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P22680 (CP7A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cholesterol 7-alpha-monooxygenase

EC=1.14.13.17
Alternative name(s):
CYPVII
Cholesterol 7-alpha-hydroxylase
Cytochrome P450 7A1
Gene names
Name:CYP7A1
Synonyms:CYP7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length504 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes a rate-limiting step in cholesterol catabolism and bile acid biosynthesis by introducing a hydrophilic moiety at position 7 of cholesterol. Important for cholesterol homeostasis. Ref.8

Catalytic activity

Cholesterol + NADPH + O2 = 7-alpha-hydroxycholesterol + NADP+ + H2O. Ref.2

Cofactor

Heme group. Ref.9

Pathway

Lipid metabolism; bile acid biosynthesis.

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.

Tissue specificity

Detected in liver. Ref.7

Induction

Up-regulated by glucose and by cholestyramine. Down-regulated by chenodeoxycholic acid. Ref.7 Ref.8

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Biological processCholesterol metabolism
Lipid metabolism
Steroid metabolism
Sterol metabolism
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityPolymorphism
   LigandHeme
Iron
Metal-binding
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbile acid biosynthetic process

Inferred from direct assay Ref.8. Source: UniProtKB

bile acid metabolic process

Traceable author statement. Source: Reactome

cellular lipid metabolic process

Traceable author statement. Source: Reactome

cellular response to cholesterol

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to glucose stimulus

Inferred from direct assay Ref.8. Source: UniProtKB

cholesterol catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

cholesterol homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of bile acid biosynthetic process

Inferred from direct assay Ref.8. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

sterol metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

intracellular membrane-bounded organelle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functioncholesterol 7-alpha-monooxygenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

heme binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 504504Cholesterol 7-alpha-monooxygenase
PRO_0000051901

Sites

Metal binding4441Iron (heme axial ligand)

Natural variations

Natural variant861H → N.
Corresponds to variant rs62621283 [ dbSNP | Ensembl ].
VAR_059152
Natural variant1001F → S. Ref.3
VAR_001259
Natural variant2331N → S. Ref.10
Corresponds to variant rs8192874 [ dbSNP | Ensembl ].
VAR_018376
Natural variant3471D → N. Ref.2 Ref.10
Corresponds to variant rs8192875 [ dbSNP | Ensembl ].
VAR_018377

Experimental info

Sequence conflict3851D → S in CAA39568. Ref.2

Secondary structure

................................................................................ 504
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22680 [UniParc].

Last modified June 1, 1994. Version 2.
Checksum: D8067E0FF6342949

FASTA50457,661
        10         20         30         40         50         60 
MMTTSLIWGI AIAACCCLWL ILGIRRRQTG EPPLENGLIP YLGCALQFGA NPLEFLRANQ 

        70         80         90        100        110        120 
RKHGHVFTCK LMGKYVHFIT NPLSYHKVLC HGKYFDWKKF HFATSAKAFG HRSIDPMDGN 

       130        140        150        160        170        180 
TTENINDTFI KTLQGHALNS LTESMMENLQ RIMRPPVSSN SKTAAWVTEG MYSFCYRVMF 

       190        200        210        220        230        240 
EAGYLTIFGR DLTRRDTQKA HILNNLDNFK QFDKVFPALV AGLPIHMFRT AHNAREKLAE 

       250        260        270        280        290        300 
SLRHENLQKR ESISELISLR MFLNDTLSTF DDLEKAKTHL VVLWASQANT IPATFWSLFQ 

       310        320        330        340        350        360 
MIRNPEAMKA ATEEVKRTLE NAGQKVSLEG NPICLSQAEL NDLPVLDSII KESLRLSSAS 

       370        380        390        400        410        420 
LNIRTAKEDF TLHLEDGSYN IRKDDIIALY PQLMHLDPEI YPDPLTFKYD RYLDENGKTK 

       430        440        450        460        470        480 
TTFYCNGLKL KYYYMPFGSG ATICPGRLFA IHEIKQFLIL MLSYFELELI EGQAKCPPLD 

       490        500 
QSRAGLGILP PLNDIEFKYK FKHL 

« Hide

References

« Hide 'large scale' references
[1]"Structure of the gene encoding human liver cholesterol 7 alpha-hydroxylase."
Nishimoto M., Noshiro M., Okuda K.
Biochim. Biophys. Acta 1172:147-150(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Molecular cloning and sequence analysis of cDNA encoding human cholesterol 7 alpha-hydroxylase."
Noshiro M., Okuda K.
FEBS Lett. 268:137-140(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, VARIANT ASN-347.
[3]"Polymorphisms of human cholesterol 7 alpha-hydroxylase."
Karam W.G., Chiang J.Y.
Biochem. Biophys. Res. Commun. 185:588-595(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-100.
[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: Liver.
[5]"Structure and nucleotide sequences of the human cholesterol 7 alpha-hydroxylase gene (CYP7)."
Wang D.P., Chiang J.Y.
Genomics 20:320-323(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-140.
Tissue: Placenta.
[6]"Transcriptional regulation of the human cholesterol 7 alpha-hydroxylase gene."
Molowa D.T., Chen W.S., Cimis G.M., Tan C.P.
Biochemistry 31:2539-2544(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-25.
[7]"Feedback regulation of bile acid synthesis in human liver: importance of HNF-4alpha for regulation of CYP7A1."
Abrahamsson A., Gustafsson U., Ellis E., Nilsson L.M., Sahlin S., Bjorkhem I., Einarsson C.
Biochem. Biophys. Res. Commun. 330:395-399(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY CHENODEOXYCHOLIC ACID AND CHOLESTYRAMINE, TISSUE SPECIFICITY.
[8]"Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes."
Li T., Chanda D., Zhang Y., Choi H.S., Chiang J.Y.
J. Lipid Res. 51:832-842(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY GLUCOSE, FUNCTION.
[9]"Crystal structure of human CYP7A1."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH HEME, COFACTOR.
[10]"Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population."
Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., Nakamura Y.
J. Hum. Genet. 48:249-270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SER-233 AND ASN-347.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X56088 mRNA. Translation: CAA39568.1.
M93133 mRNA. Translation: AAA58435.1.
BC101777 mRNA. Translation: AAI01778.1.
BC112184 mRNA. Translation: AAI12185.1.
L13460 Genomic DNA. Translation: AAA61350.1.
M89647 Genomic DNA. Translation: AAA58423.1.
CCDSCCDS6171.1.
PIRJH0659. S29818.
RefSeqNP_000771.2. NM_000780.3.
UniGeneHs.1644.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3DAXX-ray2.15A/B25-503[»]
3SN5X-ray2.75A/B25-503[»]
3V8DX-ray1.90A/B25-503[»]
ProteinModelPortalP22680.
SMRP22680. Positions 25-503.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000301645.

PTM databases

PhosphoSiteP22680.

Polymorphism databases

DMDM544084.

Proteomic databases

PaxDbP22680.
PRIDEP22680.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301645; ENSP00000301645; ENSG00000167910.
GeneID1581.
KEGGhsa:1581.
UCSCuc003xtm.4. human.

Organism-specific databases

CTD1581.
GeneCardsGC08M059452.
HGNCHGNC:2651. CYP7A1.
MIM118455. gene.
neXtProtNX_P22680.
Orphanet209902. Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency.
PharmGKBPA132.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000231026.
HOVERGENHBG051100.
InParanoidP22680.
KOK00489.
OMAGKHISLN.
OrthoDBEOG7J9VP6.
PhylomeDBP22680.
TreeFamTF105090.

Enzyme and pathway databases

BioCycMetaCyc:HS09659-MONOMER.
BRENDA1.14.13.17. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP22680.
UniPathwayUPA00221.

Gene expression databases

BgeeP22680.
CleanExHS_CYP7A1.
GenevestigatorP22680.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR024204. Cyt_P450_CYP7A1-type.
IPR002403. Cyt_P450_E_grp-IV.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PIRSFPIRSF000047. Cytochrome_CYPVIIA1. 1 hit.
PRINTSPR00465. EP450IV.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22680.
GeneWikiCholesterol_7_alpha-hydroxylase.
GenomeRNAi1581.
NextBio6495.
PROP22680.
SOURCESearch...

Entry information

Entry nameCP7A1_HUMAN
AccessionPrimary (citable) accession number: P22680
Secondary accession number(s): P78454, Q3MIL8, Q7KZ19
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM