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Protein

Signaling threshold-regulating transmembrane adapter 1

Gene

SIT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells. Involved in positive selection of T-cells.1 Publication

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • SH2 domain binding Source: HGNC

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • regulation of T cell activation Source: UniProtKB
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity

Enzyme and pathway databases

SignaLinkiQ9Y3P8.

Names & Taxonomyi

Protein namesi
Recommended name:
Signaling threshold-regulating transmembrane adapter 1
Alternative name(s):
SHP2-interacting transmembrane adapter protein
Suppression-inducing transmembrane adapter 1
gp30/40
Gene namesi
Name:SIT1
Synonyms:SIT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:17710. SIT1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 4016ExtracellularSequence analysisAdd
BLAST
Transmembranei41 – 6121HelicalSequence analysisAdd
BLAST
Topological domaini62 – 196135CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: HGNC
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi26 – 261N → Q: Abolishes glycosylation. 1 Publication
Mutagenesisi90 – 901Y → F: Reduces interaction with GRB2. Abolishes interaction with GRB2; when associated with F-188. 1 Publication
Mutagenesisi127 – 1271Y → F: No effect on interaction with PTPN11 or GRB2. 1 Publication
Mutagenesisi148 – 1481Y → F: Reduces interaction with PTPN11, no effect on inhibition of NF-AT activation. 2 Publications
Mutagenesisi169 – 1691Y → F: Abolishes interaction with CSK and impairs inhibition of NF-AT activation. 1 Publication
Mutagenesisi188 – 1881Y → F: Reduces interaction with GRB2. Abolishes interaction with GRB2; when associated with F-90. 1 Publication

Organism-specific databases

PharmGKBiPA142670914.

Polymorphism and mutation databases

BioMutaiSIT1.
DMDMi74753488.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 196172Signaling threshold-regulating transmembrane adapter 1PRO_0000045152Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi26 – 261N-linked (GlcNAc...)1 Publication
Disulfide bondi27 – 27InterchainCurated
Modified residuei80 – 801PhosphoserineCombined sources
Modified residuei83 – 831PhosphoserineBy similarity
Modified residuei90 – 901PhosphotyrosineCombined sources1 Publication
Modified residuei102 – 1021PhosphoserineCombined sources
Modified residuei127 – 1271Phosphotyrosine1 Publication
Modified residuei144 – 1441PhosphothreonineCombined sources
Modified residuei148 – 1481PhosphotyrosineCombined sources2 Publications
Modified residuei169 – 1691Phosphotyrosine1 Publication
Modified residuei182 – 1821PhosphoserineCombined sources
Modified residuei188 – 1881PhosphotyrosineCombined sources1 Publication

Post-translational modificationi

Phosphorylated on tyrosines by LCK, FYN or ZAP70 upon TCR activation; which leads to the recruitment of PTPN11, GRB2 and CSK.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9Y3P8.
PaxDbiQ9Y3P8.
PRIDEiQ9Y3P8.

PTM databases

iPTMnetiQ9Y3P8.
PhosphoSiteiQ9Y3P8.

Expressioni

Tissue specificityi

Specifically expressed in T- and B-cells. Present in plasma cells but not in germinal center B-cells (at protein level). Expressed in T- and B-cell lymphoma.2 Publications

Gene expression databases

BgeeiQ9Y3P8.
CleanExiHS_SIT1.
ExpressionAtlasiQ9Y3P8. baseline and differential.
GenevisibleiQ9Y3P8. HS.

Organism-specific databases

HPAiHPA018506.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. When phosphorylated, interacts with PTPN11/SHP2, GRB2 and CSK.2 Publications

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • SH2 domain binding Source: HGNC

Protein-protein interaction databases

BioGridi118088. 5 interactions.
IntActiQ9Y3P8. 1 interaction.
MINTiMINT-8020372.
STRINGi9606.ENSP00000259608.

Structurei

3D structure databases

ProteinModelPortaliQ9Y3P8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni90 – 934Interaction with GRB2
Regioni146 – 1516Interaction with PTPN11
Regioni169 – 1724Interaction with CSK
Regioni188 – 1914Interaction with GRB2

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IYYR. Eukaryota.
ENOG4111C3Q. LUCA.
GeneTreeiENSGT00390000016476.
HOGENOMiHOG000231524.
HOVERGENiHBG080311.
InParanoidiQ9Y3P8.
OrthoDBiEOG712TZ1.
PhylomeDBiQ9Y3P8.
TreeFamiTF337816.

Family and domain databases

InterProiIPR033269. Sit1.
[Graphical view]
PANTHERiPTHR15604. PTHR15604. 1 hit.
ProDomiPD358400. PD358400. 1 hit.
[Graphical view] [Entries sharing at least one domain]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9Y3P8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNQADPRLRA VCLWTLTSAA MSRGDNCTDL LALGIPSITQ AWGLWVLLGA
60 70 80 90 100
VTLLFLISLA AHLSQWTRGR SRSHPGQGRS GESVEEVPLY GNLHYLQTGR
110 120 130 140 150
LSQDPEPDQQ DPTLGGPARA AEEVMCYTSL QLRPPQGRIP GPGTPVKYSE
160 170 180 190
VVLDSEPKSQ ASGPEPELYA SVCAQTRRAR ASFPDQAYAN SQPAAS
Length:196
Mass (Da):21,126
Last modified:November 1, 1999 - v1
Checksum:i2A0C48C9466F7F07
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ010059 mRNA. Translation: CAB41504.1.
AJ271888 Genomic DNA. Translation: CAC81313.1.
AK314758 mRNA. Translation: BAG37296.1.
AL357874 Genomic DNA. Translation: CAI13446.1.
CH471071 Genomic DNA. Translation: EAW58370.1.
BC102029 mRNA. Translation: AAI02030.1.
BC104491 mRNA. Translation: AAI04492.1.
BC107484 mRNA. Translation: AAI07485.1.
CCDSiCCDS6582.1.
RefSeqiNP_055265.1. NM_014450.2.
UniGeneiHs.88012.

Genome annotation databases

EnsembliENST00000259608; ENSP00000259608; ENSG00000137078.
GeneIDi27240.
KEGGihsa:27240.
UCSCiuc003zxe.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ010059 mRNA. Translation: CAB41504.1.
AJ271888 Genomic DNA. Translation: CAC81313.1.
AK314758 mRNA. Translation: BAG37296.1.
AL357874 Genomic DNA. Translation: CAI13446.1.
CH471071 Genomic DNA. Translation: EAW58370.1.
BC102029 mRNA. Translation: AAI02030.1.
BC104491 mRNA. Translation: AAI04492.1.
BC107484 mRNA. Translation: AAI07485.1.
CCDSiCCDS6582.1.
RefSeqiNP_055265.1. NM_014450.2.
UniGeneiHs.88012.

3D structure databases

ProteinModelPortaliQ9Y3P8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118088. 5 interactions.
IntActiQ9Y3P8. 1 interaction.
MINTiMINT-8020372.
STRINGi9606.ENSP00000259608.

PTM databases

iPTMnetiQ9Y3P8.
PhosphoSiteiQ9Y3P8.

Polymorphism and mutation databases

BioMutaiSIT1.
DMDMi74753488.

Proteomic databases

MaxQBiQ9Y3P8.
PaxDbiQ9Y3P8.
PRIDEiQ9Y3P8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259608; ENSP00000259608; ENSG00000137078.
GeneIDi27240.
KEGGihsa:27240.
UCSCiuc003zxe.3. human.

Organism-specific databases

CTDi27240.
GeneCardsiSIT1.
HGNCiHGNC:17710. SIT1.
HPAiHPA018506.
MIMi604964. gene.
neXtProtiNX_Q9Y3P8.
PharmGKBiPA142670914.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IYYR. Eukaryota.
ENOG4111C3Q. LUCA.
GeneTreeiENSGT00390000016476.
HOGENOMiHOG000231524.
HOVERGENiHBG080311.
InParanoidiQ9Y3P8.
OrthoDBiEOG712TZ1.
PhylomeDBiQ9Y3P8.
TreeFamiTF337816.

Enzyme and pathway databases

SignaLinkiQ9Y3P8.

Miscellaneous databases

ChiTaRSiSIT1. human.
GeneWikiiSIT1.
GenomeRNAii27240.
NextBioi50125.
PROiQ9Y3P8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y3P8.
CleanExiHS_SIT1.
ExpressionAtlasiQ9Y3P8. baseline and differential.
GenevisibleiQ9Y3P8. HS.

Family and domain databases

InterProiIPR033269. Sit1.
[Graphical view]
PANTHERiPTHR15604. PTHR15604. 1 hit.
ProDomiPD358400. PD358400. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T-cell activation."
    Marie-Cardine A., Kirchgessner H., Bruyns E., Shevchenko A., Mann M., Autschbach F., Ratnofsky S., Meuer S., Schraven B.
    J. Exp. Med. 189:1181-1194(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 148-158, IDENTIFICATION BY MASS SPECTROMETRY, DIMERIZATION, GLYCOSYLATION AT ASN-26, PHOSPHORYLATION AT TYR-148, MUTAGENESIS OF ASN-26 AND TYR-148, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH PTPN11, FUNCTION.
  2. "Complete sequence, genomic organization, and chromosomal localization of the human gene encoding the SHP2-interacting transmembrane adaptor protein (SIT)."
    Huebener C., Mincheva A., Lichter P., Schraven B., Bruyns E.
    Immunogenetics 53:337-341(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Thymus.
  4. "DNA sequence and analysis of human chromosome 9."
    Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
    , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
    Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  7. "Structural and functional dissection of the cytoplasmic domain of the transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor protein)."
    Pfrepper K.-I., Marie-Cardine A., Simeoni L., Kuramitsu Y., Leo A., Spicka J., Hilgert I., Scherer J., Schraven B.
    Eur. J. Immunol. 31:1825-1836(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF TYR-90; TYR-127; TYR-148; TYR-169 AND TYR-188, PHOSPHORYLATION AT TYR-90; TYR-127; TYR-148; TYR-169 AND TYR-188, INTERACTION WITH PTPN11; GRB2 AND CSK.
  8. "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
    Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
    Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80; TYR-90; THR-144; SER-182 AND TYR-188, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  9. Cited for: TISSUE SPECIFICITY.
  10. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; THR-144; TYR-148; SER-182 AND TYR-188, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.

Entry informationi

Entry nameiSIT1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y3P8
Secondary accession number(s): B2RBP9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: November 1, 1999
Last modified: May 11, 2016
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

In contrast to its orthologs it harbors a signal sequence.Curated

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.