Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Carbonic anhydrase 3

Gene

CA3

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

Functioni

Reversible hydration of carbon dioxide.

Catalytic activityi

H2CO3 = CO2 + H2O.

Cofactori

Enzyme regulationi

Activated by proton donors such as imidazole and the dipeptide histidylhistidine. Inhibited by coumarins and sulfonamide derivatives such as acetazolamide.3 Publications

Kineticsi

  1. KM=52.0 mM for CO21 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi94 – 941Zinc; catalytic
    Metal bindingi96 – 961Zinc; catalytic
    Metal bindingi119 – 1191Zinc; catalytic
    Active sitei127 – 1271By similarity

    GO - Molecular functioni

    • carbonate dehydratase activity Source: ProtInc
    • nickel cation binding Source: Ensembl
    • zinc ion binding Source: InterPro

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi4.2.1.1. 2681.
    ReactomeiREACT_121123. Reversible hydration of carbon dioxide.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carbonic anhydrase 3 (EC:4.2.1.1)
    Alternative name(s):
    Carbonate dehydratase III
    Carbonic anhydrase III
    Short name:
    CA-III
    Gene namesi
    Name:CA3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:1374. CA3.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi64 – 641K → H: Enhanced proton transfer in catalysis. 1 Publication
    Mutagenesisi67 – 671R → H: Enhanced proton transfer in catalysis. 1 Publication
    Mutagenesisi197 – 1971F → L: Enhanced activity by at least 10-fold. 1 Publication

    Organism-specific databases

    PharmGKBiPA25990.

    Chemistry

    DrugBankiDB00819. Acetazolamide.
    DB00909. Zonisamide.

    Polymorphism and mutation databases

    BioMutaiCA3.
    DMDMi134047703.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 260259Carbonic anhydrase 3PRO_0000077426Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei182 – 1821S-glutathionyl cysteineBy similarity
    Modified residuei187 – 1871S-glutathionyl cysteineBy similarity

    Post-translational modificationi

    S-glutathionylated in hepatocytes under oxidative stress.By similarity

    Keywords - PTMi

    Acetylation, Glutathionylation

    Proteomic databases

    PaxDbiP07451.
    PRIDEiP07451.

    2D gel databases

    UCD-2DPAGEP07451.

    PTM databases

    PhosphoSiteiP07451.

    Expressioni

    Tissue specificityi

    Muscle specific.

    Developmental stagei

    At 6 weeks gestation, transcripts accumulate at low levels in the somites and at high levels throughout the notochord. As gestation continues, CA3 becomes abundant in all developing muscle masses and continues at high to moderate levels in the notochord.1 Publication

    Gene expression databases

    BgeeiP07451.
    CleanExiHS_CA3.
    ExpressionAtlasiP07451. baseline and differential.
    GenevisibleiP07451. HS.

    Organism-specific databases

    HPAiCAB004967.
    HPA021775.
    HPA026700.

    Interactioni

    Protein-protein interaction databases

    BioGridi107216. 2 interactions.
    STRINGi9606.ENSP00000285381.

    Structurei

    Secondary structure

    1
    260
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni9 – 113Combined sources
    Turni13 – 153Combined sources
    Helixi16 – 183Combined sources
    Helixi21 – 244Combined sources
    Beta strandi25 – 273Combined sources
    Helixi35 – 373Combined sources
    Beta strandi47 – 504Combined sources
    Helixi53 – 553Combined sources
    Beta strandi56 – 616Combined sources
    Beta strandi66 – 705Combined sources
    Beta strandi73 – 753Combined sources
    Beta strandi77 – 815Combined sources
    Beta strandi88 – 9710Combined sources
    Beta strandi106 – 1094Combined sources
    Beta strandi115 – 1239Combined sources
    Helixi125 – 1273Combined sources
    Helixi130 – 1334Combined sources
    Beta strandi139 – 15113Combined sources
    Helixi154 – 1607Combined sources
    Helixi161 – 1655Combined sources
    Beta strandi172 – 1743Combined sources
    Helixi180 – 1834Combined sources
    Beta strandi190 – 1956Combined sources
    Beta strandi206 – 2138Combined sources
    Beta strandi215 – 2173Combined sources
    Helixi219 – 2257Combined sources
    Beta strandi229 – 2313Combined sources
    Beta strandi233 – 2364Combined sources
    Beta strandi256 – 2583Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1Z93X-ray2.10A1-260[»]
    1Z97X-ray2.10A1-260[»]
    2HFWX-ray2.50A1-259[»]
    3UYNX-ray2.60A1-260[»]
    3UYQX-ray1.70A1-260[»]
    ProteinModelPortaliP07451.
    SMRiP07451. Positions 2-260.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP07451.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni64 – 674Involved in proton transfer
    Regioni198 – 1992Substrate bindingBy similarity

    Sequence similaritiesi

    Belongs to the alpha-carbonic anhydrase family.Curated

    Phylogenomic databases

    eggNOGiCOG3338.
    HOGENOMiHOG000112637.
    HOVERGENiHBG002837.
    InParanoidiP07451.
    KOiK01672.
    OMAiEAPFTHF.
    PhylomeDBiP07451.
    TreeFamiTF316425.

    Family and domain databases

    Gene3Di3.10.200.10. 1 hit.
    InterProiIPR001148. Carbonic_anhydrase_a.
    IPR023561. Carbonic_anhydrase_a-class.
    IPR018338. Carbonic_anhydrase_a-class_CS.
    IPR018441. Carbonic_anhydrase_CA3.
    [Graphical view]
    PANTHERiPTHR18952. PTHR18952. 1 hit.
    PTHR18952:SF96. PTHR18952:SF96. 1 hit.
    PfamiPF00194. Carb_anhydrase. 1 hit.
    [Graphical view]
    SMARTiSM01057. Carb_anhydrase. 1 hit.
    [Graphical view]
    SUPFAMiSSF51069. SSF51069. 1 hit.
    PROSITEiPS00162. ALPHA_CA_1. 1 hit.
    PS51144. ALPHA_CA_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P07451-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAKEWGYASH NGPDHWHELF PNAKGENQSP VELHTKDIRH DPSLQPWSVS
    60 70 80 90 100
    YDGGSAKTIL NNGKTCRVVF DDTYDRSMLR GGPLPGPYRL RQFHLHWGSS
    110 120 130 140 150
    DDHGSEHTVD GVKYAAELHL VHWNPKYNTF KEALKQRDGI AVIGIFLKIG
    160 170 180 190 200
    HENGEFQIFL DALDKIKTKG KEAPFTKFDP SCLFPACRDY WTYQGSFTTP
    210 220 230 240 250
    PCEECIVWLL LKEPMTVSSD QMAKLRSLLS SAENEPPVPL VSNWRPPQPI
    260
    NNRVVRASFK
    Length:260
    Mass (Da):29,557
    Last modified:March 20, 2007 - v3
    Checksum:iA305334167233FCF
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti31 – 311V → I.3 Publications
    Corresponds to variant rs20571 [ dbSNP | Ensembl ].
    VAR_016180

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M29458 Genomic DNA. Translation: AAA52293.1.
    M29452 Genomic DNA. No translation available.
    AK096880 mRNA. Translation: BAG53390.1.
    AK313254 mRNA. Translation: BAG36064.1.
    CH471068 Genomic DNA. Translation: EAW87133.1.
    BC004897 mRNA. Translation: AAH04897.1.
    AJ006473 Genomic DNA. Translation: CAA07056.1.
    CCDSiCCDS6238.1.
    PIRiA26658. CRHU3.
    RefSeqiNP_005172.1. NM_005181.3.
    UniGeneiHs.82129.

    Genome annotation databases

    EnsembliENST00000285381; ENSP00000285381; ENSG00000164879.
    GeneIDi761.
    KEGGihsa:761.
    UCSCiuc003ydj.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M29458 Genomic DNA. Translation: AAA52293.1.
    M29452 Genomic DNA. No translation available.
    AK096880 mRNA. Translation: BAG53390.1.
    AK313254 mRNA. Translation: BAG36064.1.
    CH471068 Genomic DNA. Translation: EAW87133.1.
    BC004897 mRNA. Translation: AAH04897.1.
    AJ006473 Genomic DNA. Translation: CAA07056.1.
    CCDSiCCDS6238.1.
    PIRiA26658. CRHU3.
    RefSeqiNP_005172.1. NM_005181.3.
    UniGeneiHs.82129.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1Z93X-ray2.10A1-260[»]
    1Z97X-ray2.10A1-260[»]
    2HFWX-ray2.50A1-259[»]
    3UYNX-ray2.60A1-260[»]
    3UYQX-ray1.70A1-260[»]
    ProteinModelPortaliP07451.
    SMRiP07451. Positions 2-260.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107216. 2 interactions.
    STRINGi9606.ENSP00000285381.

    Chemistry

    BindingDBiP07451.
    ChEMBLiCHEMBL2885.
    DrugBankiDB00819. Acetazolamide.
    DB00909. Zonisamide.

    PTM databases

    PhosphoSiteiP07451.

    Polymorphism and mutation databases

    BioMutaiCA3.
    DMDMi134047703.

    2D gel databases

    UCD-2DPAGEP07451.

    Proteomic databases

    PaxDbiP07451.
    PRIDEiP07451.

    Protocols and materials databases

    DNASUi761.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000285381; ENSP00000285381; ENSG00000164879.
    GeneIDi761.
    KEGGihsa:761.
    UCSCiuc003ydj.3. human.

    Organism-specific databases

    CTDi761.
    GeneCardsiGC08P086285.
    H-InvDBHIX0078885.
    HGNCiHGNC:1374. CA3.
    HPAiCAB004967.
    HPA021775.
    HPA026700.
    MIMi114750. gene.
    neXtProtiNX_P07451.
    PharmGKBiPA25990.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG3338.
    HOGENOMiHOG000112637.
    HOVERGENiHBG002837.
    InParanoidiP07451.
    KOiK01672.
    OMAiEAPFTHF.
    PhylomeDBiP07451.
    TreeFamiTF316425.

    Enzyme and pathway databases

    BRENDAi4.2.1.1. 2681.
    ReactomeiREACT_121123. Reversible hydration of carbon dioxide.

    Miscellaneous databases

    EvolutionaryTraceiP07451.
    GeneWikiiCarbonic_anhydrase_III,_muscle_specific.
    GenomeRNAii761.
    NextBioi3078.
    PROiP07451.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP07451.
    CleanExiHS_CA3.
    ExpressionAtlasiP07451. baseline and differential.
    GenevisibleiP07451. HS.

    Family and domain databases

    Gene3Di3.10.200.10. 1 hit.
    InterProiIPR001148. Carbonic_anhydrase_a.
    IPR023561. Carbonic_anhydrase_a-class.
    IPR018338. Carbonic_anhydrase_a-class_CS.
    IPR018441. Carbonic_anhydrase_CA3.
    [Graphical view]
    PANTHERiPTHR18952. PTHR18952. 1 hit.
    PTHR18952:SF96. PTHR18952:SF96. 1 hit.
    PfamiPF00194. Carb_anhydrase. 1 hit.
    [Graphical view]
    SMARTiSM01057. Carb_anhydrase. 1 hit.
    [Graphical view]
    SUPFAMiSSF51069. SSF51069. 1 hit.
    PROSITEiPS00162. ALPHA_CA_1. 1 hit.
    PS51144. ALPHA_CA_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Nucleotide sequence and derived amino acid sequence of a cDNA encoding human muscle carbonic anhydrase."
      Lloyd J., McMillan S., Hopkinson D., Edwards Y.H.
      Gene 41:233-239(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Nucleotide sequence, tissue-specific expression, and chromosome location of human carbonic anhydrase III: the human CAIII gene is located on the same chromosome as the closely linked CAI and CAII genes."
      Wade R., Gunning P., Eddy R., Shows T., Kedes L.
      Proc. Natl. Acad. Sci. U.S.A. 83:9571-9575(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    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], VARIANT ILE-31.
      Tissue: Pericardium and Skeletal muscle.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-31.
    5. "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], VARIANT ILE-31.
      Tissue: Muscle.
    6. "Human muscle carbonic anhydrase: gene structure and DNA methylation patterns in fetal and adult tissues."
      Lloyd J., Brownson C., Tweedie S., Charlton J., Edwards Y.H.
      Genes Dev. 1:594-602(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    7. "Sequence comparisons and functional studies of the proximal promoter of the carbonic anhydrase 3 (CA3) gene."
      Sowden J., Smith H., Morrison K., Edwards Y.
      Gene 214:157-165(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11, DEVELOPMENTAL STAGE.
    8. "A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases."
      Crocetti L., Maresca A., Temperini C., Hall R.A., Scozzafava A., Muehlschlegel F.A., Supuran C.T.
      Bioorg. Med. Chem. Lett. 19:1371-1375(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    9. "Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a new class of suicide inhibitors."
      Maresca A., Temperini C., Vu H., Pham N.B., Poulsen S.-A., Scozzafava A., Quinn R.J., Supuran C.T.
      J. Am. Chem. Soc. 131:3057-3062(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    10. "Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide."
      Di Fiore A., Monti S.M., Hilvo M., Parkkila S., Romano V., Scaloni A., Pedone C., Scozzafava A., Supuran C.T., De Simone G.
      Proteins 74:164-175(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
    11. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    12. "Human carbonic anhydrase III: structural and kinetic study of catalysis and proton transfer."
      Duda D.M., Tu C., Fisher S.Z., An H., Yoshioka C., Govindasamy L., Laipis P.J., Agbandje-McKenna M., Silverman D.N., McKenna R.
      Biochemistry 44:10046-10053(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-260 IN COMPLEX WITH ZINC ION, MUTAGENESIS OF PHE-197, ACTIVATION BY IMIDAZOLE AND HISTIDYLHISTIDINE.
    13. "Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III."
      Elder I., Fisher Z., Laipis P.J., Tu C., McKenna R., Silverman D.N.
      Proteins 68:337-343(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-260 IN COMPLEX WITH ZINC ION, MUTAGENESIS OF LYS-64 AND ARG-67.

    Entry informationi

    Entry nameiCAH3_HUMAN
    AccessioniPrimary (citable) accession number: P07451
    Secondary accession number(s): B2R867, B3KUC8, O60842
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1988
    Last sequence update: March 20, 2007
    Last modified: June 24, 2015
    This is version 163 of the entry and version 3 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.