RHBL4_RAT
ID RHBL4_RAT Reviewed; 316 AA.
AC Q4V8F3;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 101.
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=rRHBDD1;
DE AltName: Full=Rhomboid-like protein 4;
GN Name=Rhbdd1; Synonyms=Rhbdl4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [2]
RP 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).
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 (By similarity). {ECO:0000250}.
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. Interacts (via C-terminal
CC domain) with VCP. Interacts with ubiquitin and ubiquitinated proteins
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8TEB9}; Multi-pass membrane protein
CC {ECO:0000255}. Mitochondrion membrane {ECO:0000250|UniProtKB:Q8TEB9};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in intestine, lung, brain, kidney,
CC epididymis 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:0000250|UniProtKB:Q8TEB9}.
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; BC097416; AAH97416.1; -; mRNA.
DR RefSeq; NP_001020062.1; NM_001024891.1.
DR RefSeq; XP_008765472.1; XM_008767250.2.
DR AlphaFoldDB; Q4V8F3; -.
DR STRING; 10116.ENSRNOP00000019898; -.
DR PaxDb; Q4V8F3; -.
DR Ensembl; ENSRNOT00000107081; ENSRNOP00000082541; ENSRNOG00000054963.
DR GeneID; 316557; -.
DR KEGG; rno:316557; -.
DR UCSC; RGD:1306477; rat.
DR CTD; 84236; -.
DR RGD; 1306477; Rhbdd1.
DR eggNOG; KOG2632; Eukaryota.
DR GeneTree; ENSGT00390000010744; -.
DR HOGENOM; CLU_075166_0_0_1; -.
DR InParanoid; Q4V8F3; -.
DR OMA; SIWFAYI; -.
DR OrthoDB; 1588469at2759; -.
DR PhylomeDB; Q4V8F3; -.
DR TreeFam; TF328476; -.
DR PRO; PR:Q4V8F3; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000054963; Expressed in testis and 19 other tissues.
DR Genevisible; Q4V8F3; RN.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS: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; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR GO; GO:0036503; P:ERAD pathway; ISS:UniProtKB.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISS: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; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0010954; P:positive regulation of protein processing; ISS:UniProtKB.
DR GO; GO:0051047; P:positive regulation of secretion; ISS:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; ISS:UniProtKB.
DR GO; GO:0048515; P:spermatid differentiation; ISS: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 2: Evidence at transcript level;
KW Apoptosis; Differentiation; Endoplasmic reticulum; Hydrolase; Membrane;
KW Mitochondrion; Protease; Reference proteome; Serine protease;
KW Spermatogenesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..316
FT /note="Rhomboid-related protein 4"
FT /id="PRO_0000254192"
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="Extracellular"
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..182
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..316
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 269..284
FT /note="Ubiquitin-binding domain (UBD)"
FT /evidence="ECO:0000250"
FT REGION 301..316
FT /note="VCP/p97-interacting motif (VIM)"
FT /evidence="ECO:0000250"
FT ACT_SITE 144
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 195
FT /evidence="ECO:0000250"
SQ SEQUENCE 316 AA; 35879 MW; D4625FF07B01091F CRC64;
MQRRTRGIDT GLLLLLSQVF HIGINNIPPV TLATLAVNVW FFLNPWKPLY HSCISVEKCY
QQNDWQRLLL SPVHHGDDWH LYFNMVSMLW KGVKLEKRLG SRWFAYIIAT FSLLTGVVYL
LLQFASAELM NQPDFKRNCA VGFSGVLFAL KVLSNHYCPG GFVNILGFPV PNRFACWAEL
AAIHFCTPGT SFAGHLAGIL VGLMYTQGPL KKIMDACAGI FISNAGSSGQ QYHFNNAGPS
GYQNRYTDGR PVNYEATYRN YDIYTAGLSE EEQLERALRA SIWDRGNTRN GPIPYGFRLP
PEEEMRRQRL HRFDGQ
