SAV1_RAT
ID SAV1_RAT Reviewed; 387 AA.
AC A4V8B4;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Protein salvador homolog 1;
DE AltName: Full=45 kDa WW domain protein;
DE Short=rWW45;
GN Name=Sav1 {ECO:0000312|EMBL:CAJ98868.1}; Synonyms=Ww45;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|EMBL:CAJ98868.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Rowett {ECO:0000312|EMBL:CAJ98868.1};
RC TISSUE=Heart {ECO:0000312|EMBL:CAJ98868.1};
RA Valverde P.;
RT "WW45 expression is upregulated upon T cell activation and its targeted
RT downregulation in activated T cells decreases T cell-mediated bone
RT resorption in experimental periodontal disease in rats.";
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling
CC pathway which plays a pivotal role in organ size control and tumor
CC suppression by restricting proliferation and promoting apoptosis. The
CC core of this pathway is composed of a kinase cascade wherein STK3/MST2
CC and STK4/MST1, in complex with its regulatory protein SAV1,
CC phosphorylates and activates LATS1/2 in complex with its regulatory
CC protein MOB1, which in turn phosphorylates and inactivates YAP1
CC oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits
CC its translocation into the nucleus to regulate cellular genes important
CC for cell proliferation, cell death, and cell migration. SAV1 is
CC required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle
CC exit and terminal differentiation in developing epithelial tissues.
CC Plays a role in centrosome disjunction by regulating the localization
CC of NEK2 to centrosomes, and its ability to phosphorylate CROCC and
CC CEP250. In conjunction with STK3/MST2, activates the transcriptional
CC activity of ESR1 through the modulation of its phosphorylation (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Stabilized through interaction with STK3/MST2 or
CC STK4/MST1. Interacts (via SARAH domain) with isoform 1 of NEK2.
CC Interacts with ESR1 only in the presence of STK3/MST2. Interacts with
CC WTIP and AJUBA. {ECO:0000250|UniProtKB:Q9H4B6}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC -!- PTM: Phosphorylated by STK3/MST2 and STK4/MST1. Phosphorylation is not
CC required for SAV1 stability and may increase the number of protein
CC binding sites on the scaffold molecule (By similarity). {ECO:0000250}.
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DR EMBL; AM261215; CAJ98868.1; -; mRNA.
DR RefSeq; NP_001091050.1; NM_001097581.1.
DR AlphaFoldDB; A4V8B4; -.
DR SMR; A4V8B4; -.
DR STRING; 10116.ENSRNOP00000007314; -.
DR PhosphoSitePlus; A4V8B4; -.
DR PaxDb; A4V8B4; -.
DR Ensembl; ENSRNOT00000007314; ENSRNOP00000007314; ENSRNOG00000005264.
DR GeneID; 299116; -.
DR KEGG; rno:299116; -.
DR UCSC; RGD:1307253; rat.
DR CTD; 60485; -.
DR RGD; 1307253; Sav1.
DR eggNOG; KOG1891; Eukaryota.
DR GeneTree; ENSGT00940000156106; -.
DR HOGENOM; CLU_060422_0_0_1; -.
DR InParanoid; A4V8B4; -.
DR OMA; AARYYYP; -.
DR OrthoDB; 284488at2759; -.
DR PhylomeDB; A4V8B4; -.
DR TreeFam; TF317631; -.
DR PRO; PR:A4V8B4; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000005264; Expressed in lung and 19 other tissues.
DR ExpressionAtlas; A4V8B4; baseline and differential.
DR Genevisible; A4V8B4; RN.
DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:GOC.
DR GO; GO:0031697; F:beta-1 adrenergic receptor binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IBA:GO_Central.
DR GO; GO:0046332; F:SMAD binding; IBA:GO_Central.
DR GO; GO:0070699; F:type II activin receptor binding; IBA:GO_Central.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0001942; P:hair follicle development; ISO:RGD.
DR GO; GO:0035329; P:hippo signaling; ISS:UniProtKB.
DR GO; GO:0060575; P:intestinal epithelial cell differentiation; ISO:RGD.
DR GO; GO:0097283; P:keratinocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0030216; P:keratinocyte differentiation; ISO:RGD.
DR GO; GO:0060487; P:lung epithelial cell differentiation; ISO:RGD.
DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; ISO:RGD.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:1902174; P:positive regulation of keratinocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR GO; GO:0043113; P:receptor clustering; IBA:GO_Central.
DR GO; GO:0046620; P:regulation of organ growth; ISO:RGD.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD.
DR CDD; cd00201; WW; 2.
DR InterPro; IPR011524; SARAH_dom.
DR InterPro; IPR030030; Sav.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR PANTHER; PTHR47522; PTHR47522; 1.
DR Pfam; PF00397; WW; 1.
DR SMART; SM00456; WW; 2.
DR SUPFAM; SSF51045; SSF51045; 2.
DR PROSITE; PS50951; SARAH; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 2.
PE 2: Evidence at transcript level;
KW Cytoplasm; Nucleus; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..387
FT /note="Protein salvador homolog 1"
FT /id="PRO_0000308165"
FT DOMAIN 201..234
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 236..269
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 323..370
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4B6"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VEB2"
FT MOD_RES 212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4B6"
SQ SEQUENCE 387 AA; 45046 MW; 203716579DD10938 CRC64;
MLSRKKTKNE VSKPAEVQGK YVKKETSPLL RNLMPSFIRH GPTIPRRTDL CLPESSASAF
SASGDGVVSR NQSFLRTPVQ RTPHEVMRRE SNRLSAPSSY LVRSLADVPR EYGSSQSFLT
EVNFAVENGD SGSRYFYSDN FFDGQRRRPL GDRAQEDYRY YEYNHDLFQR MPQNQGRHTS
GIGRVTATSL GNLTNHGSED LPLPPGWSVD WTMRGRKYYI DHNTNTTHWS HPLEREGLPP
GWERVESSEF GTYYVDHTNK RAQYRHPCAP SVPRYDQPPP ITYQPQQTER NQSLLVPANP
YHTAEIPDWL QVYARAPVKY DHILKWELFQ LADLDTYQGM LKLLFMKELE QIVKLYEAYR
QALVTELENR KQRQQWYAQH HGKKFLS
