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Basic Information Integrated Annotations
Tag Content
iUUCD ID IUUC-Hsa-046730
Ensembl Protein ID ENSP00000376347.1
UniProt Accession P62993; P29354; Q14450; Q63057; Q63059; GRB2_HUMAN
Genbank Protein ID AAA58448.1; CAA44664.1; AAC37549.1; AAC72075.1; AAC72075.1; AAC72075.1; AAC72075.1; AAC72075.1; AAM21073.1; CAG46740.1; AAH00631.1
Protein Name Growth factor receptor-bound protein 2; Adapter protein GRB2; Protein Ash; SH2/SH3 adapter GRB2
Genbank Nucleotide ID M96995; X62852; L29511; AF063618; AF063614; AF063615; AF063616; AF063617; AF498925; CR541942; AC011933
Gene Name GRB2; ASH
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000177885.13 ENST00000581959.1 ENSP00000463525.1
ENSG00000177885.13 ENST00000392563.5 ENSP00000376346.1
ENSG00000177885.13 ENST00000392564.5 ENSP00000376347.1
ENSG00000177885.13 ENST00000578961.5 ENSP00000464279.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICTHPAHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
miRWalkRepTarSomamiRmiRcode
RAID2LncRNADisease
Protein-protein Interaction
IIDPINAHINTMentha
InWeb_IM
Protein 3D Structure
PDBMMDB
Disease-associated Variation
GWASdbOMIM
Drug and target
TTD
Post-translational Modifications (PTMs)
CPLMdbPAFPhosphositePlusdbPTM
HPRDPhospho.ELMUniProtPHOSIDA
BioGRIDmUbiSiDa
DNA Methylation
MethyCancerTCGAICGCCOSMIC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Unreviewed
Classification
Family E-Value Score Start End
UBD/SH3 2.40e-36 125.1 157 214
Active Site
Position(s) Description Evidence
N/A N/A N/A
Domain Profile

   UBD/SH3
   S: 2    skekvqvlydyeaqnddeLtlkkGdvvlviekeeqdegWlkgvkelegkrGlfPenFvekle 63
           +  +vq+l+d+++q+d+eL +++Gd+++v+  ++ d +W+kg    +g+ G+fP n+v+ ++
   Q: 157  QPTYVQALFDFDPQEDGELGFRRGDFIHVM--DNSDPNWWKG--ACHGQTGMFPRNYVTPVN 214
           5689*************************9..9*********..8**************997 PP
   
Organism Homo sapiens
Functional Description
(View)

Functional Description


     Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated) (PubMed:10026169, PubMed:19836242). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (By similarity). Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, IRS4, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains (PubMed:8388384, PubMed:8491186, PubMed:9553137, PubMed:11433379). It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Interacts with SOS1 (PubMed:8493579, PubMed:7664271). Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1 (PubMed:7664271). Interacts with phosphorylated MET (PubMed:11063574, PubMed:11827484). Interacts with phosphorylated TOM1L1 (By similarity). Interacts with the phosphorylated C-terminus of SH2B2 (PubMed:9233773). Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity) (PubMed:9489702, PubMed:12359715, PubMed:12486104, PubMed:12514734). Interacts with NISCH, PTPNS1 and REPS2 (PubMed:9062191, PubMed:9422736, PubMed:11912194). Interacts with syntrophin SNTA1 (By similarity). Interacts (via SH3 domains) with REPS1 (By similarity). Interacts (via SH3 domains) with PIK3C2B (PubMed:11533253). Interacts with CBL and CBLB (PubMed:10022120, PubMed:10086340). Interacts with AJUBA and CLNK (By similarity). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2 (PubMed:8723348, PubMed:9108392, PubMed:9484780, PubMed:10942756, PubMed:12171928). Interacts with PTPN11 (By similarity). Interacts with PRNP (By similarity). Interacts with RALGPS1 (PubMed:10747847). Interacts with HCST (PubMed:16582911). Interacts with KDR (By similarity). Interacts with FLT1 (tyrosine-phosphorylated) (By similarity). Interacts with GAPT and PTPRE (PubMed:10980613, PubMed:18559951). Interacts (via SH2 domain) with KIF26A (PubMed:19914172). Interacts (via SH3 2) with GAB2 (PubMed:19523899). Interacts with ADAM15 (PubMed:18296648). Interacts with THEMIS2 (By similarity). Interacts (via SH2 domain) with AXL (phosphorylated) (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:15526160, PubMed:16129412). Interacts with PTPRJ and BCR (PubMed:12475979, PubMed:15302586). Interacts with PTPN23 (PubMed:21179510). Interacts with FLT4 (tyrosine phosphorylated) (PubMed:15102829). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:8798570, PubMed:12925710). Part of a complex including TNK2, GRB2, LTK and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:8262059). Interacts with ERBB4 (PubMed:10867024). Interacts with NTRK1 (phosphorylated upon ligand-binding) (PubMed:15488758). Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:9148935). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (PubMed:20521079). Isoform 1 interacts with SCIMP (PubMed:21930792). Interacts (via SH3 domains) with GAREM1 isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation (PubMed:19509291). Interacts with DAB2 (By similarity). Interacts with TESPA1 (PubMed:22561606). Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1 (By similarity). Interacts with CD28 (PubMed:24098653). Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA (By similarity). Interacts with ASAP3 (phosphorylated form) (PubMed:22027826). Interacts (via SH3 domain) with HEV ORF3 protein (PubMed:11518702). Interacts with HCV NS5A via its SH3 domains (PubMed:10318918). Interacts with herpes simplex virus 1 UL46 (PubMed:23946459). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (By similarity). Interacts with PTPRO (phosphorylated form) (By similarity). Interacts with PTPRB (phosphorylated form) (By similarity).
 Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated) (PubMed:10026169, PubMed:19836242). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (By similarity). Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, IRS4, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains (PubMed:8388384, PubMed:8491186, PubMed:9553137, PubMed:11433379). It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Interacts with SOS1 (PubMed:8493579, PubMed:7664271). Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1 (PubMed:7664271). Interacts with phosphorylated MET (PubMed:11063574, PubMed:11827484). Interacts with phosphorylated TOM1L1 (By similarity). Interacts with the phosphorylated C-terminus of SH2B2 (PubMed:9233773). Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity) (PubMed:9489702, PubMed:12359715, PubMed:12486104, PubMed:12514734). Interacts with NISCH, PTPNS1 and REPS2 (PubMed:9062191, PubMed:9422736, PubMed:11912194). Interacts with syntrophin SNTA1 (By similarity). Interacts (via SH3 domains) with REPS1 (By similarity). Interacts (via SH3 domains) with PIK3C2B (PubMed:11533253). Interacts with CBL and CBLB (PubMed:10022120, PubMed:10086340). Interacts with AJUBA and CLNK (By similarity). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2 (PubMed:8723348, PubMed:9108392, PubMed:9484780, PubMed:10942756, PubMed:12171928). Interacts with PTPN11 (By similarity). Interacts with PRNP (By similarity). Interacts with RALGPS1 (PubMed:10747847). Interacts with HCST (PubMed:16582911). Interacts with KDR (By similarity). Interacts with FLT1 (tyrosine-phosphorylated) (By similarity). Interacts with GAPT and PTPRE (PubMed:10980613, PubMed:18559951). Interacts (via SH2 domain) with KIF26A (PubMed:19914172). Interacts (via SH3 2) with GAB2 (PubMed:19523899). Interacts with ADAM15 (PubMed:18296648). Interacts with THEMIS2 (By similarity). Interacts (via SH2 domain) with AXL (phosphorylated) (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:15526160, PubMed:16129412). Interacts with PTPRJ and BCR (PubMed:12475979, PubMed:15302586). Interacts with PTPN23 (PubMed:21179510). Interacts with FLT4 (tyrosine phosphorylated) (PubMed:15102829). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:8798570, PubMed:12925710). Part of a complex including TNK2, GRB2, LTK and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:8262059). Interacts with ERBB4 (PubMed:10867024). Interacts with NTRK1 (phosphorylated upon ligand-binding) (PubMed:15488758). Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:9148935). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (PubMed:20521079). Isoform 1 interacts with SCIMP (PubMed:21930792). Interacts (via SH3 domains) with GAREM1 isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation (PubMed:19509291). Interacts with DAB2 (By similarity). Interacts with TESPA1 (PubMed:22561606). Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1 (By similarity). Interacts with CD28 (PubMed:24098653). Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA (By similarity). Interacts with ASAP3 (phosphorylated form) (PubMed:22027826). Interacts (via SH3 domain) with HEV ORF3 protein (PubMed:11518702). Interacts with HCV NS5A via its SH3 domains (PubMed:10318918). Interacts with herpes simplex virus 1 UL46 (PubMed:23946459). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (By similarity). Interacts with PTPRO (phosphorylated form) (By similarity). Interacts with PTPRB (phosphorylated form) (By similarity).
Protein Sequence
(Fasta)
MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK NYIEMKPHPW 60
FFGKIPRAKA EEMLSKQRHD GAFLIRESES APGDFSLSVK FGNDVQHFKV LRDGAGKYFL 120
It may take some time, please wait.

Protein Fasta Sequence


>IUUC-Hsa-046730|UBD,SH3|Homo sapiens
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Nucleotide Sequence
(Fasta)
AAGTTCTCGC GGGACACCGA CGGGGAGCGG AAGCCAGGAG GTATTGCTGC TTCGGCGACC 60
GGGCGGCGGC AGCGGCGGCG GCGGCTGTGG CAGAGTCTGT GCCTGTGGCG GTGACGGCGG 120
It may take some time, please wait.

Nucleotide Fasta Sequence


>IUUC-Hsa-046730|UBD,SH3|Homo sapiens
Please wait for a moment...
Sequence Source Ensembl
Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0025--Alternative splicing
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0903--Direct protein sequencing
KW-0967--Endosome
KW-0333--Golgi apparatus
KW-0945--Host-virus interaction
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-1185--Reference proteome
KW-0677--Repeat
KW-0727--SH2 domain
KW-0728--SH3 domain
Interpro

IPR000980--SH2
IPR001452--SH3_domain
PROSITE

PS50001--SH2
PS50002--SH3
Pfam

PF00017--SH2
PF00018--SH3_1
PRINTS

PR00401--SH2DOMAIN
PR00452--SH3DOMAIN
SMART

SM00252--SH2
SM00326--SH3
Gene Ontology

GO:0005911--C:cell-cell junction
GO:0008180--C:COP9 signalosome
GO:0005737--C:cytoplasm
GO:0005829--C:cytosol
GO:0005768--C:endosome
GO:0070062--C:extracellular exosome
GO:0031234--C:extrinsic component of cytoplasmic side of plasma membrane
GO:0005794--C:Golgi apparatus
GO:0070436--C:Grb2-EGFR complex
GO:0005730--C:nucleolus
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0005886--C:plasma membrane
GO:0012506--C:vesicle membrane
GO:0016303--F:1-phosphatidylinositol-3-kinase activity
GO:0046875--F:ephrin receptor binding
GO:0005154--F:epidermal growth factor receptor binding
GO:0042802--F:identical protein binding
GO:0043560--F:insulin receptor substrate binding
GO:0005168--F:neurotrophin TRKA receptor binding
GO:0004715--F:non-membrane spanning protein tyrosine kinase activity
GO:0046934--F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity
GO:0019901--F:protein kinase binding
GO:0005088--F:Ras guanyl-nucleotide exchange factor activity
GO:0003723--F:RNA binding
GO:0017124--F:SH3 domain binding
GO:0005070--F:SH3/SH2 adaptor activity
GO:0007568--P:aging
GO:0048646--P:anatomical structure formation involved in morphogenesis
GO:0007411--P:axon guidance
GO:0060670--P:branching involved in labyrinthine layer morphogenesis
GO:0030154--P:cell differentiation
GO:0016477--P:cell migration
GO:0007267--P:cell-cell signaling
GO:0071479--P:cellular response to ionizing radiation
GO:0035635--P:entry of bacterium into host cell
GO:0007173--P:epidermal growth factor receptor signaling pathway
GO:0038128--P:ERBB2 signaling pathway
GO:0038095--P:Fc-epsilon receptor signaling pathway
GO:0038096--P:Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0008543--P:fibroblast growth factor receptor signaling pathway
GO:0045087--P:innate immune response
GO:0008286--P:insulin receptor signaling pathway
GO:0050900--P:leukocyte migration
GO:0000165--P:MAPK cascade
GO:0061024--P:membrane organization
GO:0042059--P:negative regulation of epidermal growth factor receptor signaling pathway
GO:0038083--P:peptidyl-tyrosine autophosphorylation
GO:0048015--P:phosphatidylinositol-mediated signaling
GO:0030838--P:positive regulation of actin filament polymerization
GO:2000379--P:positive regulation of reactive oxygen species metabolic process
GO:0051291--P:protein heterooligomerization
GO:0007265--P:Ras protein signal transduction
GO:0031623--P:receptor internalization
GO:0042127--P:regulation of cell proliferation
GO:0043408--P:regulation of MAPK cascade
GO:0014066--P:regulation of phosphatidylinositol 3-kinase signaling
GO:0042770--P:signal transduction in response to DNA damage
GO:0031295--P:T cell costimulation
GO:0016032--P:viral process
KEGG hsa:2885
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-001345 Ailuropoda melanoleuca 99.48 2.00e-114 404.00
IUUC-Apl-003322 Anas platyrhynchos 97.38 6.00e-112 395.00
IUUC-Aca-005193 Anolis carolinensis 97.24 4.00e-127 446.00
IUUC-Ame-010929 Astyanax mexicanus 91.24 1.00e-120 424.00
IUUC-Bta-012932 Bos taurus 100.00 1.00e-129 455.00
IUUC-Cel-018665 Caenorhabditis elegans 58.06 1.00e-71 262.00
IUUC-Cja-019225 Callithrix jacchus 100.00 1.00e-129 455.00
IUUC-Cfa-020887 Canis familiaris 100.00 1.00e-129 455.00
IUUC-Cpo-022488 Cavia porcellus 100.00 1.00e-129 455.00
IUUC-Csa-023326 Chlorocebus sabaeus 100.00 1.00e-129 455.00
IUUC-Cho-024953 Choloepus hoffmanni 82.03 6.00e-98 349.00
IUUC-Cin-025144 Ciona intestinalis 63.21 9.00e-74 269.00
IUUC-Csv-026210 Ciona savignyi 60.66 2.00e-71 261.00
IUUC-Dre-028403 Danio rerio 94.93 2.00e-124 437.00
IUUC-Dno-029187 Dasypus novemcinctus 98.62 2.00e-128 451.00
IUUC-Dor-030763 Dipodomys ordii 100.00 1.00e-129 455.00
IUUC-Dme-031741 Drosophila melanogaster 65.57 2.00e-78 285.00
IUUC-Ete-032354 Echinops telfairi 69.91 2.00e-82 298.00
IUUC-Eca-033222 Equus caballus 100.00 1.00e-129 455.00
IUUC-Eeu-034513 Erinaceus europaeus 73.73 3.00e-88 317.00
IUUC-Fca-036294 Felis catus 100.00 1.00e-129 455.00
IUUC-Fal-037130 Ficedula albicollis 96.77 1.00e-125 441.00
IUUC-Gmo-039546 Gadus morhua 93.55 7.00e-123 432.00
IUUC-Gga-041139 Gallus gallus 97.70 3.00e-127 447.00
IUUC-Gac-041968 Gasterosteus aculeatus 94.47 8.00e-124 435.00
IUUC-Ggo-044562 Gorilla gorilla 100.00 1.00e-129 455.00
IUUC-Itr-049025 Ictidomys tridecemlineatus 100.00 1.00e-129 455.00
IUUC-Lch-050230 Latimeria chalumnae 95.52 2.00e-73 269.00
IUUC-Loc-052723 Lepisosteus oculatus 95.85 2.00e-125 441.00
IUUC-Laf-053774 Loxodonta africana 98.62 2.00e-128 451.00
IUUC-Mcc-054603 Macaca mulatta 100.00 1.00e-129 455.00
IUUC-Meu-056173 Macropus eugenii 80.65 5.00e-100 356.00
IUUC-Mga-059950 Meleagris gallopavo 97.70 3.00e-127 447.00
IUUC-Mmr-060878 Microcebus murinus 100.00 1.00e-129 455.00
IUUC-Mdo-062454 Monodelphis domestica 97.70 3.00e-127 447.00
IUUC-Mmu-063913 Mus musculus 99.54 4.00e-129 453.00
IUUC-Mpu-066125 Mustela putorius furo 100.00 1.00e-129 455.00
IUUC-Mlu-068007 Myotis lucifugus 100.00 1.00e-129 455.00
IUUC-Nle-069101 Nomascus leucogenys 100.00 1.00e-129 455.00
IUUC-Opr-071075 Ochotona princeps 100.00 1.00e-129 455.00
IUUC-Ont-072253 Oreochromis niloticus 91.24 4.00e-120 423.00
IUUC-Ocu-074583 Oryctolagus cuniculus 100.00 1.00e-129 455.00
IUUC-Ola-086586 Oryzias latipes 95.51 5.00e-86 311.00
IUUC-Oga-089047 Otolemur garnettii 100.00 1.00e-129 455.00
IUUC-Oar-089904 Ovis aries 92.66 2.00e-118 417.00
IUUC-Ptr-090678 Pan troglodytes 100.00 1.00e-129 455.00
IUUC-Pan-092090 Papio anubis 100.00 1.00e-129 455.00
IUUC-Psi-093765 Pelodiscus sinensis 97.24 1.00e-126 445.00
IUUC-Pma-094650 Petromyzon marinus 85.25 1.00e-111 395.00
IUUC-Pfo-096131 Poecilia formosa 94.01 1.00e-123 435.00
IUUC-Pab-098709 Pongo abelii 100.00 1.00e-129 455.00
IUUC-Pca-100581 Procavia capensis 98.95 2.00e-113 400.00
IUUC-Pva-103066 Pteropus vampyrus 100.00 1.00e-129 455.00
IUUC-Rno-105224 Rattus norvegicus 100.00 1.00e-129 455.00
IUUC-Sce-106302 Saccharomyces cerevisiae 51.85 1.00e-15 76.30
IUUC-Sha-107247 Sarcophilus harrisii 97.91 2.00e-112 397.00
IUUC-Sar-113277 Sorex araneus 84.33 9.00e-104 369.00
IUUC-Ssc-115478 Sus scrofa 100.00 1.00e-129 455.00
IUUC-Tgu-117479 Taeniopygia guttata 96.31 2.00e-125 441.00
IUUC-Tru-118451 Takifugu rubripes 84.72 5.00e-107 380.00
IUUC-Tsy-119029 Tarsius syrichta 93.75 1.00e-83 301.00
IUUC-Tbe-128097 Tupaia belangeri 99.54 1.00e-128 451.00
IUUC-Ttr-128871 Tursiops truncatus 100.00 4.00e-90 323.00
IUUC-Vpa-130754 Vicugna pacos 100.00 1.00e-129 455.00
IUUC-Xtr-132275 Xenopus tropicalis 91.70 4.00e-123 433.00
Created Date 25-Jun-2017

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