TWSG1_HUMAN
ID TWSG1_HUMAN Reviewed; 223 AA.
AC Q9GZX9; B2RE08; D3DUH9; Q8NBI7; Q96K46;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Twisted gastrulation protein homolog 1;
DE Flags: Precursor;
GN Name=TWSG1; Synonyms=TSG; ORFNames=PSEC0250;
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 1).
RC TISSUE=Aorta;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RA Li J.M., Sha J.H., Zhou Z.M.;
RT "Human Twisted gastrulation protein: a new signal pathway for
RT spermatogenesis.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Teratocarcinoma, and Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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: 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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CHRD and BMP4. This interaction enhances
CC CHRD/BMP4 complex formation. Interacts with BMP7 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q9GZX9; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-10304067, EBI-18304435;
CC Q9GZX9; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-10304067, EBI-12142257;
CC Q9GZX9; P48165: GJA8; NbExp=3; IntAct=EBI-10304067, EBI-17458373;
CC Q9GZX9; Q9NZD1: GPRC5D; NbExp=3; IntAct=EBI-10304067, EBI-13067820;
CC Q9GZX9; Q92876: KLK6; NbExp=3; IntAct=EBI-10304067, EBI-2432309;
CC Q9GZX9; Q9HCJ2: LRRC4C; NbExp=3; IntAct=EBI-10304067, EBI-3925442;
CC Q9GZX9; O43765: SGTA; NbExp=3; IntAct=EBI-10304067, EBI-347996;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9GZX9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9GZX9-2; Sequence=VSP_042538, VSP_042539;
CC -!- DEVELOPMENTAL STAGE: Expressed in brain throughout development.
CC {ECO:0000269|PubMed:11420619}.
CC -!- DOMAIN: The N-terminal domain is sufficient to interact with BMP4.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the twisted gastrulation protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB55246.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR EMBL; AF196834; AAG43468.1; -; mRNA.
DR EMBL; AJ297391; CAC05581.1; -; mRNA.
DR EMBL; AF294628; AAG10076.1; -; mRNA.
DR EMBL; AK027629; BAB55246.1; ALT_SEQ; mRNA.
DR EMBL; AK075550; BAC11693.1; -; mRNA.
DR EMBL; AK315751; BAG38105.1; -; mRNA.
DR EMBL; AP001033; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471113; EAX01606.1; -; Genomic_DNA.
DR EMBL; CH471113; EAX01607.1; -; Genomic_DNA.
DR EMBL; BC020490; AAH20490.1; -; mRNA.
DR CCDS; CCDS11844.1; -. [Q9GZX9-1]
DR RefSeq; NP_065699.1; NM_020648.5. [Q9GZX9-1]
DR AlphaFoldDB; Q9GZX9; -.
DR BioGRID; 121338; 14.
DR CORUM; Q9GZX9; -.
DR IntAct; Q9GZX9; 9.
DR STRING; 9606.ENSP00000262120; -.
DR GlyConnect; 1867; 4 N-Linked glycans (1 site).
DR GlyGen; Q9GZX9; 2 sites, 4 N-linked glycans (1 site).
DR iPTMnet; Q9GZX9; -.
DR PhosphoSitePlus; Q9GZX9; -.
DR BioMuta; TWSG1; -.
DR DMDM; 74733506; -.
DR CPTAC; CPTAC-1513; -.
DR EPD; Q9GZX9; -.
DR jPOST; Q9GZX9; -.
DR MassIVE; Q9GZX9; -.
DR MaxQB; Q9GZX9; -.
DR PaxDb; Q9GZX9; -.
DR PeptideAtlas; Q9GZX9; -.
DR PRIDE; Q9GZX9; -.
DR ProteomicsDB; 80169; -. [Q9GZX9-1]
DR ProteomicsDB; 80170; -. [Q9GZX9-2]
DR Antibodypedia; 2970; 117 antibodies from 23 providers.
DR DNASU; 57045; -.
DR Ensembl; ENST00000262120.10; ENSP00000262120.5; ENSG00000128791.12. [Q9GZX9-1]
DR Ensembl; ENST00000583147.5; ENSP00000463331.1; ENSG00000128791.12. [Q9GZX9-2]
DR GeneID; 57045; -.
DR KEGG; hsa:57045; -.
DR MANE-Select; ENST00000262120.10; ENSP00000262120.5; NM_020648.6; NP_065699.1.
DR UCSC; uc002knz.3; human. [Q9GZX9-1]
DR CTD; 57045; -.
DR DisGeNET; 57045; -.
DR GeneCards; TWSG1; -.
DR HGNC; HGNC:12429; TWSG1.
DR HPA; ENSG00000128791; Low tissue specificity.
DR MIM; 605049; gene.
DR neXtProt; NX_Q9GZX9; -.
DR OpenTargets; ENSG00000128791; -.
DR PharmGKB; PA37089; -.
DR VEuPathDB; HostDB:ENSG00000128791; -.
DR eggNOG; ENOG502QRE9; Eukaryota.
DR GeneTree; ENSGT00390000007058; -.
DR HOGENOM; CLU_2670412_0_0_1; -.
DR InParanoid; Q9GZX9; -.
DR OMA; SCVDLCP; -.
DR OrthoDB; 1254178at2759; -.
DR PhylomeDB; Q9GZX9; -.
DR TreeFam; TF323922; -.
DR PathwayCommons; Q9GZX9; -.
DR SignaLink; Q9GZX9; -.
DR BioGRID-ORCS; 57045; 12 hits in 1079 CRISPR screens.
DR ChiTaRS; TWSG1; human.
DR GeneWiki; TWSG1; -.
DR GenomeRNAi; 57045; -.
DR Pharos; Q9GZX9; Tbio.
DR PRO; PR:Q9GZX9; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q9GZX9; protein.
DR Bgee; ENSG00000128791; Expressed in seminal vesicle and 193 other tissues.
DR ExpressionAtlas; Q9GZX9; baseline and differential.
DR Genevisible; Q9GZX9; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0008201; F:heparin binding; IEA:Ensembl.
DR GO; GO:0050431; F:transforming growth factor beta binding; IDA:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:2000515; P:negative regulation of CD4-positive, alpha-beta T cell activation; IDA:BHF-UCL.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; IDA:BHF-UCL.
DR GO; GO:0001818; P:negative regulation of cytokine production; IDA:BHF-UCL.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IEA:Ensembl.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0030510; P:regulation of BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0007435; P:salivary gland morphogenesis; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR InterPro; IPR006761; Tsg.
DR PANTHER; PTHR12312; PTHR12312; 1.
DR Pfam; PF04668; Tsg; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Glycoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..223
FT /note="Twisted gastrulation protein homolog 1"
FT /id="PRO_0000278808"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 75
FT /note="G -> D (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042538"
FT VAR_SEQ 76..223
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042539"
FT CONFLICT 35
FT /note="V -> E (in Ref. 6; BAC11693)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 223 AA; 25017 MW; 34AEB1A836871772 CRC64;
MKLHYVAVLT LAILMFLTWL PESLSCNKAL CASDVSKCLI QELCQCRPGE GNCSCCKECM
LCLGALWDEC CDCVGMCNPR NYSDTPPTSK STVEELHEPI PSLFRALTEG DTQLNWNIVS
FPVAEELSHH ENLVSFLETV NQPHHQNVSV PSNNVHAPYS SDKEHMCTVV YFDDCMSIHQ
CKISCESMGA SKYRWFHNAC CECIGPECID YGSKTVKCMN CMF
