P42224

PTMD Annotation Information

※ Protein Information

Tag Content
UniProt Accession STAT1_HUMAN; P42224;
Entrez ID 6772
GenBank Protein ID NM_007315.3; NM_139266.2; XM_006712718.1;
GenBank Nucleotide ID NP_009330.1; NP_644671.1; XP_006712781.1;
Protein Name Signal transducer and activator of transcription 1-alpha/beta (Transcription factor ISGF-3 components p91/p84)
Gene Name STAT1
Organism Homo sapiens
NCBI Taxa ID 9606
Functional DescriptionSignal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus (PubMed:28753426). ISGF3 b(view all)
Sequence
(Fasta)		MSQWYELQQL DSKFLEQVHQ LYDDSFPMEI RQYLAQWLEK QDWEHAANDV SFATIRFHDL 60
LSQLDDQYSR FSLENNFLLQ HNIRKSKRNL QDNFQEDPIQ MSMIIYSCLK EERKILENAQ 120
RFNQAQSGNI QSTVMLDKQK ELDSKVRNVK DKVMCIEHEI KSLEDLQDEY DFKCKTLQNR 180
EHETNGVAKS DQKQEQLLLK KMYLMLDNKR KEVVHKIIEL LNVTELTQNA LINDELVEWK 240
RRQQSACIGG PPNACLDQLQ NWFTIVAESL QQVRQQLKKL EELEQKYTYE HDPITKNKQV 300
LWDRTFSLFQ QLIQSSFVVE RQPCMPTHPQ RPLVLKTGVQ FTVKLRLLVK LQELNYNLKV 360
KVLFDKDVNE RNTVKGFRKF NILGTHTKVM NMEESTNGSL AAEFRHLQLK EQKNAGTRTN 420
EGPLIVTEEL HSLSFETQLC QPGLVIDLET TSLPVVVISN VSQLPSGWAS ILWYNMLVAE 480
PRNLSFFLTP PCARWAQLSE VLSWQFSSVT KRGLNVDQLN MLGEKLLGPN ASPDGLIPWT 540
RFCKENINDK NFPFWLWIES ILELIKKHLL PLWNDGCIMG FISKERERAL LKDQQPGTFL 600
LRFSESSREG AITFTWVERS QNGGEPDFHA VEPYTKKELS AVTFPDIIRN YKVMAAENIP 660
ENPLKYLYPN IDKDHAFGKY YSRPKEAPEP MELDGPKGTG YIKTELISVS EVHPSRLQTT 720
DNLLPMSPEE FDEVSRIVGS VEFDSMMNTV 751

※ PTM-Disease Association

NumPTMDiseaseCell TypeTypePTM SitePMID
1PhosphorylationLymphomaD12421984
[Reference]: SSG enhanced IFN-alpha-induced Stat1 tyrosine phosphorylation, inactivated intracellular SHP-1 and SHP-2 that negatively regulate IFN signaling, and induced cellular protein tyrosine phosphorylation in cancer cell lines.
2PhosphorylationMelanomaD12421984
[Reference]: SSG enhanced IFN-alpha-induced Stat1 tyrosine phosphorylation, inactivated intracellular SHP-1 and SHP-2 that negatively regulate IFN signaling, and induced cellular protein tyrosine phosphorylation in cancer cell lines.
3PhosphorylationChronic mucocutaneous candidiasis diseaseN21727188
[Reference]: All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance.
4PhosphorylationOral squamous cell carcinomaP23992782
[Reference]: for the group of patients who received adjuvant chemotherapy, increased PSTAT1 intensity of staining in OSCC tumors was strongly associated with better overall survival (P = .008)
5PhosphorylationNeuroblastomaP14982729
[Reference]: In NB41A3 neuroblastoma cells, IFN-gamma was found to induce the signal transducer and activator of transcription (STAT) STAT1 phosphorylation, interferon regulatory factor (IRF)-1 expression, and p42/p44 mitogen-activated protein kinase (MAPK) phosphorylation; MAPK, however, was not required for inhibition of viral replication.
6PhosphorylationEpidermoid carcinomaA431 cell lineP23178573
[Reference]: p38 MAP kinase enhances EGF-induced apoptosis in A431 carcinoma cells by promoting tyrosine phosphorylation of STAT1
7PhosphorylationChronic lymphocytic leukemiaU23936412
[Reference]: LL cells with CTLA4 down-regulation demonstrated a significant increase in proliferation and survival along with an increased expression of STAT1, STAT1 phosphorylation, NFATC2, c-Fos phosphorylation, c-Myc, Ki-67 and Bcl-2 molecules
8Tyrosine PhosphorylationMelanomaDY70117785551
[Reference]: Significant variability in P-STAT1 was observed in human melanoma cell lines following IFN-alpha treatment (P < 0.05) and IFN-alpha-induced P-STAT1 correlated with the antiproliferative effects of IFN-alpha (P = 0.042).
9Tyrosine PhosphorylationBreast cancer/tumor/carcinomaUY70124058806
[Reference]: In contrast to normal untransformed mammary cells STAT1 has been implicated in breast cancer development based on the observation that STAT1 Y701 phosphorylation is elevated in human breast tumors
10Serine PhosphorylationNephroblastomaUS72716799645
[Reference]: Accordingly, we evaluated STAT phosphorylation patterns in tumors and found that STAT1 was constitutively phosphorylated on serine 727 (S727) in 19 of 21 primary WT samples and two WT cell lines.

※ Disease Cross-ref Annotation

DatabaseAnnotation
CTD (Curated)
(count: 14)
(view all)		MESH:D001169 ; Arthritis, Experimental
MESH:D001172 ; Arthritis, Rheumatoid
MESH:D002178 ; Candidiasis, Chronic Mucocutaneous
MESH:D006528 ; Carcinoma, Hepatocellular
MESH:D003586 ; Cytomegalovirus Infections
MESH:D018450 ; Disease Progression
HGMD
(count: 7)
(view all)		CD030619; Impaired mycobacterial immunity; Small deletions
CI067915; Impaired mycobacterial immunity; Small insertions
CM064291; Impaired mycobacterial immunity; Missense/nonsense
CM064290; Impaired mycobacterial immunity; Missense/nonsense
CM030523; Impaired mycobacterial immunity; Missense/nonsense
CM012192; Impaired mycobacterial immunity; Missense/nonsense
GWASdb
(count: 4)		rs6734110; Acute lung injury; lung disease
rs2280232; Blood pressure; hypertension
rs12693591; Cognitive impairment induced by topiramate; cognitive disorder
rs41382444; Primary biliary cirrhosis; primary biliary cirrhosis

※ PTM Sites

PTM Modification Sites
Phosphorylation
(count: 17)
(view all)		 106       IQMSMIIYSCLKEER     dbPAF
162       CIEHEIKSLEDLQDE     dbPAF
170       LEDLQDEYDFKCKTL     dbPAF
184       LQNREHETNGVAKSD     dbPAF
2         ******MSQWYELQQ     dbPAF
203       QLLLKKMYLMLDNKR     dbPAF
Acetylation
(count: 10)
(view all)		 152       KVRNVKDKVMCIEHE     PLMD
173       LQDEYDFKCKTLQNR     PLMD
200       KQEQLLLKKMYLMLD     PLMD
201       QEQLLLKKMYLMLDN     PLMD
209       MYLMLDNKRKEVVHK     PLMD
296       YEHDPITKNKQVLWD     PLMD
Ubiquitination
(count: 21)
(view all)		 114       SCLKEERKILENAQR     PLMD
138       QSTVMLDKQKELDSK     PLMD
152       KVRNVKDKVMCIEHE     PLMD
173       LQDEYDFKCKTLQNR     PLMD
193       GVAKSDQKQEQLLLK     PLMD
201       QEQLLLKKMYLMLDN     PLMD
Sumoylation
(count: 6)		 114       SCLKEERKILENAQR     PLMD
193       GVAKSDQKQEQLLLK     PLMD
636       HAVEPYTKKELSAVT     PLMD
652       PDIIRNYKVMAAENI     PLMD
679       DKDHAFGKYYSRPKE     PLMD
703       PKGTGYIKTELISVS     PLMD
Glycation
(count: 2)		 511       WQFSSVTKRGLNVDQ     PLMD
525       QLNMLGEKLLGPNAS     PLMD
Malonylation
(count: 8)
(view all)		 173       LQDEYDFKCKTLQNR     PLMD
193       GVAKSDQKQEQLLLK     PLMD
200       KQEQLLLKKMYLMLD     PLMD
201       QEQLLLKKMYLMLDN     PLMD
296       YEHDPITKNKQVLWD     PLMD
361       LNYNLKVKVLFDKDV     PLMD

※ Protein-Protein Interaction

NetworkInteraction
ABSource
E7ENZ3P42224MINT
E7ESA6P42224HPRD
E9PFC7P42224HPRD
E9PLM6P42224HPRD
G3V1V9P42224HPRD
H7C2I1P42224HPRD
O14980P42224HPRD
O43707P42224IntAct
O60231P42224MINT
O60674P42224HPRD
O60684P42224HPRD
O75365P42224IntAct
O75582P42224HPRD
O75925P42224HPRD
P00533P42224HPRD
P01100P42224HPRD
P01889P42224IntAct
P03255P42224MINT
P03901P42224IntAct
P04626P42224MINT
P05412P42224HPRD
P06239P42224HPRD
P06241P42224HPRD
P08238P42224IntAct
P09619P42224HPRD
P10721P42224HPRD
P10914P42224HPRD
P12931P42224HPRD
P14136P42224IntAct
P14316P42224HPRD
P14784P42224HPRD
P15260P42224HPRD; DIP
P16234P42224HPRD
P16435P42224IntAct
P17706P42224HPRD
P17948P42224HPRD
P19438P42224HPRD
P19525P42224HPRD
P19793P42224IntAct
P20333P42224HPRD
P22455P42224HPRD
P22607P42224HPRD
P23458P42224HPRD
P25205P42224HPRD
P25791P42224HPRD; IntAct; MINT
P29597P42224HPRD
P31749P42224HPRD
P31785P42224HPRD
P32121P42224IntAct
P32246P42224HPRD
P32927P42224HPRD
P33992P42224HPRD
P35368P42224HPRD
P35968P42224HPRD
P40763P42224HPRD
P42224P42224HPRD; DIP
P42224P42229HPRD
P42224P43405HPRD
P42224P48551HPRD
P42224P51452HPRD
P42224P51681HPRD
P42224P51692HPRD
P42224P51813HPRD
P42224P52294HPRD
P42224P52630HPRD; IntAct
P42224P55060HPRD
P42224P59826IntAct
P42224P61073HPRD
P42224P63000HPRD
P42224P63244HPRD
P42224P63279HPRD
P42224P78347HPRD
P42224Q00597HPRD
P42224Q00613HPRD
P42224Q00978HPRD; IntAct
P42224Q01082IntAct
P42224Q01094IntAct
P42224Q04206HPRD
P42224Q05655HPRD
P42224Q06124HPRD
P42224Q09472HPRD
P42224Q13158HPRD
P42224Q13287HPRD; IntAct
P42224Q13555HPRD
P42224Q13557HPRD
P42224Q13813IntAct
P42224Q14203IntAct
P42224Q15155IntAct
P42224Q15628HPRD
P42224Q16531IntAct
P42224Q16539HPRD
P42224Q16836IntAct
P42224Q4LE28HPRD
P42224Q5JPE7IntAct
P42224Q6EEV6HPRD
P42224Q6IA86HPRD
P42224Q6UWB1HPRD
P42224Q7Z7K2HPRD
P42224Q8N9N8HPRD; IntAct; MINT
P42224Q969M7IntAct
P42224Q96EY1IntAct
P42224Q9NRW4MINT
P42224Q9Y2Q3IntAct
P42224Q9Y566IntAct