O75881 (CP7B1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
25-hydroxycholesterol 7-alpha-hydroxylase
EC=1.14.13.100

Alternative name(s):
Cytochrome P450 7B1
Oxysterol 7-alpha-hydroxylase

Gene names

Name:

CYP7B1

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	506 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	Cholest-5-ene-3-beta,25-diol + NADPH + O2 = cholest-5-ene-3-beta,7-alpha,25-triol + NADP+ + H2O. Cholest-5-ene-3-beta,27-diol + NADPH + O2 = cholest-5-ene-3-beta,7-alpha,27-triol + NADP+ + H2O.
Cofactor	Heme group By similarity.
Pathway	Lipid metabolism; bile acid biosynthesis.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Tissue specificity	Brain, testis, ovary, prostate, liver, colon, kidney, and small intestine.
Involvement in disease	Spastic paraplegia autosomal recessive 5A (SPG5A) [MIM:270800]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Congenital bile acid synthesis defect 3 (CBAS3) [MIM:613812]: A disorder resulting in severe cholestasis, cirrhosis and liver synthetic failure. Hepatic microsomal oxysterol 7-alpha-hydroxylase activity is undetectable. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1
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
Disease	Disease mutation Hereditary spastic paraplegia Intrahepatic cholestasis Neurodegeneration
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid biosynthetic process Traceable author statement. Source: Reactome cell death Inferred from electronic annotation. Source: UniProtKB-KW cholesterol metabolic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of intracellular estrogen receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara prostate gland epithelium morphogenesis Inferred from electronic annotation. Source: Compara xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome
Molecular_function	25-hydroxycholesterol 7alpha-hydroxylase activity Inferred from electronic annotation. Source: EC 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 oxysterol 7-alpha-hydroxylase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 506	506	25-hydroxycholesterol 7-alpha-hydroxylase		PRO_0000051906
Sites
	Metal binding	449	1	Iron (heme axial ligand) By similarity
Natural variations
	Natural variant	57	1	G → R in SPG5A. Ref.5		VAR_044382
	Natural variant	216	1	F → S in SPG5A. Ref.5		VAR_044383
	Natural variant	363	1	S → F in SPG5A. Ref.5		VAR_044384
	Natural variant	417	1	R → H in SPG5A. Ref.5		VAR_044385
Experimental info
	Sequence conflict	324	1	R → H in AAC95426. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O75881 [UniParc]. Last modified February 11, 2002. Version 2. Checksum: 07D3D4B801B6DBD9	FASTA	506	58,256
	10 20 30 40 50 60 MAGEVSAATG RFSLERLGLP GLALAAALLL LALCLLVRRT RRPGEPPLIK GWLPYLGVVL 70 80 90 100 110 120 NLRKDPLRFM KTLQKQHGDT FTVLLGGKYI TFILDPFQYQ LVIKNHKQLS FRVFSNKLLE 130 140 150 160 170 180 KAFSISQLQK NHDMNDELHL CYQFLQGKSL DILLESMMQN LKQVFEPQLL KTTSWDTAEL 190 200 210 220 230 240 YPFCSSIIFE ITFTTIYGKV IVCDNNKFIS ELRDDFLKFD DKFAYLVSNI PIELLGNVKS 250 260 270 280 290 300 IREKIIKCFS SEKLAKMQGW SEVFQSRQDV LEKYYVHEDL EIGAHHLGFL WASVANTIPT 310 320 330 340 350 360 MFWAMYYLLR HPEAMAAVRD EIDRLLQSTG QKKGSGFPIH LTREQLDSLI CLESSIFEAL 370 380 390 400 410 420 RLSSYSTTIR FVEEDLTLSS ETGDYCVRKG DLVAIFPPVL HGDPEIFEAP EEFRYDRFIE 430 440 450 460 470 480 DGKKKTTFFK RGKKLKCYLM PFGTGTSKCP GRFFALMEIK QLLVILLTYF DLEIIDDKPI 490 500 GLNYSRLLFG IQYPDSDVLF RYKVKS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7-alpha-hydroxylase gene causes severe neonatal liver disease." Setchell K.D.R., Schwarz M., O'Connell N.C., Lund E.G., Davis D.L., Lathe R., Thompson H.R., Tyson W.R., Sokol R.J., Russell D.W. J. Clin. Invest. 102:1690-1703(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN CBAS3. Tissue: Liver and Spleen.
[2]	"Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1." Wu Z.L., Martin K.O., Javitt N.B., Chiang J.Y.L. J. Lipid Res. 40:2195-2203(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Hippocampus.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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].
[5]	"Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration." Tsaousidou M.K., Ouahchi K., Warner T.T., Yang Y., Simpson M.A., Laing N.G., Wilkinson P.A., Madrid R.E., Patel H., Hentati F., Patton M.A., Hentati A., Lamont P.J., Siddique T., Crosby A.H. Am. J. Hum. Genet. 82:510-515(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SPG5A ARG-57; SER-216; PHE-363 AND HIS-417.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF029403 mRNA. Translation: AAC95426.1. AF127090 mRNA. Translation: AAD20021.1. AF176805 , AF176800, AF176801, AF176802, AF176803, AF176804 Genomic DNA. Translation: AAK11850.1. CH471068 Genomic DNA. Translation: EAW86877.1. BC136574 mRNA. Translation: AAI36575.1.
IPI	IPI00027234.
RefSeq	NP_004811.1. NM_004820.3.
UniGene	Hs.667720.
3D structure databases
ProteinModelPortal	O75881.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000310721.
PTM databases
PhosphoSite	O75881.
Proteomic databases
PaxDb	O75881.
PRIDE	O75881.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310193; ENSP00000310721; ENSG00000172817.
GeneID	9420.
KEGG	hsa:9420.
UCSC	uc003xvj.2. human.
Organism-specific databases
CTD	9420.
GeneCards	GC08M065500.
HGNC	HGNC:2652. CYP7B1.
HPA	HPA017761.
MIM	270800. phenotype. 603711. gene. 613812. phenotype.
neXtProt	NX_O75881.
Orphanet	100986. Autosomal recessive spastic paraplegia type 5A. 79302. Congenital bile acid synthesis defect type 3.
PharmGKB	PA27124.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2124.
HOGENOM	HOG000231026.
HOVERGEN	HBG051100.
InParanoid	O75881.
KO	K07430.
OMA	MFWAMYY.
OrthoDB	EOG476K08.
PhylomeDB	O75881.
Enzyme and pathway databases
BRENDA	1.14.13.100. 2681.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00221.
Gene expression databases
Bgee	O75881.
CleanEx	HS_CYP7B1.
Genevestigator	O75881.
GermOnline	ENSG00000172817. Homo sapiens.
Family and domain databases
Gene3D	1.10.630.10. 1 hit.
InterPro	IPR001128. Cyt_P450. 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. PR00385. P450.
SUPFAM	SSF48264. Cytochrome_P450. 1 hit.
PROSITE	PS00086. CYTOCHROME_P450. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	9420.
NextBio	35286.
SOURCE	Search...

Entry information

Entry name

CP7B1_HUMAN

Accession

Primary (citable) accession number: O75881
Secondary accession number(s): B2RN07, Q9UNF5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	February 11, 2002
Last modified:	May 1, 2013
This is version 120 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.