TSK_CHICK
ID TSK_CHICK Reviewed; 369 AA.
AC Q65Z91; Q4W6V7;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Tsukushi {ECO:0000303|PubMed:15363410};
DE AltName: Full=C-TSK;
DE AltName: Full=Leucine-rich repeat-containing protein 54;
DE Flags: Precursor;
GN Name=TSKU; Synonyms=LRRC54, TSK;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CHRD;
RP BMP4 AND BMP7, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=15363410; DOI=10.1016/j.devcel.2004.08.014;
RA Ohta K., Lupo G., Kuriyama S., Keynes R., Holt C.E., Harris W.A.,
RA Tanaka H., Ohnuma S.;
RT "Tsukushi functions as an organizer inducer by inhibition of BMP activity
RT in cooperation with chordin.";
RL Dev. Cell 7:347-358(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=16319115; DOI=10.1242/dev.02178;
RA Kuriyama S., Lupo G., Ohta K., Ohnuma S., Harris W.A., Tanaka H.;
RT "Tsukushi controls ectodermal patterning and neural crest specification in
RT Xenopus by direct regulation of BMP4 and X-delta-1 activity.";
RL Development 133:75-88(2006).
RN [3]
RP FUNCTION (ISOFORMS 1 AND 2), INTERACTION WITH BMP4 AND VG1 (ISOFORM 1),
RP INTERACTION WITH BMP4; BMP7 AND VG1 (ISOFORM 2), ALTERNATIVE SPLICING, AND
RP DEVELOPMENTAL STAGE (ISOFORMS 1 AND 2).
RX PubMed=16943268; DOI=10.1242/dev.02579;
RA Ohta K., Kuriyama S., Okafuji T., Gejima R., Ohnuma S., Tanaka H.;
RT "Tsukushi cooperates with VG1 to induce primitive streak and Hensen's node
RT formation in the chick embryo.";
RL Development 133:3777-3786(2006).
RN [4]
RP FUNCTION, INTERACTION WITH FZD4, AND TISSUE SPECIFICITY.
RX PubMed=21856951; DOI=10.1073/pnas.1100513108;
RA Ohta K., Ito A., Kuriyama S., Lupo G., Kosaka M., Ohnuma S., Nakagawa S.,
RA Tanaka H.;
RT "Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b
RT for binding to transmembrane protein Frizzled4.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:14962-14967(2011).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=26299926; DOI=10.1016/j.bbrc.2015.08.074;
RA Acharjee U.K., Gejima R., Felemban Athary Abdulhaleem M., Riyadh M.A.,
RA Tanaka H., Ohta K.;
RT "Tsukushi expression is dependent on Notch signaling and oscillated in the
RT presomitic mesoderm during chick somitogenesis.";
RL Biochem. Biophys. Res. Commun. 465:625-630(2015).
CC -!- FUNCTION: Contributes to various developmental events through its
CC interactions with multiple signaling pathways (PubMed:15363410,
CC PubMed:16943268, PubMed:21856951). Dorsalizing factor involved in the
CC induction of Hensen's node by inhibiting bone morphogenetic proteins
CC during gastrulation and by enhancing DVR1/VG1 activity
CC (PubMed:15363410, PubMed:16943268). Wnt signaling inhibitor which
CC competes with WNT2B for binding to Wnt receptor FZD4 and represses
CC WNT2B-dependent development of the peripheral eye (PubMed:21856951).
CC {ECO:0000269|PubMed:15363410, ECO:0000269|PubMed:16943268,
CC ECO:0000269|PubMed:21856951}.
CC -!- FUNCTION: [Isoform 1]: Shows strong bone morphogenetic protein
CC antagonistic activity. {ECO:0000269|PubMed:16943268}.
CC -!- FUNCTION: [Isoform 2]: Shows weak bone morphogenetic protein
CC antagonistic activity. {ECO:0000269|PubMed:16943268}.
CC -!- SUBUNIT: Forms a ternary complex with chordin/CHRD and BMP4.
CC {ECO:0000269|PubMed:15363410}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with FZD4 (via FZ domain); competes
CC with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing
CC peripheral eye development (PubMed:21856951). Interacts with BMP4;
CC shows stronger interaction with BMP4 than isoform 2 (PubMed:16943268).
CC Interacts with DVR1/VG1; the interaction is inhibited by BMP4
CC (PubMed:16943268). Interacts with BMP7 (PubMed:15363410).
CC {ECO:0000269|PubMed:15363410, ECO:0000269|PubMed:16943268,
CC ECO:0000269|PubMed:21856951}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with FZD4 (via FZ domain); competes
CC with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing
CC peripheral eye development (PubMed:21856951). Interacts with BMP4;
CC shows weaker interaction with BMP4 than isoform 1 (PubMed:16943268).
CC Interacts with DVR1/VG1; the interaction is inhibited by BMP4
CC (PubMed:16943268). Interacts with BMP7 (PubMed:16943268).
CC {ECO:0000269|PubMed:16943268, ECO:0000269|PubMed:21856951}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15363410}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=TSKA {ECO:0000303|PubMed:16943268};
CC IsoId=Q65Z91-1; Sequence=Displayed;
CC Name=2; Synonyms=TSKB {ECO:0000303|PubMed:16943268};
CC IsoId=Q65Z91-2; Sequence=VSP_019375;
CC -!- TISSUE SPECIFICITY: During embryonic development, expressed in the
CC middle primitive streak and Hensen's node (PubMed:15363410). Expressed
CC in the peripheral region of the developing eye (PubMed:21856951).
CC Expressed in the presomitic mesoderm during somitogenesis in a NOTCH-
CC dependent manner (PubMed:26299926). {ECO:0000269|PubMed:15363410,
CC ECO:0000269|PubMed:21856951, ECO:0000269|PubMed:26299926}.
CC -!- DEVELOPMENTAL STAGE: In the presomitic mesoderm (PSM), expression is
CC first detected at stage 7 where the first somite pair originates from
CC both sides of the neural tube (PubMed:26299926). At stage 15,
CC expression is detected in the anterior PSM (PubMed:26299926). During
CC stage 18, also expressed in the newly forming somites and the PSM that
CC reaches beyond the leg bud (PubMed:26299926). At stage 23, expressed in
CC the somites and PSM near the tip of the tail and also in the wing and
CC leg buds (PubMed:26299926). {ECO:0000269|PubMed:26299926}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 1]: Expressed throughout the emerging
CC primitive streak at stage 2 (PubMed:16943268). At stage 3, expressed in
CC both the anterior and posterior parts of the primitive streak
CC (PubMed:16943268). At stage 4, expressed in Hensen's node and the
CC anterior part of the primitive streak (PubMed:16943268). At all stages,
CC expressed at lower levels than isoform 2 (PubMed:16943268).
CC {ECO:0000269|PubMed:16943268}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 2]: Expressed throughout the emerging
CC primitive streak at stage 2 (PubMed:16943268). At stage 3, expressed in
CC both the anterior and posterior parts of the primitive streak
CC (PubMed:16943268). At stage 4, expressed in Hensen's node and
CC throughout the anterior, middle and posterior part of the primitive
CC streak with a peak of expression in the middle part (PubMed:16943268).
CC At all stages, expressed at higher levels than isoform 1
CC (PubMed:16943268). {ECO:0000269|PubMed:16943268}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15363410}.
CC -!- MISCELLANEOUS: This factor is named 'Tsukushi' because its expression
CC pattern in chick embryos is similar to the shape of the Japanese
CC horsetail plant, tsukushi. {ECO:0000303|PubMed:15363410}.
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DR EMBL; AB100033; BAD44777.1; -; mRNA.
DR EMBL; AB195969; BAD99276.1; -; mRNA.
DR RefSeq; NP_001005346.1; NM_001005346.1. [Q65Z91-1]
DR AlphaFoldDB; Q65Z91; -.
DR SMR; Q65Z91; -.
DR STRING; 9031.ENSGALP00000001104; -.
DR PaxDb; Q65Z91; -.
DR Ensembl; ENSGALT00000001106; ENSGALP00000001104; ENSGALG00000000761. [Q65Z91-1]
DR GeneID; 419088; -.
DR KEGG; gga:419088; -.
DR CTD; 25987; -.
DR VEuPathDB; HostDB:geneid_419088; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000160984; -.
DR InParanoid; Q65Z91; -.
DR OMA; QPCFPGC; -.
DR PhylomeDB; Q65Z91; -.
DR Reactome; R-GGA-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-GGA-430116; GP1b-IX-V activation signalling.
DR Reactome; R-GGA-75892; Platelet Adhesion to exposed collagen.
DR Reactome; R-GGA-76009; Platelet Aggregation (Plug Formation).
DR PRO; PR:Q65Z91; -.
DR Proteomes; UP000000539; Chromosome 1.
DR Bgee; ENSGALG00000000761; Expressed in colon and 11 other tissues.
DR ExpressionAtlas; Q65Z91; baseline and differential.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0036122; F:BMP binding; IPI:UniProtKB.
DR GO; GO:0098868; P:bone growth; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0003431; P:growth plate cartilage chondrocyte development; ISS:UniProtKB.
DR GO; GO:0090009; P:primitive streak formation; IMP:UniProtKB.
DR Gene3D; 3.80.10.10; -; 3.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF00560; LRR_1; 1.
DR Pfam; PF13855; LRR_8; 2.
DR SMART; SM00369; LRR_TYP; 7.
DR PROSITE; PS51450; LRR; 8.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Glycoprotein;
KW Leucine-rich repeat; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..369
FT /note="Tsukushi"
FT /id="PRO_0000240410"
FT DOMAIN 20..60
FT /note="LRRNT"
FT REPEAT 61..81
FT /note="LRR 1"
FT REPEAT 87..108
FT /note="LRR 2"
FT REPEAT 111..132
FT /note="LRR 3"
FT REPEAT 134..155
FT /note="LRR 4"
FT REPEAT 161..181
FT /note="LRR 5"
FT REPEAT 184..205
FT /note="LRR 6"
FT REPEAT 206..226
FT /note="LRR 7"
FT REPEAT 229..248
FT /note="LRR 8"
FT REPEAT 254..276
FT /note="LRR 9"
FT REPEAT 279..300
FT /note="LRR 10"
FT REPEAT 303..323
FT /note="LRR 11"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 333..369
FT /note="LGLGAEELLWCKTPCPRPVCRCRDKPLQSAPQNLPTP -> KGVLSCHDSHG
FT AVAAAPYVL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16319115"
FT /id="VSP_019375"
FT CONFLICT 104
FT /note="T -> A (in Ref. 2; BAD99276)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="L -> P (in Ref. 2; BAD99276)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 369 AA; 40710 MW; 7278E90E8BE6EFB1 CRC64;
MQFLAWFNML LLLPCFSTTK TCFPGCHCEV ESFGLFDSFS LTKVDCSGIG SHIVPVPIPL
DTSYLDLSSN KLETINESML TGPGYTTLVS LDLSYNNIAK ISSTTFSRLR YLESLDLSHN
SLEVLPEDCF SSSPLGDIDL SNNKLLDIAL DVFASKGQGK PLNVDLSNNM LSKITRNHEK
SIPNIQNLNL SGNRLTSVPN LQGIPLRYLN LDGNPLAKIE KGDFKGLKGL IHLSLSGLHD
FRELSPYSFK ELPALQVLDL SNNPNLRSLT AEVIFGLNSI QELNLSGTGV SSLPKTVLKY
LPSLKSITLR KNIQCFKTIK EGQYHRQIGL TKLGLGAEEL LWCKTPCPRP VCRCRDKPLQ
SAPQNLPTP
