SIT1_MOUSE
ID SIT1_MOUSE Reviewed; 180 AA.
AC Q8C503; Q9WUU5;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Signaling threshold-regulating transmembrane adapter 1;
DE AltName: Full=SHP2-interacting transmembrane adapter protein;
DE AltName: Full=Suppression-inducing transmembrane adapter 1;
GN Name=Sit1; Synonyms=Sit;
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=10209036; DOI=10.1084/jem.189.8.1181;
RA Marie-Cardine A., Kirchgessner H., Bruyns E., Shevchenko A., Mann M.,
RA Autschbach F., Ratnofsky S., Meuer S., Schraven B.;
RT "SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-
RT linked dimer regulating human T-cell activation.";
RL J. Exp. Med. 189:1181-1194(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
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 [4]
RP TISSUE SPECIFICITY, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16107703; DOI=10.1128/mcb.25.17.7557-7568.2005;
RA Simeoni L., Posevitz V., Koelsch U., Meinert I., Bruyns E., Pfeffer K.,
RA Reinhold D., Schraven B.;
RT "The transmembrane adapter protein SIT regulates thymic development and
RT peripheral T-cell functions.";
RL Mol. Cell. Biol. 25:7557-7568(2005).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
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).
CC -!- FUNCTION: Negatively regulates T-cell antigen receptor (TCR)-mediated
CC signaling. Involved in positive selection of T-cells.
CC {ECO:0000269|PubMed:16107703}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. When phosphorylated, interacts
CC with PTPN11/SHP2, GRB2 and CSK (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type III
CC membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in thymus and spleen, with highest levels
CC in immature thymocytes (at protein level).
CC {ECO:0000269|PubMed:16107703}.
CC -!- PTM: Phosphorylated on tyrosines upon TCR activation; which leads to
CC the recruitment of PTPN11, GRB2 and CSK. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile, with normal growth
CC and no obvious abnormalities. They show normal B-cell development and
CC peripheral B-cell functions, but have mildly altered thymic development
CC probably due to enhanced TCR signaling. This results in a greater
CC susceptibility to autoimmune diseases. {ECO:0000269|PubMed:16107703}.
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DR EMBL; AJ236881; CAB41506.1; -; mRNA.
DR EMBL; AK079882; BAC37773.1; -; mRNA.
DR EMBL; BC064055; AAH64055.1; -; mRNA.
DR CCDS; CCDS18096.1; -.
DR RefSeq; NP_062309.2; NM_019436.3.
DR AlphaFoldDB; Q8C503; -.
DR IntAct; Q8C503; 4.
DR STRING; 10090.ENSMUSP00000030180; -.
DR GlyGen; Q8C503; 1 site.
DR iPTMnet; Q8C503; -.
DR PhosphoSitePlus; Q8C503; -.
DR EPD; Q8C503; -.
DR jPOST; Q8C503; -.
DR MaxQB; Q8C503; -.
DR PaxDb; Q8C503; -.
DR PeptideAtlas; Q8C503; -.
DR PRIDE; Q8C503; -.
DR ProteomicsDB; 261240; -.
DR Antibodypedia; 11587; 218 antibodies from 28 providers.
DR DNASU; 54390; -.
DR Ensembl; ENSMUST00000030180; ENSMUSP00000030180; ENSMUSG00000028460.
DR GeneID; 54390; -.
DR KEGG; mmu:54390; -.
DR UCSC; uc008spw.2; mouse.
DR CTD; 27240; -.
DR MGI; MGI:1889342; Sit1.
DR VEuPathDB; HostDB:ENSMUSG00000028460; -.
DR eggNOG; ENOG502S87Q; Eukaryota.
DR GeneTree; ENSGT00390000016476; -.
DR HOGENOM; CLU_111407_0_0_1; -.
DR InParanoid; Q8C503; -.
DR OMA; LFRWTSG; -.
DR OrthoDB; 1355800at2759; -.
DR PhylomeDB; Q8C503; -.
DR TreeFam; TF337816; -.
DR BioGRID-ORCS; 54390; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Slc6a20b; mouse.
DR PRO; PR:Q8C503; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8C503; protein.
DR Bgee; ENSMUSG00000028460; Expressed in thymus and 33 other tissues.
DR Genevisible; Q8C503; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0050863; P:regulation of T cell activation; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0043029; P:T cell homeostasis; IEA:InterPro.
DR InterPro; IPR033269; Sit1.
DR PANTHER; PTHR15604; PTHR15604; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity;
KW Membrane; Phosphoprotein; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..180
FT /note="Signaling threshold-regulating transmembrane adapter
FT 1"
FT /id="PRO_0000083341"
FT TOPO_DOM 1..24
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..180
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 73..76
FT /note="Interaction with GRB2"
FT /evidence="ECO:0000250"
FT REGION 81..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..135
FT /note="Interaction with PTPN11"
FT /evidence="ECO:0000250"
FT REGION 153..156
FT /note="Interaction with CSK"
FT /evidence="ECO:0000250"
FT REGION 172..175
FT /note="Interaction with GRB2"
FT /evidence="ECO:0000250"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3P8"
FT MOD_RES 66
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5M869"
FT MOD_RES 73
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3P8"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3P8"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5M869"
FT MOD_RES 111
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3P8"
FT MOD_RES 132
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3P8"
FT MOD_RES 153
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3P8"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 172
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3P8"
FT CARBOHYD 6
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 7
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT CONFLICT 62
FT /note="L -> H (in Ref. 1; CAB41506)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 180 AA; 19578 MW; 7D1C0FD958B9BD03 CRC64;
MSRDYNCTTD DQLAWGIPSI SHAWGLWALL GVVTVLLLIS LAALLSQWTR GRRRNQEGQG
PLSGRSAEEV PLYGNLHYLQ TGRLSQEPRS EEQDPPSSGG LARGAEEAMC YTSLQLRPAQ
GRIPSSGNPI KYCEVVLDSE PKPQAPGPEP ELYASVCAQT RRGRASFPDQ AYANSQPAPS
