ID SIT1_HUMAN Reviewed; 196 AA. AC Q9Y3P8; B2RBP9; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 28-JUN-2023, entry version 145. 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; DE AltName: Full=gp30/40; DE Flags: Precursor; GN Name=SIT1; Synonyms=SIT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 148-158, IDENTIFICATION BY RP MASS SPECTROMETRY, DIMERIZATION, GLYCOSYLATION AT ASN-26, PHOSPHORYLATION RP AT TYR-148, MUTAGENESIS OF ASN-26 AND TYR-148, TISSUE SPECIFICITY, RP SUBCELLULAR LOCATION, INTERACTION WITH PTPN11, AND FUNCTION. 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 [GENOMIC DNA]. RX PubMed=11491537; DOI=10.1007/s002510100328; RA Huebener C., Mincheva A., Lichter P., Schraven B., Bruyns E.; RT "Complete sequence, genomic organization, and chromosomal localization of RT the human gene encoding the SHP2-interacting transmembrane adaptor protein RT (SIT)."; RL Immunogenetics 53:337-341(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [7] RP MUTAGENESIS OF TYR-90; TYR-127; TYR-148; TYR-169 AND TYR-188, RP PHOSPHORYLATION AT TYR-90; TYR-127; TYR-148; TYR-169 AND TYR-188, AND RP INTERACTION WITH PTPN11; GRB2 AND CSK. RX PubMed=11433379; RX DOI=10.1002/1521-4141(200106)31:6<1825::aid-immu1825>3.0.co;2-v; RA Pfrepper K.-I., Marie-Cardine A., Simeoni L., Kuramitsu Y., Leo A., RA Spicka J., Hilgert I., Scherer J., Schraven B.; RT "Structural and functional dissection of the cytoplasmic domain of the RT transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor RT protein)."; RL Eur. J. Immunol. 31:1825-1836(2001). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80; TYR-90; THR-144; SER-182 RP AND TYR-188, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [9] RP TISSUE SPECIFICITY. RX PubMed=16160011; DOI=10.1182/blood-2005-06-2273; RA Tedoldi S., Paterson J.C., Hansmann M.-L., Natkunam Y., Rudiger T., RA Angelisova P., Du M.Q., Roberton H., Roncador G., Sanchez L., Pozzobon M., RA Masir N., Barry R., Pileri S., Mason D.Y., Marafioti T., Horejsi V.; RT "Transmembrane adaptor molecules: a new category of lymphoid-cell RT markers."; RL Blood 107:213-221(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; THR-144; TYR-148; RP SER-182 AND TYR-188, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). CC -!- FUNCTION: Negatively regulates TCR (T-cell antigen receptor)-mediated CC signaling in T-cells. Involved in positive selection of T-cells. CC {ECO:0000269|PubMed:10209036}. CC -!- SUBUNIT: Homodimer; disulfide-linked. When phosphorylated, interacts CC with PTPN11/SHP2, GRB2 and CSK. {ECO:0000269|PubMed:10209036, CC ECO:0000269|PubMed:11433379}. CC -!- INTERACTION: CC Q9Y3P8; Q9BQE5: APOL2; NbExp=3; IntAct=EBI-6977215, EBI-4290634; CC Q9Y3P8; O95393: BMP10; NbExp=3; IntAct=EBI-6977215, EBI-3922513; CC Q9Y3P8; A0PK11: CLRN2; NbExp=3; IntAct=EBI-6977215, EBI-12813623; CC Q9Y3P8; O43736: ITM2A; NbExp=3; IntAct=EBI-6977215, EBI-2431769; CC Q9Y3P8; Q13021: MALL; NbExp=3; IntAct=EBI-6977215, EBI-750078; CC Q9Y3P8; P26678: PLN; NbExp=3; IntAct=EBI-6977215, EBI-692836; CC Q9Y3P8; P55061: TMBIM6; NbExp=3; IntAct=EBI-6977215, EBI-1045825; CC Q9Y3P8; Q9NV12: TMEM140; NbExp=3; IntAct=EBI-6977215, EBI-2844246; CC Q9Y3P8; Q86UF1: TSPAN33; NbExp=3; IntAct=EBI-6977215, EBI-12045841; CC Q9Y3P8; O75841: UPK1B; NbExp=3; IntAct=EBI-6977215, EBI-12237619; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10209036}; CC Single-pass type I membrane protein {ECO:0000269|PubMed:10209036}. CC -!- TISSUE SPECIFICITY: Specifically expressed in T- and B-cells. Present CC in plasma cells but not in germinal center B-cells (at protein level). CC Expressed in T- and B-cell lymphoma. {ECO:0000269|PubMed:10209036, CC ECO:0000269|PubMed:16160011}. CC -!- PTM: Phosphorylated on tyrosines by LCK, FYN or ZAP70 upon TCR CC activation; which leads to the recruitment of PTPN11, GRB2 and CSK. CC {ECO:0000269|PubMed:10209036, ECO:0000269|PubMed:11433379}. CC -!- CAUTION: In contrast to its orthologs it harbors a signal sequence. CC {ECO:0000305}. 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; AJ010059; CAB41504.1; -; mRNA. DR EMBL; AJ271888; CAC81313.1; -; Genomic_DNA. DR EMBL; AK314758; BAG37296.1; -; mRNA. DR EMBL; AL357874; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471071; EAW58370.1; -; Genomic_DNA. DR EMBL; BC102029; AAI02030.1; -; mRNA. DR EMBL; BC104491; AAI04492.1; -; mRNA. DR EMBL; BC107484; AAI07485.1; -; mRNA. DR CCDS; CCDS6582.1; -. DR RefSeq; NP_055265.1; NM_014450.2. DR AlphaFoldDB; Q9Y3P8; -. DR BioGRID; 118088; 17. DR IntAct; Q9Y3P8; 11. DR MINT; Q9Y3P8; -. DR STRING; 9606.ENSP00000259608; -. DR GlyCosmos; Q9Y3P8; 1 site, No reported glycans. DR GlyGen; Q9Y3P8; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y3P8; -. DR PhosphoSitePlus; Q9Y3P8; -. DR BioMuta; SIT1; -. DR DMDM; 74753488; -. DR jPOST; Q9Y3P8; -. DR MassIVE; Q9Y3P8; -. DR MaxQB; Q9Y3P8; -. DR PaxDb; Q9Y3P8; -. DR PeptideAtlas; Q9Y3P8; -. DR ProteomicsDB; 86053; -. DR Antibodypedia; 11587; 232 antibodies from 28 providers. DR DNASU; 27240; -. DR Ensembl; ENST00000259608.8; ENSP00000259608.3; ENSG00000137078.10. DR GeneID; 27240; -. DR KEGG; hsa:27240; -. DR MANE-Select; ENST00000259608.8; ENSP00000259608.3; NM_014450.3; NP_055265.1. DR UCSC; uc003zxe.3; human. DR AGR; HGNC:17710; -. DR CTD; 27240; -. DR DisGeNET; 27240; -. DR GeneCards; SIT1; -. DR HGNC; HGNC:17710; SIT1. DR HPA; ENSG00000137078; Tissue enriched (lymphoid). DR MIM; 604964; gene. DR neXtProt; NX_Q9Y3P8; -. DR OpenTargets; ENSG00000137078; -. DR PharmGKB; PA142670914; -. DR VEuPathDB; HostDB:ENSG00000137078; -. DR eggNOG; ENOG502S87Q; Eukaryota. DR GeneTree; ENSGT00390000016476; -. DR HOGENOM; CLU_111407_0_0_1; -. DR InParanoid; Q9Y3P8; -. DR OrthoDB; 4590319at2759; -. DR PhylomeDB; Q9Y3P8; -. DR TreeFam; TF337816; -. DR PathwayCommons; Q9Y3P8; -. DR SignaLink; Q9Y3P8; -. DR BioGRID-ORCS; 27240; 11 hits in 1152 CRISPR screens. DR ChiTaRS; SIT1; human. DR GeneWiki; SIT1; -. DR GenomeRNAi; 27240; -. DR Pharos; Q9Y3P8; Tbio. DR PRO; PR:Q9Y3P8; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q9Y3P8; protein. DR Bgee; ENSG00000137078; Expressed in granulocyte and 126 other tissues. DR ExpressionAtlas; Q9Y3P8; baseline and differential. DR Genevisible; Q9Y3P8; HS. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0042169; F:SH2 domain binding; TAS:HGNC-UCL. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0050863; P:regulation of T cell activation; IDA:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0043029; P:T cell homeostasis; IEA:InterPro. DR InterPro; IPR033269; Sit1. DR PANTHER; PTHR15604; SIGNALING THRESHOLD-REGULATING TRANSMEMBRANE ADAPTER 1; 1. DR PANTHER; PTHR15604:SF0; SIGNALING THRESHOLD-REGULATING TRANSMEMBRANE ADAPTER 1; 1. PE 1: Evidence at protein level; KW Adaptive immunity; Cell membrane; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Immunity; Membrane; Phosphoprotein; KW Reference proteome; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..196 FT /note="Signaling threshold-regulating transmembrane adapter FT 1" FT /id="PRO_0000045152" FT TOPO_DOM 25..40 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 41..61 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 62..196 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 90..93 FT /note="Interaction with GRB2" FT /evidence="ECO:0000269|PubMed:11433379" FT REGION 132..167 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 146..151 FT /note="Interaction with PTPN11" FT REGION 169..172 FT /note="Interaction with CSK" FT /evidence="ECO:0000269|PubMed:11433379" FT REGION 188..191 FT /note="Interaction with GRB2" FT /evidence="ECO:0000269|PubMed:11433379" FT MOD_RES 80 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15144186" FT MOD_RES 83 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5M869" FT MOD_RES 90 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:11433379, FT ECO:0007744|PubMed:15144186" FT MOD_RES 102 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 127 FT /note="Phosphotyrosine" FT /evidence="ECO:0000305|PubMed:11433379" FT MOD_RES 144 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:19690332" FT MOD_RES 148 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10209036, FT ECO:0000269|PubMed:11433379, ECO:0007744|PubMed:19690332" FT MOD_RES 169 FT /note="Phosphotyrosine" FT /evidence="ECO:0000305|PubMed:11433379" FT MOD_RES 182 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:19690332" FT MOD_RES 188 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:11433379, FT ECO:0007744|PubMed:15144186, ECO:0007744|PubMed:19690332" FT CARBOHYD 26 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:10209036" FT DISULFID 27 FT /note="Interchain" FT /evidence="ECO:0000305" FT MUTAGEN 26 FT /note="N->Q: Abolishes glycosylation." FT /evidence="ECO:0000269|PubMed:10209036" FT MUTAGEN 90 FT /note="Y->F: Reduces interaction with GRB2. Abolishes FT interaction with GRB2; when associated with F-188." FT /evidence="ECO:0000269|PubMed:11433379" FT MUTAGEN 127 FT /note="Y->F: No effect on interaction with PTPN11 or GRB2." FT /evidence="ECO:0000269|PubMed:11433379" FT MUTAGEN 148 FT /note="Y->F: Reduces interaction with PTPN11, no effect on FT inhibition of NF-AT activation." FT /evidence="ECO:0000269|PubMed:10209036, FT ECO:0000269|PubMed:11433379" FT MUTAGEN 169 FT /note="Y->F: Abolishes interaction with CSK and impairs FT inhibition of NF-AT activation." FT /evidence="ECO:0000269|PubMed:11433379" FT MUTAGEN 188 FT /note="Y->F: Reduces interaction with GRB2. Abolishes FT interaction with GRB2; when associated with F-90." FT /evidence="ECO:0000269|PubMed:11433379" SQ SEQUENCE 196 AA; 21126 MW; 2A0C48C9466F7F07 CRC64; MNQADPRLRA VCLWTLTSAA MSRGDNCTDL LALGIPSITQ AWGLWVLLGA VTLLFLISLA AHLSQWTRGR SRSHPGQGRS GESVEEVPLY GNLHYLQTGR LSQDPEPDQQ DPTLGGPARA AEEVMCYTSL QLRPPQGRIP GPGTPVKYSE VVLDSEPKSQ ASGPEPELYA SVCAQTRRAR ASFPDQAYAN SQPAAS //