SIKE1_HUMAN
ID SIKE1_HUMAN Reviewed; 207 AA.
AC Q9BRV8; Q5TEZ7; Q5TEZ9; Q68DZ4; Q9H778;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Suppressor of IKBKE 1;
DE AltName: Full=Suppressor of IKK-epsilon;
GN Name=SIKE1; Synonyms=SIKE;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Smooth muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Endometrial adenocarcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP IKBKE AND TBK1.
RX PubMed=16281057; DOI=10.1038/sj.emboj.7600863;
RA Huang J., Liu T., Xu L.-G., Chen D., Zhai Z., Shu H.-B.;
RT "SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-
RT triggered IRF-3 activation pathways.";
RL EMBO J. 24:4018-4028(2005).
RN [7]
RP INTERACTION WITH STRP1; STRN3 AND CDC42BPB.
RX PubMed=25743393; DOI=10.1038/ncomms7449;
RA Lant B., Yu B., Goudreault M., Holmyard D., Knight J.D., Xu P., Zhao L.,
RA Chin K., Wallace E., Zhen M., Gingras A.C., Derry W.B.;
RT "CCM-3/STRIPAK promotes seamless tube extension through endocytic
RT recycling.";
RL Nat. Commun. 6:6449-6449(2015).
CC -!- FUNCTION: Physiological suppressor of IKK-epsilon and TBK1 that plays
CC an inhibitory role in virus- and TLR3-triggered IRF3. Inhibits TLR3-
CC mediated activation of interferon-stimulated response elements (ISRE)
CC and the IFN-beta promoter. May act by disrupting the interactions of
CC IKBKE or TBK1 with TICAM1/TRIF, IRF3 and DDX58/RIG-I. Does not inhibit
CC NF-kappa-B activation pathways. {ECO:0000269|PubMed:16281057}.
CC -!- SUBUNIT: Interacts with IKBKE and TBK1 via its coiled coil region.
CC Interaction with TBK1 is disrupted upon viral infection or TLR3
CC stimulation (PubMed:16281057). Interacts with CDC42BPB
CC (PubMed:25743393). {ECO:0000269|PubMed:16281057,
CC ECO:0000269|PubMed:25743393}.
CC -!- INTERACTION:
CC Q9BRV8; O43439-4: CBFA2T2; NbExp=3; IntAct=EBI-1773646, EBI-11954144;
CC Q9BRV8; Q7L2Z9: CENPQ; NbExp=3; IntAct=EBI-1773646, EBI-2350265;
CC Q9BRV8; P78358: CTAG1B; NbExp=3; IntAct=EBI-1773646, EBI-1188472;
CC Q9BRV8; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-1773646, EBI-741158;
CC Q9BRV8; Q9UIL1-3: SCOC; NbExp=3; IntAct=EBI-1773646, EBI-10692913;
CC Q9BRV8; Q13033-2: STRN3; NbExp=4; IntAct=EBI-1773646, EBI-1053876;
CC Q9BRV8; O75558: STX11; NbExp=3; IntAct=EBI-1773646, EBI-714135;
CC Q9BRV8; Q9Y228: TRAF3IP3; NbExp=2; IntAct=EBI-1773646, EBI-765817;
CC Q9BRV8; P40222: TXLNA; NbExp=3; IntAct=EBI-1773646, EBI-359793;
CC Q9BRV8; Q8N3L3: TXLNB; NbExp=3; IntAct=EBI-1773646, EBI-6116822;
CC Q9BRV8; Q53FD0-2: ZC2HC1C; NbExp=6; IntAct=EBI-1773646, EBI-14104088;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16281057}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BRV8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BRV8-2; Sequence=VSP_027543;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in brain, heart,
CC skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine,
CC placenta, lung and leukocytes. Present in all cell lines tested (at
CC protein level). {ECO:0000269|PubMed:16281057}.
CC -!- SIMILARITY: Belongs to the SIKE family. {ECO:0000305}.
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DR EMBL; AK024821; BAB15020.1; -; mRNA.
DR EMBL; CR749219; CAH18076.1; -; mRNA.
DR EMBL; AL096773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56620.1; -; Genomic_DNA.
DR EMBL; BC005934; AAH05934.1; -; mRNA.
DR CCDS; CCDS41371.1; -. [Q9BRV8-2]
DR CCDS; CCDS878.1; -. [Q9BRV8-1]
DR RefSeq; NP_001095866.1; NM_001102396.1. [Q9BRV8-2]
DR RefSeq; NP_079349.2; NM_025073.2. [Q9BRV8-1]
DR PDB; 6AKK; X-ray; 1.50 A; A/B=72-121.
DR PDB; 6AKL; X-ray; 1.75 A; A/B=72-121.
DR PDB; 6AKM; X-ray; 2.30 A; A=5-65.
DR PDBsum; 6AKK; -.
DR PDBsum; 6AKL; -.
DR PDBsum; 6AKM; -.
DR AlphaFoldDB; Q9BRV8; -.
DR SMR; Q9BRV8; -.
DR BioGRID; 123136; 63.
DR CORUM; Q9BRV8; -.
DR IntAct; Q9BRV8; 54.
DR STRING; 9606.ENSP00000358541; -.
DR iPTMnet; Q9BRV8; -.
DR PhosphoSitePlus; Q9BRV8; -.
DR BioMuta; SIKE1; -.
DR DMDM; 74752290; -.
DR EPD; Q9BRV8; -.
DR jPOST; Q9BRV8; -.
DR MassIVE; Q9BRV8; -.
DR MaxQB; Q9BRV8; -.
DR PaxDb; Q9BRV8; -.
DR PeptideAtlas; Q9BRV8; -.
DR PRIDE; Q9BRV8; -.
DR ProteomicsDB; 78843; -. [Q9BRV8-1]
DR ProteomicsDB; 78844; -. [Q9BRV8-2]
DR Antibodypedia; 20165; 123 antibodies from 23 providers.
DR DNASU; 80143; -.
DR Ensembl; ENST00000060969.6; ENSP00000060969.6; ENSG00000052723.12. [Q9BRV8-1]
DR Ensembl; ENST00000369528.9; ENSP00000358541.5; ENSG00000052723.12. [Q9BRV8-2]
DR GeneID; 80143; -.
DR KEGG; hsa:80143; -.
DR MANE-Select; ENST00000060969.6; ENSP00000060969.6; NM_025073.3; NP_079349.2.
DR UCSC; uc001efo.5; human. [Q9BRV8-1]
DR CTD; 80143; -.
DR DisGeNET; 80143; -.
DR GeneCards; SIKE1; -.
DR HGNC; HGNC:26119; SIKE1.
DR HPA; ENSG00000052723; Low tissue specificity.
DR MIM; 611656; gene.
DR neXtProt; NX_Q9BRV8; -.
DR OpenTargets; ENSG00000052723; -.
DR PharmGKB; PA165752371; -.
DR VEuPathDB; HostDB:ENSG00000052723; -.
DR eggNOG; ENOG502QTKS; Eukaryota.
DR GeneTree; ENSGT00390000018003; -.
DR HOGENOM; CLU_073167_1_0_1; -.
DR InParanoid; Q9BRV8; -.
DR OMA; KVLCDAR; -.
DR OrthoDB; 1368908at2759; -.
DR PhylomeDB; Q9BRV8; -.
DR TreeFam; TF324337; -.
DR PathwayCommons; Q9BRV8; -.
DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway.
DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; Q9BRV8; -.
DR BioGRID-ORCS; 80143; 14 hits in 1076 CRISPR screens.
DR ChiTaRS; SIKE1; human.
DR GenomeRNAi; 80143; -.
DR Pharos; Q9BRV8; Tbio.
DR PRO; PR:Q9BRV8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BRV8; protein.
DR Bgee; ENSG00000052723; Expressed in buccal mucosa cell and 189 other tissues.
DR Genevisible; Q9BRV8; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR InterPro; IPR008555; SIKE.
DR PANTHER; PTHR12186; PTHR12186; 1.
DR Pfam; PF05769; SIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm;
KW Reference proteome.
FT CHAIN 1..207
FT /note="Suppressor of IKBKE 1"
FT /id="PRO_0000299050"
FT COILED 70..102
FT /evidence="ECO:0000255"
FT COILED 162..193
FT /evidence="ECO:0000255"
FT VAR_SEQ 53
FT /note="Q -> QVRQR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_027543"
FT CONFLICT 127
FT /note="V -> I (in Ref. 2; CAH18076)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="K -> I (in Ref. 1; BAB15020)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="L -> H (in Ref. 1; BAB15020)"
FT /evidence="ECO:0000305"
FT HELIX 5..46
FT /evidence="ECO:0007829|PDB:6AKM"
FT HELIX 75..118
FT /evidence="ECO:0007829|PDB:6AKK"
SQ SEQUENCE 207 AA; 23721 MW; 4C5598612F032988 CRC64;
MSCTIEKILT DAKTLLERLR EHDAAAESLV DQSAALHRRV AAMREAGTAL PDQYQEDASD
MKDMSKYKPH ILLSQENTQI RDLQQENREL WISLEEHQDA LELIMSKYRK QMLQLMVAKK
AVDAEPVLKA HQSHSAEIES QIDRICEMGE VMRKAVQVDD DQFCKIQEKL AQLELENKEL
RELLSISSES LQARKENSMD TASQAIK
