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Protein

Growth factor receptor-bound protein 14

Gene

GRB14

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

Functioni

Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal.2 Publications

GO - Molecular functioni

  • identical protein binding Source: CAFA
  • protein homodimerization activity Source: CAFA
  • receptor tyrosine kinase binding Source: CAFA
  • SH3/SH2 adaptor activity Source: ProtInc

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-210993 Tie2 Signaling
SignaLinkiQ14449

Names & Taxonomyi

Protein namesi
Recommended name:
Growth factor receptor-bound protein 14
Alternative name(s):
GRB14 adapter protein
Gene namesi
Name:GRB14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000115290.9
HGNCiHGNC:4565 GRB14
MIMi601524 gene
neXtProtiNX_Q14449

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

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi140K → A: Partial loss of INSR-binding. Loss of inhibition of AKT1 activation. Loss of inhibition of MAPK3 phosphorylation. Loss of NRAS-binding. 1 Publication1
Mutagenesisi245E → G: 4-fold increase in PI(3,4,5)P3-binding affinity; when associated with S-246. 1 Publication1
Mutagenesisi246Q → S: 4-fold increase in PI(3,4,5)P3-binding affinity; when associated with G-245. 1 Publication1
Mutagenesisi252K → A: Partial loss of INSR-binding. Loss of inhibition of AKT1 activation. Loss of inhibition of MAPK3 phosphorylation. Loss of translocation to the plasma membrane upon insulin-stimulation. More than 3-fold decrease in PI(3,4,5)P3-binding affinity. 1 Publication1
Mutagenesisi299G → N: No effect on PI(3,4,5)P3-binding. 1 Publication1
Mutagenesisi348Q → A: Loss of inhibition of AKT1 activation; when associated with A-349. Loss of inhibition of MAPK3 phosphorylation; when associated with A-349. No effect on INSR-binding; when associated with A-349. 1 Publication1
Mutagenesisi349N → A: Loss of inhibition of AKT1 activation; when associated with A-348. Loss of inhibition of MAPK3 phosphorylation; when associated with A-348. No effect on INSR-binding; when associated with A-348. 1 Publication1

Organism-specific databases

DisGeNETi2888
OpenTargetsiENSG00000115290
PharmGKBiPA28961

Polymorphism and mutation databases

BioMutaiGRB14
DMDMi59802920

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001503482 – 540Growth factor receptor-bound protein 14Add BLAST539

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineCombined sources1
Modified residuei372PhosphoserineBy similarity1
Modified residuei375PhosphoserineBy similarity1
Isoform 2 (identifier: Q14449-2)
Modified residuei9PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated on serine residues. Phosphorylated on tyrosine residues by TEK/TIE2.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ14449
MaxQBiQ14449
PaxDbiQ14449
PeptideAtlasiQ14449
PRIDEiQ14449
ProteomicsDBi59994

PTM databases

iPTMnetiQ14449
PhosphoSitePlusiQ14449

Expressioni

Tissue specificityi

Expressed at high levels in the liver, kidney, pancreas, testis, ovary, heart and skeletal muscle.

Gene expression databases

BgeeiENSG00000115290 Expressed in 158 organ(s), highest expression level in adrenal tissue
CleanExiHS_GRB14
ExpressionAtlasiQ14449 baseline and differential
GenevisibleiQ14449 HS

Organism-specific databases

HPAiCAB022294
HPA035052
HPA035053

Interactioni

Subunit structurei

Interacts with the cytoplasmic domain of the autophosphorylated insulin receptor (INSR), through the SH2 domain (By similarity). Interacts with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop on INSR from dephosphorylation. Binds to the ankyrin repeat region of TNKS2 via its N-terminus. Interacts with activated NRAS. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated).By similarity5 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109145, 18 interactors
DIPiDIP-42605N
IntActiQ14449, 13 interactors
MINTiQ14449
STRINGi9606.ENSP00000263915

Structurei

Secondary structure

1540
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00230
ProteinModelPortaliQ14449
SMRiQ14449
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14449

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini106 – 192Ras-associatingPROSITE-ProRule annotationAdd BLAST87
Domaini234 – 342PHPROSITE-ProRule annotationAdd BLAST109
Domaini439 – 535SH2PROSITE-ProRule annotationAdd BLAST97

Domaini

The PH domain binds relatively non-specifically and with low affinity to several phosphoinositides, the best binder being PI(3,4,5)P3.1 Publication

Sequence similaritiesi

Belongs to the GRB7/10/14 family.Curated

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IQ4V Eukaryota
ENOG410ZN6J LUCA
GeneTreeiENSGT00550000074537
HOGENOMiHOG000231904
HOVERGENiHBG000468
InParanoidiQ14449
OMAiVSPMRSI
OrthoDBiEOG091G135G
PhylomeDBiQ14449
TreeFamiTF317511

Family and domain databases

CDDicd01259 PH_APBB1IP, 1 hit
cd10414 SH2_Grb14, 1 hit
Gene3Di2.30.29.30, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR015042 BPS-dom
IPR039664 GRB/APBB1IP
IPR035035 Grb14
IPR035034 Grb14_SH2
IPR011993 PH-like_dom_sf
IPR039665 PH_APBB1IP
IPR001849 PH_domain
IPR000159 RA_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR029071 Ubiquitin-like_domsf
PANTHERiPTHR11243 PTHR11243, 1 hit
PTHR11243:SF22 PTHR11243:SF22, 1 hit
PfamiView protein in Pfam
PF08947 BPS, 1 hit
PF00169 PH, 1 hit
PF00788 RA, 1 hit
PF00017 SH2, 1 hit
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00314 RA, 1 hit
SM00252 SH2, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
PS50200 RA, 1 hit
PS50001 SH2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q14449-1) [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
MTTSLQDGQS AASRAAARDS PLAAQVCGAA QGRGDAHDLA PAPWLHARAL
60 70 80 90 100
LPLPDGTRGC AADRRKKKDL DVPEMPSIPN PFPELCCSPF TSVLSADLFP
110 120 130 140 150
KANSRKKQVI KVYSEDETSR ALDVPSDITA RDVCQLLILK NHYIDDHSWT
160 170 180 190 200
LFEHLPHIGV ERTIEDHELV IEVLSNWGIE EENKLYFRKN YAKYEFFKNP
210 220 230 240 250
MYFFPEHMVS FATETNGEIS PTQILQMFLS SSTYPEIHGF LHAKEQGKKS
260 270 280 290 300
WKKIYFFLRR SGLYFSTKGT SKEPRHLQFF SEFGNSDIYV SLAGKKKHGA
310 320 330 340 350
PTNYGFCFKP NKAGGPRDLK MLCAEEEQSR TCWVTAIRLL KYGMQLYQNY
360 370 380 390 400
MHPYQGRSGC SSQSISPMRS ISENSLVAMD FSGQKSRVIE NPTEALSVAV
410 420 430 440 450
EEGLAWRKKG CLRLGTHGSP TASSQSSATN MAIHRSQPWF HHKISRDEAQ
460 470 480 490 500
RLIIQQGLVD GVFLVRDSQS NPKTFVLSMS HGQKIKHFQI IPVEDDGEMF
510 520 530 540
HTLDDGHTRF TDLIQLVEFY QLNKGVLPCK LKHYCARIAL
Length:540
Mass (Da):60,988
Last modified:February 15, 2005 - v2
Checksum:i00472988650F7C6C
GO
Isoform 2 (identifier: Q14449-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MTTSLQDGQSAASRAAARDSP → MSLSARRVTLPAITPIILQKR
     22-108: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:453
Mass (Da):51,946
Checksum:i82469B04B7231E1C
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JD37C9JD37_HUMAN
Growth factor receptor-bound protei...
GRB14
415Annotation score:
C9JLT6C9JLT6_HUMAN
Growth factor receptor-bound protei...
GRB14
155Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06575890F → I2 PublicationsCorresponds to variant dbSNP:rs61748245Ensembl.1
Natural variantiVAR_065759507H → Y in a patient with amyotrophic lateral sclerosis. 1 PublicationCorresponds to variant dbSNP:rs144301087Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0565821 – 21MTTSL…ARDSP → MSLSARRVTLPAITPIILQK R in isoform 2. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_05658322 – 108Missing in isoform 2. 1 PublicationAdd BLAST87

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76687 mRNA Translation: AAC15861.1
AK301961 mRNA Translation: BAH13595.1
AC107075 Genomic DNA No translation available.
AC110086 Genomic DNA No translation available.
CH471058 Genomic DNA Translation: EAX11342.1
BC053559 mRNA Translation: AAH53559.1
CCDSiCCDS2222.1 [Q14449-1]
RefSeqiNP_001290351.1, NM_001303422.1 [Q14449-2]
NP_004481.2, NM_004490.2 [Q14449-1]
UniGeneiHs.411881

Genome annotation databases

EnsembliENST00000263915; ENSP00000263915; ENSG00000115290 [Q14449-1]
GeneIDi2888
KEGGihsa:2888
UCSCiuc002ucl.4 human [Q14449-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76687 mRNA Translation: AAC15861.1
AK301961 mRNA Translation: BAH13595.1
AC107075 Genomic DNA No translation available.
AC110086 Genomic DNA No translation available.
CH471058 Genomic DNA Translation: EAX11342.1
BC053559 mRNA Translation: AAH53559.1
CCDSiCCDS2222.1 [Q14449-1]
RefSeqiNP_001290351.1, NM_001303422.1 [Q14449-2]
NP_004481.2, NM_004490.2 [Q14449-1]
UniGeneiHs.411881

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AUGX-ray2.30A/B433-537[»]
2AUHX-ray3.20B361-419[»]
4K81X-ray2.40A/C/E/G106-356[»]
DisProtiDP00230
ProteinModelPortaliQ14449
SMRiQ14449
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109145, 18 interactors
DIPiDIP-42605N
IntActiQ14449, 13 interactors
MINTiQ14449
STRINGi9606.ENSP00000263915

PTM databases

iPTMnetiQ14449
PhosphoSitePlusiQ14449

Polymorphism and mutation databases

BioMutaiGRB14
DMDMi59802920

Proteomic databases

EPDiQ14449
MaxQBiQ14449
PaxDbiQ14449
PeptideAtlasiQ14449
PRIDEiQ14449
ProteomicsDBi59994

Protocols and materials databases

DNASUi2888
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263915; ENSP00000263915; ENSG00000115290 [Q14449-1]
GeneIDi2888
KEGGihsa:2888
UCSCiuc002ucl.4 human [Q14449-1]

Organism-specific databases

CTDi2888
DisGeNETi2888
EuPathDBiHostDB:ENSG00000115290.9
GeneCardsiGRB14
HGNCiHGNC:4565 GRB14
HPAiCAB022294
HPA035052
HPA035053
MIMi601524 gene
neXtProtiNX_Q14449
OpenTargetsiENSG00000115290
PharmGKBiPA28961
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQ4V Eukaryota
ENOG410ZN6J LUCA
GeneTreeiENSGT00550000074537
HOGENOMiHOG000231904
HOVERGENiHBG000468
InParanoidiQ14449
OMAiVSPMRSI
OrthoDBiEOG091G135G
PhylomeDBiQ14449
TreeFamiTF317511

Enzyme and pathway databases

ReactomeiR-HSA-210993 Tie2 Signaling
SignaLinkiQ14449

Miscellaneous databases

ChiTaRSiGRB14 human
EvolutionaryTraceiQ14449
GeneWikiiGRB14
GenomeRNAii2888
PROiPR:Q14449
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115290 Expressed in 158 organ(s), highest expression level in adrenal tissue
CleanExiHS_GRB14
ExpressionAtlasiQ14449 baseline and differential
GenevisibleiQ14449 HS

Family and domain databases

CDDicd01259 PH_APBB1IP, 1 hit
cd10414 SH2_Grb14, 1 hit
Gene3Di2.30.29.30, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR015042 BPS-dom
IPR039664 GRB/APBB1IP
IPR035035 Grb14
IPR035034 Grb14_SH2
IPR011993 PH-like_dom_sf
IPR039665 PH_APBB1IP
IPR001849 PH_domain
IPR000159 RA_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR029071 Ubiquitin-like_domsf
PANTHERiPTHR11243 PTHR11243, 1 hit
PTHR11243:SF22 PTHR11243:SF22, 1 hit
PfamiView protein in Pfam
PF08947 BPS, 1 hit
PF00169 PH, 1 hit
PF00788 RA, 1 hit
PF00017 SH2, 1 hit
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00314 RA, 1 hit
SM00252 SH2, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
PS50200 RA, 1 hit
PS50001 SH2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGRB14_HUMAN
AccessioniPrimary (citable) accession number: Q14449
Secondary accession number(s): B7Z7F9, Q7Z6I1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: February 15, 2005
Last modified: November 7, 2018
This is version 163 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 chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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