P61635 (STAT3_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Signal transducer and activator of transcription 3

Gene names

Name:

STAT3

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	770 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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. Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation. Interacts with ARL2BP; interaction is enhanced with ARL2. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 expression By similarity. Interacts with NEK6. Binds to CDK9 when activated and nuclear By similarity. Interacts with BMX By similarity. Interacts with ZIPK/DAPK3 By similarity. Identified in a complex with LYN and PAG1 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.
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 By similarity. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3.
Post-translational modification	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. 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 astrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB 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 positive regulation of Notch signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB 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 transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB sexual reproduction Inferred from sequence or structural similarity. Source: UniProtKB temperature homeostasis Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	DNA binding Inferred from sequence or structural similarity. Source: UniProtKB calcium ion binding Inferred from electronic annotation. Source: InterPro 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 transcription factor activity Inferred from electronic annotation. Source: InterPro signal transducer activity Inferred from electronic annotation. Source: InterPro
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_0000182416
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)
	P61635 [UniParc]. Last modified June 7, 2004. Version 1. Checksum: 9CEB147C73E83274	FASTA	770	87,975
	10 20 30 40 50 60 MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQLLAPWIES QDWAYAASKE SHATLVFHNL 70 80 90 100 110 120 LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME IARIVARCLW EESRLLQTAA 130 140 150 160 170 180 TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD VRKRVQDLEQ KMKVVENLLD 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 ELFRNLMKSA 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 KPPGTCLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF AEIIMGYKIM 670 680 690 700 710 720 DATNILVSPL VYLYPDIPKE DAFGKYCRPE SQEHPEADPG SAAPYLKTKF ICVTPTTCSN 730 740 750 760 770 TIDLPMSPRT LDSLMQFGNN GEAAEPSAGG QFESLTFDME LTSECATSPM

References

[1]	"The STAT5B-encoding gene was flipped across the STAT3/STAT5A-locus during ruminant evolution." Seyfert H.M., Wheeler T.T., Moolenaar A., Pitra C. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary gland.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ620655 mRNA. Translation: CAF06182.1.
IPI	IPI00714792.
RefSeq	NP_001012689.2. NM_001012671.2.
UniGene	Bt.15334.
3D structure databases
ProteinModelPortal	P61635.
SMR	P61635. Positions 136-715.
ModBase	Search...
Proteomic databases
PRIDE	P61635.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	508541.
KEGG	bta:508541.
Organism-specific databases
CTD	6774.
Phylogenomic databases
eggNOG	NOG303257.
HOGENOM	HOG000220792.
HOVERGEN	HBG055669.
InParanoid	P61635.
KO	K04692.
OrthoDB	EOG4G4GPS.
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
NextBio	20868564.

Entry information

Entry name

STAT3_BOVIN

Accession

Primary (citable) accession number: P61635

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	June 7, 2004
Last modified:	April 3, 2013
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program