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Protein

Signal transducer and activator of transcription 3

Gene

STAT3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 (PubMed:17344214). 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 (PubMed:17344214). 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 (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity.By similarity7 Publications

GO - Molecular functioni

  • chromatin DNA binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • protein dimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding Source: BHF-UCL
  • signal transducer activity Source: ProtInc
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: BHF-UCL
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Host-virus interaction, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168610-MONOMER.
ReactomeiR-HSA-1059683. Interleukin-6 signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1839117. Signaling by cytosolic FGFR1 fusion mutants.
R-HSA-186763. Downstream signal transduction.
R-HSA-198745. Signalling to STAT3.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2586552. Signaling by Leptin.
R-HSA-2892247. POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
R-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.
R-HSA-452723. Transcriptional regulation of pluripotent stem cells.
R-HSA-8849474. PTK6 Activates STAT3.
R-HSA-8875791. MET activates STAT3.
R-HSA-982772. Growth hormone receptor signaling.
SignaLinkiP40763.
SIGNORiP40763.

Names & Taxonomyi

Protein namesi
Recommended name:
Signal transducer and activator of transcription 3Imported
Alternative name(s):
Acute-phase response factor
Gene namesi
Name:STAT3Imported
Synonyms:APRFImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:11364. STAT3.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • 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. Identified in a complex with LYN and PAG1.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • mitochondrial inner membrane Source: Ensembl
  • nuclear chromatin Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • RNA polymerase II transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Hyperimmunoglobulin E recurrent infection syndrome, autosomal dominant (AD-HIES)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare disorder of immunity and connective tissue characterized by immunodeficiency, chronic eczema, recurrent Staphylococcal infections, increased serum IgE, eosinophilia, distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures.
See also OMIM:147060
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037365382R → L in AD-HIES. 1 PublicationCorresponds to variant rs113994136dbSNPEnsembl.1
Natural variantiVAR_037366382R → Q in AD-HIES; loss of function. 2 PublicationsCorresponds to variant rs113994136dbSNPEnsembl.1
Natural variantiVAR_037367382R → W in AD-HIES; loss of function; reduced DNA-binding ability. 3 PublicationsCorresponds to variant rs113994135dbSNPEnsembl.1
Natural variantiVAR_037368384F → L in AD-HIES. 1 Publication1
Natural variantiVAR_037369384F → S in AD-HIES. 1 Publication1
Natural variantiVAR_037370389T → I in AD-HIES; loss of function. 2 PublicationsCorresponds to variant rs397514766dbSNPEnsembl.1
Natural variantiVAR_075414395N → Y in AD-HIES; unknown pathological significance; reduced DNA-binding ability. 1 Publication1
Natural variantiVAR_037371423R → Q in AD-HIES. 1 PublicationCorresponds to variant rs113994137dbSNPEnsembl.1
Natural variantiVAR_075415425N → Y in AD-HIES; unknown pathological significance; reduced DNA-binding ability. 1 Publication1
Natural variantiVAR_037372437H → Y in AD-HIES; loss of function. 1 Publication1
Natural variantiVAR_037373463Missing in AD-HIES; loss of function. 2 Publications1
Natural variantiVAR_037375611S → N in AD-HIES. 1 Publication1
Natural variantiVAR_037376621F → V in AD-HIES. 1 Publication1
Natural variantiVAR_037377622T → I in AD-HIES. 1 Publication1
Natural variantiVAR_037378637V → L in AD-HIES. 1 Publication1
Natural variantiVAR_037379637V → M in AD-HIES; reduced DNA-binding ability. 2 PublicationsCorresponds to variant rs113994139dbSNPEnsembl.1
Natural variantiVAR_037380644Missing in AD-HIES. 1 Publication1
Natural variantiVAR_037381657Y → C in AD-HIES; reduced DNA-binding ability. 2 PublicationsCorresponds to variant rs193922721dbSNPEnsembl.1
Autoimmune disease, multisystem, infantile-onset, 1 (ADMIO1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by early childhood onset of a spectrum of autoimmune manifestations affecting multiple organs, including insulin-dependent diabetes mellitus and autoimmune enteropathy or celiac disease. Other features include short stature, non-specific dermatitis, hypothyroidism, autoimmune arthritis, and delayed puberty.
See also OMIM:615952
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071885392K → R in ADMIO1. 1 PublicationCorresponds to variant rs587777648dbSNPEnsembl.1
Natural variantiVAR_071886646N → K in ADMIO1. 1 PublicationCorresponds to variant rs587777649dbSNPEnsembl.1
Natural variantiVAR_071887658K → N in ADMIO1. 1 PublicationCorresponds to variant rs587777650dbSNPEnsembl.1
Natural variantiVAR_071888716T → M in ADMIO1. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi434 – 435EE → AA: Inhibits leptin-mediated transactivation of CCND1 promoter. No effect on interaction with INPP5F. 2 Publications2
Mutagenesisi705Y → F: Inhibits leptin-mediated transactivation of CCND1 promoter. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi6774.
MalaCardsiSTAT3.
MIMi147060. phenotype.
615952. phenotype.
OpenTargetsiENSG00000168610.
Orphaneti2314. Autosomal dominant hyper-IgE syndrome.
PharmGKBiPA337.

Chemistry databases

ChEMBLiCHEMBL4026.

Polymorphism and mutation databases

BioMutaiSTAT3.
DMDMi48429227.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001824172 – 770Signal transducer and activator of transcription 3Add BLAST769

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei705Phosphotyrosine; by FER and PTK6Combined sources4 Publications1
Modified residuei714PhosphothreonineCombined sources1
Modified residuei727Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCECombined sources7 Publications1
Isoform Del-701 (identifier: P40763-2)
Modified residuei704PhosphotyrosineCombined sources1

Post-translational modificationi

Tyrosine phosphorylated upon stimulation with EGF. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, LIF, CNTF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha, LEP and OSM. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. 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. Upon LPS challenge, phosphorylated within the nucleus by IRAK1. Upon erythropoietin treatment, phosphorylated on Ser-727 by RPS6KA5. Phosphorylation at Tyr-705 by PTK6 or FER leads to an increase of its transcriptional activity. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling.By similarity13 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP40763.
MaxQBiP40763.
PaxDbiP40763.
PeptideAtlasiP40763.
PRIDEiP40763.

PTM databases

iPTMnetiP40763.
PhosphoSitePlusiP40763.

Miscellaneous databases

PMAP-CutDBP40763.

Expressioni

Tissue specificityi

Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Gene expression databases

BgeeiENSG00000168610.
CleanExiHS_STAT3.
ExpressionAtlasiP40763. baseline and differential.
GenevisibleiP40763. HS.

Organism-specific databases

HPAiCAB003859.
CAB068241.
CAB068242.
HPA001671.
HPA058603.

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). Interacts with STAT3; the interaction is independent of STAT3 TYR-705 phosphorylation status (PubMed:25476455). Interacts with FGFR4 (PubMed:26675719).By similarity19 Publications
(Microbial infection) Interacts with HCV core protein.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-518675,EBI-518675
Q9DUM34EBI-518675,EBI-7971837From a different organism.
BCKDKO148742EBI-518675,EBI-1046765
BICD1Q96G012EBI-518675,EBI-1104509
BLKP514515EBI-518675,EBI-2105445
BMXP518136EBI-518675,EBI-696657
CAPN1P073842EBI-518675,EBI-1542113
CORO1AP311462EBI-518675,EBI-1046676
CSF3RQ990624EBI-518675,EBI-7331284
DAXXQ9UER74EBI-518675,EBI-77321
DIRAS3O956613EBI-518675,EBI-6139214
ECH1Q130112EBI-518675,EBI-711968
ECHS1P300843EBI-518675,EBI-719602
EGFRP0053314EBI-518675,EBI-297353
ERBB2P046269EBI-518675,EBI-641062
EZH2Q159105EBI-518675,EBI-530054
GADD45GIP1Q8TAE84EBI-518675,EBI-372506
GNL3Q9BVP22EBI-518675,EBI-641642
KHDRBS1Q076662EBI-518675,EBI-1364
LMO2P257913EBI-518675,EBI-739696
MAP3K7O433184EBI-518675,EBI-358684
MAPK9P459842EBI-518675,EBI-713568
MAPK9P45984-13EBI-518675,EBI-713586
MORC4Q8TE762EBI-518675,EBI-3940432
MRPS31Q926652EBI-518675,EBI-720602
NR4A1P227363EBI-518675,EBI-721550
OGDHLQ9ULD02EBI-518675,EBI-3940481
PGRP064013EBI-518675,EBI-78539
PTPN1P180312EBI-518675,EBI-968788
RELAQ042064EBI-518675,EBI-73886
RETP079493EBI-518675,EBI-2480756
RPS9P467812EBI-518675,EBI-351206
SOX1O005702EBI-518675,EBI-2935583
SP1P080474EBI-518675,EBI-298336
SRIP306262EBI-518675,EBI-750459
STAT1P422243EBI-518675,EBI-1057697
SULT2A1Q065202EBI-518675,EBI-3921363
SYKP434056EBI-518675,EBI-78302

GO - Molecular functioni

  • protein dimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112651. 236 interactors.
DIPiDIP-33584N.
IntActiP40763. 157 interactors.
MINTiMINT-146801.
STRINGi9606.ENSP00000264657.

Chemistry databases

BindingDBiP40763.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5AX3X-ray2.98B571-582[»]
ProteinModelPortaliP40763.
SMRiP40763.
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 importAdd 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.
GeneTreeiENSGT00760000119236.
HOGENOMiHOG000220792.
HOVERGENiHBG055669.
InParanoidiP40763.
KOiK04692.
OMAiNSMSFAE.
OrthoDBiEOG091G03O3.
PhylomeDBiP40763.
TreeFamiTF318648.

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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P40763-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES 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 KMKVVENLQD 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
KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF
660 670 680 690 700
AEIIMGYKIM DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG
710 720 730 740 750
SAAPYLKTKF ICVTPTTCSN TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG
760 770
QFESLTFDME LTSECATSPM
Length:770
Mass (Da):88,068
Last modified:June 7, 2004 - v2
Checksum:i6C00632211C8012D
GO
Isoform Del-701 (identifier: P40763-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     701-701: Missing.

Show »
Length:769
Mass (Da):87,981
Checksum:iA374A32AB9D28077
GO
Isoform 3 (identifier: P40763-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     716-722: TTCSNTI → FIDAVWK
     723-770: Missing.

Show »
Length:722
Mass (Da):83,126
Checksum:i09226A697966D947
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti133T → A in BAF84622 (PubMed:14702039).Curated1
Sequence conflicti288Q → H in AAA58374 (PubMed:7512451).Curated1
Sequence conflicti460P → S in AAA58374 (PubMed:7512451).Curated1
Sequence conflicti548K → N in AAA58374 (PubMed:7512451).Curated1
Sequence conflicti652E → V in BAF84622 (PubMed:14702039).Curated1
Sequence conflicti667V → L in AAA58374 (PubMed:7512451).Curated1
Sequence conflicti730T → A in AAA58374 (PubMed:7512451).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01868332Q → K.Corresponds to variant rs1803125dbSNPEnsembl.1
Natural variantiVAR_018679143M → I.1 PublicationCorresponds to variant rs17878478dbSNPEnsembl.1
Natural variantiVAR_037365382R → L in AD-HIES. 1 PublicationCorresponds to variant rs113994136dbSNPEnsembl.1
Natural variantiVAR_037366382R → Q in AD-HIES; loss of function. 2 PublicationsCorresponds to variant rs113994136dbSNPEnsembl.1
Natural variantiVAR_037367382R → W in AD-HIES; loss of function; reduced DNA-binding ability. 3 PublicationsCorresponds to variant rs113994135dbSNPEnsembl.1
Natural variantiVAR_037368384F → L in AD-HIES. 1 Publication1
Natural variantiVAR_037369384F → S in AD-HIES. 1 Publication1
Natural variantiVAR_037370389T → I in AD-HIES; loss of function. 2 PublicationsCorresponds to variant rs397514766dbSNPEnsembl.1
Natural variantiVAR_071885392K → R in ADMIO1. 1 PublicationCorresponds to variant rs587777648dbSNPEnsembl.1
Natural variantiVAR_075414395N → Y in AD-HIES; unknown pathological significance; reduced DNA-binding ability. 1 Publication1
Natural variantiVAR_037371423R → Q in AD-HIES. 1 PublicationCorresponds to variant rs113994137dbSNPEnsembl.1
Natural variantiVAR_075415425N → Y in AD-HIES; unknown pathological significance; reduced DNA-binding ability. 1 Publication1
Natural variantiVAR_037372437H → Y in AD-HIES; loss of function. 1 Publication1
Natural variantiVAR_037373463Missing in AD-HIES; loss of function. 2 Publications1
Natural variantiVAR_037374561F → Y.1 PublicationCorresponds to variant rs1064116dbSNPEnsembl.1
Natural variantiVAR_037375611S → N in AD-HIES. 1 Publication1
Natural variantiVAR_037376621F → V in AD-HIES. 1 Publication1
Natural variantiVAR_037377622T → I in AD-HIES. 1 Publication1
Natural variantiVAR_037378637V → L in AD-HIES. 1 Publication1
Natural variantiVAR_037379637V → M in AD-HIES; reduced DNA-binding ability. 2 PublicationsCorresponds to variant rs113994139dbSNPEnsembl.1
Natural variantiVAR_037380644Missing in AD-HIES. 1 Publication1
Natural variantiVAR_071886646N → K in ADMIO1. 1 PublicationCorresponds to variant rs587777649dbSNPEnsembl.1
Natural variantiVAR_037381657Y → C in AD-HIES; reduced DNA-binding ability. 2 PublicationsCorresponds to variant rs193922721dbSNPEnsembl.1
Natural variantiVAR_071887658K → N in ADMIO1. 1 PublicationCorresponds to variant rs587777650dbSNPEnsembl.1
Natural variantiVAR_071888716T → M in ADMIO1. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010474701Missing in isoform Del-701. 1 Publication1
Alternative sequenceiVSP_055918716 – 722TTCSNTI → FIDAVWK in isoform 3. 1 Publication7
Alternative sequenceiVSP_055919723 – 770Missing in isoform 3. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29277 mRNA. Translation: AAA58374.1.
AJ012463 mRNA. Translation: CAA10032.1.
JB252046 mRNA. No translation available.
AK291933 mRNA. Translation: BAF84622.1.
AY572796 Genomic DNA. Translation: AAS66986.1.
AC087691 Genomic DNA. No translation available.
CH471152 Genomic DNA. Translation: EAW60822.1.
BC000627 mRNA. Translation: AAH00627.1.
BC014482 mRNA. Translation: AAH14482.1.
AF029311 mRNA. Translation: AAB84254.1.
CCDSiCCDS32656.1. [P40763-1]
CCDS32657.1. [P40763-2]
CCDS59288.1. [P40763-3]
PIRiA54444.
RefSeqiNP_003141.2. NM_003150.3. [P40763-2]
NP_644805.1. NM_139276.2. [P40763-1]
NP_998827.1. NM_213662.1. [P40763-3]
XP_005257673.2. XM_005257616.3. [P40763-2]
XP_005257674.2. XM_005257617.3. [P40763-1]
XP_011523447.1. XM_011525145.2. [P40763-1]
XP_011523448.1. XM_011525146.2. [P40763-3]
XP_016880461.1. XM_017024972.1. [P40763-3]
XP_016880464.1. XM_017024975.1. [P40763-2]
UniGeneiHs.463059.

Genome annotation databases

EnsembliENST00000264657; ENSP00000264657; ENSG00000168610. [P40763-1]
ENST00000404395; ENSP00000384943; ENSG00000168610. [P40763-2]
ENST00000585517; ENSP00000467000; ENSG00000168610. [P40763-3]
ENST00000588969; ENSP00000467985; ENSG00000168610. [P40763-1]
GeneIDi6774.
KEGGihsa:6774.
UCSCiuc002hzl.2. human. [P40763-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

STAT3 entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology
STAT3base

STAT3 mutation db

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29277 mRNA. Translation: AAA58374.1.
AJ012463 mRNA. Translation: CAA10032.1.
JB252046 mRNA. No translation available.
AK291933 mRNA. Translation: BAF84622.1.
AY572796 Genomic DNA. Translation: AAS66986.1.
AC087691 Genomic DNA. No translation available.
CH471152 Genomic DNA. Translation: EAW60822.1.
BC000627 mRNA. Translation: AAH00627.1.
BC014482 mRNA. Translation: AAH14482.1.
AF029311 mRNA. Translation: AAB84254.1.
CCDSiCCDS32656.1. [P40763-1]
CCDS32657.1. [P40763-2]
CCDS59288.1. [P40763-3]
PIRiA54444.
RefSeqiNP_003141.2. NM_003150.3. [P40763-2]
NP_644805.1. NM_139276.2. [P40763-1]
NP_998827.1. NM_213662.1. [P40763-3]
XP_005257673.2. XM_005257616.3. [P40763-2]
XP_005257674.2. XM_005257617.3. [P40763-1]
XP_011523447.1. XM_011525145.2. [P40763-1]
XP_011523448.1. XM_011525146.2. [P40763-3]
XP_016880461.1. XM_017024972.1. [P40763-3]
XP_016880464.1. XM_017024975.1. [P40763-2]
UniGeneiHs.463059.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5AX3X-ray2.98B571-582[»]
ProteinModelPortaliP40763.
SMRiP40763.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112651. 236 interactors.
DIPiDIP-33584N.
IntActiP40763. 157 interactors.
MINTiMINT-146801.
STRINGi9606.ENSP00000264657.

Chemistry databases

BindingDBiP40763.
ChEMBLiCHEMBL4026.

PTM databases

iPTMnetiP40763.
PhosphoSitePlusiP40763.

Polymorphism and mutation databases

BioMutaiSTAT3.
DMDMi48429227.

Proteomic databases

EPDiP40763.
MaxQBiP40763.
PaxDbiP40763.
PeptideAtlasiP40763.
PRIDEiP40763.

Protocols and materials databases

DNASUi6774.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264657; ENSP00000264657; ENSG00000168610. [P40763-1]
ENST00000404395; ENSP00000384943; ENSG00000168610. [P40763-2]
ENST00000585517; ENSP00000467000; ENSG00000168610. [P40763-3]
ENST00000588969; ENSP00000467985; ENSG00000168610. [P40763-1]
GeneIDi6774.
KEGGihsa:6774.
UCSCiuc002hzl.2. human. [P40763-1]

Organism-specific databases

CTDi6774.
DisGeNETi6774.
GeneCardsiSTAT3.
GeneReviewsiSTAT3.
HGNCiHGNC:11364. STAT3.
HPAiCAB003859.
CAB068241.
CAB068242.
HPA001671.
HPA058603.
MalaCardsiSTAT3.
MIMi102582. gene.
147060. phenotype.
615952. phenotype.
neXtProtiNX_P40763.
OpenTargetsiENSG00000168610.
Orphaneti2314. Autosomal dominant hyper-IgE syndrome.
PharmGKBiPA337.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3667. Eukaryota.
ENOG410XPN8. LUCA.
GeneTreeiENSGT00760000119236.
HOGENOMiHOG000220792.
HOVERGENiHBG055669.
InParanoidiP40763.
KOiK04692.
OMAiNSMSFAE.
OrthoDBiEOG091G03O3.
PhylomeDBiP40763.
TreeFamiTF318648.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168610-MONOMER.
ReactomeiR-HSA-1059683. Interleukin-6 signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1839117. Signaling by cytosolic FGFR1 fusion mutants.
R-HSA-186763. Downstream signal transduction.
R-HSA-198745. Signalling to STAT3.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2586552. Signaling by Leptin.
R-HSA-2892247. POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
R-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.
R-HSA-452723. Transcriptional regulation of pluripotent stem cells.
R-HSA-8849474. PTK6 Activates STAT3.
R-HSA-8875791. MET activates STAT3.
R-HSA-982772. Growth hormone receptor signaling.
SignaLinkiP40763.
SIGNORiP40763.

Miscellaneous databases

ChiTaRSiSTAT3. human.
GeneWikiiSTAT3.
GenomeRNAii6774.
PMAP-CutDBP40763.
PROiP40763.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168610.
CleanExiHS_STAT3.
ExpressionAtlasiP40763. baseline and differential.
GenevisibleiP40763. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P40763
Secondary accession number(s): A8K7B8
, K7ENL3, O14916, Q9BW54
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: June 7, 2004
Last modified: November 30, 2016
This is version 187 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Miscellaneous

Involved in the gp130-mediated signaling pathway.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.