SAMN1_MOUSE
ID SAMN1_MOUSE Reviewed; 372 AA.
AC P57725; Q2LE09; Q5RKU0; Q6P210; Q8C6S2;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 29-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=SAM domain-containing protein SAMSN-1;
DE AltName: Full=SAM domain, SH3 domain and nuclear localization signals protein 1;
DE AltName: Full=SH3 protein expressed in lymphocytes 2;
DE AltName: Full=SH3-lymphocyte protein 2;
DE Short=SLy2;
GN Name=Samsn1;
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].
RA Groet J., Blechschmidt K., Yaspo M.-L., Rosenthal A., Nizetic D.;
RT "A mouse homologue of SAMSN1.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RA von Holleben M., Kloeter S., Beer S.;
RT "SLy: a novel family of putative adaptor proteins in lymphocytes.";
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Oviduct;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6NCr; TISSUE=Hematopoietic stem cell;
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 [5]
RP FUNCTION, INDUCTION BY IL4 AND LIPOPOLYSACCHARIDE, SUBCELLULAR LOCATION,
RP SUBUNIT, INTERACTION WITH TYROSINE PHOSPHORYLATED PROTEINS, AND TISSUE
RP SPECIFICITY.
RX PubMed=15381729; DOI=10.1084/jem.20031816;
RA Zhu Y.X., Benn S., Li Z.H., Wei E., Masih-Khan E., Trieu Y., Bali M.,
RA McGlade C.J., Claudio J.O., Stewart A.K.;
RT "The SH3-SAM adaptor HACS1 is up-regulated in B cell activation signaling
RT cascades.";
RL J. Exp. Med. 200:737-747(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-160, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90, 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90, AND IDENTIFICATION BY
RP 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90 AND SER-97, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [10]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19923443; DOI=10.1096/fj.09-140806;
RA Wang D., Stewart A.K., Zhuang L., Zhu Y., Wang Y., Shi C., Keating A.,
RA Slutsky A., Zhang H., Wen X.Y.;
RT "Enhanced adaptive immunity in mice lacking the immunoinhibitory adaptor
RT Hacs1.";
RL FASEB J. 24:947-956(2010).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-23, INTERACTION WITH
RP SAP30; HDAC1; YWHAB; YWHAE; YWHAG; YWHAH; YWHAZ AND SFN, SUBUNIT, AND
RP MUTAGENESIS OF SER-23.
RX PubMed=20478393; DOI=10.1016/j.biocel.2010.05.004;
RA Brandt S., Ellwanger K., Beuter-Gunia C., Schuster M., Hausser A.,
RA Schmitz I., Beer-Hammer S.;
RT "SLy2 targets the nuclear SAP30/HDAC1 complex.";
RL Int. J. Biochem. Cell Biol. 42:1472-1481(2010).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CTTN.
RX PubMed=21296879; DOI=10.1074/jbc.m110.155184;
RA von Holleben M., Gohla A., Janssen K.P., Iritani B.M., Beer-Hammer S.;
RT "The immunoinhibitory adapter protein SRC homology domain 3 lymphocyte
RT protein 2 (SLy2) regulates actin dynamics and B cell spreading.";
RL J. Biol. Chem. 286:13489-13501(2011).
RN [13]
RP STRUCTURE BY NMR OF 237-303.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the sterile alpha motif (SAM) domain of mouse
RT SAMSN1.";
RL Submitted (APR-2004) to the PDB data bank.
CC -!- FUNCTION: Negative regulator of B-cell activation. Down-regulates cell
CC proliferation (in vitro). Promotes RAC1-dependent membrane ruffle
CC formation and reorganization of the actin cytoskeleton. Regulates cell
CC spreading and cell polarization. Stimulates HDAC1 activity. Regulates
CC LYN activity by modulating its tyrosine phosphorylation.
CC {ECO:0000269|PubMed:15381729, ECO:0000269|PubMed:19923443,
CC ECO:0000269|PubMed:20478393, ECO:0000269|PubMed:21296879}.
CC -!- SUBUNIT: Interacts with FASLG (By similarity). Interacts with
CC phosphotyrosine containing proteins. Interacts (via SH3 domain) with
CC CTTN. Interacts (phosphorylated at Ser-23) with YWHAB, YWHAE, YWHAG,
CC YWHAH, YWHAZ and SFN. Interacts directly with SAP30 and HDAC1.
CC Identified in a complex with SAP30 and HDAC1. {ECO:0000250,
CC ECO:0000269|PubMed:15381729, ECO:0000269|PubMed:20478393,
CC ECO:0000269|PubMed:21296879}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cell projection, ruffle.
CC Note=Shuttles between cytoplasm and nucleus. Colocalizes with the actin
CC cytoskeleton and actin-rich membrane ruffles.
CC -!- TISSUE SPECIFICITY: Detected in spleen and lymph node (at protein
CC level). {ECO:0000269|PubMed:15381729}.
CC -!- INDUCTION: Up-regulated in peripheral blood B-cells by IL4 and
CC bacterial lipopolysaccharide (LPS). {ECO:0000269|PubMed:15381729}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice have normal bone
CC marrow B-cell development and normal splenic T- and B-cell populations,
CC but show an enhanced immune response upon immunization. Mice have
CC constitutively activated Lyn, due to constitutive Lyn tyrosine
CC phosphorylation. {ECO:0000269|PubMed:19923443}.
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; AF222928; AAG23356.1; -; mRNA.
DR EMBL; DQ333189; ABC59720.1; -; mRNA.
DR EMBL; AK053946; BAC35601.1; -; mRNA.
DR EMBL; BC052906; AAH52906.1; -; mRNA.
DR EMBL; BC064778; AAH64778.1; -; mRNA.
DR CCDS; CCDS37378.1; -.
DR RefSeq; NP_075869.2; NM_023380.2.
DR PDB; 1V38; NMR; -; A=239-303.
DR PDBsum; 1V38; -.
DR AlphaFoldDB; P57725; -.
DR SMR; P57725; -.
DR BioGRID; 212412; 2.
DR STRING; 10090.ENSMUSP00000109877; -.
DR iPTMnet; P57725; -.
DR PhosphoSitePlus; P57725; -.
DR EPD; P57725; -.
DR jPOST; P57725; -.
DR MaxQB; P57725; -.
DR PaxDb; P57725; -.
DR PRIDE; P57725; -.
DR ProteomicsDB; 256832; -.
DR Antibodypedia; 2139; 286 antibodies from 31 providers.
DR Ensembl; ENSMUST00000114239; ENSMUSP00000109877; ENSMUSG00000022876.
DR GeneID; 67742; -.
DR KEGG; mmu:67742; -.
DR UCSC; uc007zrs.1; mouse.
DR CTD; 64092; -.
DR MGI; MGI:1914992; Samsn1.
DR VEuPathDB; HostDB:ENSMUSG00000022876; -.
DR eggNOG; KOG4384; Eukaryota.
DR GeneTree; ENSGT00940000157806; -.
DR HOGENOM; CLU_027875_0_0_1; -.
DR InParanoid; P57725; -.
DR OMA; EVPYTGP; -.
DR OrthoDB; 278880at2759; -.
DR TreeFam; TF350709; -.
DR BioGRID-ORCS; 67742; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Samsn1; mouse.
DR EvolutionaryTrace; P57725; -.
DR PRO; PR:P57725; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P57725; protein.
DR Bgee; ENSMUSG00000022876; Expressed in granulocyte and 109 other tissues.
DR Genevisible; P57725; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0002820; P:negative regulation of adaptive immune response; IMP:UniProtKB.
DR GO; GO:0050869; P:negative regulation of B cell activation; IMP:UniProtKB.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:UniProtKB.
DR CDD; cd09561; SAM_SAMSN1; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR021090; rSAM/SH3_domain-containing.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR037623; SAMSN1_SAM.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF07647; SAM_2; 1.
DR Pfam; PF07653; SH3_2; 1.
DR Pfam; PF12485; SLY; 1.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell projection; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; SH3 domain.
FT CHAIN 1..372
FT /note="SAM domain-containing protein SAMSN-1"
FT /id="PRO_0000097575"
FT DOMAIN 163..224
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 241..305
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 90..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 129..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 304..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 20..25
FT /note="Important for interaction with 14-3-3 proteins"
FT COMPBIAS 1..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..53
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..148
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:20478393"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSI8"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSI8"
FT MOD_RES 76
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSI8"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSI8"
FT MOD_RES 160
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MUTAGEN 23
FT /note="S->A: Loss of phosphorylation site. Strongly reduced
FT interaction with YWHAG and YWHAB."
FT /evidence="ECO:0000269|PubMed:20478393"
FT CONFLICT 1..22
FT /note="MLKRKPSNASDKEKHQKPKRSS -> MPQTRRNTKNRSAG (in Ref. 1;
FT AAG23356)"
FT /evidence="ECO:0000305"
FT CONFLICT 93
FT /note="K -> E (in Ref. 4; AAH52906)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="F -> L (in Ref. 4; AAH52906)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="N -> D (in Ref. 4; AAH64778)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="L -> S (in Ref. 1; AAG23356)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="E -> D (in Ref. 4; AAH52906)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="S -> T (in Ref. 4; AAH64778)"
FT /evidence="ECO:0000305"
FT HELIX 246..251
FT /evidence="ECO:0007829|PDB:1V38"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:1V38"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:1V38"
FT HELIX 259..265
FT /evidence="ECO:0007829|PDB:1V38"
FT HELIX 270..273
FT /evidence="ECO:0007829|PDB:1V38"
FT HELIX 278..283
FT /evidence="ECO:0007829|PDB:1V38"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:1V38"
FT HELIX 289..303
FT /evidence="ECO:0007829|PDB:1V38"
SQ SEQUENCE 372 AA; 41601 MW; 2264EFEA11B15B30 CRC64;
MLKRKPSNAS DKEKHQKPKR SSSFGNFDRF RNNSVSKSDD SIEVHDRELT NGSEEQSKTS
SSGGSLGKKV RAISWTMKKK VGKKYIKALS EEKEEESGEE ALPYRNSDPM IGTHTEKISL
KASDSMDSLY SGQSSSSGIT SCSDGTSNRD SFRLDDDSPY SGPFCGRAKV HTDFTPSPYD
TDSLKIKKGD IIDIICKTPM GMWTGMLNNK VGNFKFIYVD VILEEEAAPK KIKVPRSRRR
ENHQTIQEFL ERIHLQEYTS TLLLNGYETL DDLKDIKESH LIELNIADPE DRARLLSAAE
SLLDEETTVE HEKESVPLSS NPDILSASQL EDCPRDSGCY ISSENSDNGK EDLESENLSD
MVQKIAITES SD
