FSTL4_HUMAN
ID FSTL4_HUMAN Reviewed; 842 AA.
AC Q6MZW2; Q8TBU0; Q9UPU1;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Follistatin-related protein 4;
DE AltName: Full=Follistatin-like protein 4;
DE Flags: Precursor;
GN Name=FSTL4; Synonyms=KIAA1061;
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] (ISOFORM 2), AND VARIANT MET-757.
RC TISSUE=Small intestine;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 150-842 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [5]
RP IDENTIFICATION.
RX PubMed=15527507; DOI=10.1186/1471-2148-4-43;
RA Glusman G., Kaur A., Hood L., Rowen L.;
RT "An enigmatic fourth runt domain gene in the fugu genome: ancestral gene
RT loss versus accelerated evolution.";
RL BMC Evol. Biol. 4:43-43(2004).
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6MZW2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6MZW2-2; Sequence=VSP_020800;
CC Name=3;
CC IsoId=Q6MZW2-3; Sequence=VSP_020801, VSP_020802;
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DR EMBL; BX640845; CAE45915.1; -; mRNA.
DR EMBL; AC005195; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010307; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC012614; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024300; AAH24300.1; -; mRNA.
DR EMBL; AB028984; BAA83013.1; -; mRNA.
DR CCDS; CCDS34238.1; -. [Q6MZW2-1]
DR RefSeq; NP_055897.1; NM_015082.1. [Q6MZW2-1]
DR RefSeq; XP_011541585.1; XM_011543283.1. [Q6MZW2-1]
DR AlphaFoldDB; Q6MZW2; -.
DR SMR; Q6MZW2; -.
DR BioGRID; 116730; 41.
DR IntAct; Q6MZW2; 4.
DR STRING; 9606.ENSP00000265342; -.
DR MEROPS; I01.977; -.
DR GlyGen; Q6MZW2; 1 site.
DR iPTMnet; Q6MZW2; -.
DR PhosphoSitePlus; Q6MZW2; -.
DR BioMuta; FSTL4; -.
DR DMDM; 296439344; -.
DR MassIVE; Q6MZW2; -.
DR PaxDb; Q6MZW2; -.
DR PeptideAtlas; Q6MZW2; -.
DR PRIDE; Q6MZW2; -.
DR ProteomicsDB; 66588; -. [Q6MZW2-1]
DR ProteomicsDB; 66589; -. [Q6MZW2-2]
DR ProteomicsDB; 66590; -. [Q6MZW2-3]
DR Antibodypedia; 26231; 41 antibodies from 14 providers.
DR DNASU; 23105; -.
DR Ensembl; ENST00000265342.12; ENSP00000265342.7; ENSG00000053108.17. [Q6MZW2-1]
DR Ensembl; ENST00000621681.4; ENSP00000484273.1; ENSG00000053108.17. [Q6MZW2-2]
DR GeneID; 23105; -.
DR KEGG; hsa:23105; -.
DR MANE-Select; ENST00000265342.12; ENSP00000265342.7; NM_015082.2; NP_055897.1.
DR UCSC; uc003kyn.2; human. [Q6MZW2-1]
DR CTD; 23105; -.
DR DisGeNET; 23105; -.
DR GeneCards; FSTL4; -.
DR HGNC; HGNC:21389; FSTL4.
DR HPA; ENSG00000053108; Tissue enhanced (brain).
DR neXtProt; NX_Q6MZW2; -.
DR OpenTargets; ENSG00000053108; -.
DR PharmGKB; PA134969998; -.
DR VEuPathDB; HostDB:ENSG00000053108; -.
DR eggNOG; ENOG502QPNV; Eukaryota.
DR GeneTree; ENSGT00940000158076; -.
DR HOGENOM; CLU_007849_0_0_1; -.
DR InParanoid; Q6MZW2; -.
DR OMA; LNFMALE; -.
DR OrthoDB; 1065760at2759; -.
DR PhylomeDB; Q6MZW2; -.
DR TreeFam; TF350473; -.
DR PathwayCommons; Q6MZW2; -.
DR SignaLink; Q6MZW2; -.
DR BioGRID-ORCS; 23105; 6 hits in 1059 CRISPR screens.
DR ChiTaRS; FSTL4; human.
DR GenomeRNAi; 23105; -.
DR Pharos; Q6MZW2; Tdark.
DR PRO; PR:Q6MZW2; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q6MZW2; protein.
DR Bgee; ENSG00000053108; Expressed in oocyte and 104 other tissues.
DR ExpressionAtlas; Q6MZW2; baseline and differential.
DR Genevisible; Q6MZW2; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; IEA:Ensembl.
DR GO; GO:0048403; F:brain-derived neurotrophic factor binding; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0031549; P:negative regulation of brain-derived neurotrophic factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0048671; P:negative regulation of collateral sprouting; IEA:Ensembl.
DR GO; GO:0061000; P:negative regulation of dendritic spine development; IEA:Ensembl.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR Pfam; PF07648; Kazal_2; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 2.
DR SMART; SM00280; KAZAL; 1.
DR SUPFAM; SSF100895; SSF100895; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS51465; KAZAL_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Metal-binding; Reference proteome; Repeat; Secreted;
KW Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..842
FT /note="Follistatin-related protein 4"
FT /id="PRO_0000251925"
FT DOMAIN 81..135
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 174..209
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 251..338
FT /note="Ig-like 1"
FT DOMAIN 341..426
FT /note="Ig-like 2"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 191
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 198
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..119
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 93..112
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 101..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 270..321
FT /evidence="ECO:0000250"
FT DISULFID 362..413
FT /evidence="ECO:0000250"
FT VAR_SEQ 78..246
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_020800"
FT VAR_SEQ 601..605
FT /note="TNLII -> INLEQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020801"
FT VAR_SEQ 606..842
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020802"
FT VARIANT 158
FT /note="R -> H (in dbSNP:rs17683306)"
FT /id="VAR_027727"
FT VARIANT 757
FT /note="T -> M (in dbSNP:rs3749817)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_027728"
FT CONFLICT 60
FT /note="E -> K (in Ref. 1; CAE45915)"
FT /evidence="ECO:0000305"
FT CONFLICT 240
FT /note="M -> I (in Ref. 3; AAH24300)"
FT /evidence="ECO:0000305"
FT CONFLICT 764
FT /note="L -> P (in Ref. 1; CAE45915)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 842 AA; 93096 MW; 9EEE073CD3C99517 CRC64;
MKPGGFWLHL TLLGASLPAA LGWMDPGTSR GPDVGVGESQ AEEPRSFEVT RREGLSSHNE
LLASCGKKFC SRGSRCVLSR KTGEPECQCL EACRPSYVPV CGSDGRFYEN HCKLHRAACL
LGKRITVIHS KDCFLKGDTC TMAGYARLKN VLLALQTRLQ PLQEGDSRQD PASQKRLLVE
SLFRDLDADG NGHLSSSELA QHVLKKQDLD EDLLGCSPGD LLRFDDYNSD SSLTLREFYM
AFQVVQLSLA PEDRVSVTTV TVGLSTVLTC AVHGDLRPPI IWKRNGLTLN FLDLEDINDF
GEDDSLYITK VTTIHMGNYT CHASGHEQLF QTHVLQVNVP PVIRVYPESQ AQEPGVAASL
RCHAEGIPMP RITWLKNGVD VSTQMSKQLS LLANGSELHI SSVRYEDTGA YTCIAKNEVG
VDEDISSLFI EDSARKTLAN ILWREEGLSV GNMFYVFSDD GIIVIHPVDC EIQRHLKPTE
KIFMSYEEIC PQREKNATQP CQWVSAVNVR NRYIYVAQPA LSRVLVVDIQ AQKVLQSIGV
DPLPAKLSYD KSHDQVWVLS WGDVHKSRPS LQVITEASTG QSQHLIRTPF AGVDDFFIPP
TNLIINHIRF GFIFNKSDPA VHKVDLETMM PLKTIGLHHH GCVPQAMAHT HLGGYFFIQC
RQDSPASAAR QLLVDSVTDS VLGPNGDVTG TPHTSPDGRF IVSAAADSPW LHVQEITVRG
EIQTLYDLQI NSGISDLAFQ RSFTESNQYN IYAALHTEPD LLFLELSTGK VGMLKNLKEP
PAGPAQPWGG THRIMRDSGL FGQYLLTPAR ESLFLINGRQ NTLRCEVSGI KGGTTVVWVG
EV
