O95633 (FSTL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 104.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Follistatin-related protein 3 Alternative name(s): Follistatin-like protein 3 Follistatin-related gene protein | ||||||
| Gene names |
| ||||||
| Organism | Homo sapiens (Human) | ||||||
| Taxonomic identifier | 9606 [NCBI] | ||||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 263 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | 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. Ref.8 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 |
| Subunit structure | 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. Ref.9 Ref.12 Ref.14 Ref.15 Ref.16 |
| Subcellular location | Isoform 1: Secreted Ref.7 Ref.10 Ref.13. Isoform 2: 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 initation at Met-27 according to (Ref.13). Ref.7 Ref.10 Ref.13 |
| Tissue specificity | Expressed in a wide range of tissues. Ref.7 |
| Involvement in disease | Note=A chromosomal aberration involving FSTL3 is found in a case of B-cell chronic lymphocytic leukemia. Translocation t(11;19)(q13;p13) with CCDN1. |
| Sequence similarities | Contains 2 follistatin-like domains. Contains 2 Kazal-like domains. Contains 1 TB (TGF-beta binding) domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| ADAM12 | O43184-2 | 4 | EBI-2625790,EBI-2625865 |
Alternative products
| This entry describes 2 isoforms produced by alternative initiation. [Align] [Select] | ||||||
| Isoform 1 (identifier: O95633-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: O95633-2) The sequence of this isoform differs from the canonical sequence as follows: 1-26: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 26 | 26 | Ref.6 | ||||||||||||||||||||||||||||||||||
| Chain | 27 – 263 | 237 | Follistatin-related protein 3 | PRO_0000010115 | |||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||
| Domain | 36 – 107 | 72 | TB | ||||||||||||||||||||||||||||||||||
| Domain | 99 – 119 | 21 | Follistatin-like 1 | ||||||||||||||||||||||||||||||||||
| Domain | 113 – 169 | 57 | Kazal-like 1 | ||||||||||||||||||||||||||||||||||
| Domain | 170 – 193 | 24 | Follistatin-like 2 | ||||||||||||||||||||||||||||||||||
| Domain | 189 – 245 | 57 | Kazal-like 2 | ||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||
| Glycosylation | 73 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||||||||||||||
| Glycosylation | 215 | 1 | N-linked (GlcNAc...) Ref.17 | ||||||||||||||||||||||||||||||||||
| Disulfide bond | 38 ↔ 61 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 48 ↔ 92 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 62 ↔ 95 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 99 ↔ 110 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 104 ↔ 119 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 121 ↔ 153 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 125 ↔ 146 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 135 ↔ 167 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 171 ↔ 182 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 176 ↔ 192 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 195 ↔ 229 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 200 ↔ 222 | Ref.17 | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 211 ↔ 243 | Ref.17 | |||||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 26 | 26 | Missing in isoform 2. | VSP_038553 | |||||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||||
| Mutagenesis | 27 | 1 | M → A: Nuclear localization. Ref.13 | ||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||
| Beta strand | 38 – 41 | 4 | |||||||||||||||||||||||||||||||||||
| Beta strand | 48 – 55 | 8 | |||||||||||||||||||||||||||||||||||
| Helix | 58 – 61 | 4 | |||||||||||||||||||||||||||||||||||
| Beta strand | 69 – 71 | 3 | |||||||||||||||||||||||||||||||||||
| Helix | 80 – 83 | 4 | |||||||||||||||||||||||||||||||||||
| Beta strand | 93 – 95 | 3 | |||||||||||||||||||||||||||||||||||
| Beta strand | 109 – 111 | 3 | |||||||||||||||||||||||||||||||||||
| Beta strand | 118 – 120 | 3 | |||||||||||||||||||||||||||||||||||
| Beta strand | 142 – 144 | 3 | |||||||||||||||||||||||||||||||||||
| Helix | 145 – 153 | 9 | |||||||||||||||||||||||||||||||||||
| Beta strand | 169 – 171 | 3 | |||||||||||||||||||||||||||||||||||
| Beta strand | 181 – 184 | 4 | |||||||||||||||||||||||||||||||||||
| Beta strand | 190 – 193 | 4 | |||||||||||||||||||||||||||||||||||
| Beta strand | 218 – 220 | 3 | |||||||||||||||||||||||||||||||||||
| Helix | 221 – 230 | 10 | |||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "FLRG (follistatin-related gene), a new target of chromosomal rearrangement in malignant blood disorders." Hayette S., Gadoux M., Martel S., Bertrand S., Tigaud I., Magaud J.-P., Rimokh R. Oncogene 16:2949-2954(1998) [PubMed: 9671416] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION. Tissue: Placenta. |
| [2] | "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. Gray A.M.Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [4] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta. |
| [6] | "Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-41. |
| [7] | "Human follistatin-related protein: a structural homologue of follistatin with nuclear localization." Tortoriello D.V., Sidis Y., Holtzman D.A., Holmes W.E., Schneyer A.L. Endocrinology 142:3426-3434(2001) [PubMed: 11459787] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION. |
| [8] | "Transcription activation of FLRG and follistatin by activin A, through Smad proteins, participates in a negative feedback loop to modulate activin A function." Bartholin L., Maguer-Satta V., Hayette S., Martel S., Gadoux M., Corbo L., Magaud J.P., Rimokh R. Oncogene 21:2227-2235(2002) [PubMed: 11948405] [Abstract] Cited for: FUNCTION. |
| [9] | "Differential binding and neutralization of activins A and B by follistatin and follistatin like-3 (FSTL-3/FSRP/FLRG)." Schneyer A., Schoen A., Quigg A., Sidis Y. Endocrinology 144:1671-1674(2003) [PubMed: 12697670] [Abstract] Cited for: INTERACTION WITH INHBA AND INHBB. |
| [10] | "Follistatin-related gene (FLRG) expression in human endometrium: sex steroid hormones regulate the expression of FLRG in cultured human endometrial stromal cells." Wang H.Q., Takebayashi K., Tsuchida K., Nishimura M., Noda Y. J. Clin. Endocrinol. Metab. 88:4432-4439(2003) [PubMed: 12970321] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [11] | "FLRG, member of the follistatin family, a new player in hematopoiesis." Maguer-Satta V., Rimokh R. Mol. Cell. Endocrinol. 225:109-118(2004) [PubMed: 15451575] [Abstract] Cited for: FUNCTION IN HEMATOPOIESIS. |
| [12] | "FLRG, a new ADAM12-associated protein, modulates osteoclast differentiation." Bartholin L., Destaing O., Forissier S., Martel S., Maguer-Satta V., Jurdic P., Rimokh R. Biol. Cell 97:577-588(2005) [PubMed: 15574124] [Abstract] Cited for: FUNCTION IN OSTEOCLAST DIFFERENTIATION, INTERACTION WITH ADAM8 AND ADAM12. |
| [13] | "Differential biosynthesis and intracellular transport of follistatin isoforms and follistatin-like-3." Saito S., Sidis Y., Mukherjee A., Xia Y., Schneyer A. Endocrinology 146:5052-5062(2005) [PubMed: 16150905] [Abstract] Cited for: SUBCELLULAR LOCATION, ALTERNATIVE INITIATION, MUTAGENESIS OF MET-27. |
| [14] | "A novel role for fibronectin type I domain in the regulation of human hematopoietic cell adhesiveness through binding to follistatin domains of FLRG and follistatin." Maguer-Satta V., Forissier S., Bartholin L., Martel S., Jeanpierre S., Bachelard E., Rimokh R. Exp. Cell Res. 312:434-442(2006) [PubMed: 16336961] [Abstract] Cited for: FUNCTION IN HEMATOPOIESIS, INTERACTION WITH FN1. |
| [15] | "AF10-dependent transcription is enhanced by its interaction with FLRG." Forissier S., Razanajaona D., Ay A.S., Martel S., Bartholin L., Rimokh R. Biol. Cell 99:563-571(2007) [PubMed: 17868029] [Abstract] Cited for: FUNCTION IN TRANSCRIPTION REGULATION, INTERACTION WITH MLLT10. |
| [16] | "Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development." Takehara-Kasamatsu Y., Tsuchida K., Nakatani M., Murakami T., Kurisaki A., Hashimoto O., Ohuchi H., Kurose H., Mori K., Kagami S., Noji S., Sugino H. J. Med. Invest. 54:276-288(2007) [PubMed: 17878677] [Abstract] Cited for: FUNCTION, INTERACTION WITH MSTN. |
| [17] | "The structure of FSTL3.activin A complex. Differential binding of N-terminal domains influences follistatin-type antagonist specificity." Stamler R., Keutmann H.T., Sidis Y., Kattamuri C., Schneyer A., Thompson T.B. J. Biol. Chem. 283:32831-32838(2008) [PubMed: 18768470] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 27-263 IN COMPLEX WITH INHBA, DISULFIDE BONDS, GLYCOSYLATION AT ASN-215. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | 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. | ||||||||||||||||||||||||
| IPI | IPI00025155. IPI00955041. | ||||||||||||||||||||||||
| RefSeq | NP_005851.1. NM_005860.2. | ||||||||||||||||||||||||
| UniGene | Hs.529038. | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||||||||||||||
| ProteinModelPortal | O95633. | ||||||||||||||||||||||||
| SMR | O95633. Positions 32-244. | ||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||
| IntAct | O95633. 2 interactions. | ||||||||||||||||||||||||
| STRING | O95633. | ||||||||||||||||||||||||
Protein family/group databases | |||||||||||||||||||||||||
| MEROPS | I01.968. | ||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||
| PeptideAtlas | O95633. | ||||||||||||||||||||||||
| PRIDE | O95633. | ||||||||||||||||||||||||
Protocols and materials databases | |||||||||||||||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENST00000166139; ENSP00000166139; ENSG00000070404. | ||||||||||||||||||||||||
| GeneID | 10272. | ||||||||||||||||||||||||
| KEGG | hsa:10272. | ||||||||||||||||||||||||
| UCSC | uc002lpk.1. human. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| CTD | 10272. | ||||||||||||||||||||||||
| GeneCards | GC19P000676. | ||||||||||||||||||||||||
| H-InvDB | HIX0014560. | ||||||||||||||||||||||||
| HGNC | HGNC:3973. FSTL3. | ||||||||||||||||||||||||
| HPA | CAB024899. | ||||||||||||||||||||||||
| MIM | 605343. gene. | ||||||||||||||||||||||||
| neXtProt | NX_O95633. | ||||||||||||||||||||||||
| PharmGKB | PA28390. | ||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| eggNOG | prNOG17339. | ||||||||||||||||||||||||
| GeneTree | ENSGT00440000033501. | ||||||||||||||||||||||||
| HOGENOM | HBG445393. | ||||||||||||||||||||||||
| HOVERGEN | HBG051666. | ||||||||||||||||||||||||
| InParanoid | O95633. | ||||||||||||||||||||||||
| OMA | CPRPQSC. | ||||||||||||||||||||||||
| OrthoDB | EOG4TF0M1. | ||||||||||||||||||||||||
| PhylomeDB | O95633. | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| ArrayExpress | O95633. | ||||||||||||||||||||||||
| Bgee | O95633. | ||||||||||||||||||||||||
| CleanEx | HS_FSTL3. | ||||||||||||||||||||||||
| Genevestigator | O95633. | ||||||||||||||||||||||||
| GermOnline | ENSG00000070404. Homo sapiens. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR002212. Fibril-assoc. IPR003645. Fol_N. IPR015369. Follistatin/Osteonectin_EGF. IPR002350. Prot_inh_Kazal. IPR011497. Prot_Inh_Kazal_2. IPR017878. TFG_b-bd. [Graphical view] | ||||||||||||||||||||||||
| Gene3D | G3DSA:3.90.290.10. Fibril-assoc. 1 hit. | ||||||||||||||||||||||||
| Pfam | PF09289. FOLN. 1 hit. PF07648. Kazal_2. 2 hits. [Graphical view] | ||||||||||||||||||||||||
| SMART | SM00274. FOLN. 2 hits. SM00280. KAZAL. 2 hits. [Graphical view] | ||||||||||||||||||||||||
| PROSITE | PS00282. KAZAL_1. False negative. PS51465. KAZAL_2. 2 hits. PS51364. TB. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other | |||||||||||||||||||||||||
| NextBio | 38914. | ||||||||||||||||||||||||
| PMAP-CutDB | O95633. | ||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||
Entry information
| Entry name | FSTL3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O95633 Secondary accession number(s): A8K7E3 | ||||||||
| Entry history |
| ||||||||
| Entry status | 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. | ||||||||
Relevant documents
| 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 |
| SIMILARITY comments Index of protein domains and families |

Clusters with