FSTL1_MOUSE
ID FSTL1_MOUSE Reviewed; 306 AA.
AC Q62356; Q6GTX2; Q99JI9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Follistatin-related protein 1;
DE AltName: Full=Follistatin-like protein 1;
DE AltName: Full=TGF-beta-inducible protein TSC-36;
DE Flags: Precursor;
GN Name=Fstl1; Synonyms=Frp, Fstl, Tsc36;
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].
RX PubMed=7901004; DOI=10.1111/j.1432-1033.1993.tb18212.x;
RA Shibanuma M., Mashimo J., Mita A., Kuroki T., Nose K.;
RT "Cloning from a mouse osteoblastic cell line of a set of transforming-
RT growth-factor-beta 1-regulated genes, one of which seems to encode a
RT follistatin-related polypeptide.";
RL Eur. J. Biochem. 217:13-19(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N;
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 [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-142.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [6]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=19595790; DOI=10.1016/j.gep.2009.07.001;
RA Yang Y., Liu J., Mao H., Hu Y.A., Yan Y., Zhao C.;
RT "The expression pattern of Follistatin-like 1 in mouse central nervous
RT system development.";
RL Gene Expr. Patterns 9:532-540(2009).
RN [7]
RP FUNCTION, AND INTERACTION WITH DIP2A.
RX PubMed=20054002; DOI=10.1074/jbc.m109.069468;
RA Ouchi N., Asaumi Y., Ohashi K., Higuchi A., Sono-Romanelli S., Oshima Y.,
RA Walsh K.;
RT "DIP2A functions as a FSTL1 receptor.";
RL J. Biol. Chem. 285:7127-7134(2010).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=21826198; DOI=10.1371/journal.pone.0022616;
RA Sylva M., Li V.S., Buffing A.A., van Es J.H., van den Born M.,
RA van der Velden S., Gunst Q., Koolstra J.H., Moorman A.F., Clevers H.,
RA van den Hoff M.J.;
RT "The BMP antagonist follistatin-like 1 is required for skeletal and lung
RT organogenesis.";
RL PLoS ONE 6:e22616-e22616(2011).
RN [9] {ECO:0007744|PDB:6JZA}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 20-98, DISULFIDE BOND, AND
RP SUBUNIT.
RX PubMed=31351024; DOI=10.1002/pro.3696;
RA Li X., Li L., Chang Y., Ning W., Liu X.;
RT "Structural and functional study of FK domain of Fstl1.";
RL Protein Sci. 28:1819-1829(2019).
CC -!- FUNCTION: Secreted glycoprotein that is involved in various
CC physiological processes, such as angiogenesis, regulation of the immune
CC response, cell proliferation and differentiation (By similarity). Plays
CC a role in the development of the central nervous system, skeletal
CC system, lungs, and ureter (PubMed:21826198, PubMed:19595790). Promotes
CC endothelial cell survival, migration and differentiation into network
CC structures in an AKT-dependent manner. Also promotes survival of
CC cardiac myocytes (PubMed:20054002). Initiates various signaling
CC cascades by activating different receptors on the cell surface such as
CC DIP2A, TLR4 or BMP receptors (By similarity).
CC {ECO:0000250|UniProtKB:Q12841, ECO:0000269|PubMed:19595790,
CC ECO:0000269|PubMed:20054002, ECO:0000269|PubMed:21826198}.
CC -!- SUBUNIT: Homodimer (PubMed:31351024). Interacts with SCN10A (By
CC similarity). Interacts with DIP2A; DIP2A may act as a cell surface
CC receptor for FSTL1 (PubMed:20054002). Interacts with BMP4 (By
CC similarity). Interacts with CD14; this interaction promotes TL4-
CC mediated signaling cascade (By similarity).
CC {ECO:0000250|UniProtKB:Q12841, ECO:0000250|UniProtKB:Q62632,
CC ECO:0000269|PubMed:20054002, ECO:0000269|PubMed:31351024}.
CC -!- INTERACTION:
CC Q62356; Q14689: DIP2A; Xeno; NbExp=3; IntAct=EBI-2564326, EBI-2564275;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: During central nervous system development, strongly
CC expressed in the telencephalon, diencephalon, brainstem, limbic system
CC and spinal cord (PubMed:19595790). Widely expressed in all organs
CC (PubMed:21826198). {ECO:0000269|PubMed:19595790,
CC ECO:0000269|PubMed:21826198}.
CC -!- DISRUPTION PHENOTYPE: Deletion mice die at birth from respiratory
CC distress and show multiple defects in lung development. In addition,
CC skeletal development is strongly impaired.
CC {ECO:0000269|PubMed:21826198}.
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DR EMBL; M91380; AAC37633.1; -; mRNA.
DR EMBL; AK049440; BAC33751.1; -; mRNA.
DR EMBL; AK147117; BAE27689.1; -; mRNA.
DR EMBL; CH466521; EDK97964.1; -; Genomic_DNA.
DR EMBL; BC028921; AAH28921.1; -; mRNA.
DR EMBL; BC006185; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS37339.1; -.
DR PIR; S38251; S38251.
DR RefSeq; NP_032073.2; NM_008047.5.
DR PDB; 6JZA; X-ray; 2.30 A; A=20-98.
DR PDBsum; 6JZA; -.
DR AlphaFoldDB; Q62356; -.
DR SMR; Q62356; -.
DR BioGRID; 199752; 3.
DR DIP; DIP-56414N; -.
DR IntAct; Q62356; 4.
DR STRING; 10090.ENSMUSP00000110411; -.
DR MEROPS; I01.967; -.
DR GlyGen; Q62356; 3 sites.
DR iPTMnet; Q62356; -.
DR PhosphoSitePlus; Q62356; -.
DR CPTAC; non-CPTAC-3314; -.
DR MaxQB; Q62356; -.
DR PaxDb; Q62356; -.
DR PeptideAtlas; Q62356; -.
DR PRIDE; Q62356; -.
DR ProteomicsDB; 267528; -.
DR Antibodypedia; 32794; 434 antibodies from 32 providers.
DR DNASU; 14314; -.
DR Ensembl; ENSMUST00000114763; ENSMUSP00000110411; ENSMUSG00000022816.
DR GeneID; 14314; -.
DR KEGG; mmu:14314; -.
DR UCSC; uc007zej.1; mouse.
DR CTD; 11167; -.
DR MGI; MGI:102793; Fstl1.
DR VEuPathDB; HostDB:ENSMUSG00000022816; -.
DR eggNOG; ENOG502QQAG; Eukaryota.
DR GeneTree; ENSGT00940000157784; -.
DR HOGENOM; CLU_038229_0_0_1; -.
DR InParanoid; Q62356; -.
DR OMA; HRIIQWL; -.
DR OrthoDB; 1079836at2759; -.
DR PhylomeDB; Q62356; -.
DR TreeFam; TF106409; -.
DR Reactome; R-MMU-201451; Signaling by BMP.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 14314; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Fstl1; mouse.
DR PRO; PR:Q62356; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q62356; protein.
DR Bgee; ENSMUSG00000022816; Expressed in epithelium of cochlear duct and 305 other tissues.
DR Genevisible; Q62356; MM.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045446; P:endothelial cell differentiation; IMP:UniProtKB.
DR GO; GO:0043542; P:endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030510; P:regulation of BMP signaling pathway; IBA:GO_Central.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR003645; Fol_N.
DR InterPro; IPR015369; Follistatin/Osteonectin_EGF.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR Pfam; PF09289; FOLN; 1.
DR Pfam; PF07648; Kazal_2; 1.
DR SMART; SM00274; FOLN; 1.
DR SMART; SM00280; KAZAL; 1.
DR SUPFAM; SSF100895; SSF100895; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS51465; KAZAL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Heparin-binding;
KW Phosphoprotein; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000250|UniProtKB:Q12841"
FT CHAIN 19..306
FT /note="Follistatin-related protein 1"
FT /id="PRO_0000010113"
FT DOMAIN 28..51
FT /note="Follistatin-like"
FT DOMAIN 46..98
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 142..176
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 191..226
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 231..285
FT /note="VWFC"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12841"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..40
FT /evidence="ECO:0000269|PubMed:31351024,
FT ECO:0007744|PDB:6JZA"
FT DISULFID 34..50
FT /evidence="ECO:0000269|PubMed:31351024,
FT ECO:0007744|PDB:6JZA"
FT DISULFID 52..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798,
FT ECO:0000269|PubMed:31351024, ECO:0007744|PDB:6JZA"
FT DISULFID 56..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798,
FT ECO:0000269|PubMed:31351024, ECO:0007744|PDB:6JZA"
FT DISULFID 64..96
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798,
FT ECO:0000269|PubMed:31351024, ECO:0007744|PDB:6JZA"
FT CONFLICT 235
FT /note="D -> V (in Ref. 1; AAC37633)"
FT /evidence="ECO:0000305"
FT TURN 26..31
FT /evidence="ECO:0007829|PDB:6JZA"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:6JZA"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:6JZA"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:6JZA"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:6JZA"
FT HELIX 74..84
FT /evidence="ECO:0007829|PDB:6JZA"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:6JZA"
SQ SEQUENCE 306 AA; 34554 MW; 0AEB11C6321E8FDC CRC64;
MWKRWLALSL VTIALVHGEE EPRSKSKICA NVFCGAGREC AVTEKGEPTC LCIEQCKPHK
RPVCGSNGKT YLNHCELHRD ACLTGSKIQV DYDGHCKEKK SASPSASPVV CYQANRDELR
RRLIQWLEAE IIPDGWFSKG SNYSEILDKY FKSFDNGDSH LDSSEFLKFV EQNETAINIT
TYADQENNKL LRSLCVDALI ELSDENADWK LSFQEFLKCL NPSFNPPEKK CALEDETYAD
GAETEVDCNR CVCSCGHWVC TAMTCDGKNQ KGVQTHTEEE KTGYVQELQK HQGTAEKTKK
VNTKEI
