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Protein

Signal transducer and activator of transcription 3

Gene

STAT3

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. 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. Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (By similarity). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Signal transducer and activator of transcription 3
Gene namesi
Name:STAT3
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • 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.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001824162 – 770Signal transducer and activator of transcription 3Add BLAST769

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei705Phosphotyrosine; by FER and PTK6By similarity1
Modified residuei714PhosphothreonineBy similarity1
Modified residuei727Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCEBy similarity1

Post-translational modificationi

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). Phosphorylation 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).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP61635.
PRIDEiP61635.

PTM databases

iPTMnetiP61635.

Interactioni

Subunit structurei

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 ARL2BP; the interaction is enhanced by LIF and JAK1 expression (By similarity). Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import (By similarity). Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation (By similarity). Interacts with ARL2BP; interaction is enhanced with ARL2. Interacts with NEK6 (By similarity). Binds to CDK9 when activated and nuclear. Interacts with BMX. Interacts with ZIPK/DAPK3. Interacts with PIAS3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. In prostate cancer cells, interacts with STAT3 and promotes DNA binding activity of STAT3. Interacts with STMN3, antagonizing its microtubule-destabilizing activity. Interacts with the 'Lys-129' acetylated form of BIRC5/survivin. Interacts with FER. Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic domain) (By similarity). Interacts with FGFR4 (By similarity). Interacts with STAT3; the interaction is independent of STAT3 TYR-705 phosphorylation status (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000028687.

Structurei

3D structure databases

ProteinModelPortaliP61635.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini580 – 670SH2PROSITE-ProRule annotationAdd BLAST91

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi150 – 162Essential for nuclear importBy similarityAdd BLAST13

Sequence similaritiesi

Belongs to the transcription factor STAT family.Curated
Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG3667. Eukaryota.
ENOG410XPN8. LUCA.
HOGENOMiHOG000220792.
HOVERGENiHBG055669.
InParanoidiP61635.
KOiK04692.

Family and domain databases

Gene3Di1.10.238.10. 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.
InterProiIPR011992. EF-hand-dom_pair.
IPR008967. p53-like_TF_DNA-bd.
IPR000980. SH2.
IPR001217. STAT.
IPR013800. STAT_TF_alpha.
IPR015988. STAT_TF_coiled-coil.
IPR013801. STAT_TF_DNA-bd.
IPR012345. STAT_TF_DNA-bd_sub.
IPR013799. STAT_TF_prot_interaction.
[Graphical view]
PANTHERiPTHR11801. PTHR11801. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTiSM00964. STAT_int. 1 hit.
[Graphical view]
SUPFAMiSSF47655. SSF47655. 1 hit.
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P61635-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQLLAPWIES QDWAYAASKE
60 70 80 90 100
SHATLVFHNL LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME
110 120 130 140 150
IARIVARCLW EESRLLQTAA TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD
160 170 180 190 200
VRKRVQDLEQ KMKVVENLLD DFDFNYKTLK SQGDMQDLNG NNQSVTRQKM
210 220 230 240 250
QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL ADWKRRQQIA
260 270 280 290 300
CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ
310 320 330 340 350
HRPMLEERIV ELFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR
360 370 380 390 400
LLVKFPELNY QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN
410 420 430 440 450
NGSLSAEFKH LTLREQRCGN GGRANCDASL IVTEELHLIT FETEVYHQGL
460 470 480 490 500
KIDLETHSLP VVVISNICQM PNAWASILWY NMLTNNPKNV NFFTKPPIGT
510 520 530 540 550
WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS GCQITWAKFC
560 570 580 590 600
KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST
610 620 630 640 650
KPPGTCLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF
660 670 680 690 700
AEIIMGYKIM DATNILVSPL VYLYPDIPKE DAFGKYCRPE SQEHPEADPG
710 720 730 740 750
SAAPYLKTKF ICVTPTTCSN TIDLPMSPRT LDSLMQFGNN GEAAEPSAGG
760 770
QFESLTFDME LTSECATSPM
Length:770
Mass (Da):87,975
Last modified:June 7, 2004 - v1
Checksum:i9CEB147C73E83274
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ620655 mRNA. Translation: CAF06182.1.
RefSeqiNP_001012689.2. NM_001012671.2.
UniGeneiBt.15334.

Genome annotation databases

GeneIDi508541.
KEGGibta:508541.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ620655 mRNA. Translation: CAF06182.1.
RefSeqiNP_001012689.2. NM_001012671.2.
UniGeneiBt.15334.

3D structure databases

ProteinModelPortaliP61635.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000028687.

PTM databases

iPTMnetiP61635.

Proteomic databases

PaxDbiP61635.
PRIDEiP61635.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi508541.
KEGGibta:508541.

Organism-specific databases

CTDi6774.

Phylogenomic databases

eggNOGiKOG3667. Eukaryota.
ENOG410XPN8. LUCA.
HOGENOMiHOG000220792.
HOVERGENiHBG055669.
InParanoidiP61635.
KOiK04692.

Family and domain databases

Gene3Di1.10.238.10. 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.
InterProiIPR011992. EF-hand-dom_pair.
IPR008967. p53-like_TF_DNA-bd.
IPR000980. SH2.
IPR001217. STAT.
IPR013800. STAT_TF_alpha.
IPR015988. STAT_TF_coiled-coil.
IPR013801. STAT_TF_DNA-bd.
IPR012345. STAT_TF_DNA-bd_sub.
IPR013799. STAT_TF_prot_interaction.
[Graphical view]
PANTHERiPTHR11801. PTHR11801. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTiSM00964. STAT_int. 1 hit.
[Graphical view]
SUPFAMiSSF47655. SSF47655. 1 hit.
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSTAT3_BOVIN
AccessioniPrimary (citable) accession number: P61635
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: October 5, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Involved in the gp130-mediated signaling pathway.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.