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Information on EC 3.4.21.105 - rhomboid protease and Organism(s) Homo sapiens and UniProt Accession Q9NX52

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.105 rhomboid protease
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This record set is specific for:
Homo sapiens
UNIPROT: Q9NX52 not found.
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Word Map
  • 3.4.21.105
  • flap
  • drosophila
  • medial
  • dorsal
  • posterior
  • ventral
  • glossitis
  • midline
  • trapezius
  • shoulder
  • thalamic
  • scapula
  • fossa
  • pilonidal
  • reuniens
  • serratus
  • paraventricular
  • levator
  • er-associated
  • intercostal
  • ventromedial
  • ventrolateral
  • mediodorsal
  • intralaminar
  • parafascicular
  • sacrococcygeal
  • abduct
  • electromyographic
  • paracentral
  • retrotranslocation
  • aesthetic
  • latissimus
  • cheilitis
  • birefringent
  • erector
  • anteroventral
  • nicastrin
  • anteromedial
  • supraspinatus
  • incerta
  • clavicle
  • myofascial
  • site-2
  • argos
  • extradural
  • seromas
  • petrous
  • infraspinatus
  • gurken
  • glenohumeral
  • analysis
  • medicine
  • molecular biology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains
Synonyms
rhomboid, derlin-1, rhbdd1, rhomboid protease, intramembrane protease, rhbdl2, rhbdl4, rhomboid protein, ehrom1, rho-4, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
presenilin associated rhomboid like protein
-
-
presenilin-associated rhomboid-like
-
-
presenilin-associated rhomboid-like protein
presenilins-associated rhomboid-like protein
-
-
PSARL
-
-
RHBDL
-
-
RHBDL2
RHBDL4
RHDBL-2
-
-
rhomboid intramembrane protease
-
-
rhomboid protease
-
-
rhomboid protease PSARL
-
-
rhomboid pseudoprotease
-
rhomboid-like protein
-
-
rhomboid-related protein 4
-
CAS REGISTRY NUMBER
COMMENTARY hide
713145-02-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Gurken-transmembrane domain + H2O
?
show the reaction diagram
-
-
-
?
Spitz-transmembrane domain + H2O
?
show the reaction diagram
little activity
-
-
?
adhesion protein from Toxoplasma gondii + H2O
?
show the reaction diagram
-
MIC-2, MIC-6 and MIC-12 are efficient substrates
-
-
?
alpha chain of pre-T cell receptor + H2O
?
show the reaction diagram
constitutively active receptor variant required for T cell development. cleavage contributes to ER-associated degradation, cleavage productsare translocated and degraded by the proteasome
-
-
?
amyloid precursor protein + H2O
?
show the reaction diagram
-
-
-
-
?
ephrin B3 + H2O
?
show the reaction diagram
epidermal growth factor + H2O
?
show the reaction diagram
-
efficient and specific substrate for rhomboid protease RHBDL2
-
-
?
myelin protein zero mutant L170R + H2O
?
show the reaction diagram
mutant form is unstable and efficiently cleaved by isoform RHBDL4. Wild-type myelin protein zero is not a substrate
-
-
?
opsin mutant bearing TCRalpha degron motif + H2O
?
show the reaction diagram
opsin-degron mutant is degraded by isoform RHBDL4, whereas the wild-type protein is stable
-
-
?
phosphoglycerate mutase 5 + H2O
?
show the reaction diagram
mitochondrial Ser/Thr protein phosphatase PGAM5
substrate is cleaved in its N-terminal transmembrane domain in response to mitochondrial membrane potential loss and mediated by presenilin-associated rhomboid-like protein. In response to membrane potential loss, the enzyme dissociates from substrate PINK1, a mitochondrial Ser/Thr protein kinase, and reciprocally associates with substrate PGAM5. Results suggest that the enzyme mediates differential cleavage of PINK1 and PGAM5 depending on the health status of mitochondria
-
?
polycystin-1 + H2O
?
show the reaction diagram
11-TM spanning membrane protein. Isoform RHBDL4 cleaves several truncated versions of polycystin-1 at luminal loops or juxtamembrane transmembrane regions. Wild-type olycystin-1 is not a substrate
-
-
?
protein Spitz + H2O
?
show the reaction diagram
-
UniProt Accession Code QRHBDL2 cleaves the membrane domain of Drosophila protein Spitz, when the proteins are coexpressed in mammalian cells
-
-
?
Spitz + H2O
?
show the reaction diagram
Spitz protein + H2O
?
show the reaction diagram
-
-
-
-
?
thrombomodulin + H2O
?
show the reaction diagram
-
human thrombomodulin is cleaved by the human, mouse and zebrafish RHBDL2, but not by the Drosophila Rhomboid-1 and the bacterial Aara rhomboid proteases
-
-
?
thrombomodulin + H2O
soluble thrombomodulin + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ephrin B3 + H2O
?
show the reaction diagram
-
RHBDL-2 mediated proteolytic processing may regulate intercellular interactions between ephrinB3 and eph receptors
-
-
?
epidermal growth factor + H2O
?
show the reaction diagram
-
efficient and specific substrate for rhomboid protease RHBDL2
-
-
?
Spitz + H2O
?
show the reaction diagram
-
the rhomboid active site in directly cleaves the membrane-anchored TGFalpha-like growth factor Spitz within its transmembarne domain
-
-
?
Spitz protein + H2O
?
show the reaction diagram
-
-
-
-
?
thrombomodulin + H2O
soluble thrombomodulin + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3,4-dichloroisocoumarin
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
vastus lateralis. Expression of rhomboid protease PSARL is associated with mitochondrial oxidative capacity and insulin sensitivity
Manually annotated by BRENDA team
additional information
-
RHBDL2 expression is low or absent in HEK-293T, SW-480, HCT-116, MB-453 and COS-7 cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
rhomboid displays a rapid diffusion comparable to the diffusion of small, single-pass transmembrane proteins, with a diffusion coefficient of about 0.8 microm2 per s. The rhomboid fold is able to distort surrounding lipids, overcome the viscosity limit of the membrane, and accelerate its search for substrates
malfunction
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
RHBL2_HUMAN
303
6
34021
Swiss-Prot
other Location (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
determination and classification of intramembrane rhomboid topology, modeling, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
L262V
R111A
-
processing of RHBDL2 is totally abolished
S144A
-
inactive
W110A
-
when cells are transfected with W110A, RHBDL2 is processed
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence analysis, phylogenetic analysis, overview
-
expressed in COS-1 cells as a myc-tagged fusion protein by transient transfection
-
HEK 293 cells transfected with a FLAG-tagged PARL construct
-
phylogenetic analysis
-
transfection of HEK-293T cell
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
rhombopid protease RHBDL2 is upregulated in HaCaT cells stimulated by scratch wounds. RHBDL2 is also upregulated in ex vivo tissue culture of the injured skin (3-5 days after incision)
-
treatment with tunicamycin leads to increase level in enzyme protein
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pascall, J.C.; Brown, K.D.
Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL2
Biochem. Biophys. Res. Commun.
317
244-252
2004
Homo sapiens
Manually annotated by BRENDA team
Urban, S.; Lee, J.R.; Freeman, M.
Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases
Cell
107
173-182
2001
Drosophila sp. (in: flies), Homo sapiens
Manually annotated by BRENDA team
Walder, K.; Kerr-Bayles, L.; Civitarese, A.; Jowett, J.; Curran, J.; Elliott, K.; Trevaskis, J.; Bishara, N.; Zimmet, P.; Mandarino, L.; Ravussin, E.; Blangero, J.; Kissebah, A.; Collier, G.R.
The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes
Diabetologia
48
459-468
2005
Homo sapiens, Psammomys obesus
Manually annotated by BRENDA team
Lemberg, M.K.; Menendez, J.; Misik, A.; Garcia, M.; Koth, C.M.; Freeman, M.
Mechanism of intramembrane proteolysis investigated with purified rhomboid proteases
EMBO J.
24
464-472
2005
Aquifex aeolicus, Bacillus subtilis, Drosophila sp. (in: flies), Escherichia coli, Providencia stuartii, Pseudomonas aeruginosa, Homo sapiens (Q9NX52)
Manually annotated by BRENDA team
Sik, A.; Passer, B.J.; Koonin, E.V.; Pellegrini, L.
Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pbeta, a nuclear-targeted peptide
J. Biol. Chem.
279
15323-15329
2004
Homo sapiens
Manually annotated by BRENDA team
Urban, S.; Freeman, M.
Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain
Mol. Cell
11
1425-1434
2003
Drosophila sp. (in: flies), Homo sapiens
Manually annotated by BRENDA team
Urban, S.
Rhomboid proteins: conserved membrane proteases with divergent biological functions
Genes Dev.
20
3054-3068
2006
Arabidopsis thaliana, Bacillus subtilis, Saccharomyces cerevisiae, Drosophila melanogaster, Escherichia coli, Homo sapiens, Providencia stuartii, Toxoplasma gondii
Manually annotated by BRENDA team
Lemberg, M.K.; Freeman, M.
Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases
Genome Res.
17
1634-1646
2007
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Mus musculus, Plasmodium falciparum, Toxoplasma gondii, Escherichia coli (P09391), Providencia stuartii (P46116), Bacillus subtilis (P54493), Pseudomonas aeruginosa (Q9HZC2)
Manually annotated by BRENDA team
Hatunic, M.; Stapleton, M.; Hand, E.; DeLong, C.; Crowley, V.E.; Nolan, J.J.
The Leu262Val polymorphism of presenilin associated rhomboid like protein (PARL) is associated with earlier onset of type 2 diabetes and increased urinary microalbumin creatinine ratio in an Irish case-control population
Diabetes Res. Clin. Pract.
83
316-319
2009
Homo sapiens
Manually annotated by BRENDA team
Curran, J.E.; Jowett, J.B.; Abraham, L.J.; Diepeveen, L.A.; Elliott, K.S.; Dyer, T.D.; Kerr-Bayles, L.J.; Johnson, M.P.; Comuzzie, A.G.; Moses, E.K.; Walder, K.R.; Collier, G.R.; Blangero, J.; Kissebah, A.H.
Genetic variation in PARL influences mitochondrial content
Hum. Genet.
127
183-190
2010
Homo sapiens
Manually annotated by BRENDA team
Lei, X.; Li, Y.M.
The processing of human rhomboid intramembrane serine protease RHBDL2 is required for its proteolytic activity
J. Mol. Biol.
394
815-825
2009
Homo sapiens
Manually annotated by BRENDA team
Hill, R.B.; Pellegrini, L.
The PARL family of mitochondrial rhomboid proteases
Semin. Cell Dev. Biol.
21
582-592
2010
Danio rerio, Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Mus musculus, Providencia stuartii, Schizosaccharomyces pombe, Escherichia coli (P09391)
Manually annotated by BRENDA team
Adrain, C.; Strisovsky, K.; Zettl, M.; Hu, L.; Lemberg, M.K.; Freeman, M.
Mammalian EGF receptor activation by the rhomboid protease RHBDL2
EMBO Rep.
12
421-427
2011
Homo sapiens
Manually annotated by BRENDA team
Cheng, T.L.; Wu, Y.T.; Lin, H.Y.; Hsu, F.C.; Liu, S.K.; Chang, B.I.; Chen, W.S.; Lai, C.H.; Shi, G.Y.; Wu, H.L.
Functions of rhomboid family protease RHBDL2 and thrombomodulin in wound healing
J. Invest. Dermatol.
131
2486-2494
2011
Homo sapiens
Manually annotated by BRENDA team
Greenblatt, E.J.; Olzmann, J.A.; Kopito, R.R.
Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant alpha-1 antitrypsin from the endoplasmic reticulum
Nat. Struct. Mol. Biol.
18
1147-1152
2011
Homo sapiens (Q9BUN8), Homo sapiens
Manually annotated by BRENDA team
Sekine, S.; Kanamaru, Y.; Koike, M.; Nishihara, A.; Okada, M.; Kinoshita, H.; Kamiyama, M.; Maruyama, J.; Uchiyama, Y.; Ishihara, N.; Takeda, K.; Ichijo, H.
Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5
J. Biol. Chem.
287
34635-34645
2012
Homo sapiens (Q9H300)
Manually annotated by BRENDA team
Fleig, L.; Bergbold, N.; Sahasrabudhe, P.; Geiger, B.; Kaltak, L.; Lemberg, M.K.
Ubiquitin-dependent intramembrane rhomboid protease promotes ERAD of membrane proteins
Mol. Cell
47
558-569
2012
Homo sapiens (Q8TEB9)
Manually annotated by BRENDA team
Recinto, S.J.; Paschkowsky, S.; Munter, L.M.
An alternative processing pathway of APP reveals two distinct cleavage modes for rhomboid protease RHBDL4
Biol. Chem.
399
1399-1408
2018
Homo sapiens
Manually annotated by BRENDA team
Kreutzberger, A.J.B.; Ji, M.; Aaron, J.; Mihaljevic, L.; Urban, S.
Rhomboid distorts lipids to break the viscosity-imposed speed limit of membrane diffusion
Science
363
eaao0076
2019
Escherichia coli, Homo sapiens (Q9NX52)
Manually annotated by BRENDA team