Publication1

Organism-specific databases

DisGeNETi64762
OpenTargetsiENSG00000141441
PharmGKBiPA134888032

Polymorphism and mutation databases

BioMutaiGAREM
DMDMi125991851

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002776471 – 876GRB2-associated and regulator of MAPK protein 1Add BLAST876

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei105Phosphotyrosine1 Publication1
Modified residuei453Phosphotyrosine1 Publication1
Modified residuei610PhosphoserineCombined sources1
Modified residuei614PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9H706
PaxDbiQ9H706
PeptideAtlasiQ9H706
PRIDEiQ9H706
ProteomicsDBi81068
81069 [Q9H706-2]
81070 [Q9H706-3]

PTM databases

iPTMnetiQ9H706
PhosphoSitePlusiQ9H706

Expressioni

Tissue specificityi

Isoform 1 is ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000141441 Expressed in 218 organ(s), highest expression level in frontal cortex
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122275, 9 interactors
IntActiQ9H706, 7 interactors

Structurei

Secondary structure

1876
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9H706
SMRiQ9H706
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H706

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini811 – 876SAMAdd BLAST66

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni12 – 320CABITAdd BLAST309
Regioni498 – 550Necessary for interaction with GRB21 PublicationAdd BLAST53

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi512 – 566Pro-richAdd BLAST55

Sequence similaritiesi

Belongs to the GAREM family.Curated

Phylogenomic databases

eggNOGiENOG410II0U Eukaryota
ENOG410XSPW LUCA
GeneTreeiENSGT00530000063834
HOGENOMiHOG000074085
HOVERGENiHBG060860
InParanoidiQ9H706
OMAiGGEWAPF
OrthoDBiEOG091G0K06
PhylomeDBiQ9H706
TreeFamiTF329726

Family and domain databases

InterProiView protein in InterPro
IPR025946 CABIT_dom
IPR013761 SAM/pointed_sf
PfamiView protein in Pfam
PF12736 CABIT, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3QRF3J3QRF3_HUMAN
GRB2-associated and regulator of MA...
GAREM1
36Annotation score:

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030580243T → N. Corresponds to variant dbSNP:rs671138Ensembl.1
Natural variantiVAR_030581291K → R. Corresponds to variant dbSNP:rs3744921Ensembl.1
Natural variantiVAR_030582490A → V. Corresponds to variant dbSNP:rs16962974Ensembl.1
Natural variantiVAR_030583580V → I. Corresponds to variant dbSNP:rs3891458Ensembl.1
Natural variantiVAR_030584720T → M. Corresponds to variant dbSNP:rs2276374Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023047495 – 563Missing in isoform 2. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_023048579Missing in isoform 3. 1 Publication1

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

Similar proteinsi

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DKZNMR-A801-871[»]
ProteinModelPortaliQ9H706
SMRiQ9H706
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122275, 9 interactors
IntActiQ9H706, 7 interactors

PTM databases

iPTMnetiQ9H706
PhosphoSitePlusiQ9H706

Polymorphism and mutation databases

BioMutaiGAREM
DMDMi125991851

Proteomic databases

MaxQBiQ9H706
PaxDbiQ9H706
PeptideAtlasiQ9H706
PRIDEiQ9H706
ProteomicsDBi81068
81069 [Q9H706-2]
81070 [Q9H706-3]

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
DisGeNETi64762
EuPathDBiHostDB:ENSG00000141441.15
GeneCardsiGAREM1
HGNCiHGNC:26136 GAREM1
HPAiHPA040709
HPA042046
MIMi617998 gene
neXtProtiNX_Q9H706
OpenTargetsiENSG00000141441
PharmGKBiPA134888032
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410II0U Eukaryota
ENOG410XSPW LUCA
GeneTreeiENSGT00530000063834
HOGENOMiHOG000074085
HOVERGENiHBG060860
InParanoidiQ9H706
OMAiGGEWAPF
OrthoDBiEOG091G0K06
PhylomeDBiQ9H706
TreeFamiTF329726

Miscellaneous databases

ChiTaRSiGAREM1 human
EvolutionaryTraceiQ9H706
GenomeRNAii64762
PROiPR:Q9H706
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141441 Expressed in 218 organ(s), highest expression level in frontal cortex
CleanExiHS_FAM59A
ExpressionAtlasiQ9H706 baseline and differential
GenevisibleiQ9H706 HS

Family and domain databases

InterProiView protein in InterPro
IPR025946 CABIT_dom
IPR013761 SAM/pointed_sf
PfamiView protein in Pfam
PF12736 CABIT, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGARE1_HUMAN
AccessioniPrimary (citable) accession number: Q9H706
Secondary accession number(s): Q0VAG3
, Q0VAG4, Q8ND03, Q9BSF5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: November 7, 2018
This is version 130 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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