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Protein

Rhomboid-related protein 2

Gene

RHBDL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. Known substrate: EFNB3.2 Publications

Catalytic activityi

Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei187 – 1871Nucleophile
Active sitei250 – 2501

GO - Molecular functioni

  • serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.105. 2681.

Protein family/group databases

MEROPSiS54.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Rhomboid-related protein 2 (EC:3.4.21.105)
Short name:
RRP2
Alternative name(s):
Rhomboid-like protein 2
Cleaved into the following 2 chains:
Gene namesi
Name:RHBDL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:16083. RHBDL2.

Subcellular locationi

Rhomboid-related protein 2, C-terminal fragment :
  • Cell membrane 1 Publication; Multi-pass membrane protein Sequence analysis

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei72 – 9221HelicalSequence analysisAdd
BLAST
Transmembranei128 – 14821HelicalSequence analysisAdd
BLAST
Transmembranei159 – 17921HelicalSequence analysisAdd
BLAST
Transmembranei183 – 20321HelicalSequence analysisAdd
BLAST
Transmembranei212 – 23221HelicalSequence analysisAdd
BLAST
Transmembranei245 – 26521HelicalSequence analysisAdd
BLAST
Transmembranei278 – 29821HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: GO_Central
  • mitochondrial inner membrane Source: GO_Central
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi121 – 1211W → A: Reduces protease activity. 2 Publications
Mutagenesisi122 – 1221R → A: Abolishes protease activity, prevents processing and alters localization to the plasma membrane of N-terminal fragment. 2 Publications
Mutagenesisi139 – 1391N → A: Reduces protease activity. 1 Publication
Mutagenesisi185 – 1851G → A: Abolishes protease activity. 1 Publication
Mutagenesisi187 – 1871S → A or G: Abolishes protease activity. 2 Publications
Mutagenesisi250 – 2501H → A: Abolishes protease activity. 1 Publication

Organism-specific databases

PharmGKBiPA34383.

Polymorphism and mutation databases

BioMutaiRHBDL2.
DMDMi59800189.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 303Rhomboid-related protein 2, C-terminal fragmentPRO_0000408509
Chaini1 – 303303Rhomboid-related protein 2PRO_0000206176Add
BLAST
Chaini1 – ?Rhomboid-related protein 2, N-terminal fragmentPRO_0000408510

Post-translational modificationi

Proteolytic processing of the proenzyme produces a N-terminal fragment (NTF) and a C-terminal fragment (CTF). The processing is required for activation of the protease.1 Publication

Proteomic databases

MaxQBiQ9NX52.
PaxDbiQ9NX52.
PeptideAtlasiQ9NX52.
PRIDEiQ9NX52.

PTM databases

iPTMnetiQ9NX52.
PhosphoSiteiQ9NX52.

Expressioni

Gene expression databases

BgeeiQ9NX52.
CleanExiHS_RHBDL2.
GenevisibleiQ9NX52. HS.

Organism-specific databases

HPAiHPA043807.

Interactioni

Protein-protein interaction databases

BioGridi120273. 2 interactions.
STRINGi9606.ENSP00000289248.

Structurei

3D structure databases

ProteinModelPortaliQ9NX52.
SMRiQ9NX52. Positions 70-264.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi22 – 287Poly-Glu

Sequence similaritiesi

Belongs to the peptidase S54 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2289. Eukaryota.
COG0705. LUCA.
GeneTreeiENSGT00390000005726.
HOGENOMiHOG000231407.
HOVERGENiHBG105855.
InParanoidiQ9NX52.
KOiK02857.
OMAiWMLPEKV.
OrthoDBiEOG7SN8CK.
PhylomeDBiQ9NX52.
TreeFamiTF313540.

Family and domain databases

Gene3Di1.20.1540.10. 1 hit.
InterProiIPR002610. Peptidase_S54_rhomboid.
IPR022764. Peptidase_S54_rhomboid_dom.
IPR017213. Peptidase_S54_rhomboid_met.
[Graphical view]
PANTHERiPTHR22936. PTHR22936. 1 hit.
PfamiPF01694. Rhomboid. 1 hit.
[Graphical view]
PIRSFiPIRSF037470. Rhomboid. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NX52-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAVHDLEME SMNLNMGREM KEELEEEEKM REDGGGKDRA KSKKVHRIVS
60 70 80 90 100
KWMLPEKSRG TYLERANCFP PPVFIISISL AELAVFIYYA VWKPQKQWIT
110 120 130 140 150
LDTGILESPF IYSPEKREEA WRFISYMLVH AGVQHILGNL CMQLVLGIPL
160 170 180 190 200
EMVHKGLRVG LVYLAGVIAG SLASSIFDPL RYLVGASGGV YALMGGYFMN
210 220 230 240 250
VLVNFQEMIP AFGIFRLLII ILIIVLDMGF ALYRRFFVPE DGSPVSFAAH
260 270 280 290 300
IAGGFAGMSI GYTVFSCFDK ALLKDPRFWI AIAAYLACVL FAVFFNIFLS

PAN
Length:303
Mass (Da):34,021
Last modified:February 1, 2005 - v2
Checksum:i2B6CB8291319C2D9
GO
Isoform 2 (identifier: Q9NX52-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     133-303: Missing.

Note: May be due to an intron retention. No experimental confirmation available.
Show »
Length:132
Mass (Da):15,442
Checksum:i38D3DBFBF34BC528
GO

Sequence cautioni

The sequence AAH13103.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA91168.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti273 – 2731L → M.
Corresponds to variant rs2147914 [ dbSNP | Ensembl ].
VAR_020328

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei133 – 303171Missing in isoform 2. 1 PublicationVSP_012692Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY126343 mRNA. Translation: AAM95697.1.
AL139260 Genomic DNA. Translation: CAI23052.1.
BC013103 mRNA. Translation: AAH13103.1. Different initiation.
BC137108 mRNA. Translation: AAI37109.1.
BC137110 mRNA. Translation: AAI37111.1.
AK000442 mRNA. Translation: BAA91168.1. Different initiation.
CCDSiCCDS30680.1. [Q9NX52-1]
RefSeqiNP_060291.2. NM_017821.4. [Q9NX52-1]
UniGeneiHs.524626.

Genome annotation databases

EnsembliENST00000289248; ENSP00000289248; ENSG00000158315. [Q9NX52-1]
ENST00000372990; ENSP00000362081; ENSG00000158315. [Q9NX52-1]
ENST00000540558; ENSP00000441097; ENSG00000158315. [Q9NX52-3]
GeneIDi54933.
KEGGihsa:54933.
UCSCiuc001ccu.1. human. [Q9NX52-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY126343 mRNA. Translation: AAM95697.1.
AL139260 Genomic DNA. Translation: CAI23052.1.
BC013103 mRNA. Translation: AAH13103.1. Different initiation.
BC137108 mRNA. Translation: AAI37109.1.
BC137110 mRNA. Translation: AAI37111.1.
AK000442 mRNA. Translation: BAA91168.1. Different initiation.
CCDSiCCDS30680.1. [Q9NX52-1]
RefSeqiNP_060291.2. NM_017821.4. [Q9NX52-1]
UniGeneiHs.524626.

3D structure databases

ProteinModelPortaliQ9NX52.
SMRiQ9NX52. Positions 70-264.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120273. 2 interactions.
STRINGi9606.ENSP00000289248.

Protein family/group databases

MEROPSiS54.002.

PTM databases

iPTMnetiQ9NX52.
PhosphoSiteiQ9NX52.

Polymorphism and mutation databases

BioMutaiRHBDL2.
DMDMi59800189.

Proteomic databases

MaxQBiQ9NX52.
PaxDbiQ9NX52.
PeptideAtlasiQ9NX52.
PRIDEiQ9NX52.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000289248; ENSP00000289248; ENSG00000158315. [Q9NX52-1]
ENST00000372990; ENSP00000362081; ENSG00000158315. [Q9NX52-1]
ENST00000540558; ENSP00000441097; ENSG00000158315. [Q9NX52-3]
GeneIDi54933.
KEGGihsa:54933.
UCSCiuc001ccu.1. human. [Q9NX52-1]

Organism-specific databases

CTDi54933.
GeneCardsiRHBDL2.
HGNCiHGNC:16083. RHBDL2.
HPAiHPA043807.
MIMi608962. gene.
neXtProtiNX_Q9NX52.
PharmGKBiPA34383.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2289. Eukaryota.
COG0705. LUCA.
GeneTreeiENSGT00390000005726.
HOGENOMiHOG000231407.
HOVERGENiHBG105855.
InParanoidiQ9NX52.
KOiK02857.
OMAiWMLPEKV.
OrthoDBiEOG7SN8CK.
PhylomeDBiQ9NX52.
TreeFamiTF313540.

Enzyme and pathway databases

BRENDAi3.4.21.105. 2681.

Miscellaneous databases

ChiTaRSiRHBDL2. human.
GenomeRNAii54933.
PROiQ9NX52.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NX52.
CleanExiHS_RHBDL2.
GenevisibleiQ9NX52. HS.

Family and domain databases

Gene3Di1.20.1540.10. 1 hit.
InterProiIPR002610. Peptidase_S54_rhomboid.
IPR022764. Peptidase_S54_rhomboid_dom.
IPR017213. Peptidase_S54_rhomboid_met.
[Graphical view]
PANTHERiPTHR22936. PTHR22936. 1 hit.
PfamiPF01694. Rhomboid. 1 hit.
[Graphical view]
PIRSFiPIRSF037470. Rhomboid. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of RHBDL2, a novel rhomboid-like gene, in human development."
    Jiao W., Yuan W., Wu X.
    Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Adrenal cortex and Testis.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-303 (ISOFORM 1).
    Tissue: Gastric carcinoma.
  5. "Drosophila Rhomboid-1 defines a family of putative intramembrane serine proteases."
    Urban S., Lee J.R., Freeman M.
    Cell 107:173-182(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF TRP-121; ARG-122; ASN-139; GLY-185; SER-187 AND HIS-250.
  6. "Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL2."
    Pascall J.C., Brown K.D.
    Biochem. Biophys. Res. Commun. 317:244-252(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF SER-187.
  7. "The processing of human rhomboid intramembrane serine protease RHBDL2 is required for its proteolytic activity."
    Lei X., Li Y.M.
    J. Mol. Biol. 394:815-825(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, PROTEOLYTIC PROCESSING, MUTAGENESIS OF TRP-121 AND ARG-122, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiRHBL2_HUMAN
AccessioniPrimary (citable) accession number: Q9NX52
Secondary accession number(s): B2RNT3
, B9EH75, Q6P175, Q8NER8, Q96E02
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: February 1, 2005
Last modified: July 6, 2016
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.