STEEP_HUMAN
ID STEEP_HUMAN Reviewed; 222 AA.
AC Q9H5V9; A8MPX7; B4DQN2; D3DWH9; F5GWL7; O43351;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=STING ER exit protein {ECO:0000303|PubMed:32690950};
DE Short=STEEP {ECO:0000303|PubMed:32690950};
GN Name=STEEP1 {ECO:0000312|HGNC:HGNC:26239};
GN Synonyms=CXorf56 {ECO:0000312|HGNC:HGNC:26239};
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] (ISOFORMS 1; 2 AND 3).
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 GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP INVOLVEMENT IN XLID107, AND SUBCELLULAR LOCATION.
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 [7]
RP FUNCTION, INTERACTION WITH STING1; PIK3C3 AND ATG14, SUBCELLULAR LOCATION,
RP MUTAGENESIS OF 149-LYS--TYR-178, AND IDENTIFICATION BY MASS SPECTROMETRY.
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 [8]
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
CC (PubMed:32690950). Promotes endoplasmic reticulum (ER) exit of cGAMP-
CC activated STING1 oligomers (PubMed:32690950).
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:0000269|PubMed:32690950}.
CC -!- INTERACTION:
CC Q9H5V9; O14929: HAT1; NbExp=3; IntAct=EBI-1053419, EBI-2339359;
CC Q9H5V9; Q9HAQ2: KIF9; NbExp=3; IntAct=EBI-1053419, EBI-8472129;
CC Q9H5V9; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-1053419, EBI-14066006;
CC Q9H5V9; Q9NQG5: RPRD1B; NbExp=3; IntAct=EBI-1053419, EBI-747925;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29374277,
CC ECO:0000269|PubMed:32690950}. Cytoplasm {ECO:0000269|PubMed:32690950}.
CC Note=Detected in the nucleus and cell soma of various neuronal types.
CC {ECO:0000250|UniProtKB:Q8VDP2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9H5V9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H5V9-2; Sequence=VSP_044273;
CC Name=3;
CC IsoId=Q9H5V9-3; Sequence=VSP_044274;
CC -!- DISEASE: Intellectual developmental disorder, X-linked 107 (XLID107)
CC [MIM:301013]: A form of intellectual disability, a disorder
CC characterized by significantly below average general intellectual
CC functioning associated with impairments in adaptive behavior and
CC manifested during the developmental period. Intellectual deficiency is
CC the only primary symptom of non-syndromic X-linked forms, while
CC syndromic forms present with associated physical, neurological and/or
CC psychiatric manifestations. {ECO:0000269|PubMed:29374277}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the STEEP1 family. {ECO:0000305}.
CC -!- CAUTION: May be duplicated on chromosome 8, within an intron of the
CC ERLIN2 gene. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB96348.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AK026618; BAB15510.1; -; mRNA.
DR EMBL; AK298877; BAG60994.1; -; mRNA.
DR EMBL; AK096297; BAG53251.1; -; mRNA.
DR EMBL; AC004000; AAB96348.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC004913; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005190; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471161; EAW89864.1; -; Genomic_DNA.
DR EMBL; CH471161; EAW89865.1; -; Genomic_DNA.
DR EMBL; CH471161; EAW89866.1; -; Genomic_DNA.
DR EMBL; CH471161; EAW89867.1; -; Genomic_DNA.
DR EMBL; BC023506; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS55484.1; -. [Q9H5V9-2]
DR CCDS; CCDS55485.1; -. [Q9H5V9-3]
DR RefSeq; NP_001164040.1; NM_001170569.1. [Q9H5V9-2]
DR RefSeq; NP_001164041.1; NM_001170570.1. [Q9H5V9-3]
DR RefSeq; NP_071384.1; NM_022101.3. [Q9H5V9-1]
DR AlphaFoldDB; Q9H5V9; -.
DR SMR; Q9H5V9; -.
DR BioGRID; 122000; 55.
DR IntAct; Q9H5V9; 15.
DR MINT; Q9H5V9; -.
DR STRING; 9606.ENSP00000441786; -.
DR iPTMnet; Q9H5V9; -.
DR PhosphoSitePlus; Q9H5V9; -.
DR BioMuta; CXorf56; -.
DR DMDM; 74733589; -.
DR EPD; Q9H5V9; -.
DR jPOST; Q9H5V9; -.
DR MassIVE; Q9H5V9; -.
DR MaxQB; Q9H5V9; -.
DR PaxDb; Q9H5V9; -.
DR PeptideAtlas; Q9H5V9; -.
DR PRIDE; Q9H5V9; -.
DR ProteomicsDB; 1920; -.
DR ProteomicsDB; 24155; -.
DR ProteomicsDB; 80936; -. [Q9H5V9-1]
DR Antibodypedia; 50191; 95 antibodies from 18 providers.
DR DNASU; 63932; -.
DR Ensembl; ENST00000320339.8; ENSP00000320345.4; ENSG00000018610.15. [Q9H5V9-2]
DR Ensembl; ENST00000536133.2; ENSP00000441786.1; ENSG00000018610.15. [Q9H5V9-3]
DR Ensembl; ENST00000644802.2; ENSP00000494123.2; ENSG00000018610.15. [Q9H5V9-1]
DR GeneID; 63932; -.
DR KEGG; hsa:63932; -.
DR MANE-Select; ENST00000644802.2; ENSP00000494123.2; NM_022101.4; NP_071384.1.
DR UCSC; uc004erj.3; human. [Q9H5V9-1]
DR CTD; 63932; -.
DR DisGeNET; 63932; -.
DR GeneCards; STEEP1; -.
DR HGNC; HGNC:26239; STEEP1.
DR HPA; ENSG00000018610; Low tissue specificity.
DR MalaCards; STEEP1; -.
DR MIM; 301012; gene.
DR MIM; 301013; phenotype.
DR neXtProt; NX_Q9H5V9; -.
DR OpenTargets; ENSG00000018610; -.
DR Orphanet; 777; X-linked non-syndromic intellectual disability.
DR VEuPathDB; HostDB:ENSG00000018610; -.
DR eggNOG; KOG4397; Eukaryota.
DR GeneTree; ENSGT00390000002197; -.
DR HOGENOM; CLU_099571_1_1_1; -.
DR InParanoid; Q9H5V9; -.
DR OMA; GIEKQHR; -.
DR OrthoDB; 1161089at2759; -.
DR PhylomeDB; Q9H5V9; -.
DR TreeFam; TF300272; -.
DR PathwayCommons; Q9H5V9; -.
DR SignaLink; Q9H5V9; -.
DR BioGRID-ORCS; 63932; 59 hits in 699 CRISPR screens.
DR ChiTaRS; CXorf56; human.
DR GenomeRNAi; 63932; -.
DR Pharos; Q9H5V9; Tdark.
DR PRO; PR:Q9H5V9; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9H5V9; protein.
DR Bgee; ENSG00000018610; Expressed in oocyte and 168 other tissues.
DR Genevisible; Q9H5V9; HS.
DR GO; GO:0044297; C:cell body; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090158; P:endoplasmic reticulum membrane organization; IDA:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IDA:UniProtKB.
DR InterPro; IPR029704; STEEP-like.
DR PANTHER; PTHR46355; PTHR46355; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Intellectual disability;
KW Nucleus; Reference proteome.
FT CHAIN 1..222
FT /note="STING ER exit protein"
FT /id="PRO_0000287609"
FT COILED 170..220
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..49
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044273"
FT VAR_SEQ 82..95
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044274"
FT MUTAGEN 149..178
FT /note="KDMGKFSSVTVSTIDEEEEEIEAREVADSY->ADMAKFSSVTVSTIDEEAEA
FT IEAREVADSA: Abrogates interaction with STING1 and impairs
FT STING1-mediated signaling."
FT /evidence="ECO:0000269|PubMed:32690950"
FT CONFLICT 194
FT /note="M -> V (in Ref. 1; BAG60994)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 222 AA; 25625 MW; 586CD0CE472989DF CRC64;
MPKVVSRSVV CSDTRDREEY DDGEKPLHVY YCLCGQMVLV LDCQLEKLPM RPRDRSRVID
AAKHAHKFCN TEDEETMYLR RPEGIERQYR KKCAKCGLPL FYQSQPKNAP VTFIVDGAVV
KFGQGFGKTN IYTQKQEPPK KVMMTKRTKD MGKFSSVTVS TIDEEEEEIE AREVADSYAQ
NAKVIEKQLE RKGMSKRRLQ ELAELEAKKA KMKGTLIDNQ FK
