STEEP_MOUSE
ID STEEP_MOUSE Reviewed; 222 AA.
AC Q8VDP2; A2A3V4; Q3URC0; Q8C8Z1; Q9CWC1;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=STING ER exit protein {ECO:0000250|UniProtKB:Q9H5V9};
DE Short=STEEP {ECO:0000250|UniProtKB:Q9H5V9};
GN Name=Steep1 {ECO:0000312|MGI:MGI:1924894};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RC TISSUE=Cerebellum, Embryo, Hippocampus, Olfactory bulb, Retina, and Vagina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=29374277; DOI=10.1038/s41431-017-0051-9;
RA Verkerk A.J.M.H., Zeidler S., Breedveld G., Overbeek L., Huigh D.,
RA Koster L., van der Linde H., de Esch C., Severijnen L.A., de Vries B.B.A.,
RA Swagemakers S.M.A., Willemsen R., Hoogeboom A.J.M., van der Spek P.J.,
RA Oostra B.A.;
RT "CXorf56, a dendritic neuronal protein, identified as a new candidate gene
RT for X-linked intellectual disability.";
RL Eur. J. Hum. Genet. 26:552-560(2018).
RN [6]
RP FUNCTION.
RX PubMed=32690950; DOI=10.1038/s41590-020-0730-5;
RA Zhang B.C., Nandakumar R., Reinert L.S., Huang J., Laustsen A., Gao Z.L.,
RA Sun C.L., Jensen S.B., Troldborg A., Assil S., Berthelsen M.F.,
RA Scavenius C., Zhang Y., Windross S.J., Olagnier D., Prabakaran T.,
RA Bodda C., Narita R., Cai Y., Zhang C.G., Stenmark H., Doucet C.M., Noda T.,
RA Guo Z., Goldbach-Mansky R., Hartmann R., Chen Z.J., Enghild J.J., Bak R.O.,
RA Thomsen M.K., Paludan S.R.;
RT "STEEP mediates STING ER exit and activation of signaling.";
RL Nat. Immunol. 21:868-879(2020).
RN [7]
RP ERRATUM OF PUBMED:32690950.
RX PubMed=32929276; DOI=10.1038/s41590-020-0803-5;
RA Zhang B.C., Nandakumar R., Reinert L.S., Huang J., Laustsen A., Gao Z.L.,
RA Sun C.L., Jensen S.B., Troldborg A., Assil S., Berthelsen M.F.,
RA Scavenius C., Zhang Y., Windross S.J., Olagnier D., Prabakaran T.,
RA Bodda C., Narita R., Cai Y., Zhang C.G., Stenmark H., Doucet C.M., Noda T.,
RA Guo Z., Goldbach-Mansky R., Hartmann R., Chen Z.J., Enghild J.J., Bak R.O.,
RA Thomsen M.K., Paludan S.R.;
RL Nat. Immunol. 21:1468-1469(2020).
CC -!- FUNCTION: Stimulates membrane curvature formation and subsequent
CC endoplasmic reticulum exit site (ERES) establishment by recruiting PI3K
CC complex I, leading to COPII vesicle-mediated transport (By similarity).
CC Promotes endoplasmic reticulum (ER) exit of cGAMP-activated STING1
CC oligomers (PubMed:32690950). {ECO:0000250|UniProtKB:Q9H5V9,
CC ECO:0000269|PubMed:32690950}.
CC -!- SUBUNIT: Interacts with STING1, PIK3C3, and ATG14; the STING1/STEEP1
CC interaction is increased upon STING1 cGAMP-activation and leads to
CC recruitment of PI3K complex I. {ECO:0000250|UniProtKB:Q9H5V9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29374277}. Cytoplasm
CC {ECO:0000269|PubMed:29374277}. Note=Detected in the nucleus and cell
CC soma of pyramidal neurons in the brain cortex and Purkinje cells, as
CC well as in neurons in the granular layer in the cerebellum.
CC {ECO:0000269|PubMed:29374277}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8VDP2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VDP2-2; Sequence=VSP_025569;
CC -!- TISSUE SPECIFICITY: Expressed in neurons in the brain cortex and
CC cerebellum (at protein level). {ECO:0000269|PubMed:29374277}.
CC -!- SIMILARITY: Belongs to the STEEP1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAM19776.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AK021190; BAB32323.1; -; mRNA.
DR EMBL; AK032304; BAC27802.1; -; mRNA.
DR EMBL; AK034943; BAC28890.1; -; mRNA.
DR EMBL; AK035825; BAC29201.1; -; mRNA.
DR EMBL; AK036910; BAC29635.1; -; mRNA.
DR EMBL; AK044209; BAC31816.1; -; mRNA.
DR EMBL; AK141615; BAE24768.1; -; mRNA.
DR EMBL; AL450399; CAM19776.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL450399; CAM19777.1; -; Genomic_DNA.
DR EMBL; BC021479; AAH21479.1; -; mRNA.
DR EMBL; BC051144; AAH51144.1; -; mRNA.
DR CCDS; CCDS53050.1; -. [Q8VDP2-1]
DR RefSeq; NP_084227.1; NM_029951.1. [Q8VDP2-1]
DR AlphaFoldDB; Q8VDP2; -.
DR SMR; Q8VDP2; -.
DR BioGRID; 218822; 1.
DR IntAct; Q8VDP2; 1.
DR STRING; 10090.ENSMUSP00000110904; -.
DR iPTMnet; Q8VDP2; -.
DR PhosphoSitePlus; Q8VDP2; -.
DR EPD; Q8VDP2; -.
DR MaxQB; Q8VDP2; -.
DR PaxDb; Q8VDP2; -.
DR PeptideAtlas; Q8VDP2; -.
DR PRIDE; Q8VDP2; -.
DR Antibodypedia; 50191; 95 antibodies from 18 providers.
DR DNASU; 77644; -.
DR Ensembl; ENSMUST00000047486; ENSMUSP00000040134; ENSMUSG00000006423. [Q8VDP2-1]
DR Ensembl; ENSMUST00000115248; ENSMUSP00000110903; ENSMUSG00000006423. [Q8VDP2-1]
DR GeneID; 77644; -.
DR KEGG; mmu:77644; -.
DR UCSC; uc012hfv.1; mouse. [Q8VDP2-1]
DR CTD; 63932; -.
DR MGI; MGI:1924894; Steep1.
DR VEuPathDB; HostDB:ENSMUSG00000006423; -.
DR eggNOG; KOG4397; Eukaryota.
DR GeneTree; ENSGT00390000002197; -.
DR HOGENOM; CLU_099571_1_0_1; -.
DR InParanoid; Q8VDP2; -.
DR OMA; GIEKQHR; -.
DR OrthoDB; 1161089at2759; -.
DR PhylomeDB; Q8VDP2; -.
DR TreeFam; TF300272; -.
DR BioGRID-ORCS; 77644; 18 hits in 73 CRISPR screens.
DR PRO; PR:Q8VDP2; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q8VDP2; protein.
DR Bgee; ENSMUSG00000006423; Expressed in gonadal fat pad and 258 other tissues.
DR ExpressionAtlas; Q8VDP2; baseline and differential.
DR Genevisible; Q8VDP2; MM.
DR GO; GO:0044297; C:cell body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090158; P:endoplasmic reticulum membrane organization; ISS:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; ISS:UniProtKB.
DR InterPro; IPR029704; STEEP-like.
DR PANTHER; PTHR46355; PTHR46355; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Nucleus; Reference proteome.
FT CHAIN 1..222
FT /note="STING ER exit protein"
FT /id="PRO_0000287610"
FT COILED 170..220
FT /evidence="ECO:0000255"
FT VAR_SEQ 203..222
FT /note="AELEAKKAKMKGTLIDNQFK -> VAGMLLYPVSREAGRSADRASFALGISL
FT RTSCAAERVVIPLCNTQDGK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_025569"
FT CONFLICT 200
FT /note="Q -> H (in Ref. 1; BAC31816)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="A -> D (in Ref. 1; BAE24768)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 222 AA; 25594 MW; A9EFF6A5F0D989CD CRC64;
MPKVVSRSVV CSDTRDREEY DDGEKPLHVY YCLCGQMVLV LDCQLEKLPM RPRDRSRVID
AAKHAHKFCN TEDEETTYLR RPEGIERQYR KKCAKCGLPL FYQSQPKNAP VTFIVDGAVV
KFGQGFGKTN IYTQKQEPPK KVMMTKRTKD MGKFSSVTVS TIDEEEEEIE AREVADSYAQ
NAKVIEKQLE RKGMSKRRLQ ELAELEAKKA KMKGTLIDNQ FK
