| General information | | DisProt: | DP00230 | | Name: | Growth factor receptor-bound protein 14 | | Synonym(s): | GRB14_HUMAN
GRB14 adapter protein
| | First appeared in release: | Release 2.0 (02/14/2005) | | UniProt: | Q14449 | | UniGene: | Hs.411881 | | SwissProt: | GRB14_HUMAN | | TrEMBL: | | | NCBI (GI): | 59802920 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 540 | | Percent disordered: | 14% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MTTSLQDGQS AASRAAARDS PLAAQVCGAA QGRGDAHDLA PAPWLHARAL LPLPDGTRGC - 60
AADRRKKKDL DVPEMPSIPN PFPELCCSPI TSVLSADLFP KANSRKKQVI KVYSEDETSR - 120
ALDVPSDITA RDVCQLLILK NHYIDDHSWT LFEHLPHIGV ERTIEDHELV IEVLSNWGIE - 180
EENKLYFRKN YAKYEFFKNP MYFFPEHMVS FATETNGEIS PTQILQMFLS SSTYPEIHGF - 240
LHAKEQGKKS WKKIYFFLRR SGLYFSTKGT SKEPRHLQFF SEFGNSDIYV SLAGKKKHGA - 300
PTNYGFCFKP NKAGGPRDLK MLCAEEEQSR TCWVTAIRLL KYGMQLYQNY MHPYQGRSGC - 360
SSQSISPMRS ISENSLVAMD FSGQKSRVIE NPTEALSVAV EEGLAWRKKG CLRLGTHGSP - 420
TASSQSSATN MAIHRSQPWF HHKISRDEAQ RLIIQQGLVD GVFLVRDSQS NPKTFVLSMS - 480
HGQKIKHFQI IPVEDDGEMF HTLDDGHTRF TDLIQLVEFY QLNKGVLPCK LKHYCARIAL - 540
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| Functional narrative |
Grb14 belongs to the Grb7 family of adapters and was identified as a negative regulator of insulin signal transduction. Between the PH (pleckstrin homology) and SH2 (Src homology 2) domains is a domain implicated in the interaction with receptor tyrosine kinases called PIR (phosphorylated insulin receptor interaction region). In the case of Grb14, PIR is the main binding domain and is sufficient to inhibit the insulin receptor kinase activity.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | PIR domain | | Location: | 361 - 435 | | Length: | 75 | | Region sequence: |
SSQSISPMRSISENSLVAMDFSGQKSRVIENPTEALSVAVEEGLAWRKKGCLRLGTHGSP
TASSQSSATNMAIHR | | Modification type: | Fragment
Native
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (300 K; )
- Stability at thermal extremes
| References:
- Moncoq K, Broutin I, Larue V, Perdereau D, Cailliau K, Browaeys-Poly E, Burnol AF, Ducruix A. "The PIR domain of Grb14 is an intrinsically unstructured protein: implication in insulin signaling." FEBS Lett. 2003; 554(3): 240-6. PubMed: 14623073
| Comments:
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| References |
- Holt LJ, Siddle K. "Grb10 and Grb14: enigmatic regulators of insulin action--and more?" Biochem J. 2005; 388(2): 393-406. PubMed: 15901248
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