P61635 (STAT3_BOVIN) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 99. History...
Names and origin
|Protein names||Recommended name:|
Signal transducer and activator of transcription 3
|Organism||Bos taurus (Bovine) [Reference proteome]|
|Taxonomic identifier||9913 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos|
|Sequence length||770 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA By similarity. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity By similarity. Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G By similarity.
Forms a homodimer or a heterodimer with a related family member (at least STAT1). Interacts with IL31RA, NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1. Interacts with IL23R in presence of IL23. Interacts (via SH2 domain) with NLK. Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import. Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation. Interacts with ARL2BP; interaction is enhanced with ARL2. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 expression By similarity. Interacts with NEK6. Binds to CDK9 when activated and nuclear By similarity. Interacts with BMX By similarity. Interacts with ZIPK/DAPK3 By similarity. Identified in a complex with LYN and PAG1 By similarity. Interacts with STMN3, antagonizing its microtubule-destabilizing activity By similarity. Interacts with the 'Lys-129' acetylated form of BIRC5/survivin. Interacts with FER By similarity. Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic domain) By similarity.
Cytoplasm By similarity. Nucleus By similarity. Note: Shuttles between the nucleus and the cytoplasm. Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear presence is independent of tyrosine phosphorylation. Predominantly present in the cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, accumulates in the nucleus By similarity. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3.
Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL-6, IL-11, CNTF, LIF, CSF-1, EGF, PDGF, IFN-alpha and OSM. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers and maximal transcriptional activity. ARL2BP may participate in keeping the phosphorylated state of STAT3 within the nucleus. Tyrosine phosphorylated upon stimulation with EGF. Upon LPS challenge, phosphorylated within the nucleus by IRAK1. Phosphorylated on Ser-727 by RPS6KA5 By similarity. Phosphoryation at Tyr-705 by FER or PTK6 leads to an increase of its transcriptional activity By similarity. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling By similarity.
Involved in the gp130-mediated signaling pathway.
Belongs to the transcription factor STAT family.
Contains 1 SH2 domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 770||770||Signal transducer and activator of transcription 3||PRO_0000182416|
|Domain||580 – 670||91||SH2|
|Motif||150 – 162||13||Essential for nuclear import By similarity|
Amino acid modifications
|Modified residue||705||1||Phosphotyrosine; by FER and PTK6 By similarity|
|Modified residue||727||1||Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCE By similarity|
|||"The STAT5B-encoding gene was flipped across the STAT3/STAT5A-locus during ruminant evolution."|
Seyfert H.M., Wheeler T.T., Moolenaar A., Pitra C.
Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Mammary gland.
|+||Additional computationally mapped references.|
|AJ620655 mRNA. Translation: CAF06182.1.|
|RefSeq||NP_001012689.2. NM_001012671.2. |
3D structure databases
|SMR||P61635. Positions 136-715. |
Protocols and materials databases
Genome annotation databases
Family and domain databases
|Gene3D||126.96.36.199. 1 hit. |
1.10.532.10. 1 hit.
1.20.1050.20. 1 hit.
188.8.131.520. 1 hit.
3.30.505.10. 1 hit.
|InterPro||IPR011992. EF-hand-dom_pair. |
|PANTHER||PTHR11801. PTHR11801. 1 hit. |
|Pfam||PF00017. SH2. 1 hit. |
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
|SMART||SM00252. SH2. 1 hit. |
SM00964. STAT_int. 1 hit.
|SUPFAM||SSF47655. SSF47655. 1 hit. |
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
|PROSITE||PS50001. SH2. 1 hit. |
|Accession||Primary (citable) accession number: P61635|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families