UniProtKB - O95633 (FSTL3_HUMAN)
Follistatin-related protein 3
FSTL3
Functioni
Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such us activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellular signaling; more effective on activin A than on activin B. Involved in bone formation; inhibits osteoclast differentiationc. Involved in hematopoiesis; involved in differentiation of hemopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin and seems to contribute to the adhesion of hematopoietic precursor cells to the bone marrow stroma. Isoform 2 or the nuclear form is probably involved in transcriptional regulation via interaction with MLLT10.
6 PublicationsGO - Molecular functioni
- activin binding Source: UniProtKB
- fibronectin binding Source: UniProtKB
GO - Biological processi
- cell differentiation Source: GO_Central
- hematopoietic progenitor cell differentiation Source: UniProtKB
- negative regulation of activin receptor signaling pathway Source: UniProtKB
- negative regulation of BMP signaling pathway Source: UniProtKB
- negative regulation of osteoclast differentiation Source: UniProtKB
- negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway Source: UniProtKB
- ossification Source: UniProtKB-KW
- positive regulation of cell-cell adhesion Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of BMP signaling pathway Source: GO_Central
- regulation of transcription by RNA polymerase II Source: UniProtKB
Keywordsi
Biological process | Osteogenesis, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | O95633 |
Reactomei | R-HSA-2473224, Antagonism of Activin by Follistatin R-HSA-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-8957275, Post-translational protein phosphorylation |
SignaLinki | O95633 |
SIGNORi | O95633 |
Protein family/group databases
MEROPSi | I01.968 |
Names & Taxonomyi
Protein namesi | Recommended name: Follistatin-related protein 3Alternative name(s): Follistatin-like protein 3 Follistatin-related gene protein |
Gene namesi | Name:FSTL3 Synonyms:FLRG ORF Names:UNQ674/PRO1308 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3973, FSTL3 |
MIMi | 605343, gene |
neXtProti | NX_O95633 |
VEuPathDBi | HostDB:ENSG00000070404 |
Subcellular locationi
Extracellular region or secreted
Nucleus
Note: Although alternative initiation has been demonstrated and resulted in different localization, the major source of nuclear FSTL3 appears not to depend on translation initiation at Met-27 according to.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum lumen Source: Reactome
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Keywords - Cellular componenti
Nucleus, SecretedPathology & Biotechi
Involvement in diseasei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 27 | M → A: Nuclear localization. 1 Publication | 1 |
Keywords - Diseasei
Proto-oncogeneOrganism-specific databases
DisGeNETi | 10272 |
OpenTargetsi | ENSG00000070404 |
PharmGKBi | PA28390 |
Miscellaneous databases
Pharosi | O95633, Tbio |
Genetic variation databases
BioMutai | FSTL3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 26 | 1 PublicationAdd BLAST | 26 | |
ChainiPRO_0000010115 | 27 – 263 | Follistatin-related protein 3Add BLAST | 237 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 38 ↔ 61 | PROSITE-ProRule annotation | ||
Disulfide bondi | 48 ↔ 92 | PROSITE-ProRule annotation | ||
Disulfide bondi | 62 ↔ 95 | PROSITE-ProRule annotation | ||
Glycosylationi | 73 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 99 ↔ 110 | |||
Disulfide bondi | 104 ↔ 119 | |||
Disulfide bondi | 121 ↔ 153 | |||
Disulfide bondi | 125 ↔ 146 | |||
Disulfide bondi | 135 ↔ 167 | |||
Disulfide bondi | 171 ↔ 182 | |||
Disulfide bondi | 176 ↔ 192 | |||
Disulfide bondi | 195 ↔ 229 | |||
Disulfide bondi | 200 ↔ 222 | |||
Disulfide bondi | 211 ↔ 243 | |||
Glycosylationi | 215 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Modified residuei | 255 | Phosphoserine; by FAM20C1 Publication | 1 |
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
EPDi | O95633 |
jPOSTi | O95633 |
MassIVEi | O95633 |
MaxQBi | O95633 |
PaxDbi | O95633 |
PeptideAtlasi | O95633 |
PRIDEi | O95633 |
ProteomicsDBi | 50968 [O95633-1] 50969 [O95633-2] |
TopDownProteomicsi | O95633-1 [O95633-1] |
PTM databases
GlyGeni | O95633, 3 sites |
iPTMneti | O95633 |
PhosphoSitePlusi | O95633 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000070404, Expressed in left adrenal gland and 156 other tissues |
ExpressionAtlasi | O95633, baseline and differential |
Genevisiblei | O95633, HS |
Organism-specific databases
HPAi | ENSG00000070404, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with INHBA and INHBB.
Interacts with FN1.
Interacts with ADAM12.
Isoform 2 interacts with MLLT10; the interaction enhances MLLT10 in vitro transcriptional activity and self-association.
Interacts with MSTN.
7 PublicationsBinary interactionsi
O95633
With | #Exp. | IntAct |
---|---|---|
ADAM12 - isoform 2 [O43184-2] | 4 | EBI-2625790,EBI-2625865 |
GO - Molecular functioni
- fibronectin binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 115562, 4 interactors |
IntActi | O95633, 2 interactors |
STRINGi | 9606.ENSP00000166139 |
Miscellaneous databases
RNActi | O95633, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | O95633 |
BMRBi | O95633 |
SMRi | O95633 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O95633 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 36 – 107 | TBPROSITE-ProRule annotationAdd BLAST | 72 | |
Domaini | 99 – 119 | Follistatin-like 1Add BLAST | 21 | |
Domaini | 113 – 169 | Kazal-like 1PROSITE-ProRule annotationAdd BLAST | 57 | |
Domaini | 170 – 193 | Follistatin-like 2Add BLAST | 24 | |
Domaini | 189 – 245 | Kazal-like 2PROSITE-ProRule annotationAdd BLAST | 57 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 242 – 263 | DisorderedSequence analysisAdd BLAST | 22 |
Keywords - Domaini
Repeat, SignalPhylogenomic databases
eggNOGi | KOG3649, Eukaryota |
GeneTreei | ENSGT00940000161332 |
HOGENOMi | CLU_050745_1_0_1 |
InParanoidi | O95633 |
OMAi | YISSCHM |
PhylomeDBi | O95633 |
TreeFami | TF106409 |
Family and domain databases
Gene3Di | 3.90.290.10, 1 hit |
IDEALi | IID00192 |
InterProi | View protein in InterPro IPR003645, Fol_N IPR015369, Follistatin/Osteonectin_EGF IPR002350, Kazal_dom IPR036058, Kazal_dom_sf IPR017878, TB_dom IPR036773, TB_dom_sf |
Pfami | View protein in Pfam PF09289, FOLN, 1 hit PF07648, Kazal_2, 2 hits |
SMARTi | View protein in SMART SM00274, FOLN, 2 hits SM00280, KAZAL, 2 hits |
SUPFAMi | SSF100895, SSF100895, 2 hits SSF57581, SSF57581, 1 hit |
PROSITEi | View protein in PROSITE PS51465, KAZAL_2, 2 hits PS51364, TB, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative initiation. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MRPGAPGPLW PLPWGALAWA VGFVSSMGSG NPAPGGVCWL QQGQEATCSL
60 70 80 90 100
VLQTDVTRAE CCASGNIDTA WSNLTHPGNK INLLGFLGLV HCLPCKDSCD
110 120 130 140 150
GVECGPGKAC RMLGGRPRCE CAPDCSGLPA RLQVCGSDGA TYRDECELRA
160 170 180 190 200
ARCRGHPDLS VMYRGRCRKS CEHVVCPRPQ SCVVDQTGSA HCVVCRAAPC
210 220 230 240 250
PVPSSPGQEL CGNNNVTYIS SCHMRQATCF LGRSIGVRHA GSCAGTPEEP
260
PGGESAEEEE NFV
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketK7EM71 | K7EM71_HUMAN | Follistatin-related protein 3 | FSTL3 | 40 | Annotation score: | ||
A0A087X1Q2 | A0A087X1Q2_HUMAN | Follistatin-related protein 3 | FSTL3 | 84 | Annotation score: | ||
A0A087WTD3 | A0A087WTD3_HUMAN | Follistatin-related protein 3 | FSTL3 | 91 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_038553 | 1 – 26 | Missing in isoform 2. CuratedAdd BLAST | 26 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U76702 mRNA Translation: AAC64321.1 AY358917 mRNA Translation: AAQ89276.1 AK291958 mRNA Translation: BAF84647.1 CH471242 Genomic DNA Translation: EAW61165.1 BC005839 mRNA Translation: AAH05839.1 |
CCDSi | CCDS12040.1 [O95633-1] |
RefSeqi | NP_005851.1, NM_005860.2 [O95633-1] |
Genome annotation databases
Ensembli | ENST00000166139.9; ENSP00000166139.3; ENSG00000070404.10 |
GeneIDi | 10272 |
KEGGi | hsa:10272 |
MANE-Selecti | ENST00000166139.9; ENSP00000166139.3; NM_005860.3; NP_005851.1 |
UCSCi | uc002lpk.2, human [O95633-1] |
Keywords - Coding sequence diversityi
Alternative initiation, Chromosomal rearrangementSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U76702 mRNA Translation: AAC64321.1 AY358917 mRNA Translation: AAQ89276.1 AK291958 mRNA Translation: BAF84647.1 CH471242 Genomic DNA Translation: EAW61165.1 BC005839 mRNA Translation: AAH05839.1 |
CCDSi | CCDS12040.1 [O95633-1] |
RefSeqi | NP_005851.1, NM_005860.2 [O95633-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2KCX | NMR | - | A | 97-169 | [»] | |
3B4V | X-ray | 2.48 | C/D/G/H | 27-263 | [»] | |
3SEK | X-ray | 2.40 | C | 36-244 | [»] | |
AlphaFoldDBi | O95633 | |||||
BMRBi | O95633 | |||||
SMRi | O95633 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115562, 4 interactors |
IntActi | O95633, 2 interactors |
STRINGi | 9606.ENSP00000166139 |
Protein family/group databases
MEROPSi | I01.968 |
PTM databases
GlyGeni | O95633, 3 sites |
iPTMneti | O95633 |
PhosphoSitePlusi | O95633 |
Genetic variation databases
BioMutai | FSTL3 |
Proteomic databases
EPDi | O95633 |
jPOSTi | O95633 |
MassIVEi | O95633 |
MaxQBi | O95633 |
PaxDbi | O95633 |
PeptideAtlasi | O95633 |
PRIDEi | O95633 |
ProteomicsDBi | 50968 [O95633-1] 50969 [O95633-2] |
TopDownProteomicsi | O95633-1 [O95633-1] |
Protocols and materials databases
Antibodypediai | 22353, 237 antibodies from 26 providers |
DNASUi | 10272 |
Genome annotation databases
Ensembli | ENST00000166139.9; ENSP00000166139.3; ENSG00000070404.10 |
GeneIDi | 10272 |
KEGGi | hsa:10272 |
MANE-Selecti | ENST00000166139.9; ENSP00000166139.3; NM_005860.3; NP_005851.1 |
UCSCi | uc002lpk.2, human [O95633-1] |
Organism-specific databases
CTDi | 10272 |
DisGeNETi | 10272 |
GeneCardsi | FSTL3 |
HGNCi | HGNC:3973, FSTL3 |
HPAi | ENSG00000070404, Low tissue specificity |
MIMi | 605343, gene |
neXtProti | NX_O95633 |
OpenTargetsi | ENSG00000070404 |
PharmGKBi | PA28390 |
VEuPathDBi | HostDB:ENSG00000070404 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3649, Eukaryota |
GeneTreei | ENSGT00940000161332 |
HOGENOMi | CLU_050745_1_0_1 |
InParanoidi | O95633 |
OMAi | YISSCHM |
PhylomeDBi | O95633 |
TreeFami | TF106409 |
Enzyme and pathway databases
PathwayCommonsi | O95633 |
Reactomei | R-HSA-2473224, Antagonism of Activin by Follistatin R-HSA-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-8957275, Post-translational protein phosphorylation |
SignaLinki | O95633 |
SIGNORi | O95633 |
Miscellaneous databases
BioGRID-ORCSi | 10272, 15 hits in 1084 CRISPR screens |
ChiTaRSi | FSTL3, human |
EvolutionaryTracei | O95633 |
GeneWikii | FSTL3 |
GenomeRNAii | 10272 |
Pharosi | O95633, Tbio |
PROi | PR:O95633 |
RNActi | O95633, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000070404, Expressed in left adrenal gland and 156 other tissues |
ExpressionAtlasi | O95633, baseline and differential |
Genevisiblei | O95633, HS |
Family and domain databases
Gene3Di | 3.90.290.10, 1 hit |
IDEALi | IID00192 |
InterProi | View protein in InterPro IPR003645, Fol_N IPR015369, Follistatin/Osteonectin_EGF IPR002350, Kazal_dom IPR036058, Kazal_dom_sf IPR017878, TB_dom IPR036773, TB_dom_sf |
Pfami | View protein in Pfam PF09289, FOLN, 1 hit PF07648, Kazal_2, 2 hits |
SMARTi | View protein in SMART SM00274, FOLN, 2 hits SM00280, KAZAL, 2 hits |
SUPFAMi | SSF100895, SSF100895, 2 hits SSF57581, SSF57581, 1 hit |
PROSITEi | View protein in PROSITE PS51465, KAZAL_2, 2 hits PS51364, TB, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | FSTL3_HUMAN | |
Accessioni | O95633Primary (citable) accession number: O95633 Secondary accession number(s): A8K7E3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 10, 2002 |
Last sequence update: | May 1, 1999 | |
Last modified: | May 25, 2022 | |
This is version 178 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references