TWSG1_MOUSE
ID TWSG1_MOUSE Reviewed; 222 AA.
AC Q9EP52; Q8CCB1; Q8CEM6; Q99K77; Q9ERN7;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Twisted gastrulation protein homolog 1;
DE Flags: Precursor;
GN Name=Twsg1; Synonyms=Tsg;
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], AND INTERACTION WITH CHRD AND BMP4.
RC TISSUE=Thymus;
RX PubMed=11420619; DOI=10.1007/s0033501-0005-x;
RA Graf D., Timmons P.M., Hitchins M., Episkopou V., Moore G., Ito T.,
RA Fujiyama A., Fisher A.G., Merkenschlager M.;
RT "Evolutionary conservation, developmental expression, and genomic mapping
RT of mammalian Twisted gastrulation.";
RL Mamm. Genome 12:554-560(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zakin L., Oelgeschlager M., Geissert D., De Robertis E.M.;
RT "Characterization of the mouse homolog of Twisted gastrulation.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RA Li J.M., Sha J.H., Zhou Z.M.;
RT "Mouse twisted gastrulation protein: a new signal pathway of
RT spermatogenesis.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Amnion, Colon, Liver, and Spinal cord;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [6]
RP FUNCTION, DEVELOPMENTAL STAGE, AND INTERACTION WITH CHRD AND BMP4.
RX PubMed=11260715; DOI=10.1038/35068572;
RA Scott I.C., Blitz I.L., Pappano W.N., Maas S.A., Cho K.W.Y.,
RA Greenspan D.S.;
RT "Homologues of Twisted gastrulation are extracellular cofactors in
RT antagonism of BMP signalling.";
RL Nature 410:475-478(2001).
RN [7]
RP ERRATUM OF PUBMED:11260715.
RA Scott I.C., Blitz I.L., Pappano W.N., Maas S.A., Cho K.W.Y.,
RA Greenspan D.S.;
RL Nature 411:720-720(2001).
RN [8]
RP FUNCTION.
RX PubMed=12119341; DOI=10.1084/jem.20020276;
RA Graf D., Nethisinghe S., Palmer D.B., Fisher A.G., Merkenschlager M.;
RT "The developmentally regulated expression of Twisted gastrulation reveals a
RT role for bone morphogenetic proteins in the control of T cell
RT development.";
RL J. Exp. Med. 196:163-171(2002).
RN [9]
RP FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP BMP7.
RX PubMed=15843411; DOI=10.1242/dev.01822;
RA Zakin L., Reversade B., Kuroda H., Lyons K.M., De Robertis E.M.;
RT "Sirenomelia in Bmp7 and Tsg compound mutant mice: requirement for Bmp
RT signaling in the development of ventral posterior mesoderm.";
RL Development 132:2489-2499(2005).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16905550; DOI=10.1074/jbc.m603419200;
RA Schmidl M., Adam N., Surmann-Schmitt C., Hattori T., Stock M., Dietz U.,
RA de Crombrugghe B., Poeschl E., von der Mark K.;
RT "Twisted gastrulation modulates bone morphogenetic protein-induced collagen
RT II and X expression in chondrocytes in vitro and in vivo.";
RL J. Biol. Chem. 281:31790-31800(2006).
CC -!- FUNCTION: May be involved in dorsoventral axis formation. Seems to
CC antagonize BMP signaling by forming ternary complexes with CHRD and
CC BMPs, thereby preventing BMPs from binding to their receptors. In
CC addition to the anti-BMP function, also has pro-BMP activity, partly
CC mediated by cleavage and degradation of CHRD, which releases BMPs from
CC ternary complexes. May be an important modulator of BMP-regulated
CC cartilage development and chondrocyte differentiation. May play a role
CC in thymocyte development. {ECO:0000269|PubMed:11260715,
CC ECO:0000269|PubMed:12119341, ECO:0000269|PubMed:15843411,
CC ECO:0000269|PubMed:16905550}.
CC -!- SUBUNIT: Interacts with CHRD and/or BMP4. This interaction enhances
CC CHRD/BMP4 complex formation. Interacts with BMP7.
CC {ECO:0000269|PubMed:11260715, ECO:0000269|PubMed:11420619,
CC ECO:0000269|PubMed:15843411}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in lymph node, liver, kidney, and lung.
CC Expression in the kidney was stronger in the medulla than in the
CC cortex, particularly in the cells surrounding the medullary tubules.
CC Expressed in growth plate cartilage of long bones, ribs, and digits and
CC to a lesser extent also in the resting zone of the epiphysis,
CC trabecular bone, and vertebral cartilage. Expression seems to be absent
CC from other skeletal tissues including muscle, skin, and fibroblasts.
CC {ECO:0000269|PubMed:16905550}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all embryonic stages examined.
CC Expression was low and distribution was diffuse. At the primitive
CC streak stage, detected in the extraembryonic region. Signal first
CC appeared in the embryo during the neural plate stage. Stronger and more
CC localized expression is seen after embryonic turning. Higher expression
CC is seen in the branchial arch mesenchyme, the endoderm of the
CC developing pharynx, all levels of the developing gut, the myotome
CC compartment of the somites, and some regions of surface ectoderm. At
CC 8.25 and 9.0 dpc expressed in head mesenchyme and ventral mesoderm.
CC {ECO:0000269|PubMed:11260715, ECO:0000269|PubMed:15843411}.
CC -!- DOMAIN: The N-terminal domain is sufficient to interact with BMP4.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality and sirenomelia were observed
CC only in BMP null embryos in which one or two copies of TSG were also
CC missing. When TSG and BMP7 are mutated, the siren phenotype results
CC from the fusion of the limb buds in the ventroposterior midline owing
CC to a paucity of posterior ventral mesoderm.
CC {ECO:0000269|PubMed:15843411}.
CC -!- SIMILARITY: Belongs to the twisted gastrulation protein family.
CC {ECO:0000305}.
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DR EMBL; AJ297390; CAC05586.1; -; mRNA.
DR EMBL; AF292033; AAG00605.1; -; mRNA.
DR EMBL; AF295097; AAG10080.1; -; mRNA.
DR EMBL; AK018524; BAC25557.1; -; mRNA.
DR EMBL; AK033504; BAC28326.1; -; mRNA.
DR EMBL; AK049646; BAC33857.1; -; mRNA.
DR EMBL; AK168547; BAE40422.1; -; mRNA.
DR EMBL; AK168633; BAE40493.1; -; mRNA.
DR EMBL; BC004850; AAH04850.1; -; mRNA.
DR CCDS; CCDS28942.1; -.
DR RefSeq; NP_075540.1; NM_023053.3.
DR AlphaFoldDB; Q9EP52; -.
DR BioGRID; 211157; 2.
DR STRING; 10090.ENSMUSP00000024906; -.
DR GlyGen; Q9EP52; 2 sites.
DR iPTMnet; Q9EP52; -.
DR PhosphoSitePlus; Q9EP52; -.
DR EPD; Q9EP52; -.
DR MaxQB; Q9EP52; -.
DR PaxDb; Q9EP52; -.
DR PeptideAtlas; Q9EP52; -.
DR PRIDE; Q9EP52; -.
DR ProteomicsDB; 298391; -.
DR Antibodypedia; 2970; 117 antibodies from 23 providers.
DR Ensembl; ENSMUST00000024906; ENSMUSP00000024906; ENSMUSG00000024098.
DR Ensembl; ENSMUST00000233580; ENSMUSP00000156695; ENSMUSG00000024098.
DR GeneID; 65960; -.
DR KEGG; mmu:65960; -.
DR UCSC; uc008dgq.2; mouse.
DR CTD; 57045; -.
DR MGI; MGI:2137520; Twsg1.
DR VEuPathDB; HostDB:ENSMUSG00000024098; -.
DR eggNOG; ENOG502QRE9; Eukaryota.
DR GeneTree; ENSGT00390000007058; -.
DR HOGENOM; CLU_082511_1_0_1; -.
DR InParanoid; Q9EP52; -.
DR OMA; SCVDLCP; -.
DR OrthoDB; 1254178at2759; -.
DR PhylomeDB; Q9EP52; -.
DR TreeFam; TF323922; -.
DR BioGRID-ORCS; 65960; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Twsg1; mouse.
DR PRO; PR:Q9EP52; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9EP52; protein.
DR Bgee; ENSMUSG00000024098; Expressed in cumulus cell and 263 other tissues.
DR ExpressionAtlas; Q9EP52; baseline and differential.
DR Genevisible; Q9EP52; MM.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0050431; F:transforming growth factor beta binding; ISO:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IGI:MGI.
DR GO; GO:0043010; P:camera-type eye development; IGI:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IMP:MGI.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0030097; P:hemopoiesis; IMP:MGI.
DR GO; GO:0001707; P:mesoderm formation; IGI:MGI.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:MGI.
DR GO; GO:2000515; P:negative regulation of CD4-positive, alpha-beta T cell activation; ISO:MGI.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; ISO:MGI.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISO:MGI.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:MGI.
DR GO; GO:0001503; P:ossification; IMP:MGI.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:MGI.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:MGI.
DR GO; GO:0030510; P:regulation of BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0007435; P:salivary gland morphogenesis; IMP:MGI.
DR GO; GO:0009888; P:tissue development; IGI:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR InterPro; IPR006761; Tsg.
DR PANTHER; PTHR12312; PTHR12312; 1.
DR Pfam; PF04668; Tsg; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..222
FT /note="Twisted gastrulation protein homolog 1"
FT /id="PRO_0000278809"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 6
FT /note="I -> IA (in Ref. 3; AAG10080)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="M -> R (in Ref. 3; AAG10080 and 5; AAH04850)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="V -> E (in Ref. 4; BAC28326)"
FT /evidence="ECO:0000305"
FT CONFLICT 203..204
FT /note="IG -> MR (in Ref. 3; AAG10080)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 222 AA; 24801 MW; F9B0CEE2A8DF8CA7 CRC64;
MKSHYIVLAL ASLTFLLCLP VSQSCNKALC ASDVSKCLIQ ELCQCRPGEG NCPCCKECML
CLGALWDECC DCVGMCNPRN YSDTPPTSKS TVEELHEPIP SLFRALTEGD TQLNWNIVSF
PVAEELSHHE NLVSFLETVN QLHHQNVSVP SNNVHAPFPS DKERMCTVVY FDDCMSIHQC
KISCESMGAS KYRWFHNACC ECIGPECIDY GSKTVKCMNC MF
