TSK_RAT
ID TSK_RAT Reviewed; 353 AA.
AC Q6QMY6;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 103.
DE RecName: Full=Tsukushi {ECO:0000250|UniProtKB:Q8CBR6};
DE AltName: Full=Early insulin-induced hepatic gene protein;
DE Short=EIIH;
DE AltName: Full=Leucine-rich repeat-containing protein 54;
DE Flags: Precursor;
GN Name=Tsku; Synonyms=Eiih, Lrrc54, Tsk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Wistar;
RX PubMed=15344907; DOI=10.1042/bj20040586;
RA Coffy S., Decaux J.F., Girard J., de Keyzer Y., Asfari M.;
RT "Identification of a novel rat hepatic gene induced early by insulin,
RT independently of glucose.";
RL Biochem. J. 385:165-171(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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: 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. Interacts with TGFB1; the interaction contributes to
CC regulation of the hair cycle. Interacts with netrin. Interacts with
CC CCN2. {ECO:0000250|UniProtKB:Q8CBR6}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8CBR6}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the liver, small
CC intestine and placenta. Not or barely detectable in other tissues,
CC including whole pancreas, adipose tissues, skeletal muscle, kidney,
CC spleen, brain, lung and testis. {ECO:0000269|PubMed:15344907}.
CC -!- INDUCTION: Early induced by insulin independently of glucose and by 17-
CC beta-estradiol in liver.
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; AY533242; AAS66683.1; -; mRNA.
DR EMBL; BC100644; AAI00645.1; -; mRNA.
DR RefSeq; NP_001009965.1; NM_001009965.2.
DR AlphaFoldDB; Q6QMY6; -.
DR SMR; Q6QMY6; -.
DR STRING; 10116.ENSRNOP00000029957; -.
DR GlyGen; Q6QMY6; 3 sites.
DR PaxDb; Q6QMY6; -.
DR PRIDE; Q6QMY6; -.
DR GeneID; 308843; -.
DR KEGG; rno:308843; -.
DR UCSC; RGD:1359311; rat.
DR CTD; 25987; -.
DR RGD; 1359311; Tsku.
DR eggNOG; KOG0619; Eukaryota.
DR InParanoid; Q6QMY6; -.
DR PhylomeDB; Q6QMY6; -.
DR PRO; PR:Q6QMY6; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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; ISO:RGD.
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; ISO:RGD.
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:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
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; 7.
DR PROSITE; PS51450; LRR; 8.
PE 2: Evidence at transcript level;
KW Developmental protein; Glycoprotein; Leucine-rich repeat; Neurogenesis;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..353
FT /note="Tsukushi"
FT /id="PRO_0000240409"
FT DOMAIN 18..59
FT /note="LRRNT"
FT REPEAT 60..80
FT /note="LRR 1"
FT REPEAT 86..107
FT /note="LRR 2"
FT REPEAT 110..131
FT /note="LRR 3"
FT REPEAT 133..154
FT /note="LRR 4"
FT REPEAT 160..180
FT /note="LRR 5"
FT REPEAT 186..207
FT /note="LRR 6"
FT REPEAT 208..228
FT /note="LRR 7"
FT REPEAT 231..253
FT /note="LRR 8"
FT REPEAT 256..277
FT /note="LRR 9"
FT REPEAT 281..302
FT /note="LRR 10"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 353 AA; 38091 MW; E8FBAD8E314A97EC CRC64;
MLCTLFLLLL ALGIVQTTRP CFPGCQCEEE TFGLFDSFSL IRVDCSSLGP HIVPVPIPLD
TAHLDLSSNR LETVNESVLG GPGYTTLAGL DLSHNLLTSI TPTAFSRLRY LESLDLSHNG
LAALPAEVFT SSPLSDINLS HNRLREVSIS AFTTHSQGRA LHVDLSHNLI HRLLPYPARA
SLSAPTIQSL NLSWNRLRAV PDLRDLPLRY LSLDGNPLAT INPGAFMGLA GLTHLSLASL
QGILQLPPHG FRELPGLQVL DLSGNPKLKW AGAEVFSGLG LLQELDLSGS SLVPLPETLL
HHLPALQSVS VGQDVQCRRL VREGAYHRQP GSSPKVVLHC GDTQESARGP DIL
