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

Summary

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

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_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: 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?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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 A&#x000ce;&#x000b2; peptides concentrations in the elderly. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of periodontal health measured by probing depth in adults ages 18-49 years. EBI GWAS Catalog EBI GWAS CatalogPubMed
Lupus nephritis susceptibility Loci in women with systemic lupus erythematosus. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC35848 (e-PCR)
- UniSTS:5644

G36013 (e-PCR)
- UniSTS:26904

RH98833 (e-PCR)
- UniSTS:87092

WI-16395 (e-PCR)
- UniSTS:71737

D14S1336 (e-PCR)
- UniSTS:36172

RH94145 (e-PCR)
- UniSTS:91480

STS-AA036859 (e-PCR)
- UniSTS:71284

G20638 (e-PCR)
- UniSTS:15988

HSC2BE052 (e-PCR)
- UniSTS:12921

G36269 (e-PCR)
- UniSTS:10192

SHGC-67645 (e-PCR)
- UniSTS:92625

A003P20 (e-PCR)
- UniSTS:63469

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)

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

NC_000014.9 Reference GRCh38.p14 Primary Assembly

Range

50633580..50668306 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Alternate T2T-CHM13v2.0

Genomic

NC_060938.1 Alternate T2T-CHM13v2.0

Range

44839725..44874442 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

B3KTQ1, H0YJH0
XM_054376542.1 → XP_054232517.1 protein salvador homolog 1 isoform X2