Reviewed, UniProtKB/Swiss-Prot P42224 (STAT1_HUMAN)

Names and origin

Protein names

Recommended name:
    Signal transducer and activator of transcription 1-alpha/beta
Alternative name(s):
    Transcription factor ISGF-3 components p91/p84

Gene names

Name:

STAT1

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

General annotation (Comments)

Function	Signal transducer and activator of transcription that mediates signaling by interferons (IFNs). Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Ref.12 Ref.15 Ref.16 Ref.17
Subunit structure	Isoform alpha homodimerizes upon IFN-gamma induced phosphorylation. Heterodimer with STAT2 upon IFN-alpha/beta induced phosphorylation. Interacts with NMI. Interacts with Sendai virus C', C, Y1 and Y2 proteins, Nipah virus P, V and W proteins, and rabies virus phosphoprotein preventing activation of ISRE and GAS promoter By similarity. Interacts with HCV core protein; the interaction results in STAT1 degradation. Interacts with PIAS1; the interaction requires phosphorylation on Ser-727 and inhibits STAT1 activation.
Subcellular location	Cytoplasm. Nucleus. Note: Translocated into the nucleus in response to IFN-gamma-induced tyrosine phosphorylation and dimerization. Ref.17
Post-translational modification	Phosphorylated on tyrosine and serine residues in response to IFN-alpha, IFN-gamma, PDGF and EGF. Phosphorylation on Tyr-701 (lacking in beta form) by JAK promotes dimerization and subsequent translocation to the nucleus. Phosphorylation on Ser-727 by several kinases including MAPK14, ERK1/2 and CAMKII on IFN-gamma stimulation, regulates STAT1 transcriptional activity. Phosphorylation on Ser-727 promotes sumoylation though increasing interaction with PIAS. Phosphorylation on Ser-727 by PKCdelta induces apoptosis in response to DNA-damaging agents. Ref.17 Ref.9 Ref.10 Ref.11 Ref.19 Ref.20 Ref.21 Ref.23 Sumoylated by SUMO1, SUMO2 and SUMO3. Sumoylation is enhanced by IFN-gamma-induced phosphorylation on Ser-727, and by interaction with PIAS proteins. Enhances the transactivation activity. Ref.15 Ref.16 Ref.19
Involvement in disease	Defects in STAT1 are the cause of STAT1 deficiency [MIM:600555]. Patients generally suffer from mycobacterial or viral diseases. In the case of complete deficiency, patients can die of viral disease. Ref.27 Defects in STAT1 are a cause of mendelian susceptibility to mycobacterial disease (MSMD) [MIM:209950]; also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. Ref.26
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	Antiviral defense Host-virus interaction Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	SH2 domain
Ligand	DNA-binding
Molecular function	Activator
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	I-kappaB kinase/NF-kappaB cascade Traceable author statement. Source: ProtInc activation of caspase activity Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro response to virus Inferred from electronic annotation. Source: UniProtKB-KW transcription from RNA polymerase II promoter Ref.25 Traceable author statement. Source: ProtInc tyrosine phosphorylation of STAT protein Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleolus Inferred from direct assay. Source: HPA
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro hematopoietin/interferon-class (D200-domain) cytokine receptor signal transducer activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: UniProtKB transcription factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LPLUNC3	P59826	1	EBI-1057697,EBI-1055244
NMI	Q13287	1	EBI-1057697,EBI-372942
STAT2	P52630	3	EBI-1057697,EBI-1546963

Alternative products

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

Isoform Alpha (identifier: P42224-1)

Also known as: p91;

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 Beta (identifier: P42224-2)

Also known as: p84;

The sequence of this isoform differs from the canonical sequence as follows:
     713-750: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 750

750

Signal transducer and activator of transcription 1-alpha/beta

PRO_0000182410

Regions

Domain

573 – 670

98

SH2

Amino acid modifications

Modified residue

701

1

Phosphotyrosine; by JAK Ref.10 Ref.23

Modified residue

727

1

Phosphoserine; by MAPK14 Ref.17 Ref.9 Ref.19 Ref.20 Ref.21

Cross-link

703

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15 Ref.16

Natural variations

Alternative sequence

713 – 750

38

Missing in isoform Beta.

VSP_006282

Natural variant

30

1

I → T: dbSNP rs34255470.

VAR_034521

Natural variant

491

1

P → A in a breast cancer sample; somatic mutation. Ref.29

VAR_036001

Natural variant

600

1

L → P in STAT1 deficiency; complete. Ref.27

VAR_018265

Natural variant

706

1

L → S in MSMD; loss of GAF and ISGF3 activation; impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Ref.26

VAR_018266

Experimental info

Mutagenesis

110

1

K → R: Sumoylated. Ref.16

Mutagenesis

701

1

Y → F: No effect on basal sumoylation. Enhances sumoylation in the presence of MAPK stimulation. Ref.19

Mutagenesis

703

1

K → R: Abolishes sumoylation by SUMO1. Increased IFN-gamma-mediated transactivation. Ref.15 Ref.16

Mutagenesis

727

1

S → A: Decreased transcriptional activation. No effect on basal sumoylation. No enhancement of sumoylation on MAPK stimulation. No PKCdelta-induced apoptosis. Ref.17 Ref.19

Mutagenesis

727

1

S → D: No change in enhancement of MAPK-induced sumoylation. Basal interaction with PIAS1. Interaction with PIAS1 increased on MAPK stimulation. Ref.17 Ref.19

Mutagenesis

727

1

S → E: No change in enhancement of MAPK-induced sumoylation. Ref.17 Ref.19

Secondary structure

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750

Helix Strand Turn

Details...

Helix

3 – 7

5

Turn

12 – 14

3

Helix

15 – 19

5

Helix

28 – 33

6

Helix

35 – 40

6

Helix

43 – 46

4

Helix

50 – 74

25

Helix

77 – 94

18

Helix

98 – 117

20

Helix

121 – 125

5

Helix

137 – 179

43

Helix

198 – 247

50

Helix

257 – 286

30

Helix

293 – 316

24

Beta strand

317 – 321

5

Beta strand

334 – 336

3

Beta strand

339 – 347

9

Helix

352 – 354

3

Turn

355 – 357

3

Beta strand

359 – 365

7

Helix

370 – 373

4

Beta strand

374 – 376

3

Beta strand

386 – 389

4

Beta strand

391 – 395

5

Turn

396 – 398

3

Beta strand

399 – 408

10

Beta strand

421 – 425

5

Beta strand

433 – 441

9

Beta strand

444 – 451

8

Beta strand

455 – 460

6

Helix

461 – 463

3

Helix

464 – 477

14

Helix

486 – 488

3

Helix

495 – 509

15

Helix

516 – 526

11

Helix

539 – 543

5

Beta strand

550 – 552

3

Helix

554 – 568

15

Helix

570 – 574

5

Helix

584 – 590

7

Turn

591 – 593

3

Beta strand

601 – 603

3

Beta strand

612 – 616

5

Beta strand

621 – 624

4

Beta strand

629 – 631

3

Helix

636 – 640

5

Helix

644 – 649

6

Beta strand

657 – 659

3

Helix

673 – 677

5

Turn

678 – 680

3

Beta strand

705 – 709

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha (p91) [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 054A813522364BA6	FASTA	750	87,335
	10 20 30 40 50 60 MSQWYELQQL DSKFLEQVHQ LYDDSFPMEI RQYLAQWLEK QDWEHAANDV SFATIRFHDL 70 80 90 100 110 120 LSQLDDQYSR FSLENNFLLQ HNIRKSKRNL QDNFQEDPIQ MSMIIYSCLK EERKILENAQ 130 140 150 160 170 180 RFNQAQSGNI QSTVMLDKQK ELDSKVRNVK DKVMCIEHEI KSLEDLQDEY DFKCKTLQNR 190 200 210 220 230 240 EHETNGVAKS DQKQEQLLLK KMYLMLDNKR KEVVHKIIEL LNVTELTQNA LINDELVEWK 250 260 270 280 290 300 RRQQSACIGG PPNACLDQLQ NWFTIVAESL QQVRQQLKKL EELEQKYTYE HDPITKNKQV 310 320 330 340 350 360 LWDRTFSLFQ QLIQSSFVVE RQPCMPTHPQ RPLVLKTGVQ FTVKLRLLVK LQELNYNLKV 370 380 390 400 410 420 KVLFDKDVNE RNTVKGFRKF NILGTHTKVM NMEESTNGSL AAEFRHLQLK EQKNAGTRTN 430 440 450 460 470 480 EGPLIVTEEL HSLSFETQLC QPGLVIDLET TSLPVVVISN VSQLPSGWAS ILWYNMLVAE 490 500 510 520 530 540 PRNLSFFLTP PCARWAQLSE VLSWQFSSVT KRGLNVDQLN MLGEKLLGPN ASPDGLIPWT 550 560 570 580 590 600 RFCKENINDK NFPFWLWIES ILELIKKHLL PLWNDGCIMG FISKERERAL LKDQQPGTFL 610 620 630 640 650 660 LRFSESSREG AITFTWVERS QNGGEPDFHA VEPYTKKELS AVTFPDIIRN YKVMAAENIP 670 680 690 700 710 720 ENPLKYLYPN IDKDHAFGKY YSRPKEAPEP MELDGPKGTG YIKTELISVS EVHPSRLQTT 730 740 750 DNLLPMSPEE FDEVSRIVGS VEFDSMMNTV
	Isoform Beta (p84). Checksum: 31408601223700BB	FASTA	712	83,043
	10 20 30 40 50 60 MSQWYELQQL DSKFLEQVHQ LYDDSFPMEI RQYLAQWLEK QDWEHAANDV SFATIRFHDL 70 80 90 100 110 120 LSQLDDQYSR FSLENNFLLQ HNIRKSKRNL QDNFQEDPIQ MSMIIYSCLK EERKILENAQ 130 140 150 160 170 180 RFNQAQSGNI QSTVMLDKQK ELDSKVRNVK DKVMCIEHEI KSLEDLQDEY DFKCKTLQNR 190 200 210 220 230 240 EHETNGVAKS DQKQEQLLLK KMYLMLDNKR KEVVHKIIEL LNVTELTQNA LINDELVEWK 250 260 270 280 290 300 RRQQSACIGG PPNACLDQLQ NWFTIVAESL QQVRQQLKKL EELEQKYTYE HDPITKNKQV 310 320 330 340 350 360 LWDRTFSLFQ QLIQSSFVVE RQPCMPTHPQ RPLVLKTGVQ FTVKLRLLVK LQELNYNLKV 370 380 390 400 410 420 KVLFDKDVNE RNTVKGFRKF NILGTHTKVM NMEESTNGSL AAEFRHLQLK EQKNAGTRTN 430 440 450 460 470 480 EGPLIVTEEL HSLSFETQLC QPGLVIDLET TSLPVVVISN VSQLPSGWAS ILWYNMLVAE 490 500 510 520 530 540 PRNLSFFLTP PCARWAQLSE VLSWQFSSVT KRGLNVDQLN MLGEKLLGPN ASPDGLIPWT 550 560 570 580 590 600 RFCKENINDK NFPFWLWIES ILELIKKHLL PLWNDGCIMG FISKERERAL LKDQQPGTFL 610 620 630 640 650 660 LRFSESSREG AITFTWVERS QNGGEPDFHA VEPYTKKELS AVTFPDIIRN YKVMAAENIP 670 680 690 700 710 ENPLKYLYPN IDKDHAFGKY YSRPKEAPEP MELDGPKGTG YIKTELISVS EV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Proteins of transcription factor ISGF-3: one gene encodes the 91- and 84-kDa ISGF-3 proteins that are activated by interferon alpha." Schindler C., Fu X.-Y., Improta T., Aebersold R., Darnell J.E. Jr. Proc. Natl. Acad. Sci. U.S.A. 89:7836-7839(1992) [PubMed: 1502203] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 514-524; 654-660 AND 667-672.
[2]	NIEHS SNPs program Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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 ALPHA). Tissue: Placenta.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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 BETA). Tissue: Brain.
[8]	"The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2." Yan R., Qureshi S., Zhong Z., Wen Z., Darnell J.E. Jr. Nucleic Acids Res. 23:459-463(1995) [PubMed: 7885841] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]	"Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation." Wen Z., Zhong Z., Darnell J.E. Jr. Cell 82:241-250(1995) [PubMed: 7543024] [Abstract] Cited for: PHOSPHORYLATION AT SER-727, MUTAGENESIS.
[10]	"Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor." Quelle F.W., Thierfelder W., Witthuhn B.A., Tang B., Cohen S., Ihle J.N. J. Biol. Chem. 270:20775-20780(1995) [PubMed: 7657660] [Abstract] Cited for: PHOSPHORYLATION AT TYR-701.
[11]	"The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the transduction of IFN-alpha signals." Gupta S., Yan H., Wong L.H., Ralph S., Krolewski J., Schindler C. EMBO J. 15:1075-1084(1996) [PubMed: 8605877] [Abstract] Cited for: TYROSINE PHOSPHORYLATION, HETERODIMERIZATION, DNA-BINDING, MUTAGENESIS.
[12]	"Inhibition of Stat1-mediated gene activation by PIAS1." Liu B., Liao J., Rao X., Kushner S.A., Chung C.D., Chang D.D., Shuai K. Proc. Natl. Acad. Sci. U.S.A. 95:10626-10631(1998) [PubMed: 9724754] [Abstract] Cited for: INTERACTION WITH PIAS1, FUNCTION. Tissue: B-cell.
[13]	"Viral inhibition of interferon signal transduction." Cebulla C.M., Miller D.M., Sedmak D.D. Intervirology 42:325-330(1999) [PubMed: 10702714] [Abstract] Cited for: REVIEW.
[14]	"Sendai virus C protein physically associates with Stat1." Takeuchi K., Komatsu T., Yokoo J., Kato A., Shioda T., Nagai Y., Gotoh B. Genes Cells 6:545-557(2001) [PubMed: 11442634] [Abstract] Cited for: INTERACTION WITH SENDAI VIRUS C PROTEIN.
[15]	"PIAS proteins promote SUMO-1 conjugation to STAT1." Ungureanu D., Vanhatupa S., Kotaja N., Yang J., Aittomaeki S., Jaenne O.A., Palvimo J.J., Silvennoinen O. Blood 102:3311-3313(2003) [PubMed: 12855578] [Abstract] Cited for: SUMOYLATION AT LYS-703, FUNCTION, MUTAGENESIS OF LYS-703.
[16]	"SUMO modification of STAT1 and its role in PIAS-mediated inhibition of gene activation." Rogers R.S., Horvath C.M., Matunis M.J. J. Biol. Chem. 278:30091-30097(2003) [PubMed: 12764129] [Abstract] Cited for: SUMOYLATION AT LYS-703, FUNCTION, MUTAGENESIS OF LYS-110 AND LYS-703.
[17]	"Protein kinase Cdelta regulates apoptosis via activation of STAT1." DeVries T.A., Kalkofen R.L., Matassa A.A., Reyland M.E. J. Biol. Chem. 279:45603-45612(2004) [PubMed: 15322115] [Abstract] Cited for: PHOSPHORYLATION AT SER-727, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-727.
[18]	"Hepatitis C virus expression suppresses interferon signaling by degrading STAT1." Lin W., Choe W.H., Hiasa Y., Kamegaya Y., Blackard J.T., Schmidt E.V., Chung R.T. Gastroenterology 128:1034-1041(2005) [PubMed: 15825084] [Abstract] Cited for: INTERACTION WITH HEPATITIS C VIRUS CORE PROTEIN.
[19]	"MAPK-induced Ser727 phosphorylation promotes SUMOylation of STAT1." Vanhatupa S., Ungureanu D., Paakkunainen M., Silvennoinen O. Biochem. J. 409:179-185(2008) [PubMed: 17897103] [Abstract] Cited for: PHOSPHORYLATION AT SER-727, INTERACTION WITH PIAS1, SUMOYLATION, MUTAGENESIS OF TYR-701 AND SER-727.
[20]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, MASS SPECTROMETRY.
[21]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, MASS SPECTROMETRY.
[22]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[23]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-701, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[24]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, MASS SPECTROMETRY. Tissue: T-cell.
[25]	"Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA." Chen X., Vinkemeier U., Zhao Y., Jeruzalmi D., Darnell J.E. Jr., Kuriyan J. Cell 93:827-839(1998) [PubMed: 9630226] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 136-710.
[26]	"Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation." Dupuis S., Dargemont C., Fieschi C., Thomassin N., Rosenzweig S., Harris J., Holland S.M., Schreiber R.D., Casanova J.-L. Science 293:300-303(2001) [PubMed: 11452125] [Abstract] Cited for: VARIANT MSMD SER-706.
[27]	"Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency." Dupuis S., Jouanguy E., Al-Hajjar S., Fieschi C., Al-Mohsen I.Z., Al-Jumaah S., Yang K., Chapgier A., Eidenschenk C., Eid P., Al-Ghonaium A., Tufenkeji H., Frayha H., Al-Gazlan S., Al-Rayes H., Schreiber R.D., Gresser I., Casanova J.L. Nat. Genet. 33:388-391(2003) [PubMed: 12590259] [Abstract] Cited for: VARIANT STAT1 DEFICIENCY PRO-600.
[28]	"Nipah virus V and W proteins have a common STAT1-binding domain yet inhibit STAT1 activation from the cytoplasmic and nuclear compartments, respectively." Shaw M.L., Garcia-Sastre A., Palese P., Basler C.F. J. Virol. 78:5633-5641(2004) [PubMed: 15140960] [Abstract] Cited for: INTERACTION WITH NIPAH V AND W PROTEINS.
[29]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-491.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

STAT1base

STAT1 mutation db

Wikipedia

STAT1 entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

M97935 mRNA. Translation: AAB64012.1.
M97936 mRNA. No translation available.
AY865620 Genomic DNA. Translation: AAW56072.1.
AK315002 mRNA. Translation: BAG37497.1.
BT007241 mRNA. Translation: AAP35905.1.
AC067945 Genomic DNA. Translation: AAY24183.1.
CH471058 Genomic DNA. Translation: EAX10850.1.
CH471058 Genomic DNA. Translation: EAX10851.1.
BC002704 mRNA. Translation: AAH02704.1.
U18662 Genomic DNA. No translation available.
U18663 Genomic DNA. No translation available.
U18664 Genomic DNA. No translation available.
U18665 Genomic DNA. No translation available.
U18666 Genomic DNA. No translation available.
U18667 Genomic DNA. No translation available.
U18668 Genomic DNA. No translation available.
U18669 Genomic DNA. No translation available.
U18670 Genomic DNA. No translation available.

IPI

IPI00030781.
IPI00218188.

PIR

A46159.

RefSeq

NP_009330.1.
NP_644671.1.

UniGene

Hs.642990

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BF5	X-ray	2.90	A	136-710	[»]
1YVL	X-ray	3.00	A/B	1-683	[»]
2KA6	NMR	-	B	710-750	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:218N.

IntAct

P42224. 11 interactions.

STRING

P42224.

PTM databases

PhosphoSite

P42224.

Proteomic databases

PeptideAtlas

P42224.

PRIDE

P42224.

Genome annotation databases

Ensembl

ENST00000361099; ENSP00000354394; ENSG00000115415; Homo sapiens. [Genome view]
ENST00000409465; ENSP00000386244; ENSG00000115415; Homo sapiens. [Genome view]

GeneID

6772.

KEGG

hsa:6772.

UCSC

uc002usj.2. human.

Organism-specific databases

CTD

6772.

GeneCards

GC02M191542.

H-InvDB

HIX0002682.

HGNC

HGNC:11362. STAT1.

HPA

CAB004049.
HPA000931.
HPA000982.

MIM

209950. phenotype.
600555. gene+phenotype.

Orphanet

748. Mendelian susceptibility to atypical mycobacteria.

PharmGKB

PA36183.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P42224.

HOVERGEN

P42224.

OMA

LVEWKQR

OrthoDB

EOG9V19K9

Enzyme and pathway databases

Pathway_Interaction_DB

epopathway. EPO signaling pathway.
fgf_pathway. FGF signaling pathway.
ifngpathway. IFN-gamma pathway.
il12_2pathway. IL12-mediated signaling events.
il2_1pathway. IL2-mediated signaling events.
il23pathway. IL23-mediated signaling events.
il27pathway. IL27-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
pdgfrbpathway. PDGFR-beta signaling pathway.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_16888. Signaling by PDGF.

Gene expression databases

ArrayExpress

P42224.

Bgee

P42224.

CleanEx

HS_STAT1.

Genevestigator

P42224.

GermOnline

ENSG00000115415. 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

DrugBank

DB01073. Fludarabine.

NextBio

26428.

PMAP-CutDB

P42224.

SOURCE

Search...

Entry information

Entry name

STAT1_HUMAN

Accession

Primary (citable) accession number: P42224
Secondary accession number(s): B2RCA0, Q53S88, Q53XW4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1997
Last modified:	November 24, 2009
This is version 126 of the entry and version 2 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.