P22680 (CP7A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	504 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Cholesterol metabolism Lipid metabolism Steroid metabolism Sterol metabolism
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid biosynthetic process Inferred from direct assay Ref.8. Source: UniProtKB 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 xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome
Molecular_function	cholesterol 7-alpha-monooxygenase activity Inferred from sequence or structural similarity. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 504

504

Cholesterol 7-alpha-monooxygenase

PRO_0000051901

Sites

Metal binding

444

1

Iron (heme axial ligand)

Natural variations

Natural variant

86

1

H → N.
Corresponds to variant rs62621283 [ dbSNP | Ensembl ].

VAR_059152

Natural variant

100

1

F → S. Ref.3

VAR_001259

Natural variant

233

1

N → S. Ref.10
Corresponds to variant rs8192874 [ dbSNP | Ensembl ].

VAR_018376

Natural variant

347

1

D → N. Ref.2 Ref.10
Corresponds to variant rs8192875 [ dbSNP | Ensembl ].

VAR_018377

Experimental info

Sequence conflict

385

1

D → S in CAA39568. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

504

Helix Strand Turn

Details...

Beta strand

34 – 41

8

Turn

42 – 45

4

Helix

46 – 48

3

Helix

52 – 63

12

Beta strand

65 – 71

7

Beta strand

74 – 79

6

Helix

82 – 84

3

Helix

85 – 89

5

Beta strand

95 – 98

4

Helix

99 – 109

11

Helix

116 – 118

3

Beta strand

119 – 121

3

Helix

125 – 133

9

Helix

135 – 153

19

Helix

160 – 163

4

Beta strand

167 – 170

4

Helix

171 – 188

18

Helix

195 – 197

3

Helix

198 – 220

23

Helix

225 – 227

3

Helix

229 – 241

13

Helix

244 – 247

4

Helix

255 – 267

13

Helix

272 – 287

16

Helix

290 – 303

14

Helix

305 – 321

17

Beta strand

328 – 331

4

Helix

337 – 341

5

Helix

344 – 357

14

Beta strand

358 – 360

3

Beta strand

362 – 373

12

Beta strand

378 – 381

4

Beta strand

386 – 389

4

Helix

392 – 395

4

Turn

398 – 400

3

Beta strand

401 – 403

3

Turn

409 – 412

4

Beta strand

417 – 419

3

Helix

447 – 464

18

Beta strand

465 – 469

5

Turn

470 – 473

4

Helix

481 – 483

3

Beta strand

485 – 488

4

Beta strand

491 – 493

3

Beta strand

496 – 501

6

Sequences

	Sequence		Length	Mass (Da)
	P22680 [UniParc]. Last modified June 1, 1994. Version 2. Checksum: D8067E0FF6342949	FASTA	504	57,661
	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

References

	« Hide 'large scale' referencesShow '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

Wikipedia

Cholesterol-7 alpha-hydroxylase entry

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.

IPI

IPI00305356.

PIR

JH0659. S29818.

RefSeq

NP_000771.2. NM_000780.3.

UniGene

Hs.1644.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DAX	X-ray	2.15	A/B	25-503	[»]
3SN5	X-ray	2.75	A/B	25-503	[»]
3V8D	X-ray	1.90	A/B	25-503	[»]

ProteinModelPortal

P22680.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000301645.

PTM databases

PhosphoSite

P22680.

Polymorphism databases

DMDM

544084.

Proteomic databases

PaxDb

P22680.

PRIDE

P22680.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301645; ENSP00000301645; ENSG00000167910.

GeneID

1581.

KEGG

hsa:1581.

UCSC

uc003xtm.4. human.

Organism-specific databases

CTD

1581.

GeneCards

GC08M059452.

HGNC

HGNC:2651. CYP7A1.

MIM

118455. gene.

neXtProt

NX_P22680.

Orphanet

209902. Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency.

PharmGKB

PA132.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2124.

HOGENOM

HOG000231026.

HOVERGEN

HBG051100.

InParanoid

P22680.

KO

K00489.

OMA

GCALQFG.

OrthoDB

EOG4B5P4W.

PhylomeDB

P22680.

Enzyme and pathway databases

BioCyc

MetaCyc:HS09659-MONOMER.

BRENDA

1.14.13.17. 2681.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P22680.

UniPathway

UPA00221.

Gene expression databases

Bgee

P22680.

CleanEx

HS_CYP7A1.

Genevestigator

P22680.

GermOnline

ENSG00000167910. Homo sapiens.

Family and domain databases

Gene3D

1.10.630.10. 1 hit.

InterPro

IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR024204. Cyt_P450_CYP7A1-type.
IPR002403. Cyt_P450_E_grp-IV.
[Graphical view]

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PIRSF

PIRSF000047. Cytochrome_CYPVIIA1. 1 hit.

PRINTS

PR00465. EP450IV.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1851.

EvolutionaryTrace

P22680.

GenomeRNAi

1581.

NextBio

6495.

SOURCE

Search...

Entry information

Entry name

CP7A1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.