RHBL4_MOUSE
ID RHBL4_MOUSE Reviewed; 315 AA.
AC Q8BHC7; Q99K13; Q9D5L8;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Rhomboid-related protein 4;
DE Short=RRP4;
DE EC=3.4.21.105;
DE AltName: Full=Rhomboid domain-containing protein 1;
DE Short=mRHBDD1;
DE AltName: Full=Rhomboid-like protein 4;
GN Name=Rhbdd1; Synonyms=Rhbdl4; ORFNames=MSD-50, MSD50;
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].
RC STRAIN=Swiss Webster / NIH; TISSUE=Testis;
RA Wang Y., Miao S.Y., Zhang X.D., Qiao Y., Liang G., Wang L.F.;
RT "A new spermatogenesis-related gene.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart, Testis, 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; 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 FUNCTION IN APOPTOSIS, AND TISSUE SPECIFICITY.
RX PubMed=19358743; DOI=10.1186/1471-2121-10-25;
RA Wang Y., Song W., Li S., Guan X., Miao S., Zong S., Koide S.S., Wang L.;
RT "GC-1 mRHBDD1 knockdown spermatogonia cells lose their spermatogenic
RT capacity in mouse seminiferous tubules.";
RL BMC Cell Biol. 10:25-25(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, and Testis;
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 [6]
RP FUNCTION, INTERACTION WITH PTCRA; UBIQUITIN AND VCP, TOPOLOGY, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF SER-144; LEU-274 AND LEU-278.
RX PubMed=22795130; DOI=10.1016/j.molcel.2012.06.008;
RA Fleig L., Bergbold N., Sahasrabudhe P., Geiger B., Kaltak L., Lemberg M.K.;
RT "Ubiquitin-dependent intramembrane rhomboid protease promotes ERAD of
RT membrane proteins.";
RL Mol. Cell 47:558-569(2012).
CC -!- FUNCTION: Intramembrane-cleaving serine protease that cleaves single
CC transmembrane or multi-pass membrane proteins in the hydrophobic plane
CC of the membrane, luminal loops and juxtamembrane regions. Involved in
CC regulated intramembrane proteolysis and the subsequent release of
CC functional polypeptides from their membrane anchors. Functional
CC component of endoplasmic reticulum-associated degradation (ERAD) for
CC misfolded membrane proteins. Required for the degradation process of
CC some specific misfolded endoplasmic reticulum (ER) luminal proteins.
CC Participates in the transfer of misfolded proteins from the ER to the
CC cytosol, where they are destroyed by the proteasome in a ubiquitin-
CC dependent manner. Functions in BIK, MPZ, PKD1, PTCRA, RHO, STEAP3 and
CC TRAC processing. Involved in the regulation of exosomal secretion;
CC inhibits the TSAP6-mediated secretion pathway. Involved in the
CC regulation of apoptosis; modulates BIK-mediated apoptotic activity.
CC Also plays a role in the regulation of spermatogenesis; inhibits
CC apoptotic activity in spermatogonia. {ECO:0000269|PubMed:19358743,
CC ECO:0000269|PubMed:22795130}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves type-1 transmembrane domains using a catalytic dyad
CC composed of serine and histidine that are contributed by different
CC transmembrane domains.; EC=3.4.21.105;
CC -!- ACTIVITY REGULATION: Inhibited by aprotinin. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with BIK and STEAP3 (By similarity). Interacts (via
CC C-terminal domain) with VCP/P97. Interacts with ubiquitin and
CC ubiquitinated proteins. {ECO:0000250, ECO:0000269|PubMed:22795130}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22795130}; Multi-pass membrane protein
CC {ECO:0000305}. Mitochondrion membrane {ECO:0000250|UniProtKB:Q8TEB9};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in testis (at protein level). Expressed
CC in intestine, lung, brain, kidney, epididymis, stomach, muscle, spleen,
CC liver, heart and testis. {ECO:0000269|PubMed:19358743}.
CC -!- SIMILARITY: Belongs to the peptidase S54 family. {ECO:0000305}.
CC -!- CAUTION: One study reported that the protein is not localized in the
CC mitochondrion. {ECO:0000305|PubMed:22795130}.
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DR EMBL; AY973322; AAY41235.1; -; mRNA.
DR EMBL; AK015167; BAB29735.1; -; mRNA.
DR EMBL; AK029751; BAC26597.1; -; mRNA.
DR EMBL; AK076751; BAC36465.1; -; mRNA.
DR EMBL; AK079448; BAC37647.1; -; mRNA.
DR EMBL; AK142277; BAE25005.1; -; mRNA.
DR EMBL; BC005518; AAH05518.1; -; mRNA.
DR CCDS; CCDS15097.1; -.
DR RefSeq; NP_001116157.1; NM_001122685.1.
DR RefSeq; NP_084053.3; NM_029777.3.
DR RefSeq; XP_006496637.1; XM_006496574.3.
DR AlphaFoldDB; Q8BHC7; -.
DR BioGRID; 218363; 1.
DR IntAct; Q8BHC7; 1.
DR STRING; 10090.ENSMUSP00000137770; -.
DR ChEMBL; CHEMBL3259510; -.
DR MEROPS; S54.954; -.
DR iPTMnet; Q8BHC7; -.
DR PhosphoSitePlus; Q8BHC7; -.
DR EPD; Q8BHC7; -.
DR MaxQB; Q8BHC7; -.
DR PaxDb; Q8BHC7; -.
DR PeptideAtlas; Q8BHC7; -.
DR PRIDE; Q8BHC7; -.
DR ProteomicsDB; 253270; -.
DR Antibodypedia; 3019; 75 antibodies from 25 providers.
DR DNASU; 76867; -.
DR Ensembl; ENSMUST00000027322; ENSMUSP00000027322; ENSMUSG00000026142.
DR Ensembl; ENSMUST00000140020; ENSMUSP00000137770; ENSMUSG00000026142.
DR GeneID; 76867; -.
DR KEGG; mmu:76867; -.
DR UCSC; uc007brq.3; mouse.
DR CTD; 84236; -.
DR MGI; MGI:1924117; Rhbdd1.
DR VEuPathDB; HostDB:ENSMUSG00000026142; -.
DR eggNOG; KOG2632; Eukaryota.
DR GeneTree; ENSGT00390000010744; -.
DR HOGENOM; CLU_075166_0_0_1; -.
DR InParanoid; Q8BHC7; -.
DR OMA; SIWFAYI; -.
DR OrthoDB; 1588469at2759; -.
DR PhylomeDB; Q8BHC7; -.
DR TreeFam; TF328476; -.
DR BRENDA; 3.4.21.108; 3474.
DR BioGRID-ORCS; 76867; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Rhbdl3; mouse.
DR PRO; PR:Q8BHC7; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8BHC7; protein.
DR Bgee; ENSMUSG00000026142; Expressed in seminal vesicle and 209 other tissues.
DR Genevisible; Q8BHC7; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0034620; P:cellular response to unfolded protein; IDA:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB.
DR GO; GO:0036503; P:ERAD pathway; IDA:UniProtKB.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; IDA:UniProtKB.
DR GO; GO:0033619; P:membrane protein proteolysis; ISS:UniProtKB.
DR GO; GO:1904211; P:membrane protein proteolysis involved in retrograde protein transport, ER to cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0010954; P:positive regulation of protein processing; IDA:UniProtKB.
DR GO; GO:0051047; P:positive regulation of secretion; ISS:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB.
DR GO; GO:0048515; P:spermatid differentiation; IMP:UniProtKB.
DR Gene3D; 1.20.1540.10; -; 1.
DR InterPro; IPR022764; Peptidase_S54_rhomboid_dom.
DR InterPro; IPR035952; Rhomboid-like_sf.
DR Pfam; PF01694; Rhomboid; 1.
DR SUPFAM; SSF144091; SSF144091; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Differentiation; Endoplasmic reticulum; Hydrolase; Membrane;
KW Mitochondrion; Protease; Reference proteome; Serine protease;
KW Spermatogenesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..315
FT /note="Rhomboid-related protein 4"
FT /id="PRO_0000254190"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..103
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 125..137
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 155..180
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..315
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 269..284
FT /note="Ubiquitin-binding domain (UBD)"
FT REGION 301..315
FT /note="VCP/p97-interacting motif (VIM)"
FT ACT_SITE 144
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 195
FT /evidence="ECO:0000250"
FT MUTAGEN 144
FT /note="S->A: Enzyme inactivation. Reduces the cleavage of
FT PTCRA and TRAC. Does not inhibit interaction with PTCRA.
FT Stimulates interaction with ubiquitinated proteins."
FT /evidence="ECO:0000269|PubMed:22795130"
FT MUTAGEN 274
FT /note="L->A: Inhibits interaction with ubiquitin and
FT ubiquitinated proteins; when associated with A-278. Reduces
FT the cleavage of PTCRA; when associated with A-278."
FT /evidence="ECO:0000269|PubMed:22795130"
FT MUTAGEN 278
FT /note="L->A: Inhibits interaction with ubiquitin and
FT ubiquitinated proteins; when associated with A-274. Reduces
FT the cleavage of PTCRA; when associated with A-274."
FT /evidence="ECO:0000269|PubMed:22795130"
FT CONFLICT 130
FT /note="L -> M (in Ref. 3; AAH05518)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="T -> M (in Ref. 3; AAH05518)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="A -> S (in Ref. 3; AAH05518)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="R -> G (in Ref. 2; BAB29735)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="R -> Q (in Ref. 2; BAB29735)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 315 AA; 35776 MW; 3222D8AFEDFB8626 CRC64;
MQRRTRGINT GLLLLLSQVF QIGINNIPPV TLATLAVNVW FFLNPWKPLY HSCISVEKCY
QQKDWQRLLL SPLHHGDDWH LYFNMVSMLW KGVKLERRLG SRWFAYVIAT FSLLTGVVYL
LLQFTVAELL NQPDFKRNCA VGFSGVLFAL KVLSNHYCPG GFVNILGFPV PNRFACWAEL
VAIHFCTPGT SFAGHLAGIL VGLMYTQGPL KKIMDTCAGI FISHAGPSGQ QNHFNNAGPS
GYQNHYADGR PVTYDATYRN YDVYTAGLSE EEQLERALRA SIWDRGNTRN GPMPYGFRLP
PEEMRRQRLH RFDGQ
