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Q6UWW8

- EST3_HUMAN

UniProt

Q6UWW8 - EST3_HUMAN

Protein

Carboxylesterase 3

Gene

CES3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 96 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
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    Functioni

    Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows low catalytic efficiency for hydrolysis of CPT-11 (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin), a prodrug for camptothecin used in cancer therapeutics.

    Catalytic activityi

    A carboxylic ester + H2O = an alcohol + a carboxylate.PROSITE-ProRule annotation

    Kineticsi

    1. KM=137 µM for 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin1 Publication
    2. KM=460 µM for 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei229 – 2291Acyl-ester intermediatePROSITE-ProRule annotation
    Active sitei347 – 3471Charge relay systemBy similarity
    Active sitei460 – 4601Charge relay systemBy similarity

    GO - Molecular functioni

    1. carboxylic ester hydrolase activity Source: UniProtKB-EC

    Keywords - Molecular functioni

    Hydrolase, Serine esterase

    Enzyme and pathway databases

    BioCyciMetaCyc:HS10576-MONOMER.
    SABIO-RKQ6UWW8.

    Protein family/group databases

    MEROPSiS09.958.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carboxylesterase 3 (EC:3.1.1.1)
    Alternative name(s):
    Liver carboxylesterase 31 homolog
    Gene namesi
    Name:CES3
    ORF Names:UNQ869/PRO1887
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:1865. CES3.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum lumen Source: UniProtKB-SubCell
    2. extracellular vesicular exosome Source: UniProt

    Keywords - Cellular componenti

    Endoplasmic reticulum

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA26418.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2626Sequence AnalysisAdd
    BLAST
    Chaini27 – 571545Carboxylesterase 3PRO_0000305191Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi97 ↔ 124By similarity
    Glycosylationi105 – 1051N-linked (GlcNAc...)2 Publications
    Disulfide bondi281 ↔ 292By similarity

    Post-translational modificationi

    N-glycosylated.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiQ6UWW8.
    PaxDbiQ6UWW8.
    PRIDEiQ6UWW8.

    PTM databases

    PhosphoSiteiQ6UWW8.

    Expressioni

    Tissue specificityi

    Expressed in liver, colon and small intestine.3 Publications

    Gene expression databases

    ArrayExpressiQ6UWW8.
    BgeeiQ6UWW8.
    CleanExiHS_CES3.
    GenevestigatoriQ6UWW8.

    Organism-specific databases

    HPAiHPA041008.
    HPA041307.

    Interactioni

    Protein-protein interaction databases

    BioGridi117043. 1 interaction.
    IntActiQ6UWW8. 1 interaction.
    STRINGi9606.ENSP00000304782.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6UWW8.
    SMRiQ6UWW8. Positions 34-548.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi568 – 5714Prevents secretion from ERSequence Analysis

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiCOG2272.
    HOGENOMiHOG000091866.
    HOVERGENiHBG008839.
    InParanoidiQ6UWW8.
    KOiK15743.
    OMAiQFWSETL.
    OrthoDBiEOG7RBZ7R.
    PhylomeDBiQ6UWW8.
    TreeFamiTF315470.

    Family and domain databases

    Gene3Di3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    IPR002018. CarbesteraseB.
    IPR019826. Carboxylesterase_B_AS.
    [Graphical view]
    PfamiPF00135. COesterase. 1 hit.
    [Graphical view]
    SUPFAMiSSF53474. SSF53474. 2 hits.
    PROSITEiPS00122. CARBOXYLESTERASE_B_1. 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: Q6UWW8-1) [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

    MERAVRVESG VLVGVVCLLL ACPATATGPE VAQPEVDTTL GRVRGRQVGV    50
    KGTDRLVNVF LGIPFAQPPL GPDRFSAPHP AQPWEGVRDA STAPPMCLQD 100
    VESMNSSRFV LNGKQQIFSV SEDCLVLNVY SPAEVPAGSG RPVMVWVHGG 150
    ALITGAATSY DGSALAAYGD VVVVTVQYRL GVLGFFSTGD EHAPGNQGFL 200
    DVVAALRWVQ ENIAPFGGDL NCVTVFGGSA GGSIISGLVL SPVAAGLFHR 250
    AITQSGVITT PGIIDSHPWP LAQKIANTLA CSSSSPAEMV QCLQQKEGEE 300
    LVLSKKLKNT IYPLTVDGTV FPKSPKELLK EKPFHSVPFL MGVNNHEFSW 350
    LIPRGWGLLD TMEQMSREDM LAISTPVLTS LDVPPEMMPT VIDEYLGSNS 400
    DAQAKCQAFQ EFMGDVFINV PTVSFSRYLR DSGSPVFFYE FQHRPSSFAK 450
    IKPAWVKADH GAEGAFVFGG PFLMDESSRL AFPEATEEEK QLSLTMMAQW 500
    THFARTGDPN SKALPPWPQF NQAEQYLEIN PVPRAGQKFR EAWMQFWSET 550
    LPSKIQQWHQ KQKNRKAQED L 571
    Length:571
    Mass (Da):62,282
    Last modified:July 5, 2004 - v1
    Checksum:iF2200968FDE072D2
    GO
    Isoform 2 (identifier: Q6UWW8-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-361: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:210
    Mass (Da):24,106
    Checksum:i875CDDA899639F65
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti372 – 3721A → S in BAB15123. (PubMed:14702039)Curated
    Sequence conflicti481 – 4833Missing in AAH53670. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti129 – 1291V → I.1 Publication
    Corresponds to variant rs61745806 [ dbSNP | Ensembl ].
    VAR_060699
    Natural varianti151 – 1511A → T.1 Publication
    Corresponds to variant rs71647891 [ dbSNP | Ensembl ].
    VAR_060700
    Natural varianti160 – 1601Y → H.1 Publication
    Corresponds to variant rs71647892 [ dbSNP | Ensembl ].
    VAR_060701
    Natural varianti191 – 1911E → K.1 Publication
    Corresponds to variant rs61742964 [ dbSNP | Ensembl ].
    VAR_060702
    Natural varianti213 – 2131I → N.1 Publication
    Corresponds to variant rs71647894 [ dbSNP | Ensembl ].
    VAR_060703
    Natural varianti367 – 3671R → W.1 Publication
    Corresponds to variant rs61743167 [ dbSNP | Ensembl ].
    VAR_060704
    Natural varianti523 – 5231A → V.1 Publication
    VAR_060705
    Natural varianti555 – 5551I → V.1 Publication
    Corresponds to variant rs8059252 [ dbSNP | Ensembl ].
    VAR_060706

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 361361Missing in isoform 2. 1 PublicationVSP_044994Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY358609 mRNA. Translation: AAQ88972.1.
    AK025389 mRNA. Translation: BAB15123.1.
    EU595874 Genomic DNA. Translation: ACD11491.1.
    AC009084 Genomic DNA. No translation available.
    CH471092 Genomic DNA. Translation: EAW83060.1.
    BC053670 mRNA. Translation: AAH53670.1.
    CCDSiCCDS10826.1. [Q6UWW8-1]
    CCDS54023.1. [Q6UWW8-2]
    RefSeqiNP_001172105.1. NM_001185176.1. [Q6UWW8-2]
    NP_001172106.1. NM_001185177.1.
    NP_079198.2. NM_024922.5. [Q6UWW8-1]
    UniGeneiHs.268700.

    Genome annotation databases

    EnsembliENST00000303334; ENSP00000304782; ENSG00000172828. [Q6UWW8-1]
    ENST00000394037; ENSP00000377602; ENSG00000172828.
    ENST00000543856; ENSP00000445559; ENSG00000172828. [Q6UWW8-2]
    GeneIDi23491.
    KEGGihsa:23491.
    UCSCiuc002eqt.3. human. [Q6UWW8-1]

    Polymorphism databases

    DMDMi74758561.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY358609 mRNA. Translation: AAQ88972.1 .
    AK025389 mRNA. Translation: BAB15123.1 .
    EU595874 Genomic DNA. Translation: ACD11491.1 .
    AC009084 Genomic DNA. No translation available.
    CH471092 Genomic DNA. Translation: EAW83060.1 .
    BC053670 mRNA. Translation: AAH53670.1 .
    CCDSi CCDS10826.1. [Q6UWW8-1 ]
    CCDS54023.1. [Q6UWW8-2 ]
    RefSeqi NP_001172105.1. NM_001185176.1. [Q6UWW8-2 ]
    NP_001172106.1. NM_001185177.1.
    NP_079198.2. NM_024922.5. [Q6UWW8-1 ]
    UniGenei Hs.268700.

    3D structure databases

    ProteinModelPortali Q6UWW8.
    SMRi Q6UWW8. Positions 34-548.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117043. 1 interaction.
    IntActi Q6UWW8. 1 interaction.
    STRINGi 9606.ENSP00000304782.

    Protein family/group databases

    MEROPSi S09.958.

    PTM databases

    PhosphoSitei Q6UWW8.

    Polymorphism databases

    DMDMi 74758561.

    Proteomic databases

    MaxQBi Q6UWW8.
    PaxDbi Q6UWW8.
    PRIDEi Q6UWW8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000303334 ; ENSP00000304782 ; ENSG00000172828 . [Q6UWW8-1 ]
    ENST00000394037 ; ENSP00000377602 ; ENSG00000172828 .
    ENST00000543856 ; ENSP00000445559 ; ENSG00000172828 . [Q6UWW8-2 ]
    GeneIDi 23491.
    KEGGi hsa:23491.
    UCSCi uc002eqt.3. human. [Q6UWW8-1 ]

    Organism-specific databases

    CTDi 23491.
    GeneCardsi GC16P066995.
    HGNCi HGNC:1865. CES3.
    HPAi HPA041008.
    HPA041307.
    MIMi 605279. gene.
    neXtProti NX_Q6UWW8.
    PharmGKBi PA26418.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2272.
    HOGENOMi HOG000091866.
    HOVERGENi HBG008839.
    InParanoidi Q6UWW8.
    KOi K15743.
    OMAi QFWSETL.
    OrthoDBi EOG7RBZ7R.
    PhylomeDBi Q6UWW8.
    TreeFami TF315470.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS10576-MONOMER.
    SABIO-RK Q6UWW8.

    Miscellaneous databases

    GeneWikii Carboxylesterase_3.
    GenomeRNAii 23491.
    NextBioi 45851.
    PROi Q6UWW8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q6UWW8.
    Bgeei Q6UWW8.
    CleanExi HS_CES3.
    Genevestigatori Q6UWW8.

    Family and domain databases

    Gene3Di 3.40.50.1820. 1 hit.
    InterProi IPR029058. AB_hydrolase.
    IPR002018. CarbesteraseB.
    IPR019826. Carboxylesterase_B_AS.
    [Graphical view ]
    Pfami PF00135. COesterase. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53474. SSF53474. 2 hits.
    PROSITEi PS00122. CARBOXYLESTERASE_B_1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3."
      Sanghani S.P., Quinney S.K., Fredenburg T.B., Davis W.I., Murry D.J., Bosron W.F.
      Drug Metab. Dispos. 32:505-511(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
      Tissue: Liver.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    3. "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] (ISOFORM 2).
      Tissue: Colon mucosa.
    4. NIEHS SNPs program
      Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-129; THR-151; HIS-160; LYS-191; ASN-213; TRP-367; VAL-523 AND VAL-555.
    5. "The sequence and analysis of duplication-rich human chromosome 16."
      Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
      , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
      Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "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] (ISOFORM 1).
      Tissue: Eye.
    8. "Carboxylesterases expressed in human colon tumor tissue and their role in CPT-11 hydrolysis."
      Sanghani S.P., Quinney S.K., Fredenburg T.B., Sun Z., Davis W.I., Murry D.J., Cummings O.W., Seitz D.E., Bosron W.F.
      Clin. Cancer Res. 9:4983-4991(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    9. "Hydrolysis of capecitabine to 5'-deoxy-5-fluorocytidine by human carboxylesterases and inhibition by loperamide."
      Quinney S.K., Sanghani S.P., Davis W.I., Hurley T.D., Sun Z., Murry D.J., Bosron W.F.
      J. Pharmacol. Exp. Ther. 313:1011-1016(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    10. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-105.
      Tissue: Liver.

    Entry informationi

    Entry nameiEST3_HUMAN
    AccessioniPrimary (citable) accession number: Q6UWW8
    Secondary accession number(s): B2Z3W9
    , F5H242, Q7Z6J1, Q9H6X7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 2, 2007
    Last sequence update: July 5, 2004
    Last modified: October 1, 2014
    This is version 96 of the entry and version 1 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 16
      Human chromosome 16: 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