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P49675

- STAR_HUMAN

UniProt

P49675 - STAR_HUMAN

Protein

Steroidogenic acute regulatory protein, mitochondrial

Gene

STAR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 2 (19 Jul 2005)
      Previous versions | rss
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    Functioni

    Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Mediates the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone.

    Pathwayi

    GO - Molecular functioni

    1. cholesterol binding Source: Ensembl
    2. cholesterol transporter activity Source: InterPro

    GO - Biological processi

    1. bile acid biosynthetic process Source: Ensembl
    2. biphenyl metabolic process Source: Ensembl
    3. brain development Source: Ensembl
    4. C21-steroid hormone biosynthetic process Source: Reactome
    5. cellular response to alkaloid Source: Ensembl
    6. cellular response to antibiotic Source: Ensembl
    7. cellular response to cadmium ion Source: Ensembl
    8. cellular response to cAMP Source: Ensembl
    9. cellular response to dexamethasone stimulus Source: Ensembl
    10. cellular response to epinephrine stimulus Source: Ensembl
    11. cellular response to fibroblast growth factor stimulus Source: Ensembl
    12. cellular response to follicle-stimulating hormone stimulus Source: Ensembl
    13. cellular response to glucose stimulus Source: Ensembl
    14. cellular response to growth hormone stimulus Source: Ensembl
    15. cellular response to insulin stimulus Source: Ensembl
    16. cellular response to interferon-alpha Source: Ensembl
    17. cellular response to interferon-gamma Source: Ensembl
    18. cellular response to lipopolysaccharide Source: Ensembl
    19. cellular response to luteinizing hormone stimulus Source: Ensembl
    20. cellular response to transforming growth factor beta stimulus Source: Ensembl
    21. cholesterol metabolic process Source: UniProtKB-UniPathway
    22. circadian sleep/wake cycle, REM sleep Source: Ensembl
    23. dibenzo-p-dioxin metabolic process Source: Ensembl
    24. diterpenoid metabolic process Source: Ensembl
    25. estrogen biosynthetic process Source: Ensembl
    26. fractalkine metabolic process Source: Ensembl
    27. glucocorticoid metabolic process Source: Ensembl
    28. insecticide metabolic process Source: Ensembl
    29. intracellular cholesterol transport Source: Ensembl
    30. male gonad development Source: Ensembl
    31. negative regulation of neuron apoptotic process Source: Ensembl
    32. phenol-containing compound metabolic process Source: Ensembl
    33. phthalate metabolic process Source: Ensembl
    34. positive regulation of gene expression Source: Ensembl
    35. positive regulation of neurogenesis Source: Ensembl
    36. progesterone biosynthetic process Source: Ensembl
    37. regulation of neuronal synaptic plasticity Source: Ensembl
    38. regulation of steroid biosynthetic process Source: Ensembl
    39. response to activity Source: Ensembl
    40. response to corticosterone Source: Ensembl
    41. response to drug Source: Ensembl
    42. response to estrogen Source: Ensembl
    43. response to ethanol Source: Ensembl
    44. response to fungicide Source: Ensembl
    45. response to herbicide Source: Ensembl
    46. response to hydrogen peroxide Source: Ensembl
    47. response to ionizing radiation Source: Ensembl
    48. response to lead ion Source: Ensembl
    49. response to leptin Source: Ensembl
    50. response to nicotine Source: Ensembl
    51. response to nutrient Source: Ensembl
    52. small molecule metabolic process Source: Reactome
    53. steroid biosynthetic process Source: ProtInc
    54. steroid metabolic process Source: Reactome
    55. testosterone biosynthetic process Source: Ensembl

    Keywords - Biological processi

    Lipid transport, Steroidogenesis, Transport

    Keywords - Ligandi

    Lipid-binding

    Enzyme and pathway databases

    ReactomeiREACT_11038. Pregnenolone biosynthesis.
    UniPathwayiUPA00296.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Steroidogenic acute regulatory protein, mitochondrial
    Short name:
    StAR
    Alternative name(s):
    START domain-containing protein 1
    Short name:
    StARD1
    Gene namesi
    Name:STAR
    Synonyms:STARD1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:11359. STAR.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Ensembl
    2. mitochondrial crista Source: Ensembl
    3. mitochondrial intermembrane space Source: Reactome
    4. neuronal cell body Source: Ensembl
    5. neuron projection Source: Ensembl

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Adrenal hyperplasia 1 (AH1) [MIM:201710]: The most severe form of adrenal hyperplasia. It is a condition characterized by onset of profound adrenocortical insufficiency shortly after birth, hyperpigmentation reflecting increased production of pro-opiomelanocortin, elevated plasma renin activity as a consequence of reduced aldosterone synthesis, and male pseudohermaphroditism resulting from deficient fetal testicular testosterone synthesis. Affected individuals are phenotypic females irrespective of gonadal sex, and frequently die in infancy if mineralocorticoid and glucocorticoid replacement are not instituted.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti169 – 1691E → G in AH1; partial loss of activity. 1 Publication
    VAR_014236
    Natural varianti169 – 1691E → K in AH1; partial loss of activity. 1 Publication
    VAR_014237
    Natural varianti182 – 1821R → L in AH1; partial loss of activity. 1 Publication
    VAR_005627
    Natural varianti217 – 2171R → T in AH1. 1 Publication
    Corresponds to variant rs28938471 [ dbSNP | Ensembl ].
    VAR_014238
    Natural varianti218 – 2181A → V in AH1; partial loss of activity. 3 Publications
    VAR_014239
    Natural varianti225 – 2251M → T in AH1. 1 Publication
    VAR_014240
    Natural varianti272 – 2721Missing in AH1; partial loss of activity. 1 Publication
    VAR_014241
    Natural varianti275 – 2751L → P in AH1; partial loss of activity. 1 Publication
    VAR_014242

    Keywords - Diseasei

    Congenital adrenal hyperplasia, Disease mutation

    Organism-specific databases

    MIMi201710. phenotype.
    Orphaneti325524. Classic congenital lipoid adrenal hyperplasia due to STAR deficency.
    361. Familial glucocorticoid deficiency.
    325529. Non-classic congenital lipoid adrenal hyperplasia due to STAR deficency.
    PharmGKBiPA36181.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 6363MitochondrionBy similarityAdd
    BLAST
    Chaini64 – 285222Steroidogenic acute regulatory protein, mitochondrialPRO_0000033316Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei57 – 571Phosphoserine; by PKA1 Publication
    Modified residuei195 – 1951Phosphoserine; by PKA1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP49675.
    PaxDbiP49675.
    PRIDEiP49675.

    PTM databases

    PhosphoSiteiP49675.

    Expressioni

    Tissue specificityi

    Expressed in gonads, adrenal cortex and kidney.

    Gene expression databases

    ArrayExpressiP49675.
    BgeeiP49675.
    CleanExiHS_STAR.
    GenevestigatoriP49675.

    Organism-specific databases

    HPAiCAB032598.
    HPA023644.
    HPA027318.

    Interactioni

    Subunit structurei

    May interact with TSPO.By similarity

    Protein-protein interaction databases

    BioGridi112647. 3 interactions.
    IntActiP49675. 1 interaction.
    MINTiMINT-1403878.
    STRINGi9606.ENSP00000276449.

    Structurei

    Secondary structure

    1
    285
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi70 – 9122
    Beta strandi97 – 1015
    Beta strandi107 – 1126
    Beta strandi114 – 1163
    Beta strandi118 – 12811
    Helixi130 – 1378
    Turni138 – 1403
    Helixi141 – 1433
    Beta strandi152 – 1598
    Beta strandi161 – 17111
    Beta strandi182 – 19211
    Beta strandi197 – 1993
    Beta strandi215 – 2173
    Beta strandi224 – 2307
    Beta strandi233 – 24311
    Helixi253 – 27422

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IMGmodel-A67-280[»]
    2I93model-A67-280[»]
    3P0LX-ray3.40A/B/C/D66-284[»]
    ProteinModelPortaliP49675.
    SMRiP49675. Positions 66-276.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP49675.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini67 – 280214STARTPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 START domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiNOG239518.
    HOGENOMiHOG000142452.
    HOVERGENiHBG010529.
    InParanoidiP49675.
    KOiK16931.
    OMAiLATFKLC.
    OrthoDBiEOG74FF0Z.
    PhylomeDBiP49675.
    TreeFamiTF313869.

    Family and domain databases

    Gene3Di3.30.530.20. 1 hit.
    InterProiIPR000799. StAR.
    IPR023393. START-like_dom.
    IPR002913. START_lipid-bd_dom.
    [Graphical view]
    PfamiPF01852. START. 1 hit.
    [Graphical view]
    PRINTSiPR00978. STARPROTEIN.
    SMARTiSM00234. START. 1 hit.
    [Graphical view]
    PROSITEiPS50848. START. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P49675-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLLATFKLCA GSSYRHMRNM KGLRQQAVMA ISQELNRRAL GGPTPSTWIN    50
    QVRRRSSLLG SRLEETLYSD QELAYLQQGE EAMQKALGIL SNQEGWKKES 100
    QQDNGDKVMS KVVPDVGKVF RLEVVVDQPM ERLYEELVER MEAMGEWNPN 150
    VKEIKVLQKI GKDTFITHEL AAEAAGNLVG PRDFVSVRCA KRRGSTCVLA 200
    GMATDFGNMP EQKGVIRAEH GPTCMVLHPL AGSPSKTKLT WLLSIDLKGW 250
    LPKSIINQVL SQTQVDFANH LRKRLESHPA SEARC 285
    Length:285
    Mass (Da):31,914
    Last modified:July 19, 2005 - v2
    Checksum:i2683086C20DE88AB
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti121 – 1211R → W.
    Corresponds to variant rs34908868 [ dbSNP | Ensembl ].
    VAR_034520
    Natural varianti169 – 1691E → G in AH1; partial loss of activity. 1 Publication
    VAR_014236
    Natural varianti169 – 1691E → K in AH1; partial loss of activity. 1 Publication
    VAR_014237
    Natural varianti182 – 1821R → L in AH1; partial loss of activity. 1 Publication
    VAR_005627
    Natural varianti203 – 2031A → D.3 Publications
    Corresponds to variant rs1042854 [ dbSNP | Ensembl ].
    VAR_005628
    Natural varianti217 – 2171R → T in AH1. 1 Publication
    Corresponds to variant rs28938471 [ dbSNP | Ensembl ].
    VAR_014238
    Natural varianti218 – 2181A → V in AH1; partial loss of activity. 3 Publications
    VAR_014239
    Natural varianti225 – 2251M → T in AH1. 1 Publication
    VAR_014240
    Natural varianti272 – 2721Missing in AH1; partial loss of activity. 1 Publication
    VAR_014241
    Natural varianti275 – 2751L → P in AH1; partial loss of activity. 1 Publication
    VAR_014242

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U17280 mRNA. Translation: AAC50141.1.
    U29105
    , U29099, U29100, U29101, U29102, U29103, U29104 Genomic DNA. Translation: AAC50234.1.
    S79669 mRNA. Translation: AAB35726.1.
    AF035277 mRNA. Translation: AAB88174.1.
    BC010550 mRNA. Translation: AAH10550.1.
    CCDSiCCDS6102.1.
    PIRiI38248.
    RefSeqiNP_000340.2. NM_000349.2.
    UniGeneiHs.521535.

    Genome annotation databases

    EnsembliENST00000276449; ENSP00000276449; ENSG00000147465.
    GeneIDi6770.
    KEGGihsa:6770.
    UCSCiuc003xkv.1. human.

    Polymorphism databases

    DMDMi71152974.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Steroidogenic acute regulatory protein entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U17280 mRNA. Translation: AAC50141.1 .
    U29105
    , U29099 , U29100 , U29101 , U29102 , U29103 , U29104 Genomic DNA. Translation: AAC50234.1 .
    S79669 mRNA. Translation: AAB35726.1 .
    AF035277 mRNA. Translation: AAB88174.1 .
    BC010550 mRNA. Translation: AAH10550.1 .
    CCDSi CCDS6102.1.
    PIRi I38248.
    RefSeqi NP_000340.2. NM_000349.2.
    UniGenei Hs.521535.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1IMG model - A 67-280 [» ]
    2I93 model - A 67-280 [» ]
    3P0L X-ray 3.40 A/B/C/D 66-284 [» ]
    ProteinModelPortali P49675.
    SMRi P49675. Positions 66-276.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112647. 3 interactions.
    IntActi P49675. 1 interaction.
    MINTi MINT-1403878.
    STRINGi 9606.ENSP00000276449.

    PTM databases

    PhosphoSitei P49675.

    Polymorphism databases

    DMDMi 71152974.

    Proteomic databases

    MaxQBi P49675.
    PaxDbi P49675.
    PRIDEi P49675.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000276449 ; ENSP00000276449 ; ENSG00000147465 .
    GeneIDi 6770.
    KEGGi hsa:6770.
    UCSCi uc003xkv.1. human.

    Organism-specific databases

    CTDi 6770.
    GeneCardsi GC08M038018.
    HGNCi HGNC:11359. STAR.
    HPAi CAB032598.
    HPA023644.
    HPA027318.
    MIMi 201710. phenotype.
    600617. gene.
    neXtProti NX_P49675.
    Orphaneti 325524. Classic congenital lipoid adrenal hyperplasia due to STAR deficency.
    361. Familial glucocorticoid deficiency.
    325529. Non-classic congenital lipoid adrenal hyperplasia due to STAR deficency.
    PharmGKBi PA36181.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG239518.
    HOGENOMi HOG000142452.
    HOVERGENi HBG010529.
    InParanoidi P49675.
    KOi K16931.
    OMAi LATFKLC.
    OrthoDBi EOG74FF0Z.
    PhylomeDBi P49675.
    TreeFami TF313869.

    Enzyme and pathway databases

    UniPathwayi UPA00296 .
    Reactomei REACT_11038. Pregnenolone biosynthesis.

    Miscellaneous databases

    ChiTaRSi STAR. human.
    EvolutionaryTracei P49675.
    GenomeRNAii 6770.
    NextBioi 26420.
    PROi P49675.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49675.
    Bgeei P49675.
    CleanExi HS_STAR.
    Genevestigatori P49675.

    Family and domain databases

    Gene3Di 3.30.530.20. 1 hit.
    InterProi IPR000799. StAR.
    IPR023393. START-like_dom.
    IPR002913. START_lipid-bd_dom.
    [Graphical view ]
    Pfami PF01852. START. 1 hit.
    [Graphical view ]
    PRINTSi PR00978. STARPROTEIN.
    SMARTi SM00234. START. 1 hit.
    [Graphical view ]
    PROSITEi PS50848. START. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13."
      Sugawara T., Holt J.A., Driscoll D., Strauss J.F. III, Lin D., Miller W.L., Patterson D., Clancy K.P., Hart I.M., Clark B.J., Stocco D.M.
      Proc. Natl. Acad. Sci. U.S.A. 92:4778-4782(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-203.
      Tissue: Adrenal cortex.
    2. "Structure of the human steroidogenic acute regulatory protein (StAR) gene: StAR stimulates mitochondrial cholesterol 27-hydroxylase activity."
      Sugawara T., Lin D., Holt J.A., Martin K.O., Javitt N.B., Miller W.L., Strauss J.F. III
      Biochemistry 34:12506-12512(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-203.
      Tissue: Placenta.
    3. "The human steroidogenic acute regulatory (StAR) gene is expressed in the urogenital system and encodes a mitochondrial polypeptide."
      Gradi A., Tang-Wai R., McBride H.M., Chu L.L., Shore G.C., Pelletier J.
      Biochim. Biophys. Acta 1258:228-233(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. Yu W., Sarginson J., Gibbs R.A.
      Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    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].
      Tissue: Brain.
    6. "The steroidogenic acute regulatory protein (StAR): a window into the complexities of intracellular cholesterol trafficking."
      Strauss J.F. III, Kallen C.B., Christenson L.K., Watari H., Devoto L., Arakane F., Kiriakidou M., Sugawara T.
      Recent Prog. Horm. Res. 54:369-394(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-57 AND SER-195.
    7. Cited for: X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 66-284.
    8. "The pathophysiology and genetics of congenital lipoid adrenal hyperplasia."
      Bose H.S., Sugawara T., Strauss J.F. III, Miller W.L.
      N. Engl. J. Med. 335:1870-1878(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AH1 GLY-169; LYS-169; LEU-182; VAL-218; ARG-272 DEL AND PRO-275, CHARACTERIZATION OF VARIANTS.
    9. "Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia."
      Nakae J., Tajima T., Sugawara T., Arakane F., Hanaki K., Hotsubo T., Igarashi N., Igarashi Y., Ishii T., Koda N., Kondo T., Kohno H., Nakagawa Y., Tachibana K., Takeshima Y., Tsubouchi K., Strauss J.F. III, Fujieda K.
      Hum. Mol. Genet. 6:571-576(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AH1 VAL-218 AND THR-225.
    10. "A novel frameshift mutation 840delA and a novel polymorphism D203A in the steroidogenic acute regulatory protein gene in a Japanese patient with congenital lipoid adrenal hyperplasia."
      Katsumata N., Tanae A., Shinagawa T., Nagashima-Miyokawa A., Shimizu M., Yasunaga T., Tanaka T., Hibi I.
      Hum. Mutat. Suppl. 1:S304-S307(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ASP-203.
    11. "A novel compound heterozygous mutation in the steroidogenic acute regulatory protein gene in a patient with congenital lipoid adrenal hyperplasia."
      Katsumata N., Kawada Y., Yamamoto Y., Noda M., Nimura A., Horikawa R., Tanaka T.
      J. Clin. Endocrinol. Metab. 84:3983-3987(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AH1 THR-217 AND VAL-218.

    Entry informationi

    Entry nameiSTAR_HUMAN
    AccessioniPrimary (citable) accession number: P49675
    Secondary accession number(s): Q16396
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: July 19, 2005
    Last modified: October 1, 2014
    This is version 150 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 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3