RHDF1_MOUSE
ID RHDF1_MOUSE Reviewed; 856 AA.
AC Q6PIX5; A2AVE2; Q04843; Q5DTF4; Q6PJ49; Q8VIK0;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Inactive rhomboid protein 1;
DE Short=iRhom1;
DE AltName: Full=Epidermal growth factor receptor-related protein;
DE AltName: Full=Rhomboid family member 1;
GN Name=Rhbdf1; Synonyms=Dist1, Irhom1, Kiaa4242;
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] (ISOFORM 2).
RC TISSUE=Thymus;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11157800; DOI=10.1093/hmg/10.4.371;
RA Flint J., Tufarelli C., Peden J., Clark K., Daniels R.J., Hardison R.,
RA Miller W., Philipsen S., Tan-Un K.C., McMorrow T., Frampton J., Alter B.P.,
RA Frischauf A.-M., Higgs D.R.;
RT "Comparative genome analysis delimits a chromosomal domain and identifies
RT key regulatory elements in the alpha globin cluster.";
RL Hum. Mol. Genet. 10:371-382(2001).
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] (ISOFORM 1).
RC STRAIN=Czech II, and 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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 511-670, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Fetal liver;
RX PubMed=8318735; DOI=10.1007/bf00357090;
RA Kielman M.F., Smits R., Devi T.S., Fodde R., Bernini L.F.;
RT "Homology of a 130-kb region enclosing the alpha-globin gene cluster, the
RT alpha-locus controlling region, and two non-globin genes in human and
RT mouse.";
RL Mamm. Genome 4:314-323(1993).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176; THR-180 AND THR-183, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, and Pancreas;
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 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).
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:0000250|UniProtKB:Q96CC6}.
CC -!- SUBUNIT: Homodimer, or homooligomer. Interacts with TGFA and HBEGF (By
CC similarity). Interacts with EGF; may retain EGF in the endoplasmic
CC reticulum and regulates its degradation through the endoplasmic
CC reticulum-associated degradation (ERAD) (PubMed:21439629). Interacts
CC (via cytoplasmic N-terminus) with FRMD8/iTAP; this interaction leads to
CC mutual protein stabilization (By similarity). Interacts with
CC ADAM17/TACE (By similarity). {ECO:0000250|UniProtKB:Q96CC6,
CC ECO:0000269|PubMed:21439629}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q96CC6}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q96CC6};
CC Multi-pass membrane protein {ECO:0000255}. Note=Predominantly localized
CC in the endoplasmic reticulum membrane. {ECO:0000250|UniProtKB:Q96CC6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6PIX5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PIX5-2; Sequence=VSP_034190, VSP_034191;
CC -!- TISSUE SPECIFICITY: Expressed in the duodenum, as well as in fetal
CC liver and head. {ECO:0000269|PubMed:8318735}.
CC -!- SIMILARITY: Belongs to the peptidase S54 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA02574.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAL32367.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAD90543.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AK220566; BAD90543.1; ALT_INIT; mRNA.
DR EMBL; AY016021; AAL32367.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL929446; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC023469; AAH23469.1; -; mRNA.
DR EMBL; BC027346; AAH27346.1; -; mRNA.
DR EMBL; M99623; AAA02574.1; ALT_INIT; mRNA.
DR CCDS; CCDS24519.1; -. [Q6PIX5-1]
DR RefSeq; NP_034247.2; NM_010117.2. [Q6PIX5-1]
DR AlphaFoldDB; Q6PIX5; -.
DR STRING; 10090.ENSMUSP00000020524; -.
DR MEROPS; S54.952; -.
DR GlyConnect; 2388; 1 N-Linked glycan (1 site).
DR GlyGen; Q6PIX5; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; Q6PIX5; -.
DR PhosphoSitePlus; Q6PIX5; -.
DR jPOST; Q6PIX5; -.
DR MaxQB; Q6PIX5; -.
DR PaxDb; Q6PIX5; -.
DR PeptideAtlas; Q6PIX5; -.
DR PRIDE; Q6PIX5; -.
DR ProteomicsDB; 253272; -. [Q6PIX5-1]
DR ProteomicsDB; 253273; -. [Q6PIX5-2]
DR Antibodypedia; 22449; 38 antibodies from 13 providers.
DR DNASU; 13650; -.
DR Ensembl; ENSMUST00000020524; ENSMUSP00000020524; ENSMUSG00000020282. [Q6PIX5-1]
DR GeneID; 13650; -.
DR KEGG; mmu:13650; -.
DR UCSC; uc007ijb.2; mouse. [Q6PIX5-1]
DR CTD; 64285; -.
DR MGI; MGI:104328; Rhbdf1.
DR VEuPathDB; HostDB:ENSMUSG00000020282; -.
DR eggNOG; KOG2290; Eukaryota.
DR GeneTree; ENSGT00940000156278; -.
DR HOGENOM; CLU_011531_1_1_1; -.
DR InParanoid; Q6PIX5; -.
DR OMA; GGTENMA; -.
DR OrthoDB; 1253228at2759; -.
DR PhylomeDB; Q6PIX5; -.
DR TreeFam; TF312988; -.
DR BioGRID-ORCS; 13650; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Rhbdf1; mouse.
DR PRO; PR:Q6PIX5; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q6PIX5; protein.
DR Bgee; ENSMUSG00000020282; Expressed in interventricular septum and 221 other tissues.
DR ExpressionAtlas; Q6PIX5; baseline and differential.
DR Genevisible; Q6PIX5; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0050709; P:negative regulation of protein secretion; ISS:UniProtKB.
DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0050708; P:regulation of protein secretion; ISO:MGI.
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 Alternative splicing; Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..856
FT /note="Inactive rhomboid protein 1"
FT /id="PRO_0000340108"
FT TOPO_DOM 1..412
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 413..433
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 434..656
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 657..677
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 678..692
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 693..713
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 714..715
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 716..736
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 737..747
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 748..768
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 769..773
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 774..794
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 795..804
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 805..825
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 826..856
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96CC6"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 180
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 183
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96CC6"
FT CARBOHYD 584
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 266..282
FT /note="EGVLHEEMSTYPDEVFE -> VRRAWGVAPSPLSLDPP (in isoform
FT 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_034190"
FT VAR_SEQ 283..856
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_034191"
FT CONFLICT 27
FT /note="A -> V (in Ref. 4; AAH27346)"
FT /evidence="ECO:0000305"
FT CONFLICT 41
FT /note="L -> V (in Ref. 4; AAH27346)"
FT /evidence="ECO:0000305"
FT CONFLICT 664..666
FT /note="HAG -> LAA (in Ref. 5; AAA02574)"
FT /evidence="ECO:0000305"
FT CONFLICT 674
FT /note="V -> I (in Ref. 4; AAH27346)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 856 AA; 97292 MW; BE8A3B32058793A5 CRC64;
MSEARRDSTS SLQRKKPPWL KLDIPAAVPP AAEEPSFLQP LRRQAFLRSV SMPAETARVP
SPHHEPRRLV LQRQTSITQT IRRGTADWFG VSKDSDSTQK WQRKSIRHCS QRYGKLKPQV
IRELDLPSQD NVSLTSTETP PPLYVGPCQL GMQKIIDPLA RGRAFRMADD TADGLSAPHT
PVTPGAASLC SFSSSRSGFN RLPRRRKRES VAKMSFRAAA ALVKGRSIRD GTLRRGQRRS
FTPASFLEED MVDFPDELDT SFFAREGVLH EEMSTYPDEV FESPSEAALK DWEKAPDQAD
LTGGALDRSE LERSHLMLPL ERGWRKQKEG GPLAPQPKVR LRQEVVSAAG PRRGQRIAVP
VRKLFAREKR PYGLGMVGRL TNRTYRKRID SYVKRQIEDM DDHRPFFTYW LTFVHSLVTI
LAVCIYGIAP VGFSQHETVD SVLRKRGVYE NVKYVQQENF WIGPSSEALI HLGAKFSPCM
RQDPQVHSFI LAAREREKHS ACCVRNDRSG CVQTSKEECS STLAVWVKWP VHPSAPDLAG
NKRQFGSVCH QDPRVCDEPS SEDPHEWPED ITKWPICTKS SAGNHTNHPH MDCVITGRPC
CIGTKGRCEI TSREYCDFMR GYFHEEATLC SQVHCMDDVC GLLPFLNPEV PDQFYRLWLS
LFLHAGILHC LVSVCFQMTV LRDLEKLAGW HRIAIIYLLS GITGNLASAI FLPYRAEVGP
AGSQFGILAC LFVELFQSWQ ILARPWRAFF KLLAVVLFLF AFGLLPWIDN FAHISGFVSG
LFLSFAFLPY ISFGKFDLYR KRCQIIIFQV VFLGLLAGLV VLFYFYPVRC EWCEFLTCIP
FTDKFCEKYE LDAQLH
