SAV1_MOUSE
ID SAV1_MOUSE Reviewed; 386 AA.
AC Q8VEB2; Q9D9N9; Q9ER46;
DT 11-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Protein salvador homolog 1;
DE AltName: Full=45 kDa WW domain protein;
DE Short=mWW45;
GN Name=Sav1; Synonyms=Ww45, Wwp3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11027580; DOI=10.1006/bbrc.2000.3582;
RA Valverde P.;
RT "Cloning, expression and mapping of hWW45, a novel WW-domain containing
RT gene.";
RL Biochem. Biophys. Res. Commun. 276:990-998(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 111-386.
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18369314; DOI=10.1038/emboj.2008.63;
RA Lee J.H., Kim T.S., Yang T.H., Koo B.K., Oh S.P., Lee K.P., Oh H.J.,
RA Lee S.H., Kong Y.Y., Kim J.M., Lim D.S.;
RT "A crucial role of WW45 in developing epithelial tissues in the mouse.";
RL EMBO J. 27:1231-1242(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-137, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20080689; DOI=10.1073/pnas.0911427107;
RA Lu L., Li Y., Kim S.M., Bossuyt W., Liu P., Qiu Q., Wang Y., Halder G.,
RA Finegold M.J., Lee J.S., Johnson R.L.;
RT "Hippo signaling is a potent in vivo growth and tumor suppressor pathway in
RT the mammalian liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:1437-1442(2010).
RN [7]
RP STRUCTURE BY NMR OF 198-233.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first WW domain from the mouse salvador homolog
RT 1 protein (Sav1).";
RL Submitted (OCT-2007) to the PDB data bank.
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, ECO:0000269|PubMed:18369314,
CC ECO:0000269|PubMed:20080689}.
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 -!- TISSUE SPECIFICITY: Ubiquitously expressed in adult tissues with the
CC highest level found in testis.
CC -!- DEVELOPMENTAL STAGE: Expression was detected in 7 dpc embryos.
CC Expression levels decreased at day 11 and remained low at days 15 and
CC 17.
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}.
CC -!- DISRUPTION PHENOTYPE: Mice show progressive hepatomegaly with a 2-fold
CC increase in liver mass relative to total body mass at 1 month of age
CC and a 3-fold increase by 3 months of age. Embryos display unchecked
CC proliferation and defects in terminal differentiation of epithelial
CC cells. {ECO:0000269|PubMed:18369314, ECO:0000269|PubMed:20080689}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ292968; CAC13977.1; -; mRNA.
DR EMBL; BC019377; AAH19377.1; -; mRNA.
DR EMBL; AK006655; BAB24691.2; -; mRNA.
DR CCDS; CCDS25956.1; -.
DR PIR; JC7508; JC7508.
DR RefSeq; NP_071311.1; NM_022028.2.
DR PDB; 2DWV; NMR; -; A/B=231-266.
DR PDB; 2YSB; NMR; -; A=198-233.
DR PDB; 7BQF; X-ray; 1.70 A; A=196-285.
DR PDB; 7BQG; X-ray; 1.55 A; A=196-272.
DR PDBsum; 2DWV; -.
DR PDBsum; 2YSB; -.
DR PDBsum; 7BQF; -.
DR PDBsum; 7BQG; -.
DR AlphaFoldDB; Q8VEB2; -.
DR SMR; Q8VEB2; -.
DR BioGRID; 211016; 1.
DR IntAct; Q8VEB2; 4.
DR MINT; Q8VEB2; -.
DR STRING; 10090.ENSMUSP00000021467; -.
DR iPTMnet; Q8VEB2; -.
DR PhosphoSitePlus; Q8VEB2; -.
DR EPD; Q8VEB2; -.
DR MaxQB; Q8VEB2; -.
DR PaxDb; Q8VEB2; -.
DR PRIDE; Q8VEB2; -.
DR ProteomicsDB; 256707; -.
DR Antibodypedia; 23683; 253 antibodies from 27 providers.
DR DNASU; 64010; -.
DR Ensembl; ENSMUST00000021467; ENSMUSP00000021467; ENSMUSG00000021067.
DR GeneID; 64010; -.
DR KEGG; mmu:64010; -.
DR UCSC; uc007nte.2; mouse.
DR CTD; 60485; -.
DR MGI; MGI:1927144; Sav1.
DR VEuPathDB; HostDB:ENSMUSG00000021067; -.
DR eggNOG; KOG1891; Eukaryota.
DR GeneTree; ENSGT00940000156106; -.
DR HOGENOM; CLU_060422_0_0_1; -.
DR InParanoid; Q8VEB2; -.
DR OMA; AARYYYP; -.
DR OrthoDB; 284488at2759; -.
DR PhylomeDB; Q8VEB2; -.
DR TreeFam; TF317631; -.
DR BioGRID-ORCS; 64010; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Sav1; mouse.
DR EvolutionaryTrace; Q8VEB2; -.
DR PRO; PR:Q8VEB2; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8VEB2; protein.
DR Bgee; ENSMUSG00000021067; Expressed in gastrula and 243 other tissues.
DR Genevisible; Q8VEB2; MM.
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; ISO:MGI.
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:MGI.
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; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR GO; GO:0035329; P:hippo signaling; IMP:UniProtKB.
DR GO; GO:0060575; P:intestinal epithelial cell differentiation; IMP:MGI.
DR GO; GO:0097283; P:keratinocyte apoptotic process; IMP:MGI.
DR GO; GO:0030216; P:keratinocyte differentiation; IMP:MGI.
DR GO; GO:0060487; P:lung epithelial cell differentiation; IMP:MGI.
DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IMP:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IGI:MGI.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IGI:MGI.
DR GO; GO:1902174; P:positive regulation of keratinocyte apoptotic process; IMP:MGI.
DR GO; GO:0050821; P:protein stabilization; IDA:MGI.
DR GO; GO:0043113; P:receptor clustering; IBA:GO_Central.
DR GO; GO:0046620; P:regulation of organ growth; IMP:MGI.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IMP:MGI.
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 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..386
FT /note="Protein salvador homolog 1"
FT /id="PRO_0000076061"
FT DOMAIN 200..233
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 235..268
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 322..369
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT COILED 345..374
FT /evidence="ECO:0000255"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4B6"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 211
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4B6"
FT CONFLICT 67
FT /note="V -> I (in Ref. 2; AAH19377)"
FT /evidence="ECO:0000305"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:7BQG"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:2YSB"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:7BQG"
FT TURN 221..224
FT /evidence="ECO:0007829|PDB:7BQG"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:7BQG"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:2YSB"
FT STRAND 241..246
FT /evidence="ECO:0007829|PDB:7BQG"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:7BQG"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:7BQG"
FT TURN 256..259
FT /evidence="ECO:0007829|PDB:7BQG"
FT STRAND 260..264
FT /evidence="ECO:0007829|PDB:7BQG"
SQ SEQUENCE 386 AA; 44845 MW; 310F8E19F20257C2 CRC64;
MLSRKKTKNE VSKPAEVQGK YVKKETSPLL RNLMPSFIRH GPTIPRRTDL CLPDSSATAF
SASGDGVVSR NQSFLRTAIQ RTPHEVMRRE SHRLSAPSYL VRSLADVPRE CGSSQSFLTE
VNFAVENGDS GSRYFFSDNF FDGQRRRPLG DRAQEDYRYY EYNHDLFQRM PQSQGRHTSG
IGRVTATSLG NLTNHGSEDL PLPPGWSVDW TMRGRKYYID HNTNTTHWSH PLEREGLPPG
WERVESSEFG TYYVDHTNKR AQYRHPCAPS VPRYDQPPPI TYQPQQTERN QSLLVPANPY
HTAEIPDWLQ VYARAPVKYD HILKWELFQL ADLDTYQGML KLLFMKELEQ IVKLYEAYRQ
ALLTELENRK QRQQWYAQQH GKTFLS
