THMS1_HUMAN
ID THMS1_HUMAN Reviewed; 641 AA.
AC Q8N1K5; A1L4F0; A8K7N1; B3KT31; B3KW32; B3KY07; F5H1J9; Q5T3C4; Q5T3C5;
AC Q6MZT7;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 3.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Protein THEMIS;
DE AltName: Full=Thymocyte-expressed molecule involved in selection;
GN Name=THEMIS; Synonyms=C6orf190, C6orf207;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-630.
RC TISSUE=Caudate nucleus, Spleen, and 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-630.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-630.
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 430-641 (ISOFORM 1), AND VARIANT
RP VAL-630.
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-584, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-584, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE 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: Plays a central role in late thymocyte development by
CC controlling both positive and negative T-cell selection. Required to
CC sustain and/or integrate signals required for proper lineage commitment
CC and maturation of T-cells. Regulates T-cell development through T-cell
CC antigen receptor (TCR) signaling and in particular through the
CC regulation of calcium influx and phosphorylation of Erk.
CC {ECO:0000250|UniProtKB:Q8BGW0}.
CC -!- SUBUNIT: Interacts with PLCG1, ITK, GRB2, and LAT.
CC {ECO:0000250|UniProtKB:Q8BGW0}.
CC -!- INTERACTION:
CC Q8N1K5; P62993: GRB2; NbExp=10; IntAct=EBI-2873538, EBI-401755;
CC Q8N1K5; Q96LA8: PRMT6; NbExp=2; IntAct=EBI-2873538, EBI-912440;
CC Q8N1K5; P29350: PTPN6; NbExp=4; IntAct=EBI-2873538, EBI-78260;
CC Q8N1K5; P0C745: HBZ; Xeno; NbExp=3; IntAct=EBI-2873538, EBI-16218595;
CC Q8N1K5-1; P62993: GRB2; NbExp=10; IntAct=EBI-15102259, EBI-401755;
CC Q8N1K5-1; P06239: LCK; NbExp=3; IntAct=EBI-15102259, EBI-1348;
CC Q8N1K5-1; P19174: PLCG1; NbExp=3; IntAct=EBI-15102259, EBI-79387;
CC Q8N1K5-1; P43403: ZAP70; NbExp=3; IntAct=EBI-15102259, EBI-1211276;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BGW0}. Nucleus
CC {ECO:0000250|UniProtKB:Q8BGW0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8N1K5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N1K5-2; Sequence=VSP_037965;
CC Name=3;
CC IsoId=Q8N1K5-3; Sequence=VSP_037964;
CC Name=4;
CC IsoId=Q8N1K5-4; Sequence=VSP_055714;
CC -!- PTM: Phosphorylated on Tyr residues quickly after TCR stimulation.
CC {ECO:0000250|UniProtKB:Q8BGW0}.
CC -!- SIMILARITY: Belongs to the themis family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC05194.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAG52943.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK094863; BAG52943.1; ALT_INIT; mRNA.
DR EMBL; CH471051; EAW48092.1; -; Genomic_DNA.
DR EMBL; BC130516; AAI30517.1; -; mRNA.
DR EMBL; AK124031; BAG53994.1; -; mRNA.
DR EMBL; AK128377; BAG54669.1; -; mRNA.
DR EMBL; AK292046; BAF84735.1; -; mRNA.
DR EMBL; AL035470; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356432; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL365224; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK097903; BAC05194.1; ALT_SEQ; mRNA.
DR EMBL; BX640890; CAE45941.1; -; mRNA.
DR CCDS; CCDS34534.1; -. [Q8N1K5-1]
DR CCDS; CCDS55055.1; -. [Q8N1K5-2]
DR CCDS; CCDS55056.1; -. [Q8N1K5-4]
DR RefSeq; NP_001010923.1; NM_001010923.2. [Q8N1K5-1]
DR RefSeq; NP_001158157.1; NM_001164685.1. [Q8N1K5-4]
DR RefSeq; NP_001158159.1; NM_001164687.1. [Q8N1K5-2]
DR RefSeq; NP_001305460.1; NM_001318531.1. [Q8N1K5-3]
DR RefSeq; XP_011534118.1; XM_011535816.1. [Q8N1K5-3]
DR AlphaFoldDB; Q8N1K5; -.
DR BioGRID; 132289; 6.
DR IntAct; Q8N1K5; 13.
DR MINT; Q8N1K5; -.
DR STRING; 9606.ENSP00000357231; -.
DR iPTMnet; Q8N1K5; -.
DR PhosphoSitePlus; Q8N1K5; -.
DR BioMuta; THEMIS; -.
DR DMDM; 150421530; -.
DR jPOST; Q8N1K5; -.
DR MassIVE; Q8N1K5; -.
DR MaxQB; Q8N1K5; -.
DR PeptideAtlas; Q8N1K5; -.
DR PRIDE; Q8N1K5; -.
DR ProteomicsDB; 25677; -.
DR ProteomicsDB; 71609; -. [Q8N1K5-1]
DR ProteomicsDB; 71610; -. [Q8N1K5-2]
DR ProteomicsDB; 71611; -. [Q8N1K5-3]
DR Antibodypedia; 49883; 248 antibodies from 34 providers.
DR DNASU; 387357; -.
DR Ensembl; ENST00000368248.5; ENSP00000357231.2; ENSG00000172673.12. [Q8N1K5-1]
DR Ensembl; ENST00000368250.5; ENSP00000357233.2; ENSG00000172673.12. [Q8N1K5-1]
DR Ensembl; ENST00000537166.5; ENSP00000439863.1; ENSG00000172673.12. [Q8N1K5-2]
DR Ensembl; ENST00000610842.4; ENSP00000480630.2; ENSG00000275122.4. [Q8N1K5-1]
DR Ensembl; ENST00000613862.2; ENSP00000480967.1; ENSG00000275122.4. [Q8N1K5-1]
DR Ensembl; ENST00000614155.3; ENSP00000484170.2; ENSG00000275122.4. [Q8N1K5-2]
DR Ensembl; ENST00000630369.2; ENSP00000487358.1; ENSG00000172673.12. [Q8N1K5-4]
DR GeneID; 387357; -.
DR KEGG; hsa:387357; -.
DR MANE-Select; ENST00000368248.5; ENSP00000357231.2; NM_001010923.3; NP_001010923.1.
DR UCSC; uc010kfb.3; human. [Q8N1K5-1]
DR CTD; 387357; -.
DR DisGeNET; 387357; -.
DR GeneCards; THEMIS; -.
DR HGNC; HGNC:21569; THEMIS.
DR HPA; ENSG00000172673; Tissue enriched (lymphoid).
DR MIM; 613607; gene.
DR neXtProt; NX_Q8N1K5; -.
DR OpenTargets; ENSG00000172673; -.
DR PharmGKB; PA165618330; -.
DR VEuPathDB; HostDB:ENSG00000172673; -.
DR eggNOG; ENOG502QSJR; Eukaryota.
DR GeneTree; ENSGT00530000063770; -.
DR InParanoid; Q8N1K5; -.
DR OMA; KVPVGCQ; -.
DR OrthoDB; 337909at2759; -.
DR PhylomeDB; Q8N1K5; -.
DR TreeFam; TF333479; -.
DR PathwayCommons; Q8N1K5; -.
DR SignaLink; Q8N1K5; -.
DR BioGRID-ORCS; 387357; 9 hits in 1038 CRISPR screens.
DR ChiTaRS; THEMIS; human.
DR GeneWiki; Protein_THEMIS; -.
DR GenomeRNAi; 387357; -.
DR Pharos; Q8N1K5; Tbio.
DR PRO; PR:Q8N1K5; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8N1K5; protein.
DR Bgee; ENSG00000172673; Expressed in lymph node and 95 other tissues.
DR ExpressionAtlas; Q8N1K5; baseline and differential.
DR Genevisible; Q8N1K5; HS.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0008180; C:COP9 signalosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0043383; P:negative T cell selection; ISS:UniProtKB.
DR GO; GO:0043368; P:positive T cell selection; ISS:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB.
DR InterPro; IPR025946; CABIT_dom.
DR InterPro; IPR039671; THEMIS.
DR PANTHER; PTHR15215; PTHR15215; 1.
DR Pfam; PF12736; CABIT; 2.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cytoplasm; Developmental protein;
KW Immunity; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..641
FT /note="Protein THEMIS"
FT /id="PRO_0000252378"
FT REGION 1..259
FT /note="CABIT 1"
FT REGION 260..518
FT /note="CABIT 2"
FT REGION 614..641
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 584
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15144186,
FT ECO:0007744|PubMed:19690332"
FT VAR_SEQ 1..97
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_037964"
FT VAR_SEQ 1..35
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037965"
FT VAR_SEQ 586
FT /note="K -> KAGVQWRDLGSLQPLPPGFKQFSASASHVAGITGTPHHVQ (in
FT isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_055714"
FT VARIANT 284
FT /note="V -> G (in dbSNP:rs11968051)"
FT /id="VAR_027846"
FT VARIANT 630
FT /note="I -> V (in dbSNP:rs675531)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|Ref.3"
FT /id="VAR_027847"
FT CONFLICT 63
FT /note="I -> V (in Ref. 1; BAF84735)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="S -> F (in Ref. 1; BAG53994)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="Y -> C (in Ref. 1; BAG53994)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="E -> K (in Ref. 1; BAG53994)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="N -> S (in Ref. 5; CAE45941)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 641 AA; 73452 MW; 30B5325242212E94 CRC64;
MALSLEEFVH SLDLRTLPRV LEIQAGIYLE GSIYEMFGNE CCFSTGEVIK ITGLKVKKII
AEICEQIEGC ESLQPFELPM NFPGLFKIVA DKTPYLTMEE ITRTIHIGPS RLGHPCFYHQ
KDIKLENLII KQGEQIMLNS VEEIDGEIMV SCAVARNHQT HSFNLPLSQE GEFYECEDER
IYTLKEIVEW KIPKNRTRTV NLTDFSNKWD STNPFPKDFY GTLILKPVYE IQGVMKFRKD
IIRILPSLDV EVKDITDSYD ANWFLQLLST EDLFEMTSKE FPIVTEVIEA PEGNHLPQSI
LQPGKTIVIH KKYQASRILA SEIRSNFPKR HFLIPTSYKG KFKRRPREFP TAYDLEIAKS
EKEPLHVVAT KAFHSPHDKL SSVSVGDQFL VHQSETTEVL CEGIKKVVNV LACEKILKKS
YEAALLPLYM EGGFVEVIHD KKQYPISELC KQFRLPFNVK VSVRDLSIEE DVLAATPGLQ
LEEDITDSYL LISDFANPTE CWEIPVGRLN MTVQLVSNFS RDAEPFLVRT LVEEITEEQY
YMMRRYESSA SHPPPRPPKH PSVEETKLTL LTLAEERTVD LPKSPKRHHV DITKKLHPNQ
AGLDSKVLIG SQNDLVDEEK ERSNRGATAI AETFKNEKHQ K
