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Reviewed, UniProtKB/Swiss-Prot P05093 (CP17A_HUMAN)

Last modified July 22, 2008. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Cytochrome P450 17A1
    EC=1.14.99.9
Alternative name(s):
    CYPXVII
    P450-C17
      Short name(s)=P450c17
    Steroid 17-alpha-monooxygenase
    Steroid 17-alpha-hydroxylase/17,20 lyase
Gene names
Name: CYP17A1
Synonyms: CYP17, S17AH
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length508 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.

Catalytic activity

A steroid + AH(2) + O(2) = a 17-alpha-hydroxysteroid + A + H(2)O.

Cofactor

Heme group.

Enzyme regulation

Regulated predominantly by intracellular cAMP levels.

Pathway

Lipid metabolism; steroid biosynthesis.

Subcellular location

MembranePotential. Membrane; Single-pass membrane protein.

Post-translational modification

Phosphorylation is necessary for 17,20-lyase, but not for 17-alpha-hydroxylase activity.

Involvement in disease

Defects in CYP17A1 are the cause of adrenal hyperplasia type 5 (AH5) [MIM:202110]. AH5 is a form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: "salt wasting" (SW, the most severe type), "simple virilizing" (SV, less severely affected patients), with normal aldosterone biosynthesis, "non-classic form" or late onset (NC or LOAH), and "cryptic" (asymptomatic).

Sequence similarities

Belongs to the cytochrome P450 family.

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Ontologies

Keywords

   Biological processSteroidogenesis
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseCongenital adrenal hyperplasia
Disease mutation
   LigandHeme
Iron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   PTMPhosphoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Biological processsex differentiation

Traceable author statement. Source: ProtInc

steroid biosynthetic process Ref.2

Traceable author statement. Source: ProtInc

   Cellular componentendoplasmic reticulum membrane Ref.9

Inferred from Experiment. Source: Reactome

   Molecular functionoxygen binding Ref.10

Traceable author statement. Source: ProtInc

steroid 17-alpha-monooxygenase activity Ref.9

Traceable author statement. Source: ProtInc

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 508508Cytochrome P450 17A1

Sites

Metal binding4421Iron (heme axial ligand)

Natural variations

Natural variant221C → W: dbSNP rs762563.
Natural variant351P → L in AH5; 38% 17alpha-hydroxylase activity and 33% 17,20-lyase activity.
Natural variant531Missing in AH5; 10% 17alpha-hydroxylase activity and 13% 17,20-lyase activity.
Natural variant641Y → S in AH5.
Natural variant931F → C in AH5.
Natural variant961R → W in AH5; 25% of both 17alpha-hydroxylase and 17,20-lyase activities.
Natural variant1061S → P in AH5.
Natural variant1121I → II in AH5.
Natural variant1141F → V in AH5.
Natural variant1161D → V in AH5.
Natural variant1771N → D in AH5; 10% 17alpha-hydroxylase and 17,20-lyase activities.
Natural variant3291Y → D in AH5.
Natural variant3301Missing in AH5; complete loss of both 17alpha-hydroxylase and 17,20-lyase activities.
Natural variant3421P → T in AH5.
Natural variant3471R → C in AH5.
Natural variant3471R → H in AH5; selectively ablates 17,20-lyase activity, while preserving most 17alpha-hydroxylase activity.
Natural variant3581R → Q in AH5; selectively ablates 17,20-lyase activity, while preserving most 17alpha-hydroxylase activity.
Natural variant3621R → C in AH5.
Natural variant3731H → L in AH5.
Natural variant4061W → R in AH5.
Natural variant4171F → C in AH5; ablates both 17,20-lyase activity and 17alpha-hydroxylase activity; loss of heme-binding and loss of phosphorylation.
Natural variant4281P → L in AH5.
Natural variant4401R → H in AH5.
Natural variant487 – 4893Missing in AH5.
Natural variant4961R → C in AH5.
Natural variant4961R → H in AH5; 30% 17alpha-hydroxylase activity and 29% 17,20-lyase activity.

Secondary structure

1 ....................................................................................... 508
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P05093-1 [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: E5454E9E18F96B0E

FASTA50857,371
        10         20         30         40         50         60 
MWELVALLLL TLAYLFWPKR RCPGAKYPKS LLSLPLVGSL PFLPRHGHMH NNFFKLQKKY 

        70         80         90        100        110        120 
GPIYSVRMGT KTTVIVGHHQ LAKEVLIKKG KDFSGRPQMA TLDIASNNRK GIAFADSGAH 

       130        140        150        160        170        180 
WQLHRRLAMA TFALFKDGDQ KLEKIICQEI STLCDMLATH NGQSIDISFP VFVAVTNVIS 

       190        200        210        220        230        240 
LICFNTSYKN GDPELNVIQN YNEGIIDNLS KDSLVDLVPW LKIFPNKTLE KLKSHVKIRN 

       250        260        270        280        290        300 
DLLNKILENY KEKFRSDSIT NMLDTLMQAK MNSDNGNAGP DQDSELLSDN HILTTIGDIF 

       310        320        330        340        350        360 
GAGVETTTSV VKWTLAFLLH NPQVKKKLYE EIDQNVGFSR TPTISDRNRL LLLEATIREV 

       370        380        390        400        410        420 
LRLRPVAPML IPHKANVDSS IGEFAVDKGT EVIINLWALH HNEKEWHQPD QFMPERFLNP 

       430        440        450        460        470        480 
AGTQLISPSV SYLPFGAGPR SCIGEILARQ ELFLIMAWLL QRFDLEVPDD GQLPSLEGIP 

       490        500 
KVVFLIDSFK VKIKVRQAWR EAQAEGST

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References

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[1]"Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues."
Chung B.-C., Picado-Leonard J., Haniu M., Bienkowski M., Hall P.F., Shively J.E., Miller W.L.
Proc. Natl. Acad. Sci. U.S.A. 84:407-411(1987) [PubMed: 3025870] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cloning and sequence of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): similarity with the gene for P450c21."
Picado-Leonard J., Miller W.L.
DNA 6:439-448(1987) [PubMed: 3500022] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Characterization of complementary deoxyribonucleic acid for human adrenocortical 17 alpha-hydroxylase: a probe for analysis of 17 alpha-hydroxylase deficiency."
Bradshaw K.D., Waterman M.R., Couch R.T., Simpson E.R., Zuber M.X.
Mol. Endocrinol. 1:348-354(1987) [PubMed: 3274893] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE.
[4]"Tissue-specific, cyclic adenosine 3',5'-monophosphate-induced, and phorbol ester-repressed transcription from the human P450c17 promoter in mouse cells."
Brentano S.T., Picado-Leonard J., Mellon S.H., Moore C.C., Miller W.L.
Mol. Endocrinol. 4:1972-1979(1990) [PubMed: 1964490] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Structural characterization of normal and mutant human steroid 17 alpha-hydroxylase genes: molecular basis of one example of combined 17 alpha-hydroxylase/17,20 lyase deficiency."