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Protein

Signal transducer and activator of transcription 6

Gene

STAT6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166888-MONOMER.
ReactomeiR-HSA-186763. Downstream signal transduction.
R-HSA-3249367. STAT6-mediated induction of chemokines.
SignaLinkiP42226.
SIGNORiP42226.

Names & Taxonomyi

Protein namesi
Recommended name:
Signal transducer and activator of transcription 6
Alternative name(s):
IL-4 Stat
Gene namesi
Name:STAT6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11368. STAT6.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Translocated into the nucleus in response to phosphorylation.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi802L → A: Abolishes the interaction with NCOA1; when associated with A-805. 1 Publication1
Mutagenesisi805L → A: Abolishes the interaction with NCOA1; when associated with A-802. 1 Publication1

Organism-specific databases

DisGeNETi6778.
MalaCardsiSTAT6.
OpenTargetsiENSG00000166888.
Orphaneti2126. Solitary fibrous tumor.
PharmGKBiPA339.

Chemistry databases

ChEMBLiCHEMBL5401.

Polymorphism and mutation databases

BioMutaiSTAT6.
DMDMi1174459.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001824332 – 847Signal transducer and activator of transcription 6Add BLAST846

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei641Phosphotyrosine; by JAKBy similarity1

Post-translational modificationi

Tyrosine phosphorylated following stimulation by IL4/interleukin-4 and IL3/interleukin-3 (By similarity). Dephosphorylation on tyrosine residues by PTPN2 negatively regulates the IL4/interleukin-4 mediated signaling.By similarity1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP42226.
MaxQBiP42226.
PaxDbiP42226.
PeptideAtlasiP42226.
PRIDEiP42226.

PTM databases

iPTMnetiP42226.
PhosphoSitePlusiP42226.

Expressioni

Gene expression databases

BgeeiENSG00000166888.
CleanExiHS_STAT6.
ExpressionAtlasiP42226. baseline and differential.
GenevisibleiP42226. HS.

Organism-specific databases

HPAiHPA001861.

Interactioni

Subunit structurei

Forms a homodimer or a heterodimer with a related family member (By similarity). Interacts with NCOA1 via its C-terminal LXXLL motif.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-1186478,EBI-1186478
EP300Q094722EBI-1186478,EBI-447295
IL4RP243944EBI-1186478,EBI-367009
TBK1Q9UHD27EBI-1186478,EBI-356402
TMEM173Q86WV612EBI-1186478,EBI-2800345

GO - Molecular functioni

  • protein phosphatase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112655. 61 interactors.
DIPiDIP-39855N.
IntActiP42226. 34 interactors.
MINTiMINT-8020389.
STRINGi9606.ENSP00000300134.

Chemistry databases

BindingDBiP42226.

Structurei

Secondary structure

1847
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi132 – 147Combined sources16
Helixi148 – 150Combined sources3
Helixi186 – 211Combined sources26
Turni212 – 214Combined sources3
Helixi222 – 241Combined sources20
Beta strandi244 – 246Combined sources3
Helixi256 – 271Combined sources16
Beta strandi272 – 277Combined sources6
Beta strandi281 – 284Combined sources4
Beta strandi288 – 295Combined sources8
Helixi298 – 301Combined sources4
Beta strandi310 – 316Combined sources7
Turni318 – 321Combined sources4
Beta strandi340 – 342Combined sources3
Beta strandi344 – 346Combined sources3
Beta strandi348 – 350Combined sources3
Turni351 – 354Combined sources4
Beta strandi355 – 365Combined sources11
Helixi379 – 381Combined sources3
Beta strandi384 – 392Combined sources9
Beta strandi401 – 406Combined sources6
Beta strandi410 – 413Combined sources4
Beta strandi415 – 417Combined sources3
Helixi420 – 431Combined sources12
Beta strandi444 – 447Combined sources4
Helixi448 – 463Combined sources16
Helixi471 – 482Combined sources12
Turni489 – 494Combined sources6
Beta strandi496 – 498Combined sources3
Helixi499 – 503Combined sources5
Beta strandi510 – 512Combined sources3
Helixi514 – 528Combined sources15
Helixi530 – 534Combined sources5
Helixi544 – 551Combined sources8
Beta strandi558 – 563Combined sources6
Beta strandi565 – 569Combined sources5
Beta strandi571 – 578Combined sources8
Beta strandi584 – 589Combined sources6
Helixi594 – 599Combined sources6
Helixi602 – 607Combined sources6
Turni616 – 618Combined sources3
Helixi621 – 624Combined sources4
Turni625 – 628Combined sources4
Beta strandi638 – 640Combined sources3
Beta strandi644 – 650Combined sources7
Helixi799 – 807Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1OJ5X-ray2.20B795-808[»]
4Y5UX-ray2.71A/B113-658[»]
4Y5WX-ray3.10A/B/C/D113-658[»]
5D39X-ray3.20A/B/C/D123-658[»]
ProteinModelPortaliP42226.
SMRiP42226.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42226.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini517 – 632SH2PROSITE-ProRule annotationAdd BLAST116

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi802 – 806LXXLL motif5

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.
HOGENOMiHOG000230988.
HOVERGENiHBG107486.
InParanoidiP42226.
KOiK11225.
OMAiKFQAGVR.
OrthoDBiEOG091G03O3.
PhylomeDBiP42226.
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.
IPR028187. STAT6_C.
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.
PF14596. STAT6_C. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTiSM00252. SH2. 1 hit.
SM00964. 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: P42226-1) [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
MSLWGLVSKM PPEKVQRLYV DFPQHLRHLL GDWLESQPWE FLVGSDAFCC
60 70 80 90 100
NLASALLSDT VQHLQASVGE QGEGSTILQH ISTLESIYQR DPLKLVATFR
110 120 130 140 150
QILQGEKKAV MEQFRHLPMP FHWKQEELKF KTGLRRLQHR VGEIHLLREA
160 170 180 190 200
LQKGAEAGQV SLHSLIETPA NGTGPSEALA MLLQETTGEL EAAKALVLKR
210 220 230 240 250
IQIWKRQQQL AGNGAPFEES LAPLQERCES LVDIYSQLQQ EVGAAGGELE
260 270 280 290 300
PKTRASLTGR LDEVLRTLVT SCFLVEKQPP QVLKTQTKFQ AGVRFLLGLR
310 320 330 340 350
FLGAPAKPPL VRADMVTEKQ ARELSVPQGP GAGAESTGEI INNTVPLENS
360 370 380 390 400
IPGNCCSALF KNLLLKKIKR CERKGTESVT EEKCAVLFSA SFTLGPGKLP
410 420 430 440 450
IQLQALSLPL VVIVHGNQDN NAKATILWDN AFSEMDRVPF VVAERVPWEK
460 470 480 490 500
MCETLNLKFM AEVGTNRGLL PEHFLFLAQK IFNDNSLSME AFQHRSVSWS
510 520 530 540 550
QFNKEILLGR GFTFWQWFDG VLDLTKRCLR SYWSDRLIIG FISKQYVTSL
560 570 580 590 600
LLNEPDGTFL LRFSDSEIGG ITIAHVIRGQ DGSPQIENIQ PFSAKDLSIR
610 620 630 640 650
SLGDRIRDLA QLKNLYPKKP KDEAFRSHYK PEQMGKDGRG YVPATIKMTV
660 670 680 690 700
ERDQPLPTPE LQMPTMVPSY DLGMAPDSSM SMQLGPDMVP QVYPPHSHSI
710 720 730 740 750
PPYQGLSPEE SVNVLSAFQE PHLQMPPSLG QMSLPFDQPH PQGLLPCQPQ
760 770 780 790 800
EHAVSSPDPL LCSDVTMVED SCLSQPVTAF PQGTWIGEDI FPPLLPPTEQ
810 820 830 840
DLTKLLLEGQ GESGGGSLGA QPLLQPSHYG QSGISMSHMD LRANPSW
Length:847
Mass (Da):94,135
Last modified:November 1, 1995 - v1
Checksum:iF35075F1C1F2A677
GO
Isoform 2 (identifier: P42226-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-174: Missing.
     175-177: PSE → MEQ

Show »
Length:673
Mass (Da):74,456
Checksum:i7A050ADF43A669BB
GO
Isoform 3 (identifier: P42226-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-110: Missing.

Note: No experimental confirmation available.
Show »
Length:737
Mass (Da):81,748
Checksum:i8A076ABC6053A831
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti149E → Q in AAC67525 (PubMed:9782085).Curated1
Sequence conflicti246G → D in BAH14513 (PubMed:14702039).Curated1
Sequence conflicti733S → N in AAC67525 (PubMed:9782085).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_013094181M → R.1 PublicationCorresponds to variant rs3024952dbSNPEnsembl.1
Natural variantiVAR_059812419D → N.Corresponds to variant rs11172102dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0318711 – 174Missing in isoform 2. 1 PublicationAdd BLAST174
Alternative sequenceiVSP_0452821 – 110Missing in isoform 3. 1 PublicationAdd BLAST110
Alternative sequenceiVSP_031872175 – 177PSE → MEQ in isoform 2. 1 Publication3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16031 mRNA. Translation: AAA57193.1.
AF067575, AF067572, AF067573 Genomic DNA. Translation: AAC67525.1.
AB103089 mRNA. Translation: BAD89432.1.
AK290431 mRNA. Translation: BAF83120.1.
AK316142 mRNA. Translation: BAH14513.1.
AF417842 Genomic DNA. Translation: AAL06595.1.
AC023237 Genomic DNA. No translation available.
BC075852 mRNA. Translation: AAH75852.1.
CCDSiCCDS53804.1. [P42226-3]
CCDS8931.1. [P42226-1]
PIRiA54740.
RefSeqiNP_001171549.1. NM_001178078.1. [P42226-1]
NP_001171550.1. NM_001178079.1. [P42226-1]
NP_001171551.1. NM_001178080.1. [P42226-3]
NP_003144.3. NM_003153.4. [P42226-1]
XP_006719638.1. XM_006719575.2. [P42226-1]
UniGeneiHs.524518.

Genome annotation databases

EnsembliENST00000300134; ENSP00000300134; ENSG00000166888. [P42226-1]
ENST00000454075; ENSP00000401486; ENSG00000166888. [P42226-1]
ENST00000537215; ENSP00000444530; ENSG00000166888. [P42226-3]
ENST00000538913; ENSP00000445409; ENSG00000166888. [P42226-3]
ENST00000543873; ENSP00000438451; ENSG00000166888. [P42226-1]
ENST00000556155; ENSP00000451742; ENSG00000166888. [P42226-1]
GeneIDi6778.
KEGGihsa:6778.
UCSCiuc001sna.5. human. [P42226-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16031 mRNA. Translation: AAA57193.1.
AF067575, AF067572, AF067573 Genomic DNA. Translation: AAC67525.1.
AB103089 mRNA. Translation: BAD89432.1.
AK290431 mRNA. Translation: BAF83120.1.
AK316142 mRNA. Translation: BAH14513.1.
AF417842 Genomic DNA. Translation: AAL06595.1.
AC023237 Genomic DNA. No translation available.
BC075852 mRNA. Translation: AAH75852.1.
CCDSiCCDS53804.1. [P42226-3]
CCDS8931.1. [P42226-1]
PIRiA54740.
RefSeqiNP_001171549.1. NM_001178078.1. [P42226-1]
NP_001171550.1. NM_001178079.1. [P42226-1]
NP_001171551.1. NM_001178080.1. [P42226-3]
NP_003144.3. NM_003153.4. [P42226-1]
XP_006719638.1. XM_006719575.2. [P42226-1]
UniGeneiHs.524518.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1OJ5X-ray2.20B795-808[»]
4Y5UX-ray2.71A/B113-658[»]
4Y5WX-ray3.10A/B/C/D113-658[»]
5D39X-ray3.20A/B/C/D123-658[»]
ProteinModelPortaliP42226.
SMRiP42226.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112655. 61 interactors.
DIPiDIP-39855N.
IntActiP42226. 34 interactors.
MINTiMINT-8020389.
STRINGi9606.ENSP00000300134.

Chemistry databases

BindingDBiP42226.
ChEMBLiCHEMBL5401.

PTM databases

iPTMnetiP42226.
PhosphoSitePlusiP42226.

Polymorphism and mutation databases

BioMutaiSTAT6.
DMDMi1174459.

Proteomic databases

EPDiP42226.
MaxQBiP42226.
PaxDbiP42226.
PeptideAtlasiP42226.
PRIDEiP42226.

Protocols and materials databases

DNASUi6778.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300134; ENSP00000300134; ENSG00000166888. [P42226-1]
ENST00000454075; ENSP00000401486; ENSG00000166888. [P42226-1]
ENST00000537215; ENSP00000444530; ENSG00000166888. [P42226-3]
ENST00000538913; ENSP00000445409; ENSG00000166888. [P42226-3]
ENST00000543873; ENSP00000438451; ENSG00000166888. [P42226-1]
ENST00000556155; ENSP00000451742; ENSG00000166888. [P42226-1]
GeneIDi6778.
KEGGihsa:6778.
UCSCiuc001sna.5. human. [P42226-1]

Organism-specific databases

CTDi6778.
DisGeNETi6778.
GeneCardsiSTAT6.
HGNCiHGNC:11368. STAT6.
HPAiHPA001861.
MalaCardsiSTAT6.
MIMi601512. gene.
neXtProtiNX_P42226.
OpenTargetsiENSG00000166888.
Orphaneti2126. Solitary fibrous tumor.
PharmGKBiPA339.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3667. Eukaryota.
ENOG410XPN8. LUCA.
GeneTreeiENSGT00760000119236.
HOGENOMiHOG000230988.
HOVERGENiHBG107486.
InParanoidiP42226.
KOiK11225.
OMAiKFQAGVR.
OrthoDBiEOG091G03O3.
PhylomeDBiP42226.
TreeFamiTF318648.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166888-MONOMER.
ReactomeiR-HSA-186763. Downstream signal transduction.
R-HSA-3249367. STAT6-mediated induction of chemokines.
SignaLinkiP42226.
SIGNORiP42226.

Miscellaneous databases

ChiTaRSiSTAT6. human.
EvolutionaryTraceiP42226.
GeneWikiiSTAT6.
GenomeRNAii6778.
PROiP42226.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166888.
CleanExiHS_STAT6.
ExpressionAtlasiP42226. baseline and differential.
GenevisibleiP42226. 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.
IPR028187. STAT6_C.
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.
PF14596. STAT6_C. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTiSM00252. SH2. 1 hit.
SM00964. 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 nameiSTAT6_HUMAN
AccessioniPrimary (citable) accession number: P42226
Secondary accession number(s): A8K316
, B7ZA27, F5GXI9, Q5FBW5, Q71UP4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 172 of the entry and version 1 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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.