TSK_HUMAN
ID TSK_HUMAN Reviewed; 353 AA.
AC Q8WUA8; B3KQT7; Q6UXK1; Q9UG10; Q9UJX9;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Tsukushi {ECO:0000303|PubMed:30232710};
DE AltName: Full=E2-induced gene 4 protein;
DE AltName: Full=Leucine-rich repeat-containing protein 54;
DE Flags: Precursor;
GN Name=TSKU; Synonyms=E2IG4, LRRC54, TSK; ORFNames=UNQ850/PRO1788;
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].
RX PubMed=11085516;
RA Charpentier A.H., Bednarek A.K., Daniel R.L., Hawkins K.A., Laflin K.J.,
RA Gaddis S., MacLeod M.C., Aldaz C.M.;
RT "Effects of estrogen on global gene expression: identification of novel
RT targets of estrogen action.";
RL Cancer Res. 60:5977-5983(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-344.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-344.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-344.
RC TISSUE=Placenta;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-344.
RC TISSUE=Colon;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 112-353, AND VARIANT GLU-344.
RC TISSUE=Uterus;
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 [7]
RP INTERACTION WITH CCN2.
RX PubMed=30232710; DOI=10.1007/s12079-018-0487-x;
RA Ohta K., Aoyama E., Ahmad S.A.I., Ito N., Anam M.B., Kubota S.,
RA Takigawa M.;
RT "CCN2/CTGF binds the small leucine rich proteoglycan protein Tsukushi.";
RL J. Cell Commun. Signal. 13:113-118(2019).
CC -!- FUNCTION: Contributes to various developmental events and other
CC processes such as wound healing and cholesterol homeostasis through its
CC interactions with multiple signaling pathways. Wnt signaling inhibitor
CC which competes with WNT2B for binding to Wnt receptor FZD4 and
CC represses WNT2B-dependent development of the peripheral eye. Plays a
CC role in regulating the hair cycle by controlling TGFB1 signaling.
CC Required for the development of the anterior commissure in the brain by
CC inhibiting neurite outgrowth. Essential for terminal differentiation of
CC hippocampal neural stem cells. Plays a role in regulating bone
CC elongation and bone mass by modulating growth plate chondrocyte
CC function and overall body size. Required for development of the inner
CC ear through its involvement in stereocilia formation in inner hair
CC cells. Facilitates wound healing by inhibiting secretion of TGFB1 from
CC macrophages which prevents myofibroblast differentiation, maintaining
CC inflammatory cell quiescence. Plays a role in cholesterol homeostasis
CC by reducing circulating high-density lipoprotein cholesterol, lowering
CC cholesterol efflux capacity and decreasing cholesterol-to-bile acid
CC conversion in the liver. In one study, shown to negatively regulate
CC sympathetic innervation in brown fat, leading to reduced energy
CC expenditure. In another study, shown not to affect brown fat
CC thermogenic capacity, body weight gain or glucose homeostasis.
CC {ECO:0000250|UniProtKB:Q8CBR6}.
CC -!- SUBUNIT: Interacts with FZD4 (via FZ domain); competes with WNT2B for
CC binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye
CC development (By similarity). Interacts with TGFB1; the interaction
CC contributes to regulation of the hair cycle (By similarity). Interacts
CC with netrin (By similarity). Interacts with CCN2 (PubMed:30232710).
CC {ECO:0000250|UniProtKB:Q8CBR6, ECO:0000269|PubMed:30232710}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8CBR6}.
CC -!- INDUCTION: By 17-beta-estradiol.
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:0000250|UniProtKB:Q65Z91}.
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DR EMBL; AF191019; AAF09483.1; -; mRNA.
DR EMBL; AY358317; AAQ88683.1; -; mRNA.
DR EMBL; BT007440; AAP36108.1; -; mRNA.
DR EMBL; AK075476; BAG52149.1; -; mRNA.
DR EMBL; BC020975; AAH20975.1; -; mRNA.
DR EMBL; AL110276; CAB53711.1; -; mRNA.
DR CCDS; CCDS8246.1; -.
DR PIR; T14791; T14791.
DR RefSeq; NP_001245139.1; NM_001258210.1.
DR RefSeq; NP_001305406.1; NM_001318477.1.
DR RefSeq; NP_001305407.1; NM_001318478.1.
DR RefSeq; NP_001305408.1; NM_001318479.1.
DR RefSeq; NP_056331.2; NM_015516.3.
DR AlphaFoldDB; Q8WUA8; -.
DR SMR; Q8WUA8; -.
DR BioGRID; 117468; 8.
DR IntAct; Q8WUA8; 3.
DR MINT; Q8WUA8; -.
DR STRING; 9606.ENSP00000434847; -.
DR GlyGen; Q8WUA8; 2 sites.
DR iPTMnet; Q8WUA8; -.
DR PhosphoSitePlus; Q8WUA8; -.
DR BioMuta; TSKU; -.
DR DMDM; 116242832; -.
DR EPD; Q8WUA8; -.
DR jPOST; Q8WUA8; -.
DR MassIVE; Q8WUA8; -.
DR MaxQB; Q8WUA8; -.
DR PaxDb; Q8WUA8; -.
DR PeptideAtlas; Q8WUA8; -.
DR PRIDE; Q8WUA8; -.
DR ProteomicsDB; 74652; -.
DR Antibodypedia; 2163; 84 antibodies from 18 providers.
DR DNASU; 25987; -.
DR Ensembl; ENST00000333090.5; ENSP00000332668.4; ENSG00000182704.8.
DR Ensembl; ENST00000527881.1; ENSP00000434847.1; ENSG00000182704.8.
DR Ensembl; ENST00000612930.1; ENSP00000482145.1; ENSG00000182704.8.
DR GeneID; 25987; -.
DR KEGG; hsa:25987; -.
DR MANE-Select; ENST00000333090.5; ENSP00000332668.4; NM_015516.4; NP_056331.2.
DR UCSC; uc001oxt.4; human.
DR CTD; 25987; -.
DR DisGeNET; 25987; -.
DR GeneCards; TSKU; -.
DR HGNC; HGNC:28850; TSKU.
DR HPA; ENSG00000182704; Tissue enhanced (liver).
DR MIM; 608015; gene.
DR neXtProt; NX_Q8WUA8; -.
DR OpenTargets; ENSG00000182704; -.
DR PharmGKB; PA162407150; -.
DR VEuPathDB; HostDB:ENSG00000182704; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000160984; -.
DR HOGENOM; CLU_785168_0_0_1; -.
DR InParanoid; Q8WUA8; -.
DR OMA; QPCFPGC; -.
DR OrthoDB; 1168051at2759; -.
DR PhylomeDB; Q8WUA8; -.
DR TreeFam; TF343079; -.
DR PathwayCommons; Q8WUA8; -.
DR SignaLink; Q8WUA8; -.
DR BioGRID-ORCS; 25987; 17 hits in 1068 CRISPR screens.
DR ChiTaRS; TSKU; human.
DR GenomeRNAi; 25987; -.
DR Pharos; Q8WUA8; Tbio.
DR PRO; PR:Q8WUA8; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8WUA8; protein.
DR Bgee; ENSG00000182704; Expressed in decidua and 164 other tissues.
DR ExpressionAtlas; Q8WUA8; baseline and differential.
DR Genevisible; Q8WUA8; HS.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0050431; F:transforming growth factor beta binding; ISS:UniProtKB.
DR GO; GO:0021960; P:anterior commissure morphogenesis; ISS:UniProtKB.
DR GO; GO:0098868; P:bone growth; ISS:UniProtKB.
DR GO; GO:0043010; P:camera-type eye development; ISS:UniProtKB.
DR GO; GO:0033344; P:cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0061073; P:ciliary body morphogenesis; ISS:UniProtKB.
DR GO; GO:0021540; P:corpus callosum morphogenesis; IEA:Ensembl.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0003431; P:growth plate cartilage chondrocyte development; ISS:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; ISS:UniProtKB.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; ISS:UniProtKB.
DR GO; GO:0021670; P:lateral ventricle development; IEA:Ensembl.
DR GO; GO:1904761; P:negative regulation of myofibroblast differentiation; ISS:UniProtKB.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; ISS:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0042635; P:positive regulation of hair cycle; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0042060; P:wound healing; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF13855; LRR_8; 2.
DR SMART; SM00369; LRR_TYP; 8.
DR PROSITE; PS51450; LRR; 8.
PE 1: Evidence at protein level;
KW Developmental protein; Glycoprotein; Leucine-rich repeat; Neurogenesis;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..353
FT /note="Tsukushi"
FT /id="PRO_0000240407"
FT DOMAIN 17..58
FT /note="LRRNT"
FT REPEAT 59..80
FT /note="LRR 1"
FT REPEAT 85..106
FT /note="LRR 2"
FT REPEAT 109..130
FT /note="LRR 3"
FT REPEAT 132..153
FT /note="LRR 4"
FT REPEAT 159..179
FT /note="LRR 5"
FT REPEAT 185..206
FT /note="LRR 6"
FT REPEAT 207..227
FT /note="LRR 7"
FT REPEAT 230..249
FT /note="LRR 8"
FT REPEAT 255..276
FT /note="LRR 9"
FT REPEAT 280..301
FT /note="LRR 10"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 208
FT /note="R -> C (in dbSNP:rs3740772)"
FT /id="VAR_028725"
FT VARIANT 248
FT /note="S -> N (in dbSNP:rs11236938)"
FT /id="VAR_028726"
FT VARIANT 308
FT /note="V -> I (in dbSNP:rs3740771)"
FT /id="VAR_028727"
FT VARIANT 344
FT /note="D -> E (in dbSNP:rs1149621)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16303743,
FT ECO:0000269|PubMed:17974005, ECO:0000269|Ref.3"
FT /id="VAR_026726"
FT CONFLICT 336
FT /note="A -> P (in Ref. 2; AAQ88683)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 353 AA; 37807 MW; 80F073221B8A38A5 CRC64;
MPWPLLLLLA VSGAQTTRPC FPGCQCEVET FGLFDSFSLT RVDCSGLGPH IMPVPIPLDT
AHLDLSSNRL EMVNESVLAG PGYTTLAGLD LSHNLLTSIS PTAFSRLRYL ESLDLSHNGL
TALPAESFTS SPLSDVNLSH NQLREVSVSA FTTHSQGRAL HVDLSHNLIH RLVPHPTRAG
LPAPTIQSLN LAWNRLHAVP NLRDLPLRYL SLDGNPLAVI GPGAFAGLGG LTHLSLASLQ
RLPELAPSGF RELPGLQVLD LSGNPKLNWA GAEVFSGLSS LQELDLSGTN LVPLPEALLL
HLPALQSVSV GQDVRCRRLV REGTYPRRPG SSPKVALHCV DTRDSAARGP TIL
