Q9H4B6 · SAV1_HUMAN
- ProteinProtein salvador homolog 1
- GeneSAV1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids383 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:29063833).
The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. Plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation
The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. Plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Enzyme and pathway databases
The subsequence HASGIGRVAATSLGNLTNHGSEDLPLPPGWSVDWTMRGRKYYIDHNTNTTHWSHPLEREGLPPGWERVESSEFGTYYVDH, which contains the WW domain, shows transcriptional activator activity in a high-throughput recruitment assay.
Names & Taxonomy
Protein names
- Recommended nameProtein salvador homolog 1
- Alternative names
Gene names
- Community suggested namesSAV1
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H4B6
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_015880 | 185 | in a colon cancer cell line | |||
Sequence: A → D | ||||||
Mutagenesis | 346 | Loss of interaction with STK3. | ||||
Sequence: E → A | ||||||
Mutagenesis | 350 | Loss of interaction with STK3. | ||||
Sequence: I → A | ||||||
Mutagenesis | 357 | Loss of interaction with STK3. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 358 | Loss of interaction with STK3. | ||||
Sequence: R → A | ||||||
Mutagenesis | 361 | Loss of interaction with STK3. | ||||
Sequence: L → A | ||||||
Mutagenesis | 365 | Loss of interaction with STK3. | ||||
Sequence: L → A | ||||||
Mutagenesis | 368 | Loss of interaction with STK3. | ||||
Sequence: R → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 447 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000076060 | 1-383 | UniProt | Protein salvador homolog 1 | |||
Sequence: MLSRKKTKNEVSKPAEVQGKYVKKETSPLLRNLMPSFIRHGPTIPRRTDICLPDSSPNAFSTSGDVVSRNQSFLRTPIQRTPHEIMRRESNRLSAPSYLARSLADVPREYGSSQSFVTEVSFAVENGDSGSRYYYSDNFFDGQRKRPLGDRAHEDYRYYEYNHDLFQRMPQNQGRHASGIGRVAATSLGNLTNHGSEDLPLPPGWSVDWTMRGRKYYIDHNTNTTHWSHPLEREGLPPGWERVESSEFGTYYVDHTNKKAQYRHPCAPSVPRYDQPPPVTYQPQQTERNQSLLVPANPYHTAEIPDWLQVYARAPVKYDHILKWELFQLADLDTYQGMLKLLFMKELEQIVKMYEAYRQALLTELENRKQRQQWYAQQHGKNF | |||||||
Modified residue (large scale data) | 27 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 56 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 76 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 90 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 94 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 94 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 136 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 136 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 210 | UniProt | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Phosphorylated by STK3/MST2 and STK4/MST1. Phosphorylation is not required for SAV1 stability and may increase the number of protein binding sites on the scaffold molecule.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitously expressed in adult tissues with highest expression in the pancreas, aorta and interventricular septum and lowest expression in skeletal muscle. Expression was higher in fetal than in the adult heart. Expressed in various cell lines.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer. Stabilized through interaction with STK3/MST2 or STK4/MST1 (PubMed:15688006, PubMed:16930133, PubMed:19212654, PubMed:28087714, PubMed:29063833).
Interacts (via SARAH domain) with isoform 1 of NEK2 (PubMed:21076410).
Interacts with ESR1 only in the presence of STK3/MST2 (PubMed:21104395).
Interacts with WTIP and AJUBA (PubMed:20303269).
Interacts (via SARAH domain) with isoform 1 of NEK2 (PubMed:21076410).
Interacts with ESR1 only in the presence of STK3/MST2 (PubMed:21104395).
Interacts with WTIP and AJUBA (PubMed:20303269).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9H4B6 | HAX1 O00165 | 7 | EBI-1017775, EBI-357001 | |
BINARY | Q9H4B6 | SAV1 Q9H4B6 | 2 | EBI-1017775, EBI-1017775 | |
BINARY | Q9H4B6 | STK3 Q13188 | 29 | EBI-1017775, EBI-992580 | |
BINARY | Q9H4B6 | STK4 Q13043 | 22 | EBI-1017775, EBI-367376 | |
BINARY | Q9H4B6 | STK4 Q13043-1 | 2 | EBI-1017775, EBI-15638366 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 199-232 | WW 1 | ||||
Sequence: LPLPPGWSVDWTMRGRKYYIDHNTNTTHWSHPLE | ||||||
Domain | 234-267 | WW 2 | ||||
Sequence: EGLPPGWERVESSEFGTYYVDHTNKKAQYRHPCA | ||||||
Domain | 321-368 | SARAH | ||||
Sequence: ILKWELFQLADLDTYQGMLKLLFMKELEQIVKMYEAYRQALLTELENR | ||||||
Coiled coil | 344-373 | |||||
Sequence: MKELEQIVKMYEAYRQALLTELENRKQRQQ |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length383
- Mass (Da)44,634
- Last updated2003-07-11 v2
- Checksum4012C40A8601417A
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 5 | in Ref. 1; CAC13972 | ||||
Sequence: K → Q | ||||||
Sequence conflict | 18 | in Ref. 3; CAG33578 | ||||
Sequence: Q → R | ||||||
Sequence conflict | 292 | in Ref. 2; BAB13835 | ||||
Sequence: L → F |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ292969 EMBL· GenBank· DDBJ | CAC13972.1 EMBL· GenBank· DDBJ | mRNA | ||
AK021500 EMBL· GenBank· DDBJ | BAB13835.1 EMBL· GenBank· DDBJ | mRNA | ||
AK023071 EMBL· GenBank· DDBJ | BAB14390.1 EMBL· GenBank· DDBJ | mRNA | ||
AK290883 EMBL· GenBank· DDBJ | BAF83572.1 EMBL· GenBank· DDBJ | mRNA | ||
CR457297 EMBL· GenBank· DDBJ | CAG33578.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471078 EMBL· GenBank· DDBJ | EAW65702.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471078 EMBL· GenBank· DDBJ | EAW65704.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC020537 EMBL· GenBank· DDBJ | AAH20537.1 EMBL· GenBank· DDBJ | mRNA |