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    SAV1 salvador family WW domain containing protein 1 [ Homo sapiens (human) ]

    Gene ID: 60485, updated on 14-Nov-2024

    Summary

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    Official Symbol
    SAV1provided by HGNC
    Official Full Name
    salvador family WW domain containing protein 1provided by HGNC
    Primary source
    HGNC:HGNC:17795
    See related
    Ensembl:ENSG00000151748 MIM:607203; AllianceGenome:HGNC:17795
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SAV; WW45; WWP4
    Summary
    WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein with two WW domains, a SARAH domain, and a coiled-coil region and is ubiquitously expressed in adult tissues. This protein binds to MST1 (mammalian sterile 20-like kinase 1) and promotes MST1-induced apoptosis. It has also been shown to bind to HAX1 (hematopoietic cell-specific protein 1 (HS1)-associated protein X-1) and to attenuate the anti-apoptotic effects of HAX1. Studies in human and mouse suggest this gene acts as a tumor suppressor. [provided by RefSeq, Aug 2012]
    Expression
    Ubiquitous expression in thyroid (RPKM 16.7), testis (RPKM 15.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SAV1 in Genome Data Viewer
    Location:
    14q22.1
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (50633580..50668306, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (44839725..44874442, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (51100298..51135024, complement)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene mitogen-activated protein kinase kinase kinase kinase 5 Neighboring gene uncharacterized LOC124903312 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8358 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8359 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5723 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:51026957-51027456 Neighboring gene atlastin GTPase 1 Neighboring gene small nuclear ribonucleoprotein polypeptide G pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8360 Neighboring gene RNA, 7SL, cytoplasmic 452, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:51123951-51124450 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8361 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5725 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5726 Neighboring gene ZFP64 zinc finger protein pseudogene 1 Neighboring gene uncharacterized LOC124903313 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr14:51210620-51211819 Neighboring gene ninein

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Smoke-induced SAV1 Gene Promoter Hypermethylation Disrupts YAP Negative Feedback and Promotes Malignant Progression of Non-small Cell Lung Cancer.
      Title: Smoke-induced SAV1 Gene Promoter Hypermethylation Disrupts YAP Negative Feedback and Promotes Malignant Progression of Non-small Cell Lung Cancer.
    2. ALKBH5 Promotes Multiple Myeloma Tumorigenicity through inducing m(6)A-demethylation of SAV1 mRNA and Myeloma Stem Cell Phenotype.
      Title: ALKBH5 Promotes Multiple Myeloma Tumorigenicity through inducing m(6)A-demethylation of SAV1 mRNA and Myeloma Stem Cell Phenotype.
    3. Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites.
      Title: Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites.
    4. RNA-binding protein Musashi2 regulates Hippo signaling via SAV1 and MOB1 in pancreatic cancer.
      Title: RNA-binding protein Musashi2 regulates Hippo signaling via SAV1 and MOB1 in pancreatic cancer.
    5. BCL-2 is a new regulator of MST pathway. First, protein levels of MST2 and SAV1 were reduced significantly by co-expression of BCL-2. Physical interaction of BCL-2 with SAV1 was correlated with proteasomal degradation of SAV1 and MST2 proteins.
      Title: Mammalian Hippo kinase pathway is downregulated by BCL-2 via protein degradation.
    6. Authors report that SAV1, a Hippo signaling component, inhibits Akt, a function independent of its role in Hippo signaling. Binding to a proline-tyrosine motif in the Akt-PH domain, SAV1 suppresses Akt activation by blocking Akt's movement to plasma membrane. Authors further identify cancer-associated SAV1 mutations with impaired ability to bind Akt, leading to Akt hyperactivation.
      Title: MERTK mediated novel site Akt phosphorylation alleviates SAV1 suppression.
    7. SAV1 suppresses tumor growth in colorectal cancer and is regulated by miR-21.
      Title: SAV1, regulated by microRNA-21, suppresses tumor growth in colorectal cancer.
    8. These results suggest Salvador enhances the effects of Hippo kinase activity at multiple points in the Hippo pathway.
      Title: Salvador has an extended SARAH domain that mediates binding to Hippo kinase.
    9. Here, the authors discover SAV1-mediated inhibition of the PP2A complex STRIPAK(SLMAP) as a key mechanism of MST1/2 activation.
      Title: SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK.
    10. WW45 has suppressive roles in lung cancer through a pathway involving Hedgehog/Gli1 signaling.
      Title: WW45, a Gli1 binding protein, negatively regulated Hedgehog signaling in lung cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (24)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly.
    EBI GWAS Catalog
    Genome-wide association study of periodontal health measured by probing depth in adults ages 18-49 years.
    EBI GWAS Catalog
    Lupus nephritis susceptibility Loci in women with systemic lupus erythematosus.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables molecular adaptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine/threonine kinase activator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transcription regulator activator activity IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cardiac muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in epithelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in hair follicle development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in hippo signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in hippo signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in hippo signaling ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in intestinal epithelial cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in keratinocyte apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in keratinocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in lung epithelial cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of cardiac muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of cell population proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of epithelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of fat cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of keratinocyte apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within protein stabilization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of stem cell population maintenance IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in ventricular septum morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    protein salvador homolog 1
    Names
    1700040G09Rik
    45 kDa WW domain protein
    WW domain-containing adaptor 45
    hWW45
    salvador homolog 1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_021818.4 → NP_068590.1  protein salvador homolog 1

      See identical proteins and their annotated locations for NP_068590.1

      Status: REVIEWED

      Source sequence(s)
      AK023071, BC006385, DA479812, DB543756
      Consensus CDS
      CCDS9701.1
      UniProtKB/Swiss-Prot
      A8K4B8, D3DSB6, Q6IA58, Q9H4B6, Q9H949, Q9HAK9
      Related
      ENSP00000324729.4, ENST00000324679.5
      Conserved Domains (1) summary
      cd00201
      Location:202 → 232
      WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      50633580..50668306 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011537057.4 → XP_011535359.1  protein salvador homolog 1 isoform X1

      See identical proteins and their annotated locations for XP_011535359.1

      UniProtKB/TrEMBL
      B3KTQ1, H0YJH0
      Related
      ENSP00000451492.1, ENST00000555720.5
      Conserved Domains (1) summary
      cd00201
      Location:169 → 199
      WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...

    2. XM_047431659.1 → XP_047287615.1  protein salvador homolog 1 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      44839725..44874442 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054376541.1 → XP_054232516.1  protein salvador homolog 1 isoform X1

      UniProtKB/TrEMBL
      B3KTQ1

    2. XM_054376542.1 → XP_054232517.1  protein salvador homolog 1 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H4B6.2 GenPept UniProtKB/Swiss-Prot:Q9H4B6

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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