P52631 (STAT3_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Signal transducer and activator of transcription 3

Gene names

Name:

Stat3

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	770 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	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 By similarity. Interacts with ARL2BP; interaction is enhanced with ARL2. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 expression By similarity. Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation. Interacts with NEK6. Binds to CDK9 when activated and nuclear By similarity. Interacts with BMX By similarity. Interacts with ZIPK/DAPK3 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. Ref.3
Subcellular location	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. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3 By similarity.
Tissue specificity	Detected in lung, heart, oviduct, ovary, uterus and kidney (at protein level). Detected in ovary, oviduct, and at lower levels in uterus and lung.
Post-translational modification	Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. 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.
Miscellaneous	Involved in the gp130-mediated signaling pathway.
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	SH2 domain
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JAK-STAT cascade involved in growth hormone signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB acute-phase response Inferred from expression pattern Ref.1. Source: RGD astrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB cell proliferation Inferred from electronic annotation. Source: Compara eating behavior Inferred from sequence or structural similarity. Source: UniProtKB eye photoreceptor cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB glucose homeostasis Inferred from sequence or structural similarity. Source: UniProtKB interleukin-6-mediated signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of Notch signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB protein import into nucleus Inferred from sequence or structural similarity. Source: UniProtKB radial glial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB response to cytokine stimulus Inferred from direct assay PubMed 18270592. Source: RGD response to drug Inferred from expression pattern PubMed 18031608. Source: RGD response to estradiol stimulus Inferred from expression pattern PubMed 17916759. Source: RGD response to ethanol Inferred from expression pattern PubMed 17916759. Source: RGD sexual reproduction Inferred from sequence or structural similarity. Source: UniProtKB stem cell maintenance Inferred from electronic annotation. Source: Compara temperature homeostasis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from electronic annotation. Source: Compara protein dimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein kinase binding Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay PubMed 16648019. Source: RGD sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: RGD transcription regulatory region DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 770	770	Signal transducer and activator of transcription 3		PRO_0000182419
Regions
	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

Sequences

	Sequence		Length	Mass (Da)
	P52631 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: D74A0C76954754ED	FASTA	770	88,040
	10 20 30 40 50 60 MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE SHATLVFHNL 70 80 90 100 110 120 LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME IARIVARCLW EESRLLQTAA 130 140 150 160 170 180 TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK 190 200 210 220 230 240 SQGDMQDLNG NNQSVTRQKM QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL 250 260 270 280 290 300 ADWKRRQQIA CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ 310 320 330 340 350 360 HRPMLEERIV DLFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR LLVKFPELNY 370 380 390 400 410 420 QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN NGSLSAEFKH LTLREQRCGN 430 440 450 460 470 480 GGRANCDASL IVTEELHLIT FETEVYHQGL KIDLETHSLP VVVISNICQM PNAWASILWY 490 500 510 520 530 540 NMLTNNPKNV NFFTKPPIGT WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS 550 560 570 580 590 600 GCQITWAKFC KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST 610 620 630 640 650 660 KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF AEIIMGYKIM 670 680 690 700 710 720 DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG SAAPYLKTKF ICVTPTTCSN 730 740 750 760 770 TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG QFESLTFDMD LTSECATSPM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements." Ripperger J.A., Fritz S., Richter K., Hocke G.M., Lottspeich F., Fey G.H. J. Biol. Chem. 270:29998-30006(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[3]	"Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin." Kwon H., Jeong K., Hwang E.M., Park J.-Y., Hong S.-G., Choi W.-S., Pak Y. Biochim. Biophys. Acta 1793:1325-1333(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CAV2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X91810 mRNA. Translation: CAA62920.1. BC087025 mRNA. Translation: AAH87025.1.
IPI	IPI00208224.
RefSeq	NP_036879.1. NM_012747.2.
UniGene	Rn.10247.
3D structure databases
ProteinModelPortal	P52631.
SMR	P52631. Positions 136-715.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000026760.
PTM databases
PhosphoSite	P52631.
Proteomic databases
PaxDb	P52631.
PRIDE	P52631.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000026760; ENSRNOP00000026760; ENSRNOG00000019742.
GeneID	25125.
KEGG	rno:25125.
Organism-specific databases
CTD	6774.
RGD	3772. Stat3.
Phylogenomic databases
eggNOG	NOG303257.
GeneTree	ENSGT00550000074337.
HOGENOM	HOG000220792.
HOVERGEN	HBG055669.
InParanoid	P52631.
KO	K04692.
OrthoDB	EOG4G4GPS.
Enzyme and pathway databases
Reactome	REACT_111984. Signal Transduction.
Gene expression databases
ArrayExpress	P52631.
Genevestigator	P52631.
GermOnline	ENSRNOG00000019742. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.238.10. 1 hit. 1.10.532.10. 1 hit. 1.20.1050.20. 1 hit. 2.60.40.630. 1 hit. 3.30.505.10. 1 hit.
InterPro	IPR011992. EF-hand-like_dom. IPR008967. p53-like_TF_DNA-bd. IPR000980. SH2. IPR013800. STAT_TF_alpha. IPR015988. STAT_TF_coiled-coil. IPR001217. STAT_TF_core. IPR013801. STAT_TF_DNA-bd. IPR012345. STAT_TF_DNA-bd_sub. IPR013799. STAT_TF_prot_interaction. [Graphical view]
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. [Graphical view]
SMART	SM00252. SH2. 1 hit. SM00964. STAT_int. 1 hit. [Graphical view]
SUPFAM	SSF49417. P53_like_DNA_bnd. 1 hit. SSF47655. STAT. 1 hit. SSF48092. STAT. 1 hit.
PROSITE	PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1764933.
NextBio	605521.

Entry information

Entry name

STAT3_RAT

Accession

Primary (citable) accession number: P52631

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program