THNS2_HUMAN
ID THNS2_HUMAN Reviewed; 484 AA.
AC Q86YJ6; B3KTB1; B5MDX8; B7WPF8; D9ZZB8; Q6P2M7; Q6PI27; Q9NV54;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Threonine synthase-like 2;
DE Short=TSH2;
DE EC=4.2.3.-;
DE AltName: Full=Secreted osteoclastogenic factor of activated T-cells;
DE Short=SOFAT;
GN Name=THNSL2;
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] (ISOFORM SOFAT), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Peripheral blood T-cell;
RX PubMed=19877052; DOI=10.1002/art.24877;
RA Rifas L., Weitzmann M.N.;
RT "A novel T cell cytokine, secreted osteoclastogenic factor of activated T
RT cells, induces osteoclast formation in a RANKL-independent manner.";
RL Arthritis Rheum. 60:3324-3335(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 63-484 (ISOFORM 4), AND VARIANT GLU-41.
RC TISSUE=Ovarian carcinoma, and Tongue;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 54-484 (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE
RP MRNA] OF 140-431 (ISOFORM 3), AND VARIANTS GLU-41 AND GLY-324.
RC TISSUE=Brain, Colon, and Skin;
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).
CC -!- FUNCTION: [Isoform 1]: Acts as a catabolic phospho-lyase on both
CC gamma- and beta-phosphorylated substrates. Degrades O-phospho-threonine
CC (PThr) to alpha-ketobutyrate, ammonia and phosphate (By similarity).
CC {ECO:0000250}.
CC -!- FUNCTION: [Isoform SOFAT]: Potent inducer of osteoblastic production of
CC IL6. May act to exacerbate inflammation and/or bone turnover under
CC inflammatory conditions. {ECO:0000269|PubMed:19877052}.
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: [Isoform SOFAT]: Secreted. Note=Secreted by
CC activated T-cells via a calcineurin-independent pathway.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q86YJ6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86YJ6-2; Sequence=VSP_028469;
CC Name=3;
CC IsoId=Q86YJ6-3; Sequence=VSP_028470;
CC Name=4;
CC IsoId=Q86YJ6-4; Sequence=VSP_028468;
CC Name=SOFAT;
CC IsoId=Q86YJ6-5; Sequence=VSP_041659, VSP_041660;
CC -!- SIMILARITY: Belongs to the threonine synthase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAX88906.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA91904.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; HM185274; ADL14696.1; -; mRNA.
DR EMBL; AK001778; BAA91904.1; ALT_INIT; mRNA.
DR EMBL; AK095303; BAG53023.1; -; mRNA.
DR EMBL; AC092836; AAX88906.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC035315; AAH35315.1; -; mRNA.
DR EMBL; BC047758; AAH47758.2; -; mRNA.
DR EMBL; BC064423; AAH64423.1; -; mRNA.
DR CCDS; CCDS2002.2; -. [Q86YJ6-1]
DR CCDS; CCDS58718.1; -. [Q86YJ6-2]
DR RefSeq; NP_001231605.1; NM_001244676.1. [Q86YJ6-2]
DR RefSeq; NP_060741.3; NM_018271.4. [Q86YJ6-1]
DR RefSeq; XP_005264457.1; XM_005264400.4.
DR RefSeq; XP_005264458.1; XM_005264401.4. [Q86YJ6-1]
DR RefSeq; XP_005264460.1; XM_005264403.4.
DR RefSeq; XP_006712106.1; XM_006712043.2. [Q86YJ6-2]
DR AlphaFoldDB; Q86YJ6; -.
DR SMR; Q86YJ6; -.
DR BioGRID; 120549; 1.
DR IntAct; Q86YJ6; 3.
DR STRING; 9606.ENSP00000327323; -.
DR PhosphoSitePlus; Q86YJ6; -.
DR BioMuta; THNSL2; -.
DR DMDM; 313104279; -.
DR EPD; Q86YJ6; -.
DR MassIVE; Q86YJ6; -.
DR MaxQB; Q86YJ6; -.
DR PaxDb; Q86YJ6; -.
DR PeptideAtlas; Q86YJ6; -.
DR PRIDE; Q86YJ6; -.
DR ProteomicsDB; 70421; -. [Q86YJ6-1]
DR ProteomicsDB; 70422; -. [Q86YJ6-2]
DR ProteomicsDB; 70423; -. [Q86YJ6-3]
DR ProteomicsDB; 70424; -. [Q86YJ6-4]
DR ProteomicsDB; 70425; -. [Q86YJ6-5]
DR Antibodypedia; 32227; 139 antibodies from 28 providers.
DR DNASU; 55258; -.
DR Ensembl; ENST00000324166.7; ENSP00000327323.5; ENSG00000144115.18. [Q86YJ6-1]
DR Ensembl; ENST00000343544.8; ENSP00000339563.4; ENSG00000144115.18. [Q86YJ6-2]
DR Ensembl; ENST00000496844.6; ENSP00000501447.1; ENSG00000144115.18. [Q86YJ6-3]
DR Ensembl; ENST00000674334.2; ENSP00000501453.1; ENSG00000144115.18. [Q86YJ6-1]
DR GeneID; 55258; -.
DR KEGG; hsa:55258; -.
DR MANE-Select; ENST00000674334.2; ENSP00000501453.1; NM_018271.5; NP_060741.3.
DR UCSC; uc002ssw.5; human. [Q86YJ6-1]
DR CTD; 55258; -.
DR DisGeNET; 55258; -.
DR GeneCards; THNSL2; -.
DR HGNC; HGNC:25602; THNSL2.
DR HPA; ENSG00000144115; Low tissue specificity.
DR MIM; 611261; gene.
DR neXtProt; NX_Q86YJ6; -.
DR OpenTargets; ENSG00000144115; -.
DR PharmGKB; PA162405692; -.
DR VEuPathDB; HostDB:ENSG00000144115; -.
DR eggNOG; KOG2616; Eukaryota.
DR GeneTree; ENSGT00940000158503; -.
DR HOGENOM; CLU_015170_1_1_1; -.
DR InParanoid; Q86YJ6; -.
DR OMA; FGRIAFQ; -.
DR OrthoDB; 1361511at2759; -.
DR PhylomeDB; Q86YJ6; -.
DR TreeFam; TF329641; -.
DR PathwayCommons; Q86YJ6; -.
DR SignaLink; Q86YJ6; -.
DR BioGRID-ORCS; 55258; 8 hits in 1064 CRISPR screens.
DR ChiTaRS; THNSL2; human.
DR GenomeRNAi; 55258; -.
DR Pharos; Q86YJ6; Tbio.
DR PRO; PR:Q86YJ6; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q86YJ6; protein.
DR Bgee; ENSG00000144115; Expressed in right lobe of liver and 161 other tissues.
DR ExpressionAtlas; Q86YJ6; baseline and differential.
DR Genevisible; Q86YJ6; HS.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0030170; F:pyridoxal phosphate binding; ISS:BHF-UCL.
DR GO; GO:0070905; F:serine binding; ISS:BHF-UCL.
DR GO; GO:0046360; P:2-oxobutyrate biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0016311; P:dephosphorylation; ISS:BHF-UCL.
DR GO; GO:0009071; P:serine family amino acid catabolic process; ISS:BHF-UCL.
DR Gene3D; 3.40.50.1100; -; 2.
DR Gene3D; 3.90.1380.10; -; 1.
DR InterPro; IPR001926; PLP-dep.
DR InterPro; IPR029144; Thr_synth_N.
DR InterPro; IPR037158; Thr_synth_N_sf.
DR InterPro; IPR004450; Thr_synthase-like.
DR InterPro; IPR036052; Trypto_synt_PLP_dependent.
DR Pfam; PF00291; PALP; 1.
DR Pfam; PF14821; Thr_synth_N; 1.
DR SUPFAM; SSF53686; SSF53686; 1.
DR TIGRFAMs; TIGR00260; thrC; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytokine; Lyase; Pyridoxal phosphate;
KW Reference proteome; Secreted.
FT CHAIN 1..484
FT /note="Threonine synthase-like 2"
FT /id="PRO_0000306407"
FT MOD_RES 113
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..158
FT /note="Missing (in isoform SOFAT)"
FT /evidence="ECO:0000303|PubMed:19877052"
FT /id="VSP_041659"
FT VAR_SEQ 214..274
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_028468"
FT VAR_SEQ 360..484
FT /note="LSEAVTSVSVSDEAITQTMGRCWDENQYLLCPHSAVAVNYHYQQIDRQQPST
FT PRCCLAPASAAKFPEAVLAAGLTPETPAEIVALEHKETRCTLMRRGDNWMLMLRDTIED
FT LSRQWRSHALNTSQ -> WERQDYEKMAVMECDGCCVELCLGNCGPRRGSVTDIPGTAM
FT VRGGG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028469"
FT VAR_SEQ 360..484
FT /note="LSEAVTSVSVSDEAITQTMGRCWDENQYLLCPHSAVAVNYHYQQIDRQQPST
FT PRCCLAPASAAKFPEAVLAAGLTPETPAEIVALEHKETRCTLMRRGDNWMLMLRDTIED
FT LSRQWRSHALNTSQ -> HSPVLPRPCLCSQVPGSCPGCWPDP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028470"
FT VAR_SEQ 360..484
FT /note="LSEAVTSVSVSDEAITQTMGRCWDENQYLLCPHSAVAVNYHYQQIDRQQPST
FT PRCCLAPASAAKFPEAVLAAGLTPETPAEIVALEHKETRCTLMRRGDNWMLMLRDTIED
FT LSRQWRSHALNTSQ -> WERQDYEKMAVMECDGCCVELCLGNCGPRRGSVTDIPGTAM
FT VRGGD (in isoform SOFAT)"
FT /evidence="ECO:0000303|PubMed:19877052"
FT /id="VSP_041660"
FT VARIANT 41
FT /note="G -> E (in dbSNP:rs4129190)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_054635"
FT VARIANT 108
FT /note="V -> I (in dbSNP:rs35541720)"
FT /id="VAR_054636"
FT VARIANT 204
FT /note="T -> N (in dbSNP:rs34136143)"
FT /id="VAR_054637"
FT VARIANT 324
FT /note="R -> G (in dbSNP:rs17855905)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_054638"
FT CONFLICT 63
FT /note="I -> V (in Ref. 2; BAA91904)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 484 AA; 54116 MW; F177B2B7DE6E8752 CRC64;
MWYVSTRGVA PRVNFEGALF SGYAPDGGLF MPEELPQLDR GTLCQWSTLS YPGLVKELCA
LFIGSELLPK DELNDLIDRA FSRFRHREVV HLSRLRNGLN VLELWHGVTY AFKDLSLSCT
TQFLQYFLEK REKHVTVVVG TSGDTGSAAI ESVQGAKNMD IIVLLPKGHC TKIQELQMTT
VLKQNVHVFG VEGNSDELDE PIKTVFADVA FVKKHNLMSL NSINWSRVLV QMAHHFFAYF
QCTPSLDTHP LPLVEVVVPT GAAGNLAAGY IAQKIGLPIR LVVAVNRNDI IHRTVQQGDF
SLSEAVKSTL ASAMDIQVPY NMERVFWLLS GSDSQVTRAL MEQFERTQSV NLPKELHSKL
SEAVTSVSVS DEAITQTMGR CWDENQYLLC PHSAVAVNYH YQQIDRQQPS TPRCCLAPAS
AAKFPEAVLA AGLTPETPAE IVALEHKETR CTLMRRGDNW MLMLRDTIED LSRQWRSHAL
NTSQ
