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Q9H300

- PARL_HUMAN

UniProt

Q9H300 - PARL_HUMAN

Protein

Presenilins-associated rhomboid-like protein, mitochondrial

Gene

PARL

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 2 (03 Apr 2007)
      Previous versions | rss
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    Functioni

    Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptoptic signals By similarity. Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain.By similarity2 Publications

    Catalytic activityi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei277 – 2771NucleophileBy similarity
    Active sitei335 – 3351By similarity

    GO - Molecular functioni

    1. serine-type endopeptidase activity Source: InterPro

    GO - Biological processi

    1. negative regulation of intrinsic apoptotic signaling pathway Source: Ensembl
    2. negative regulation of release of cytochrome c from mitochondria Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Protein family/group databases

    MEROPSiS54.009.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Presenilins-associated rhomboid-like protein, mitochondrial (EC:3.4.21.105)
    Alternative name(s):
    Mitochondrial intramembrane cleaving protease PARL
    Cleaved into the following chain:
    P-beta
    Short name:
    Pbeta
    Gene namesi
    Name:PARL
    Synonyms:PSARL
    ORF Names:PRO2207
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:18253. PARL.

    Subcellular locationi

    Mitochondrion inner membrane 1 Publication; Multi-pass membrane protein 1 Publication
    Peptide P-beta : Nucleus
    Note: Translocated into the nucleus by an unknown mechanism.

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. mitochondrial inner membrane Source: UniProtKB-SubCell
    3. mitochondrion Source: HPA
    4. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi65 – 651S → D: Strongly reduces the beta cleavage; when associated with D-69 and D-70. 1 Publication
    Mutagenesisi69 – 691T → D: Strongly reduces the beta cleavage; when associated with D-65 and D-70. 1 Publication
    Mutagenesisi70 – 701S → D: Strongly reduces the beta cleavage; when associated with D-65 and D-69. 1 Publication
    Mutagenesisi76 – 761R → E: Abolishes the beta cleavage. 1 Publication
    Mutagenesisi76 – 761R → G: Abolishes the beta cleavage. 1 Publication
    Mutagenesisi77 – 771S → E: Abolishes the beta cleavage. 1 Publication
    Mutagenesisi78 – 781A → E: Abolishes the beta cleavage. 1 Publication
    Mutagenesisi79 – 791L → E: Abolishes the beta cleavage. 1 Publication

    Organism-specific databases

    PharmGKBiPA134939789.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 5252Mitochondrion1 PublicationAdd
    BLAST
    Chaini53 – 379327Presenilins-associated rhomboid-like protein, mitochondrialPRO_0000027386Add
    BLAST
    Peptidei53 – 7725P-beta1 PublicationPRO_0000027387Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei65 – 651Phosphoserine1 Publication
    Modified residuei69 – 691Phosphothreonine1 Publication
    Modified residuei70 – 701Phosphoserine1 Publication

    Post-translational modificationi

    P-beta is proteolytically processed (beta-cleavage) in a PARL-dependent manner. The cleavage is inhibited when residues Ser-65, Thr-69 and Ser-70 are all phosphorylated.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9H300.
    PaxDbiQ9H300.
    PRIDEiQ9H300.

    PTM databases

    PhosphoSiteiQ9H300.

    Miscellaneous databases

    PMAP-CutDBQ9H300.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9H300.
    BgeeiQ9H300.
    CleanExiHS_PARL.
    GenevestigatoriQ9H300.

    Organism-specific databases

    HPAiHPA019545.

    Interactioni

    Subunit structurei

    Interacts with PSEN1 and PSEN2. Binds OPA1.1 Publication

    Protein-protein interaction databases

    BioGridi120678. 2 interactions.
    STRINGi9606.ENSP00000325421.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9H300.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini53 – 10149Mitochondrial matrixSequence AnalysisAdd
    BLAST
    Topological domaini122 – 16746Mitochondrial intermembraneSequence AnalysisAdd
    BLAST
    Topological domaini188 – 20720Mitochondrial matrixSequence AnalysisAdd
    BLAST
    Topological domaini231 – 24414Mitochondrial intermembraneSequence AnalysisAdd
    BLAST
    Topological domaini263 – 27210Mitochondrial matrixSequence Analysis
    Topological domaini290 – 2956Mitochondrial intermembraneSequence Analysis
    Topological domaini319 – 33214Mitochondrial matrixSequence AnalysisAdd
    BLAST
    Topological domaini355 – 37925Mitochondrial intermembraneSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei102 – 12120HelicalSequence AnalysisAdd
    BLAST
    Transmembranei168 – 18720HelicalSequence AnalysisAdd
    BLAST
    Transmembranei208 – 23023HelicalSequence AnalysisAdd
    BLAST
    Transmembranei245 – 26218HelicalSequence AnalysisAdd
    BLAST
    Transmembranei273 – 28917HelicalSequence AnalysisAdd
    BLAST
    Transmembranei296 – 31823HelicalSequence AnalysisAdd
    BLAST
    Transmembranei333 – 35422HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase S54 family.Curated

    Keywords - Domaini

    Transit peptide, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0705.
    HOGENOMiHOG000230670.
    HOVERGENiHBG082107.
    InParanoidiQ9H300.
    KOiK09650.
    OMAiHEMRTNS.
    OrthoDBiEOG7NGQBT.
    PhylomeDBiQ9H300.
    TreeFamiTF313603.

    Family and domain databases

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

    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. Align

    Isoform 1 (identifier: Q9H300-1) [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

    MAWRGWAQRG WGCGQAWGAS VGGRSCEELT AVLTPPQLLG RRFNFFIQQK    50
    CGFRKAPRKV EPRRSDPGTS GEAYKRSALI PPVEETVFYP SPYPIRSLIK 100
    PLFFTVGFTG CAFGSAAIWQ YESLKSRVQS YFDGIKADWL DSIRPQKEGD 150
    FRKEINKWWN NLSDGQRTVT GIIAANVLVF CLWRVPSLQR TMIRYFTSNP 200
    ASKVLCSPML LSTFSHFSLF HMAANMYVLW SFSSSIVNIL GQEQFMAVYL 250
    SAGVISNFVS YVGKVATGRY GPSLGASGAI MTVLAAVCTK IPEGRLAIIF 300
    LPMFTFTAGN ALKAIIAMDT AGMILGWKFF DHAAHLGGAL FGIWYVTYGH 350
    ELIWKNREPL VKIWHEIRTN GPKKGGGSK 379
    Length:379
    Mass (Da):42,190
    Last modified:April 3, 2007 - v2
    Checksum:i2B07EF04C7130B0B
    GO
    Isoform 2 (identifier: Q9H300-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         203-253: KVLCSPMLLSTFSHFSLFHMAANMYVLWSFSSSIVNILGQEQFMAVYLSAG → S

    Show »
    Length:329
    Mass (Da):36,589
    Checksum:i55E752160C632DBF
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti137 – 1371A → G.
    Corresponds to variant rs4912470 [ dbSNP | Ensembl ].
    VAR_029801
    Natural varianti262 – 2621V → L.2 Publications
    Corresponds to variant rs3732581 [ dbSNP | Ensembl ].
    VAR_021578

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei203 – 25351KVLCS…YLSAG → S in isoform 2. 1 PublicationVSP_013310Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF197937 mRNA. Translation: AAG28519.1.
    BC003653 mRNA. Translation: AAH03653.1.
    BC014058 mRNA. Translation: AAH14058.1.
    AF116692 mRNA. Translation: AAF71112.1.
    CCDSiCCDS3248.1. [Q9H300-1]
    CCDS33897.1. [Q9H300-2]
    RefSeqiNP_001032728.1. NM_001037639.1. [Q9H300-2]
    NP_061092.3. NM_018622.5. [Q9H300-1]
    UniGeneiHs.478469.

    Genome annotation databases

    EnsembliENST00000311101; ENSP00000310676; ENSG00000175193. [Q9H300-2]
    ENST00000317096; ENSP00000325421; ENSG00000175193. [Q9H300-1]
    GeneIDi55486.
    KEGGihsa:55486.
    UCSCiuc003fmd.3. human. [Q9H300-1]
    uc003fme.3. human. [Q9H300-2]

    Polymorphism databases

    DMDMi143811433.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF197937 mRNA. Translation: AAG28519.1 .
    BC003653 mRNA. Translation: AAH03653.1 .
    BC014058 mRNA. Translation: AAH14058.1 .
    AF116692 mRNA. Translation: AAF71112.1 .
    CCDSi CCDS3248.1. [Q9H300-1 ]
    CCDS33897.1. [Q9H300-2 ]
    RefSeqi NP_001032728.1. NM_001037639.1. [Q9H300-2 ]
    NP_061092.3. NM_018622.5. [Q9H300-1 ]
    UniGenei Hs.478469.

    3D structure databases

    ProteinModelPortali Q9H300.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 120678. 2 interactions.
    STRINGi 9606.ENSP00000325421.

    Protein family/group databases

    MEROPSi S54.009.

    PTM databases

    PhosphoSitei Q9H300.

    Polymorphism databases

    DMDMi 143811433.

    Proteomic databases

    MaxQBi Q9H300.
    PaxDbi Q9H300.
    PRIDEi Q9H300.

    Protocols and materials databases

    DNASUi 55486.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000311101 ; ENSP00000310676 ; ENSG00000175193 . [Q9H300-2 ]
    ENST00000317096 ; ENSP00000325421 ; ENSG00000175193 . [Q9H300-1 ]
    GeneIDi 55486.
    KEGGi hsa:55486.
    UCSCi uc003fmd.3. human. [Q9H300-1 ]
    uc003fme.3. human. [Q9H300-2 ]

    Organism-specific databases

    CTDi 55486.
    GeneCardsi GC03M183547.
    HGNCi HGNC:18253. PARL.
    HPAi HPA019545.
    MIMi 607858. gene.
    neXtProti NX_Q9H300.
    PharmGKBi PA134939789.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0705.
    HOGENOMi HOG000230670.
    HOVERGENi HBG082107.
    InParanoidi Q9H300.
    KOi K09650.
    OMAi HEMRTNS.
    OrthoDBi EOG7NGQBT.
    PhylomeDBi Q9H300.
    TreeFami TF313603.

    Miscellaneous databases

    GeneWikii PARL.
    GenomeRNAii 55486.
    NextBioi 59867.
    PMAP-CutDB Q9H300.
    PROi Q9H300.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9H300.
    Bgeei Q9H300.
    CleanExi HS_PARL.
    Genevestigatori Q9H300.

    Family and domain databases

    Gene3Di 1.20.1540.10. 1 hit.
    InterProi IPR002610. Peptidase_S54_rhomboid.
    IPR022764. Peptidase_S54_rhomboid_dom.
    [Graphical view ]
    PANTHERi PTHR22936. PTHR22936. 1 hit.
    Pfami PF01694. Rhomboid. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of presenilin-1 and -2."
      Pellegrini L., Passer B.J., Canelles M., Lefterov I., Ganjei J.K., Fowlkes B.J., Koonin E.V., D'Adamio L.
      J. Alzheimers Dis. 3:181-190(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-262, INTERACTION WITH PSEN1 AND PSEN2.
    2. "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: Lung.
    3. "Functional prediction of the coding sequences of 121 new genes deduced by analysis of cDNA clones from human fetal liver."
      Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Ouyang S., Luo L., Bi J., Liu M., He F.
      Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 192-379 (ISOFORM 1), VARIANT LEU-262.
      Tissue: Fetal liver.
    4. "Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pbeta, a nuclear-targeted peptide."
      Sik A., Passer B.J., Koonin E.V., Pellegrini L.
      J. Biol. Chem. 279:15323-15329(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 53-61 AND 78-85, FUNCTION IN BETA CLEAVAGE, MUTAGENESIS OF ARG-76; SER-77; ALA-78 AND LEU-79.
    5. "Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology."
      Jeyaraju D.V., Xu L., Letellier M.-C., Bandaru S., Zunino R., Berg E.A., McBride H.M., Pellegrini L.
      Proc. Natl. Acad. Sci. U.S.A. 103:18562-18567(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT SER-65; THR-69 AND SER-70 OF P-BETA, MUTAGENESIS OF SER-65; THR-69 AND SER-70, SUBCELLULAR LOCATION, TOPOLOGY, BETA-CLEAVAGE.

    Entry informationi

    Entry nameiPARL_HUMAN
    AccessioniPrimary (citable) accession number: Q9H300
    Secondary accession number(s): Q96CQ4, Q9BTJ6, Q9P1E3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 12, 2005
    Last sequence update: April 3, 2007
    Last modified: October 1, 2014
    This is version 115 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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 3
      Human chromosome 3: 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

    External Data

    Dasty 3