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O43186

- CRX_HUMAN

UniProt

O43186 - CRX_HUMAN

Protein

Cone-rod homeobox protein

Gene

CRX

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 1 (01 Jun 1998)
      Previous versions | rss
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    Functioni

    Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors.1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi39 – 9860HomeoboxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin binding Source: Ensembl
    2. leucine zipper domain binding Source: UniProtKB
    3. nuclear hormone receptor binding Source: UniProtKB
    4. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
    5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
    6. sequence-specific DNA binding transcription factor activity Source: UniProtKB

    GO - Biological processi

    1. circadian rhythm Source: Ensembl
    2. organ morphogenesis Source: ProtInc
    3. positive regulation of photoreceptor cell differentiation Source: Ensembl
    4. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
    5. regulation of transcription, DNA-templated Source: UniProtKB
    6. response to stimulus Source: UniProtKB-KW
    7. retina development in camera-type eye Source: Ensembl
    8. visual perception Source: ProtInc

    Keywords - Molecular functioni

    Activator, Developmental protein

    Keywords - Biological processi

    Differentiation, Neurogenesis, Sensory transduction, Transcription, Transcription regulation, Vision

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cone-rod homeobox protein
    Gene namesi
    Name:CRX
    Synonyms:CORD2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:2383. CRX.

    Subcellular locationi

    Nucleus PROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleus Source: UniProtKB
    2. transcription factor complex Source: Ensembl

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Leber congenital amaurosis 7 (LCA7) [MIM:613829]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti42 – 421E → K Found in a patient with LCA7. 1 Publication
    VAR_067189
    Natural varianti88 – 881K → N in LCA7; reduces NRL transactivation and reduces steady state levels of CRX and NRL; altered localization to the cytoplasm. 1 Publication
    VAR_063919
    Natural varianti90 – 901R → W in LCA7; reduced DNA-binding ability, transcriptional synergy and interaction with NRL. 1 Publication
    VAR_008714
    Natural varianti146 – 1494Missing in LCA7. 1 Publication
    VAR_007947
    Cone-rod dystrophy 2 (CORD2) [MIM:120970]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti41 – 411R → W in CORD2; exhibits reduced DNA binding, transcriptional synergy and interaction with NRL. 1 Publication
    VAR_003750
    Natural varianti80 – 801E → A in CORD2. 2 Publications
    Corresponds to variant rs28939682 [ dbSNP | Ensembl ].
    VAR_003751
    Natural varianti242 – 2421V → M in CORD2. 1 Publication
    VAR_007949
    Retinitis pigmentosa (RP) [MIM:268000]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti41 – 411R → Q in RP. 2 Publications
    VAR_007946
    Natural varianti122 – 1221G → D in RP.
    Corresponds to variant rs61748441 [ dbSNP | Ensembl ].
    VAR_008282

    Keywords - Diseasei

    Cone-rod dystrophy, Disease mutation, Leber congenital amaurosis, Retinitis pigmentosa

    Organism-specific databases

    MIMi120970. phenotype.
    268000. phenotype.
    613829. phenotype.
    Orphaneti1872. Cone rod dystrophy.
    65. Leber congenital amaurosis.
    791. Retinitis pigmentosa.
    PharmGKBiPA26903.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 299299Cone-rod homeobox proteinPRO_0000048862Add
    BLAST

    Proteomic databases

    PaxDbiO43186.
    PRIDEiO43186.

    PTM databases

    PhosphoSiteiO43186.

    Expressioni

    Tissue specificityi

    Retina.

    Gene expression databases

    ArrayExpressiO43186.
    BgeeiO43186.
    CleanExiHS_CRX.
    GenevestigatoriO43186.

    Organism-specific databases

    HPAiHPA036762.
    HPA036763.

    Interactioni

    Subunit structurei

    Interacts (via the homeobox) with NRL (via the leucine-zipper domain). Interacts with PDC, RAX2, RORB and SCA7.2 Publications

    Protein-protein interaction databases

    BioGridi107796. 11 interactions.
    IntActiO43186. 3 interactions.
    MINTiMINT-1442706.
    STRINGi9606.ENSP00000221996.

    Structurei

    3D structure databases

    ProteinModelPortaliO43186.
    SMRiO43186. Positions 34-95.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the paired homeobox family.Curated
    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG324074.
    HOGENOMiHOG000082677.
    HOVERGENiHBG004028.
    InParanoidiO43186.
    KOiK09337.
    OMAiQTKARPA.
    PhylomeDBiO43186.
    TreeFamiTF351179.

    Family and domain databases

    Gene3Di1.10.10.60. 1 hit.
    InterProiIPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    IPR013851. Otx_TF_C.
    [Graphical view]
    PfamiPF00046. Homeobox. 1 hit.
    PF03529. TF_Otx. 1 hit.
    [Graphical view]
    SMARTiSM00389. HOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    PROSITEiPS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O43186-1 [UniParc]FASTAAdd to Basket

    « Hide

    MMAYMNPGPH YSVNALALSG PSVDLMHQAV PYPSAPRKQR RERTTFTRSQ    50
    LEELEALFAK TQYPDVYARE EVALKINLPE SRVQVWFKNR RAKCRQQRQQ 100
    QKQQQQPPGG QAKARPAKRK AGTSPRPSTD VCPDPLGISD SYSPPLPGPS 150
    GSPTTAVATV SIWSPASESP LPEAQRAGLV ASGPSLTSAP YAMTYAPASA 200
    FCSSPSAYGS PSSYFSGLDP YLSPMVPQLG GPALSPLSGP SVGPSLAQSP 250
    TSLSGQSYGA YSPVDSLEFK DPTGTWKFTY NPMDPLDYKD QSAWKFQIL 299
    Length:299
    Mass (Da):32,261
    Last modified:June 1, 1998 - v1
    Checksum:i46747C09277A0864
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti41 – 411R → Q in RP. 2 Publications
    VAR_007946
    Natural varianti41 – 411R → W in CORD2; exhibits reduced DNA binding, transcriptional synergy and interaction with NRL. 1 Publication
    VAR_003750
    Natural varianti42 – 421E → K Found in a patient with LCA7. 1 Publication
    VAR_067189
    Natural varianti80 – 801E → A in CORD2. 2 Publications
    Corresponds to variant rs28939682 [ dbSNP | Ensembl ].
    VAR_003751
    Natural varianti88 – 881K → N in LCA7; reduces NRL transactivation and reduces steady state levels of CRX and NRL; altered localization to the cytoplasm. 1 Publication
    VAR_063919
    Natural varianti90 – 901R → W in LCA7; reduced DNA-binding ability, transcriptional synergy and interaction with NRL. 1 Publication
    VAR_008714
    Natural varianti122 – 1221G → D in RP.
    Corresponds to variant rs61748441 [ dbSNP | Ensembl ].
    VAR_008282
    Natural varianti141 – 1411S → F in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036438
    Natural varianti146 – 1494Missing in LCA7. 1 Publication
    VAR_007947
    Natural varianti154 – 1541T → A.1 Publication
    VAR_067190
    Natural varianti158 – 1581A → T.1 Publication
    Corresponds to variant rs61748445 [ dbSNP | Ensembl ].
    VAR_007948
    Natural varianti242 – 2421V → M in CORD2. 1 Publication
    VAR_007949

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF024711 Genomic DNA. Translation: AAB88418.1.
    BT007364 mRNA. Translation: AAP36028.1.
    AC008745 Genomic DNA. No translation available.
    BC016664 mRNA. No translation available.
    BC053672 mRNA. No translation available.
    DQ426868 mRNA. Translation: ABD90533.1.
    CCDSiCCDS12706.1.
    RefSeqiNP_000545.1. NM_000554.4.
    UniGeneiHs.617342.
    Hs.633434.
    Hs.639114.

    Genome annotation databases

    EnsembliENST00000221996; ENSP00000221996; ENSG00000105392.
    ENST00000539067; ENSP00000445565; ENSG00000105392.
    GeneIDi1406.
    KEGGihsa:1406.
    UCSCiuc002phq.4. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Mutations of the CRX gene

    Retina International's Scientific Newsletter

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF024711 Genomic DNA. Translation: AAB88418.1 .
    BT007364 mRNA. Translation: AAP36028.1 .
    AC008745 Genomic DNA. No translation available.
    BC016664 mRNA. No translation available.
    BC053672 mRNA. No translation available.
    DQ426868 mRNA. Translation: ABD90533.1 .
    CCDSi CCDS12706.1.
    RefSeqi NP_000545.1. NM_000554.4.
    UniGenei Hs.617342.
    Hs.633434.
    Hs.639114.

    3D structure databases

    ProteinModelPortali O43186.
    SMRi O43186. Positions 34-95.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107796. 11 interactions.
    IntActi O43186. 3 interactions.
    MINTi MINT-1442706.
    STRINGi 9606.ENSP00000221996.

    PTM databases

    PhosphoSitei O43186.

    Proteomic databases

    PaxDbi O43186.
    PRIDEi O43186.

    Protocols and materials databases

    DNASUi 1406.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000221996 ; ENSP00000221996 ; ENSG00000105392 .
    ENST00000539067 ; ENSP00000445565 ; ENSG00000105392 .
    GeneIDi 1406.
    KEGGi hsa:1406.
    UCSCi uc002phq.4. human.

    Organism-specific databases

    CTDi 1406.
    GeneCardsi GC19P048347.
    GeneReviewsi CRX.
    HGNCi HGNC:2383. CRX.
    HPAi HPA036762.
    HPA036763.
    MIMi 120970. phenotype.
    268000. phenotype.
    602225. gene.
    613829. phenotype.
    neXtProti NX_O43186.
    Orphaneti 1872. Cone rod dystrophy.
    65. Leber congenital amaurosis.
    791. Retinitis pigmentosa.
    PharmGKBi PA26903.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG324074.
    HOGENOMi HOG000082677.
    HOVERGENi HBG004028.
    InParanoidi O43186.
    KOi K09337.
    OMAi QTKARPA.
    PhylomeDBi O43186.
    TreeFami TF351179.

    Miscellaneous databases

    ChiTaRSi CRX. human.
    GeneWikii CRX_(gene).
    GenomeRNAii 1406.
    NextBioi 5749.
    PROi O43186.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43186.
    Bgeei O43186.
    CleanExi HS_CRX.
    Genevestigatori O43186.

    Family and domain databases

    Gene3Di 1.10.10.60. 1 hit.
    InterProi IPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    IPR013851. Otx_TF_C.
    [Graphical view ]
    Pfami PF00046. Homeobox. 1 hit.
    PF03529. TF_Otx. 1 hit.
    [Graphical view ]
    SMARTi SM00389. HOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46689. SSF46689. 1 hit.
    PROSITEi PS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor."
      Freund C.L., Gregory-Evans C.Y., Furukawa T., Papaioannou M., Looser J., Ploder L., Bellingham J., Ng D., Herbrick J.-A.S., Duncan A., Scherer S.W., Tsui L.-C., Loutradis-Anagnostou A., Jacobson S.G., Cepko C.L., Bhattacharya S.S., McInnes R.R.
      Cell 91:543-553(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CORD2 ALA-80.
    2. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    3. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "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].
      Tissue: Eye.
    5. "Mapping of transcription start sites of human retina expressed genes."
      Roni V., Carpio R., Wissinger B.
      BMC Genomics 8:42-42(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-54.
      Tissue: Retina.
    6. "Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression."
      Kimura A., Singh D., Wawrousek E.F., Kikuchi M., Nakamura M., Shinohara T.
      J. Biol. Chem. 275:1152-1160(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation."
      Mitton K.P., Swain P.K., Chen S., Xu S., Zack D.J., Swaroop A.
      J. Biol. Chem. 275:29794-29799(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NRL, CHARACTERIZATION OF VARIANT CORD2 TRP-41, CHARACTERIZATION OF VARIANT LCA7 TRP-90.
    8. Cited for: INTERACTION WITH RAX2.
    9. "Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration."
      Swain P.K., Chen S., Wang Q.-L., Affatigato L.M., Coats C.L., Brady K.D., Fishman G.A., Jacobson S.G., Swaroop A., Stone E., Sieving P.A., Zack D.J.
      Neuron 19:1329-1336(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CORD2 TRP-41 AND MET-242, VARIANT RP GLN-41, VARIANT THR-158.
    10. "A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene."
      Sohocki M.M., Sullivan L.S., Mintz-Hittner H.A., Birch D., Heckenlively J.R., Freund C.L., McInnes R.R., Daiger S.P.
      Am. J. Hum. Genet. 63:1307-1315(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT RP GLN-41, VARIANT CORD2 ALA-80, VARIANT LCA7 146-LEU--PRO-149 DEL.
    11. "Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function."
      Swaroop A., Wang Q.-L., Wu W., Cook J., Coats C., Xu S., Chen S., Zack D.J., Sieving P.A.
      Hum. Mol. Genet. 8:299-305(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LCA7 TRP-90.
    12. Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-141.
    13. "Molecular characterization of Leber congenital amaurosis in Koreans."
      Seong M.W., Kim S.Y., Yu Y.S., Hwang J.M., Kim J.Y., Park S.S.
      Mol. Vis. 14:1429-1436(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ALA-154.
    14. "Two novel CRX mutant proteins causing autosomal dominant Leber congenital amaurosis interact differently with NRL."
      Nichols L.L. II, Alur R.P., Boobalan E., Sergeev Y.V., Caruso R.C., Stone E.M., Swaroop A., Johnson M.A., Brooks B.P.
      Hum. Mutat. 31:E1472-E1483(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LCA7 ASN-88, CHARACTERIZATION OF VARIANT LCA7 ASN-88.
    15. "Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis."
      Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q., Hejtmancik J.F.
      PLoS ONE 6:E19458-E19458(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LYS-42.

    Entry informationi

    Entry nameiCRX_HUMAN
    AccessioniPrimary (citable) accession number: O43186
    Secondary accession number(s): Q0QD45
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: June 1, 1998
    Last modified: October 1, 2014
    This is version 143 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 19
      Human chromosome 19: 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