SASH1_MOUSE
ID SASH1_MOUSE Reviewed; 1230 AA.
AC P59808;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 15-AUG-2003, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=SAM and SH3 domain-containing protein 1;
GN Name=Sash1;
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=12771949; DOI=10.1038/sj.onc.1206474;
RA Zeller C., Hinzmann B., Seitz S., Prokoph H., Burkhardt-Goettges E.,
RA Fischer J., Jandrig B., Estevez-Schwarz L., Rosenthal A., Scherneck S.;
RT "SASH1 - a candidate tumour suppressor gene on chromosome 6q24.3 is
RT downregulated in breast cancer.";
RL Oncogene 22:2972-2983(2003).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-400, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83 AND SER-831, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83; SER-241; SER-400 AND
RP SER-813, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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 TISSUE SPECIFICITY.
RX PubMed=23776175; DOI=10.4049/jimmunol.1200583;
RA Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J.,
RA Fuller M.E., Blonder J., Veenstra T.D., Karsan A.;
RT "SASH1 is a scaffold molecule in endothelial TLR4 signaling.";
RL J. Immunol. 191:892-901(2013).
CC -!- FUNCTION: Is a positive regulator of NF-kappa-B signaling downstream of
CC TLR4 activation. It acts as a scaffold molecule to assemble a molecular
CC complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby
CC facilitating NF-kappa-B signaling activation. Regulates TRAF6 and
CC MAP3K7 ubiquitination. Involved in the regulation of cell mobility.
CC Regulates lipolysaccharide (LPS)-induced endothelial cell migration. Is
CC involved in the regulation of skin pigmentation through the control of
CC melanocyte migration in the epidermis. {ECO:0000250|UniProtKB:O94885}.
CC -!- SUBUNIT: Interacts with GNAS. Interacts with IQGAP1. Interacts with
CC TRAF6 (via C-terminus); the interaction is LPS-dependent. Interacts
CC with MAP3K7, CHUK and IKBKB. {ECO:0000250|UniProtKB:O94885}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O94885}.
CC -!- TISSUE SPECIFICITY: Expressed in the microvascular endothelium of
CC various organs, as well as in parenchymal cells. Expressed in the
CC endothelium but not lymphoid cells of spleen and thymus.
CC {ECO:0000269|PubMed:23776175}.
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; AJ507736; CAD47812.1; -; mRNA.
DR CCDS; CCDS23692.1; -.
DR RefSeq; NP_780364.3; NM_175155.4.
DR AlphaFoldDB; P59808; -.
DR SMR; P59808; -.
DR BioGRID; 213862; 3.
DR STRING; 10090.ENSMUSP00000015449; -.
DR iPTMnet; P59808; -.
DR PhosphoSitePlus; P59808; -.
DR jPOST; P59808; -.
DR MaxQB; P59808; -.
DR PaxDb; P59808; -.
DR PRIDE; P59808; -.
DR ProteomicsDB; 256597; -.
DR DNASU; 70097; -.
DR GeneID; 70097; -.
DR KEGG; mmu:70097; -.
DR CTD; 23328; -.
DR MGI; MGI:1917347; Sash1.
DR eggNOG; KOG4384; Eukaryota.
DR InParanoid; P59808; -.
DR OrthoDB; 949260at2759; -.
DR PhylomeDB; P59808; -.
DR BioGRID-ORCS; 70097; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Sash1; mouse.
DR PRO; PR:P59808; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P59808; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISO:MGI.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; ISO:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:MGI.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; ISO:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISO:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:MGI.
DR GO; GO:0010632; P:regulation of epithelial cell migration; ISO:MGI.
DR GO; GO:1902498; P:regulation of protein autoubiquitination; ISO:MGI.
DR GO; GO:1900044; P:regulation of protein K63-linked ubiquitination; ISO:MGI.
DR CDD; cd09559; SAM_SASH1_repeat1; 1.
DR CDD; cd09492; SAM_SASH1_repeat2; 1.
DR CDD; cd11967; SH3_SASH1; 1.
DR Gene3D; 1.10.150.50; -; 2.
DR InterPro; IPR021090; rSAM/SH3_domain-containing.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR037627; SASH1_SAM_repeat1.
DR InterPro; IPR037630; SASH1_SAM_repeat2.
DR InterPro; IPR035720; SASH1_SH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF07647; SAM_2; 1.
DR Pfam; PF07653; SH3_2; 1.
DR Pfam; PF12485; SLY; 1.
DR SMART; SM00454; SAM; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF47769; SSF47769; 2.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 2.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Phosphoprotein; Reference proteome; Repeat; SH3 domain;
KW Tumor suppressor.
FT CHAIN 1..1230
FT /note="SAM and SH3 domain-containing protein 1"
FT /id="PRO_0000097598"
FT DOMAIN 547..608
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 626..690
FT /note="SAM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 1160..1224
FT /note="SAM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 211..249
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 439..566
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 610..633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 705..792
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 818..875
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 844..852
FT /note="Required for interaction with TRAF6"
FT /evidence="ECO:0000250|UniProtKB:O94885"
FT REGION 915..1045
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..291
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 502..528
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 529..546
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 705..761
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 848..869
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 939..954
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1014..1028
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 400
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 813
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 831
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
SQ SEQUENCE 1230 AA; 135591 MW; DDE421DB74FE49AF CRC64;
MEEDAGAASP APEPEPEVDP ARELEPEAGV SESISRLWTD VMGILDGSLG NIDDLAQQYA
DYYNTCFSDV CERMEELRKR RVSQDLDVEK PDASPTSLQL RSQIEESLGF CSAVSTPEVE
RKYPLHKSNS EDGCVGKGDW KKKNKYFWQN FRKNQKGIMR QTSKGEDVGY VASEITMSDE
ERIQLMMMVK EKMITIEEAL ARLKEYEAQH RQSSTLDPAD WPDGSYPTLD GSSTCNSREQ
SDDETEDSVK FKRLHKLVNS TRRVRKKLIR VEEMKKPSAE GGEEHVFENS PVQDERSALY
SGVHKKPFFY DGSPEKPPED DADSLTPSPS SSSLDTWGAG RKLVKTFSKG ESRGLIKPPK
KMGTFFSYPE EEKAQKVSRS LTEGEMKKGL GSLSHGRTCS FGGFDLTNRS LHVGSNNSDP
AGKEGDFVYK EVIKSPPAPR ISLGKKVRSV KETMRKRMSK KYSSPVSEQD SGLDGMPSSP
ASGKPDSEHV DKPKLKAGGS VESLRSSLSG QSSMSGQTVS TTDSSTSNRE SVKSEDGDDE
EPPYRGPFCG RARVHTDFTP SPYDTDSLKL KKGDIIDIIS KPPMGTWMGL LNNKVGTFKF
IYVDVLNEEE EKPKRPTRRR KKGRPSQPKS VEDLLDRINL KEHMPTFLFN GYEDLDTFKL
LEEEDLDELN IRDPEHRAVL LTAVELLQEY DSNSDQSGSQ EKLLVDNQGL SGRSPRDSGC
YESSENLENA KTHKPSVLST KSSTESNLKS FTRSQPGNYP TLPLMKSGEV RKQGEEGRLG
RGLAPDTAKS CDVPSVTDLS KNRRSLPVSI CRSCETLEGP EPVESWPRSH SLDDLQGDAD
VGKNVPTEMP ETCSQNVPEV PQKTSACTSK ALPRGRDPTA DVMLLTQSKR FSDPPKTMAK
KLDGSVVASN LGIAPPQCIP RDFEAQPPVK PGLTRTSLEG LRKGHDHHPL GTKEGVDGEQ
SAPETRTQSR HPSQPPPVPA KKSRERLANG LHLVPSPEAP ILPLKKASPA SPVSPSDCPS
PREPRPSSGT EPGSPACTRP PPWLAELPES TSLQEHGVKL GPVLSRKVSC VRGVDLEMLT
ENKLQAEGID LTEEPYSDKH GRCGIPEALV QRYAEDLEQP ERDVATNMDQ IRVKLLRKQH
RMAIPSGGLT EICRKPLSPG CVASMSDWLI SIGLPMYTST LSDAGFSTLS QVPSLSHSCL
QEAGITEERH IRKLITAARL FKLPPSPEAM
