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Q2TBA0

- KLH40_HUMAN

UniProt

Q2TBA0 - KLH40_HUMAN

Protein

Kelch-like protein 40

Gene

KLHL40

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 70 (01 Oct 2014)
      Sequence version 2 (06 Feb 2007)
      Previous versions | rss
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    Functioni

    Required for skeletal muscle development.1 Publication

    GO - Biological processi

    1. multicellular organismal development Source: UniProtKB-KW

    Keywords - Molecular functioni

    Developmental protein

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Kelch-like protein 40
    Alternative name(s):
    Kelch repeat and BTB domain-containing protein 5
    Sarcosynapsin
    Gene namesi
    Name:KLHL40
    Synonyms:KBTBD5, SRYP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:30372. KLHL40.

    Subcellular locationi

    CytoplasmmyofibrilsarcomereA band 1 Publication

    GO - Cellular componenti

    1. A band Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Nemaline myopathy 8 (NEM8) [MIM:615348]: A severe form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM8 is characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth. Most patients die in infancy. Skeletal muscle biopsy shows numerous small nemaline bodies, often with no normal myofibrils.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti34 – 341D → H in NEM8. 1 Publication
    VAR_069836
    Natural varianti86 – 861L → P in NEM8. 1 Publication
    VAR_069837
    Natural varianti194 – 1941V → E in NEM8. 1 Publication
    VAR_069838
    Natural varianti201 – 2011W → L in NEM8. 1 Publication
    VAR_069839
    Natural varianti311 – 3111R → L in NEM8. 1 Publication
    VAR_069840
    Natural varianti397 – 3971P → L in NEM8. 1 Publication
    VAR_069841
    Natural varianti455 – 4551H → R in NEM8. 1 Publication
    VAR_069842
    Natural varianti469 – 4691G → C in NEM8. 1 Publication
    VAR_069843
    Natural varianti506 – 5061T → P in NEM8. 1 Publication
    VAR_069844
    Natural varianti528 – 5281E → K in NEM8. 1 Publication
    VAR_069845
    Natural varianti538 – 5381A → P in NEM8. 1 Publication
    VAR_069846
    Natural varianti588 – 5881E → K in NEM8. 1 Publication
    VAR_069847

    Keywords - Diseasei

    Disease mutation, Nemaline myopathy

    Organism-specific databases

    MIMi615348. phenotype.
    Orphaneti171430. Severe congenital nemaline myopathy.
    PharmGKBiPA134908127.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 621621Kelch-like protein 40PRO_0000274235Add
    BLAST

    Proteomic databases

    PaxDbiQ2TBA0.
    PRIDEiQ2TBA0.

    PTM databases

    PhosphoSiteiQ2TBA0.

    Expressioni

    Tissue specificityi

    Highly expressed in fetal (19, 23 and 31 weeks of gestation) and adult skeletal muscle; expression levels tend to be higher in fetal compared to postnatal muscles (at protein level). Aslo expressed in fetal and adult heart.1 Publication

    Gene expression databases

    BgeeiQ2TBA0.
    CleanExiHS_KBTBD5.
    GenevestigatoriQ2TBA0.

    Organism-specific databases

    HPAiHPA024463.

    Interactioni

    Protein-protein interaction databases

    IntActiQ2TBA0. 1 interaction.
    MINTiMINT-8330030.

    Structurei

    Secondary structure

    1
    621
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi317 – 3248
    Beta strandi327 – 3326
    Turni333 – 3364
    Beta strandi337 – 3426
    Beta strandi349 – 3557
    Beta strandi361 – 3699
    Beta strandi374 – 3763
    Beta strandi378 – 3869
    Turni387 – 3904
    Beta strandi391 – 3944
    Beta strandi398 – 4003
    Beta strandi402 – 4043
    Beta strandi406 – 4105
    Beta strandi413 – 4175
    Beta strandi420 – 4234
    Beta strandi432 – 4365
    Turni437 – 4404
    Beta strandi441 – 4444
    Beta strandi456 – 4605
    Beta strandi463 – 4675
    Beta strandi480 – 4845
    Turni485 – 4884
    Beta strandi489 – 4924
    Beta strandi504 – 5085
    Beta strandi511 – 5188
    Beta strandi520 – 53112
    Turni532 – 5354
    Beta strandi536 – 5405
    Beta strandi551 – 5555
    Beta strandi558 – 56912
    Beta strandi575 – 58713
    Turni588 – 5914
    Beta strandi592 – 5987
    Beta strandi607 – 6137
    Helixi615 – 6173
    Beta strandi618 – 6203

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4ASCX-ray1.78A314-621[»]
    ProteinModelPortaliQ2TBA0.
    SMRiQ2TBA0. Positions 29-262, 314-621.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini33 – 9866BTBPROSITE-ProRule annotationAdd
    BLAST
    Domaini133 – 239107BACKAdd
    BLAST
    Repeati360 – 41253Kelch 1Add
    BLAST
    Repeati413 – 46250Kelch 2Add
    BLAST
    Repeati463 – 51048Kelch 3Add
    BLAST
    Repeati512 – 55746Kelch 4Add
    BLAST
    Repeati559 – 61355Kelch 5Add
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi270 – 2756Poly-Lys

    Sequence similaritiesi

    Contains 1 BTB (POZ) domain.PROSITE-ProRule annotation
    Contains 5 Kelch repeats.Curated

    Keywords - Domaini

    Kelch repeat, Repeat

    Phylogenomic databases

    eggNOGiNOG290520.
    HOGENOMiHOG000231966.
    HOVERGENiHBG052215.
    InParanoidiQ2TBA0.
    KOiK10473.
    OMAiVYGHAVL.
    OrthoDBiEOG7M6D6S.
    PhylomeDBiQ2TBA0.
    TreeFamiTF351653.

    Family and domain databases

    Gene3Di2.120.10.80. 1 hit.
    3.30.710.10. 1 hit.
    InterProiIPR011705. BACK.
    IPR000210. BTB/POZ-like.
    IPR011333. BTB/POZ_fold.
    IPR013069. BTB_POZ.
    IPR017096. Kelch-like_gigaxonin-typ.
    IPR015915. Kelch-typ_b-propeller.
    IPR006652. Kelch_1.
    [Graphical view]
    PfamiPF07707. BACK. 1 hit.
    PF00651. BTB. 1 hit.
    PF01344. Kelch_1. 3 hits.
    [Graphical view]
    PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
    SMARTiSM00875. BACK. 1 hit.
    SM00225. BTB. 1 hit.
    SM00612. Kelch. 4 hits.
    [Graphical view]
    SUPFAMiSSF54695. SSF54695. 1 hit.
    PROSITEiPS50097. BTB. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q2TBA0-1) [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

    MALGLEQAEE QRLYQQTLLQ DGLKDMLDHG KFLDCVVRAG EREFPCHRLV    50
    LAACSPYFRA RFLAEPERAG ELHLEEVSPD VVAQVLHYLY TSEIALDEAS 100
    VQDLFAAAHR FQIPSIFTIC VSFLQKRLCL SNCLAVFRLG LLLDCARLAV 150
    AARDFICAHF TLVARDADFL GLSADELIAI ISSDGLNVEK EEAVFEAVMR 200
    WAGSGDAEAQ AERQRALPTV FESVRCRLLP RAFLESRVER HPLVRAQPEL 250
    LRKVQMVKDA HEGRITTLRK KKKGKDGAGA KEADKGTSKA KAEEDEEAER 300
    ILPGILNDTL RFGMFLQDLI FMISEEGAVA YDPAANECYC ASLSNQVPKN 350
    HVSLVTKENQ VFVAGGLFYN EDNKEDPMSA YFLQFDHLDS EWLGMPPLPS 400
    PRCLFGLGEA LNSIYVVGGR EIKDGERCLD SVMCYDRLSF KWGESDPLPY 450
    VVYGHTVLSH MDLVYVIGGK GSDRKCLNKM CVYDPKKFEW KELAPMQTAR 500
    SLFGATVHDG RIIVAAGVTD TGLTSSAEVY SITDNKWAPF EAFPQERSSL 550
    SLVSLVGTLY AIGGFATLET ESGELVPTEL NDIWRYNEEE KKWEGVLREI 600
    AYAAGATFLP VRLNVLCLTK M 621
    Length:621
    Mass (Da):69,257
    Last modified:February 6, 2007 - v2
    Checksum:i53492478F08A5A2D
    GO
    Isoform 2 (identifier: Q2TBA0-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         444-604: ESDPLPYVVY...GVLREIAYAA → HRHRADQFCRSVQHHRQQVGTLRGLPTGA
         605-621: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:472
    Mass (Da):52,893
    Checksum:i6A64676A03325797
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti34 – 341D → H in NEM8. 1 Publication
    VAR_069836
    Natural varianti86 – 861L → P in NEM8. 1 Publication
    VAR_069837
    Natural varianti194 – 1941V → E in NEM8. 1 Publication
    VAR_069838
    Natural varianti201 – 2011W → L in NEM8. 1 Publication
    VAR_069839
    Natural varianti311 – 3111R → L in NEM8. 1 Publication
    VAR_069840
    Natural varianti345 – 3451N → S.2 Publications
    Corresponds to variant rs6805421 [ dbSNP | Ensembl ].
    VAR_030214
    Natural varianti397 – 3971P → L in NEM8. 1 Publication
    VAR_069841
    Natural varianti455 – 4551H → R in NEM8. 1 Publication
    VAR_069842
    Natural varianti469 – 4691G → C in NEM8. 1 Publication
    VAR_069843
    Natural varianti506 – 5061T → P in NEM8. 1 Publication
    VAR_069844
    Natural varianti528 – 5281E → K in NEM8. 1 Publication
    VAR_069845
    Natural varianti538 – 5381A → P in NEM8. 1 Publication
    VAR_069846
    Natural varianti588 – 5881E → K in NEM8. 1 Publication
    VAR_069847
    Natural varianti617 – 6171C → R.1 Publication
    Corresponds to variant rs123509 [ dbSNP | Ensembl ].
    VAR_030215

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei444 – 604161ESDPL…IAYAA → HRHRADQFCRSVQHHRQQVG TLRGLPTGA in isoform 2. 1 PublicationVSP_022681Add
    BLAST
    Alternative sequencei605 – 62117Missing in isoform 2. 1 PublicationVSP_022682Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY177390 mRNA. Translation: AAO06908.1.
    AY176040 mRNA. Translation: AAO22141.1.
    AK056577 mRNA. Translation: BAB71222.1.
    BC110491 mRNA. Translation: AAI10492.1.
    CCDSiCCDS2703.1. [Q2TBA0-1]
    RefSeqiNP_689606.2. NM_152393.3. [Q2TBA0-1]
    UniGeneiHs.350288.

    Genome annotation databases

    EnsembliENST00000287777; ENSP00000287777; ENSG00000157119. [Q2TBA0-1]
    GeneIDi131377.
    KEGGihsa:131377.
    UCSCiuc003clv.1. human. [Q2TBA0-1]

    Polymorphism databases

    DMDMi125950763.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY177390 mRNA. Translation: AAO06908.1 .
    AY176040 mRNA. Translation: AAO22141.1 .
    AK056577 mRNA. Translation: BAB71222.1 .
    BC110491 mRNA. Translation: AAI10492.1 .
    CCDSi CCDS2703.1. [Q2TBA0-1 ]
    RefSeqi NP_689606.2. NM_152393.3. [Q2TBA0-1 ]
    UniGenei Hs.350288.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4ASC X-ray 1.78 A 314-621 [» ]
    ProteinModelPortali Q2TBA0.
    SMRi Q2TBA0. Positions 29-262, 314-621.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q2TBA0. 1 interaction.
    MINTi MINT-8330030.

    PTM databases

    PhosphoSitei Q2TBA0.

    Polymorphism databases

    DMDMi 125950763.

    Proteomic databases

    PaxDbi Q2TBA0.
    PRIDEi Q2TBA0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000287777 ; ENSP00000287777 ; ENSG00000157119 . [Q2TBA0-1 ]
    GeneIDi 131377.
    KEGGi hsa:131377.
    UCSCi uc003clv.1. human. [Q2TBA0-1 ]

    Organism-specific databases

    CTDi 131377.
    GeneCardsi GC03P042727.
    HGNCi HGNC:30372. KLHL40.
    HPAi HPA024463.
    MIMi 615340. gene.
    615348. phenotype.
    neXtProti NX_Q2TBA0.
    Orphaneti 171430. Severe congenital nemaline myopathy.
    PharmGKBi PA134908127.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG290520.
    HOGENOMi HOG000231966.
    HOVERGENi HBG052215.
    InParanoidi Q2TBA0.
    KOi K10473.
    OMAi VYGHAVL.
    OrthoDBi EOG7M6D6S.
    PhylomeDBi Q2TBA0.
    TreeFami TF351653.

    Miscellaneous databases

    ChiTaRSi KBTBD5. human.
    GenomeRNAii 131377.
    NextBioi 82900.
    PROi Q2TBA0.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q2TBA0.
    CleanExi HS_KBTBD5.
    Genevestigatori Q2TBA0.

    Family and domain databases

    Gene3Di 2.120.10.80. 1 hit.
    3.30.710.10. 1 hit.
    InterProi IPR011705. BACK.
    IPR000210. BTB/POZ-like.
    IPR011333. BTB/POZ_fold.
    IPR013069. BTB_POZ.
    IPR017096. Kelch-like_gigaxonin-typ.
    IPR015915. Kelch-typ_b-propeller.
    IPR006652. Kelch_1.
    [Graphical view ]
    Pfami PF07707. BACK. 1 hit.
    PF00651. BTB. 1 hit.
    PF01344. Kelch_1. 3 hits.
    [Graphical view ]
    PIRSFi PIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
    SMARTi SM00875. BACK. 1 hit.
    SM00225. BTB. 1 hit.
    SM00612. Kelch. 4 hits.
    [Graphical view ]
    SUPFAMi SSF54695. SSF54695. 1 hit.
    PROSITEi PS50097. BTB. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Structure, gene organization and expression analysis of human sarcosynapsin."
      Goudou D., Bitoun M., Rieger F., Perin J.-P., Alliel P.M.
      Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Heart.
    2. "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), VARIANT SER-345.
      Tissue: Tongue.
    3. "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), VARIANTS SER-345 AND ARG-617.
    4. Cited for: X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 314-621.
    5. "Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy."
      Ravenscroft G., Miyatake S., Lehtokari V.L., Todd E.J., Vornanen P., Yau K.S., Hayashi Y.K., Miyake N., Tsurusaki Y., Doi H., Saitsu H., Osaka H., Yamashita S., Ohya T., Sakamoto Y., Koshimizu E., Imamura S., Yamashita M.
      , Ogata K., Shiina M., Bryson-Richardson R.J., Vaz R., Ceyhan O., Brownstein C.A., Swanson L.C., Monnot S., Romero N.B., Amthor H., Kresoje N., Sivadorai P., Kiraly-Borri C., Haliloglu G., Talim B., Orhan D., Kale G., Charles A.K., Fabian V.A., Davis M.R., Lammens M., Sewry C.A., Manzur A., Muntoni F., Clarke N.F., North K.N., Bertini E., Nevo Y., Willichowski E., Silberg I.E., Topaloglu H., Beggs A.H., Allcock R.J., Nishino I., Wallgren-Pettersson C., Matsumoto N., Laing N.G.
      Am. J. Hum. Genet. 93:6-18(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS NEM8 HIS-34; PRO-86; GLU-194; LEU-201; LEU-311; LEU-397; ARG-455; CYS-469; PRO-506; LYS-528; PRO-538 AND LYS-588, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiKLH40_HUMAN
    AccessioniPrimary (citable) accession number: Q2TBA0
    Secondary accession number(s): Q86SI1, Q96MR2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 6, 2007
    Last sequence update: February 6, 2007
    Last modified: October 1, 2014
    This is version 70 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

    3D-structure, Complete proteome, 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3