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P49821

- NDUV1_HUMAN

UniProt

P49821 - NDUV1_HUMAN

Protein

NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial

Gene

NDUFV1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 153 (01 Oct 2014)
      Sequence version 4 (02 May 2002)
      Previous versions | rss
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    Functioni

    Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone By similarity.By similarity

    Catalytic activityi

    NADH + ubiquinone + 5 H+(In) = NAD+ + ubiquinol + 4 H+(Out).
    NADH + acceptor = NAD+ + reduced acceptor.

    Cofactori

    Binds 1 FMN.Curated
    Binds 1 4Fe-4S cluster.Curated

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi379 – 3791Iron-sulfur (4Fe-4S)Sequence Analysis
    Metal bindingi382 – 3821Iron-sulfur (4Fe-4S)Sequence Analysis
    Metal bindingi385 – 3851Iron-sulfur (4Fe-4S)Sequence Analysis
    Metal bindingi425 – 4251Iron-sulfur (4Fe-4S)Sequence Analysis

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi87 – 9610NAD(H)By similarity
    Nucleotide bindingi199 – 24749FMNBy similarityAdd
    BLAST

    GO - Molecular functioni

    1. 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
    2. FMN binding Source: InterPro
    3. metal ion binding Source: UniProtKB-KW
    4. NAD binding Source: InterPro
    5. NADH dehydrogenase (ubiquinone) activity Source: UniProtKB

    GO - Biological processi

    1. cellular metabolic process Source: Reactome
    2. mitochondrial electron transport, NADH to ubiquinone Source: UniProtKB
    3. respiratory electron transport chain Source: Reactome
    4. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Electron transport, Respiratory chain, Transport

    Keywords - Ligandi

    4Fe-4S, Flavoprotein, FMN, Iron, Iron-sulfur, Metal-binding, NAD, Ubiquinone

    Enzyme and pathway databases

    ReactomeiREACT_22393. Respiratory electron transport.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial (EC:1.6.5.3, EC:1.6.99.3)
    Alternative name(s):
    Complex I-51kD
    Short name:
    CI-51kD
    NADH dehydrogenase flavoprotein 1
    NADH-ubiquinone oxidoreductase 51 kDa subunit
    Gene namesi
    Name:NDUFV1
    Synonyms:UQOR1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:7716. NDUFV1.

    Subcellular locationi

    GO - Cellular componenti

    1. mitochondrial inner membrane Source: UniProtKB
    2. mitochondrial respiratory chain complex I Source: UniProtKB

    Keywords - Cellular componenti

    Membrane, Mitochondrion, Mitochondrion inner membrane

    Pathology & Biotechi

    Involvement in diseasei

    Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti423 – 4231T → M in LS. 1 Publication
    VAR_008847
    Mitochondrial complex I deficiency (MT-C1D) [MIM:252010]: A disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti214 – 2141E → K in MT-C1D. 1 Publication
    VAR_019534
    Natural varianti341 – 3411A → V in MT-C1D. 1 Publication
    VAR_008846

    Keywords - Diseasei

    Disease mutation, Leigh syndrome

    Organism-specific databases

    MIMi252010. phenotype.
    256000. phenotype.
    Orphaneti2609. Isolated NADH-CoQ reductase deficiency.
    255241. Leigh syndrome with leukodystrophy.
    PharmGKBiPA31526.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 2020MitochondrionBy similarityAdd
    BLAST
    Chaini21 – 464444NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrialPRO_0000019976Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei81 – 811N6-acetyllysine; alternateBy similarity
    Modified residuei81 – 811N6-succinyllysine; alternateBy similarity
    Modified residuei104 – 1041N6-acetyllysineBy similarity
    Modified residuei375 – 3751N6-acetyllysineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiP49821.
    PaxDbiP49821.
    PRIDEiP49821.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00028520.
    IPI00221298.

    PTM databases

    PhosphoSiteiP49821.

    Expressioni

    Gene expression databases

    ArrayExpressiP49821.
    BgeeiP49821.
    CleanExiHS_NDUFV1.
    GenevestigatoriP49821.

    Organism-specific databases

    HPAiHPA045211.

    Interactioni

    Subunit structurei

    Complex I is composed of 45 different subunits. This is a component of the flavoprotein-sulfur (FP) fragment of the enzyme.1 Publication

    Protein-protein interaction databases

    BioGridi110802. 36 interactions.
    IntActiP49821. 4 interactions.
    MINTiMINT-1444762.
    STRINGi9606.ENSP00000322450.

    Structurei

    3D structure databases

    ProteinModelPortaliP49821.
    SMRiP49821. Positions 38-445.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the complex I 51 kDa subunit family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG1894.
    HOVERGENiHBG006542.
    InParanoidiP49821.
    KOiK03942.
    OMAiKWSFMNP.
    OrthoDBiEOG7327NS.
    PhylomeDBiP49821.
    TreeFamiTF300381.

    Family and domain databases

    InterProiIPR001949. NADH-UbQ_OxRdtase_51kDa_CS.
    IPR019575. NADH-UbQ_OxRdtase_Fsu_4Fe4S-bd.
    IPR011537. NADH-UbQ_OxRdtase_suF.
    IPR011538. NADH_UbQ_OxRdtase_51kDa_su.
    IPR019554. Soluble_ligand-bd.
    [Graphical view]
    PfamiPF01512. Complex1_51K. 1 hit.
    PF10589. NADH_4Fe-4S. 1 hit.
    PF10531. SLBB. 1 hit.
    [Graphical view]
    SMARTiSM00928. NADH_4Fe-4S. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR01959. nuoF_fam. 1 hit.
    PROSITEiPS00644. COMPLEX1_51K_1. 1 hit.
    PS00645. COMPLEX1_51K_2. 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: P49821-1) [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

    MLATRRLLGW SLPARVSVRF SGDTTAPKKT SFGSLKDEDR IFTNLYGRHD    50
    WRLKGSLSRG DWYKTKEILL KGPDWILGEI KTSGLRGRGG AGFPTGLKWS 100
    FMNKPSDGRP KYLVVNADEG EPGTCKDREI LRHDPHKLLE GCLVGGRAMG 150
    ARAAYIYIRG EFYNEASNLQ VAIREAYEAG LIGKNACGSG YDFDVFVVRG 200
    AGAYICGEET ALIESIEGKQ GKPRLKPPFP ADVGVFGCPT TVANVETVAV 250
    SPTICRRGGT WFAGFGRERN SGTKLFNISG HVNHPCTVEE EMSVPLKELI 300
    EKHAGGVTGG WDNLLAVIPG GSSTPLIPKS VCETVLMDFD ALVQAQTGLG 350
    TAAVIVMDRS TDIVKAIARL IEFYKHESCG QCTPCREGVD WMNKVMARFV 400
    RGDARPAEID SLWEISKQIE GHTICALGDG AAWPVQGLIR HFRPELEERM 450
    QRFAQQHQAR QAAS 464
    Length:464
    Mass (Da):50,817
    Last modified:May 2, 2002 - v4
    Checksum:i8C261EA3B0267256
    GO
    Isoform 2 (identifier: P49821-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         16-24: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:455
    Mass (Da):49,868
    Checksum:i14B14974F7966121
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti80 – 801I → V in AAB24883. (PubMed:1478657)Curated
    Sequence conflicti150 – 1501G → A in AAB29698. (PubMed:8288251)Curated
    Sequence conflicti306 – 3061G → F in CAA76757. (PubMed:9892733)Curated
    Sequence conflicti313 – 3131N → Y in CAA76757. (PubMed:9892733)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti76 – 761I → V.
    Corresponds to variant rs1800670 [ dbSNP | Ensembl ].
    VAR_014480
    Natural varianti214 – 2141E → K in MT-C1D. 1 Publication
    VAR_019534
    Natural varianti277 – 2771N → Y.
    Corresponds to variant rs1043770 [ dbSNP | Ensembl ].
    VAR_014481
    Natural varianti341 – 3411A → V in MT-C1D. 1 Publication
    VAR_008846
    Natural varianti423 – 4231T → M in LS. 1 Publication
    VAR_008847

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei16 – 249Missing in isoform 2. 1 PublicationVSP_003730

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y17379
    , Y17380, Y17381, Y17382, Y17383 Genomic DNA. Translation: CAA76757.1.
    AF053069 Genomic DNA. Translation: AAC39750.1.
    AF053070 mRNA. Translation: AAC39722.1.
    AF092131 mRNA. Translation: AAD40373.1.
    CR456739 mRNA. Translation: CAG33020.1.
    CH471076 Genomic DNA. Translation: EAW74655.1.
    BC008146 mRNA. Translation: AAH08146.1.
    BC015645 mRNA. Translation: AAH15645.1.
    AH004147 Genomic DNA. Translation: AAB24883.1.
    S67973 mRNA. Translation: AAB29698.2. Sequence problems.
    CCDSiCCDS53669.1. [P49821-2]
    CCDS8173.1. [P49821-1]
    PIRiJE0092.
    RefSeqiNP_001159574.1. NM_001166102.1. [P49821-2]
    NP_009034.2. NM_007103.3. [P49821-1]
    UniGeneiHs.7744.

    Genome annotation databases

    EnsembliENST00000322776; ENSP00000322450; ENSG00000167792. [P49821-1]
    ENST00000529927; ENSP00000436766; ENSG00000167792. [P49821-2]
    GeneIDi4723.
    KEGGihsa:4723.
    UCSCiuc001omj.2. human. [P49821-1]
    uc001omk.4. human. [P49821-2]

    Polymorphism databases

    DMDMi20455501.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y17379
    , Y17380 , Y17381 , Y17382 , Y17383 Genomic DNA. Translation: CAA76757.1 .
    AF053069 Genomic DNA. Translation: AAC39750.1 .
    AF053070 mRNA. Translation: AAC39722.1 .
    AF092131 mRNA. Translation: AAD40373.1 .
    CR456739 mRNA. Translation: CAG33020.1 .
    CH471076 Genomic DNA. Translation: EAW74655.1 .
    BC008146 mRNA. Translation: AAH08146.1 .
    BC015645 mRNA. Translation: AAH15645.1 .
    AH004147 Genomic DNA. Translation: AAB24883.1 .
    S67973 mRNA. Translation: AAB29698.2 . Sequence problems.
    CCDSi CCDS53669.1. [P49821-2 ]
    CCDS8173.1. [P49821-1 ]
    PIRi JE0092.
    RefSeqi NP_001159574.1. NM_001166102.1. [P49821-2 ]
    NP_009034.2. NM_007103.3. [P49821-1 ]
    UniGenei Hs.7744.

    3D structure databases

    ProteinModelPortali P49821.
    SMRi P49821. Positions 38-445.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110802. 36 interactions.
    IntActi P49821. 4 interactions.
    MINTi MINT-1444762.
    STRINGi 9606.ENSP00000322450.

    Chemistry

    ChEMBLi CHEMBL2363065.
    DrugBanki DB00157. NADH.

    PTM databases

    PhosphoSitei P49821.

    Polymorphism databases

    DMDMi 20455501.

    2D gel databases

    REPRODUCTION-2DPAGE IPI00028520.
    IPI00221298.

    Proteomic databases

    MaxQBi P49821.
    PaxDbi P49821.
    PRIDEi P49821.

    Protocols and materials databases

    DNASUi 4723.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000322776 ; ENSP00000322450 ; ENSG00000167792 . [P49821-1 ]
    ENST00000529927 ; ENSP00000436766 ; ENSG00000167792 . [P49821-2 ]
    GeneIDi 4723.
    KEGGi hsa:4723.
    UCSCi uc001omj.2. human. [P49821-1 ]
    uc001omk.4. human. [P49821-2 ]

    Organism-specific databases

    CTDi 4723.
    GeneCardsi GC11P067374.
    HGNCi HGNC:7716. NDUFV1.
    HPAi HPA045211.
    MIMi 161015. gene.
    252010. phenotype.
    256000. phenotype.
    neXtProti NX_P49821.
    Orphaneti 2609. Isolated NADH-CoQ reductase deficiency.
    255241. Leigh syndrome with leukodystrophy.
    PharmGKBi PA31526.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1894.
    HOVERGENi HBG006542.
    InParanoidi P49821.
    KOi K03942.
    OMAi KWSFMNP.
    OrthoDBi EOG7327NS.
    PhylomeDBi P49821.
    TreeFami TF300381.

    Enzyme and pathway databases

    Reactomei REACT_22393. Respiratory electron transport.

    Miscellaneous databases

    ChiTaRSi NDUFV1. human.
    GeneWikii NDUFV1.
    GenomeRNAii 4723.
    NextBioi 18214.
    PROi P49821.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49821.
    Bgeei P49821.
    CleanExi HS_NDUFV1.
    Genevestigatori P49821.

    Family and domain databases

    InterProi IPR001949. NADH-UbQ_OxRdtase_51kDa_CS.
    IPR019575. NADH-UbQ_OxRdtase_Fsu_4Fe4S-bd.
    IPR011537. NADH-UbQ_OxRdtase_suF.
    IPR011538. NADH_UbQ_OxRdtase_51kDa_su.
    IPR019554. Soluble_ligand-bd.
    [Graphical view ]
    Pfami PF01512. Complex1_51K. 1 hit.
    PF10589. NADH_4Fe-4S. 1 hit.
    PF10531. SLBB. 1 hit.
    [Graphical view ]
    SMARTi SM00928. NADH_4Fe-4S. 1 hit.
    [Graphical view ]
    TIGRFAMsi TIGR01959. nuoF_fam. 1 hit.
    PROSITEi PS00644. COMPLEX1_51K_1. 1 hit.
    PS00645. COMPLEX1_51K_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The structure of the human NDUFV1 gene encoding the 51-kDa subunit of mitochondrial complex I."
      de Coo R.F.M., Buddiger P.A., Smeets H.J.M., van Oost B.A.
      Mamm. Genome 10:49-53(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Cloning of the human mitochondrial 51 kDa subunit (NDUFV1) reveals a 100% antisense homology of its 3'UTR with the 5'UTR of the gamma-interferon inducible protein (IP-30) precursor: is this a link between mitochondrial myopathy and inflammation?"
      Schuelke M., Loeffen J., Mariman E., Smeitink J., van den Heuvel L.
      Biochem. Biophys. Res. Commun. 245:599-606(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Pituitary.
    4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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: Brain and Eye.
    7. "The human mitochondrial NADH: ubiquinone oxidoreductase 51-kDa subunit maps adjacent to the glutathione S-transferase P1-1 gene on chromosome 11q13."
      Spencer S.R., Taylor J.B., Cowell I.G., Xia C.L., Pemble S.E., Ketterer B.
      Genomics 14:1116-1118(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-130.
    8. "Chromosomal localization of the human gene encoding the 51-kDa subunit of mitochondrial complex I (NDUFV1) to 11q13."
      Ali S.T., Duncan A.M.V., Schappert K.T., Heng H.H.Q., Tsui L.-C., Chow W., Robinson B.H.
      Genomics 18:435-439(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 87-305.
      Tissue: Kidney.
    9. "The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification."
      Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., Ghosh S.S., Capaldi R.A.
      J. Biol. Chem. 278:13619-13622(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
    10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. "Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy."
      Schuelke M., Smeitink J., Mariman E., Loeffen J., Plecko B., Trijbels F., Stockler-Ipsiroglu S., van den Heuvel L.
      Nat. Genet. 21:260-261(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MT-C1D VAL-341, VARIANT LS MET-423.
    12. "Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency."
      Benit P., Chretien D., Kadhom N., de Lonlay-Debeney P., Cormier-Daire V., Cabral A., Peudenier S., Rustin P., Munnich A., Roetig A.
      Am. J. Hum. Genet. 68:1344-1352(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MT-C1D LYS-214.

    Entry informationi

    Entry nameiNDUV1_HUMAN
    AccessioniPrimary (citable) accession number: P49821
    Secondary accession number(s): O60924
    , O60940, Q16104, Q6IBR3, Q96BF8, Q96HS7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: May 2, 2002
    Last modified: October 1, 2014
    This is version 153 of the entry and version 4 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 11
      Human chromosome 11: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3