Reviewed, UniProtKB/Swiss-Prot P42226 (STAT6_HUMAN)

Names and origin

Protein names

Recommended name:
    Signal transducer and activator of transcription 6
Alternative name(s):
    IL-4 Stat

Gene names

Name:

STAT6

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	847 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Carries out a dual function: signal transduction and activation of transcription. Involved in interleukin-4 signalling.
Subunit structure	Forms a homodimer or a heterodimer with a related family member By similarity. Interacts with NCOA1 via its C-terminal LXXLL motif.
Subcellular location	Cytoplasm. Nucleus. Note: Translocated into the nucleus in response to phosphorylation.
Post-translational modification	Tyrosine phosphorylated following stimulation by IL-4 and IL-3 By similarity.
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct signal transducer activity Inferred from electronic annotation. Source: InterPro transcription factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NMI	Q13287	1	EBI-1186478,EBI-372942

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P42226-1)

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.

Isoform 2 (identifier: P42226-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 847

847

Signal transducer and activator of transcription 6

PRO_0000182433

Regions

Domain

517 – 632

116

SH2

Motif

802 – 806

5

LXXLL motif

Amino acid modifications

Modified residue

641

1

Phosphotyrosine; by JAK By similarity

Natural variations

Alternative sequence

1 – 174

174

Missing in isoform 2.

VSP_031871

Alternative sequence

175 – 177

3

PSE → MEQ in isoform 2.

VSP_031872

Natural variant

181

1

M → R: dbSNP rs3024952. Ref.5

VAR_013094

Natural variant

419

1

D → N: dbSNP rs11172102.

VAR_059812

Experimental info

Mutagenesis

802

1

L → A: Abolishes the interaction with NCOA1; when associated with A-805. Ref.7

Mutagenesis

805

1

L → A: Abolishes the interaction with NCOA1; when associated with A-802. Ref.7

Sequence conflict

149

1

E → Q in AAC67525. Ref.2

Sequence conflict

733

1

S → N in AAC67525. Ref.2

Secondary structure

1

.

.

.

847

Helix Strand Turn

Details...

Helix

799 – 807

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: F35075F1C1F2A677	FASTA	847	94,135
	10 20 30 40 50 60 MSLWGLVSKM PPEKVQRLYV DFPQHLRHLL GDWLESQPWE FLVGSDAFCC NLASALLSDT 70 80 90 100 110 120 VQHLQASVGE QGEGSTILQH ISTLESIYQR DPLKLVATFR QILQGEKKAV MEQFRHLPMP 130 140 150 160 170 180 FHWKQEELKF KTGLRRLQHR VGEIHLLREA LQKGAEAGQV SLHSLIETPA NGTGPSEALA 190 200 210 220 230 240 MLLQETTGEL EAAKALVLKR IQIWKRQQQL AGNGAPFEES LAPLQERCES LVDIYSQLQQ 250 260 270 280 290 300 EVGAAGGELE PKTRASLTGR LDEVLRTLVT SCFLVEKQPP QVLKTQTKFQ AGVRFLLGLR 310 320 330 340 350 360 FLGAPAKPPL VRADMVTEKQ ARELSVPQGP GAGAESTGEI INNTVPLENS IPGNCCSALF 370 380 390 400 410 420 KNLLLKKIKR CERKGTESVT EEKCAVLFSA SFTLGPGKLP IQLQALSLPL VVIVHGNQDN 430 440 450 460 470 480 NAKATILWDN AFSEMDRVPF VVAERVPWEK MCETLNLKFM AEVGTNRGLL PEHFLFLAQK 490 500 510 520 530 540 IFNDNSLSME AFQHRSVSWS QFNKEILLGR GFTFWQWFDG VLDLTKRCLR SYWSDRLIIG 550 560 570 580 590 600 FISKQYVTSL LLNEPDGTFL LRFSDSEIGG ITIAHVIRGQ DGSPQIENIQ PFSAKDLSIR 610 620 630 640 650 660 SLGDRIRDLA QLKNLYPKKP KDEAFRSHYK PEQMGKDGRG YVPATIKMTV ERDQPLPTPE 670 680 690 700 710 720 LQMPTMVPSY DLGMAPDSSM SMQLGPDMVP QVYPPHSHSI PPYQGLSPEE SVNVLSAFQE 730 740 750 760 770 780 PHLQMPPSLG QMSLPFDQPH PQGLLPCQPQ EHAVSSPDPL LCSDVTMVED SCLSQPVTAF 790 800 810 820 830 840 PQGTWIGEDI FPPLLPPTEQ DLTKLLLEGQ GESGGGSLGA QPLLQPSHYG QSGISMSHMD LRANPSW
	Isoform 2. Checksum: 7A050ADF43A669BB	FASTA	673	74,456
	10 20 30 40 50 60 MEQALAMLLQ ETTGELEAAK ALVLKRIQIW KRQQQLAGNG APFEESLAPL QERCESLVDI 70 80 90 100 110 120 YSQLQQEVGA AGGELEPKTR ASLTGRLDEV LRTLVTSCFL VEKQPPQVLK TQTKFQAGVR 130 140 150 160 170 180 FLLGLRFLGA PAKPPLVRAD MVTEKQAREL SVPQGPGAGA ESTGEIINNT VPLENSIPGN 190 200 210 220 230 240 CCSALFKNLL LKKIKRCERK GTESVTEEKC AVLFSASFTL GPGKLPIQLQ ALSLPLVVIV 250 260 270 280 290 300 HGNQDNNAKA TILWDNAFSE MDRVPFVVAE RVPWEKMCET LNLKFMAEVG TNRGLLPEHF 310 320 330 340 350 360 LFLAQKIFND NSLSMEAFQH RSVSWSQFNK EILLGRGFTF WQWFDGVLDL TKRCLRSYWS 370 380 390 400 410 420 DRLIIGFISK QYVTSLLLNE PDGTFLLRFS DSEIGGITIA HVIRGQDGSP QIENIQPFSA 430 440 450 460 470 480 KDLSIRSLGD RIRDLAQLKN LYPKKPKDEA FRSHYKPEQM GKDGRGYVPA TIKMTVERDQ 490 500 510 520 530 540 PLPTPELQMP TMVPSYDLGM APDSSMSMQL GPDMVPQVYP PHSHSIPPYQ GLSPEESVNV 550 560 570 580 590 600 LSAFQEPHLQ MPPSLGQMSL PFDQPHPQGL LPCQPQEHAV SSPDPLLCSD VTMVEDSCLS 610 620 630 640 650 660 QPVTAFPQGT WIGEDIFPPL LPPTEQDLTK LLLEGQGESG GGSLGAQPLL QPSHYGQSGI 670 SMSHMDLRAN PSW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An interleukin-4-induced transcription factor: IL-4 Stat." Hou J., Schindler U., Henzel W.J., Ho T., Brasseur M., McKnight S.L. Science 265:1701-1706(1994) [PubMed: 8085155] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Localization of the human stat6 gene to chromosome 12q13.3-q14.1, a region implicated in multiple solid tumors." Patel B.K., Keck C.L., O'Leary R.S., Popescu N.C., LaRochelle W.J. Genomics 52:192-200(1998) [PubMed: 9782085] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"STAT6 mRNA, nirs splice variant 2." Tabata Y., Sameshima E., Hayashi A., Iida K., Mitsuyama M., Kanai S., Furuya T., Saito T. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	SeattleSNPs variation discovery resource Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-181.
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[7]	"An LXXLL motif in the transactivation domain of STAT6 mediates recruitment of NCoA-1/SRC-1." Litterst C.M., Pfitzner E. J. Biol. Chem. 277:36052-36060(2002) [PubMed: 12138096] [Abstract] Cited for: INTERACTION WITH NCOA1, MUTAGENESIS OF LEU-802 AND LEU-805.
[8]	"Structure of the NCoA-1/SRC-1 PAS-B domain bound to the LXXLL motif of the STAT6 transactivation domain." Razeto A., Ramakrishnan V., Litterst C.M., Giller K., Griesinger C., Carlomagno T., Lakomek N., Heimburg T., Lodrini M., Pfitzner E., Becker S. J. Mol. Biol. 336:319-329(2004) [PubMed: 14757047] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 795-808 IN COMPLEX WITH 257-385 OF NCOA1.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

U16031 mRNA. Translation: AAA57193.1.
AF067575, AF067572, AF067573 Genomic DNA. Translation: AAC67525.1.
AB103089 mRNA. Translation: BAD89432.1.
AK290431 mRNA. Translation: BAF83120.1.
AF417842 Genomic DNA. Translation: AAL06595.1.
BC075852 mRNA. Translation: AAH75852.1.

IPI

IPI00030782.
IPI00792907.

PIR

A54740.

RefSeq

NP_003144.3.

UniGene

Hs.524518

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OJ5	X-ray	2.20	B	795-808	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P42226. 1 interaction.

STRING

P42226.

PTM databases

PhosphoSite

P42226.

Proteomic databases

PRIDE

P42226.

Genome annotation databases

Ensembl

ENST00000300134; ENSP00000300134; ENSG00000166888; Homo sapiens. [Genome view]

GeneID

6778.

KEGG

hsa:6778.

UCSC

uc001sna.1. human.

Organism-specific databases

CTD

6778.

GeneCards

GC12M055775.

H-InvDB

HIX0036673.

HGNC

HGNC:11368. STAT6.

HPA

CAB002613.
HPA001861.

MIM

601512. gene.

PharmGKB

PA339.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P42226.

HOVERGEN

P42226.

OMA

QTKFQAG

OrthoDB

EOG9RZ1KR

Enzyme and pathway databases

Pathway_Interaction_DB

il12_2pathway. IL12-mediated signaling events.
il4_2pathway. IL4-mediated signaling events.

Reactome

REACT_16888. Signaling by PDGF.

Gene expression databases

ArrayExpress

P42226.

Bgee

P42226.

CleanEx

HS_STAT6.

Genevestigator

P42226.

GermOnline

ENSG00000166888. Homo sapiens.

Family and domain databases

InterPro

IPR011992. EF-Hand_type.
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]

Gene3D

G3DSA:1.10.238.10. EF-Hand_type. 1 hit.
G3DSA:3.30.505.10. SH2. 1 hit.
G3DSA:1.20.1050.20. STAT_alpha. 1 hit.
G3DSA:2.60.40.630. STAT_DNA_bd_sub. 1 hit.
G3DSA:1.10.532.10. STAT_protein_interaction. 1 hit.

PANTHER

PTHR11801. STAT. 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.
[Graphical view]

PROSITE

PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

26458.

SOURCE

Search...

Entry information

Entry name

STAT6_HUMAN

Accession

Primary (citable) accession number: P42226
Secondary accession number(s): A8K316, Q5FBW5, Q71UP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	November 24, 2009
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.