RHBL4_PONAB
ID RHBL4_PONAB Reviewed; 318 AA.
AC Q5RBS4;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 70.
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 AltName: Full=Rhomboid-like protein 4;
GN Name=RHBDD1; Synonyms=RHBDL4;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 -!- 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}.
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DR EMBL; CR858560; CAH90786.1; -; mRNA.
DR RefSeq; NP_001125444.1; NM_001131972.1.
DR AlphaFoldDB; Q5RBS4; -.
DR SMR; Q5RBS4; -.
DR STRING; 9601.ENSPPYP00000014790; -.
DR MEROPS; S54.008; -.
DR GeneID; 100172352; -.
DR KEGG; pon:100172352; -.
DR CTD; 84236; -.
DR eggNOG; KOG2632; Eukaryota.
DR InParanoid; Q5RBS4; -.
DR Proteomes; UP000001595; Unplaced.
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: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: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..318
FT /note="Rhomboid-related protein 4"
FT /id="PRO_0000254191"
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..106
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..127
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..137
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 155..179
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..318
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 271..286
FT /note="Ubiquitin-binding domain (UBD)"
FT /evidence="ECO:0000250"
FT REGION 285..318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 303..318
FT /note="VCP/p97-interacting motif (VIM)"
FT /evidence="ECO:0000250"
FT COMPBIAS 302..318
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 144
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 195
FT /evidence="ECO:0000250"
SQ SEQUENCE 318 AA; 36128 MW; F1304BAF27D8AC97 CRC64;
MQRRSRGINT GLILLLSQIF HVGINNIPPV TLATLALNIW FFLNPQKPLY SSCLSVEKCY
QQRDWQRLLL SPLHHADDWH LYFNTASVLW KGINLERRLG SRWFAYVITT FSVLTGVVYL
LLQFAVAEFM DEPDFKRSCA VGFSGVLFAL KVLNNHYCPG GFVNILGFPV PNRFACWVEL
VAIHLFSPGT SFAGHQAGIL VGLMYTQGPL KKIMEACAGL GGFSSSVGYP GQQYYFNSSG
SSGYQDYYPH GRPDHYEEAP RNYDTYTAGL SEEEQLERAL QASLWDRGHT RNSPPPYGFH
LSPEEEMRRQ RLHRFDSQ
