RHDF2_MOUSE
ID RHDF2_MOUSE Reviewed; 827 AA.
AC Q80WQ6; Q3TBR9; Q8BJ70; Q8K2I7;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Inactive rhomboid protein 2;
DE Short=iRhom2;
DE AltName: Full=Rhomboid family member 2;
DE AltName: Full=Rhomboid veinlet-like protein 6;
DE AltName: Full=Rhomboid-related protein;
GN Name=Rhbdf2; Synonyms=Irhom2, Rhbdl6, Rhor;
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 [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Skin;
RA Kong X., Li S., Shi Y., Teng X., Hu L., Zhu Y.;
RT "Molecular cloning of a mouse rhomboid-related gene.";
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Dendritic cell, and Skin;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Embryo, and 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60; SER-83; SER-87; SER-293;
RP SER-295 AND SER-298, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293; SER-295 AND SER-298, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and 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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EGF.
RX PubMed=21439629; DOI=10.1016/j.cell.2011.02.047;
RA Zettl M., Adrain C., Strisovsky K., Lastun V., Freeman M.;
RT "Rhomboid family pseudoproteases use the ER quality control machinery to
RT regulate intercellular signaling.";
RL Cell 145:79-91(2011).
RN [8]
RP INTERACTION WITH FRMD8.
RX PubMed=29897336; DOI=10.7554/elife.35012;
RA Kuenzel U., Grieve A.G., Meng Y., Sieber B., Cowley S.A., Freeman M.;
RT "FRMD8 promotes inflammatory and growth factor signalling by stabilising
RT the iRhom/ADAM17 sheddase complex.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Regulates ADAM17 protease, a sheddase of the epidermal growth
CC factor (EGF) receptor ligands and TNF, thereby plays a role in sleep,
CC cell survival, proliferation, migration and inflammation. Does not
CC exhibit any protease activity on its own.
CC {ECO:0000269|PubMed:21439629}.
CC -!- SUBUNIT: Interacts with EGF (PubMed:21439629). Interacts (via
CC cytoplasmic N-terminus) with FRMD8/iTAP; this interaction leads to
CC mutual protein stabilization (PubMed:29897336). Interacts with
CC ADAM17/TACE (By similarity). {ECO:0000250|UniProtKB:Q6PJF5,
CC ECO:0000269|PubMed:21439629, ECO:0000269|PubMed:29897336}.
CC -!- INTERACTION:
CC Q80WQ6; Q9Z0F8: Adam17; NbExp=6; IntAct=EBI-647271, EBI-7848498;
CC Q80WQ6; P78536: ADAM17; Xeno; NbExp=2; IntAct=EBI-647271, EBI-78188;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:21439629}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:21439629}.
CC -!- SIMILARITY: Belongs to the peptidase S54 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY167043; AAO34122.1; -; mRNA.
DR EMBL; AK028872; BAC26163.1; -; mRNA.
DR EMBL; AK171085; BAE42238.1; -; mRNA.
DR EMBL; AL607039; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC031398; AAH31398.1; -; mRNA.
DR EMBL; BC052182; AAH52182.1; -; mRNA.
DR CCDS; CCDS25672.1; -.
DR RefSeq; NP_001161152.1; NM_001167680.1.
DR RefSeq; NP_766160.2; NM_172572.3.
DR AlphaFoldDB; Q80WQ6; -.
DR DIP; DIP-49675N; -.
DR IntAct; Q80WQ6; 4.
DR MINT; Q80WQ6; -.
DR STRING; 10090.ENSMUSP00000099317; -.
DR MEROPS; S54.953; -.
DR GlyConnect; 2389; 1 N-Linked glycan (1 site).
DR GlyGen; Q80WQ6; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; Q80WQ6; -.
DR PhosphoSitePlus; Q80WQ6; -.
DR EPD; Q80WQ6; -.
DR jPOST; Q80WQ6; -.
DR MaxQB; Q80WQ6; -.
DR PaxDb; Q80WQ6; -.
DR PeptideAtlas; Q80WQ6; -.
DR PRIDE; Q80WQ6; -.
DR ProteomicsDB; 254863; -.
DR Antibodypedia; 19692; 81 antibodies from 21 providers.
DR DNASU; 217344; -.
DR Ensembl; ENSMUST00000103028; ENSMUSP00000099317; ENSMUSG00000020806.
DR Ensembl; ENSMUST00000103029; ENSMUSP00000099318; ENSMUSG00000020806.
DR GeneID; 217344; -.
DR KEGG; mmu:217344; -.
DR UCSC; uc007mls.3; mouse.
DR CTD; 79651; -.
DR MGI; MGI:2442473; Rhbdf2.
DR VEuPathDB; HostDB:ENSMUSG00000020806; -.
DR eggNOG; KOG2290; Eukaryota.
DR GeneTree; ENSGT00940000159027; -.
DR HOGENOM; CLU_011531_1_1_1; -.
DR InParanoid; Q80WQ6; -.
DR OMA; IKRSFAY; -.
DR OrthoDB; 1253228at2759; -.
DR PhylomeDB; Q80WQ6; -.
DR TreeFam; TF312988; -.
DR BioGRID-ORCS; 217344; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Rhbdf2; mouse.
DR PRO; PR:Q80WQ6; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q80WQ6; protein.
DR Bgee; ENSMUSG00000020806; Expressed in granulocyte and 142 other tissues.
DR Genevisible; Q80WQ6; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0050709; P:negative regulation of protein secretion; IDA:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:1904683; P:regulation of metalloendopeptidase activity; IGI:MGI.
DR GO; GO:0050708; P:regulation of protein secretion; IBA:GO_Central.
DR Gene3D; 1.20.1540.10; -; 1.
DR InterPro; IPR022764; Peptidase_S54_rhomboid_dom.
DR InterPro; IPR035952; Rhomboid-like_sf.
DR InterPro; IPR022241; Rhomboid_SP.
DR Pfam; PF01694; Rhomboid; 1.
DR Pfam; PF12595; Rhomboid_SP; 1.
DR SUPFAM; SSF144091; SSF144091; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..827
FT /note="Inactive rhomboid protein 2"
FT /id="PRO_0000341939"
FT TOPO_DOM 1..381
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 403..627
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 628..648
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 649..663
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 664..684
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 685..686
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 687..707
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 708..718
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 719..739
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 740..744
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 745..765
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 766..773
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 774..794
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 795..827
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..26
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT CONFLICT 728
FT /note="L -> P (in Ref. 2; BAC26163)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 827 AA; 93434 MW; 650052E5A4BD9CA5 CRC64;
MASADKNGSN LPSVSGSRLQ SRKPPNLSIT IPPPESQAPG EQDSMLPERR KNPAYLKSVS
LQEPRGRWQE GAEKRPGFRR QASLSQSIRK STAQWFGVSG DWEGKRQNWH RRSLHHCSVH
YGRLKASCQR ELELPSQEVP SFQGTESPKP CKMPKIVDPL ARGRAFRHPD EVDRPHAAHP
PLTPGVLSLT SFTSVRSGYS HLPRRKRISV AHMSFQAAAA LLKGRSVLDA TGQRCRHVKR
SFAYPSFLEE DAVDGADTFD SSFFSKEEMS SMPDDVFESP PLSASYFRGV PHSASPVSPD
GVHIPLKEYS GGRALGPGTQ RGKRIASKVK HFAFDRKKRH YGLGVVGNWL NRSYRRSISS
TVQRQLESFD SHRPYFTYWL TFVHIIITLL VICTYGIAPV GFAQHVTTQL VLKNRGVYES
VKYIQQENFW IGPSSIDLIH LGAKFSPCIR KDQQIEQLVR RERDIERTSG CCVQNDRSGC
IQTLKKDCSE TLATFVKWQN DTGPSDKSDL SQKQPSAVVC HQDPRTCEEP ASSGAHIWPD
DITKWPICTE QAQSNHTGLL HIDCKIKGRP CCIGTKGSCE ITTREYCEFM HGYFHEDATL
CSQVHCLDKV CGLLPFLNPE VPDQFYRIWL SLFLHAGIVH CLVSVVFQMT ILRDLEKLAG
WHRISIIFIL SGITGNLASA IFLPYRAEVG PAGSQFGLLA CLFVELFQSW QLLERPWKAF
FNLSAIVLFL FICGLLPWID NIAHIFGFLS GMLLAFAFLP YITFGTSDKY RKRALILVSL
LVFAGLFASL VLWLYIYPIN WPWIEYLTCF PFTSRFCEKY ELDQVLH
