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Protein

25-hydroxycholesterol 7-alpha-hydroxylase

Gene

CYP7B1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

Cholest-5-ene-3-beta,25-diol + NADPH + O2 = cholest-5-ene-3-beta,7-alpha,25-triol + NADP+ + H2O.
(25R)-cholest-5-ene-3-beta,26-diol + NADPH + O2 = (25R)-cholest-5-ene-3-beta,7-alpha,26-triol + NADP+ + H2O.

Cofactori

hemeBy similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi449 – 4491Iron (heme axial ligand)By similarity

GO - Molecular functioni

  1. 25-hydroxycholesterol 7alpha-hydroxylase activity Source: UniProtKB-EC
  2. heme binding Source: InterPro
  3. iron ion binding Source: InterPro
  4. oxysterol 7-alpha-hydroxylase activity Source: ProtInc

GO - Biological processi

  1. bile acid biosynthetic process Source: Reactome
  2. bile acid metabolic process Source: Reactome
  3. cholesterol metabolic process Source: UniProtKB-KW
  4. negative regulation of intracellular estrogen receptor signaling pathway Source: Ensembl
  5. positive regulation of epithelial cell proliferation Source: Ensembl
  6. prostate gland epithelium morphogenesis Source: Ensembl
  7. small molecule metabolic process Source: Reactome
  8. sterol metabolic process Source: Reactome
  9. transmembrane transport Source: Reactome
  10. xenobiotic metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Keywords - Ligandi

Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BRENDAi1.14.13.100. 2681.
ReactomeiREACT_11041. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
REACT_11048. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
REACT_11054. Synthesis of bile acids and bile salts.
REACT_13812. Endogenous sterols.
REACT_267709. Defective CYP7B1 causes Spastic paraplegia 5A, autosomal recessive (SPG5A) and Congenital bile acid synthesis defect 3 (CBAS3).
REACT_268444. Orphan transporters.
UniPathwayiUPA00221.

Names & Taxonomyi

Protein namesi
Recommended name:
25-hydroxycholesterol 7-alpha-hydroxylase (EC:1.14.13.100)
Alternative name(s):
Cytochrome P450 7B1
Oxysterol 7-alpha-hydroxylase
Gene namesi
Name:CYP7B1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:2652. CYP7B1.

Subcellular locationi

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 5A, autosomal recessive (SPG5A)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:270800
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti57 – 571G → R in SPG5A. 1 Publication
VAR_044382
Natural varianti216 – 2161F → S in SPG5A. 1 Publication
VAR_044383
Natural varianti363 – 3631S → F in SPG5A. 1 Publication
VAR_044384
Natural varianti417 – 4171R → H in SPG5A. 1 Publication
VAR_044385
Congenital bile acid synthesis defect 3 (CBAS3)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disorder resulting in severe cholestasis, cirrhosis and liver synthetic failure. Hepatic microsomal oxysterol 7-alpha-hydroxylase activity is undetectable.

See also OMIM:613812

Keywords - Diseasei

Disease mutation, Hereditary spastic paraplegia, Intrahepatic cholestasis, Neurodegeneration

Organism-specific databases

MIMi270800. phenotype.
613812. phenotype.
Orphaneti100986. Autosomal recessive spastic paraplegia type 5A.
79302. Congenital bile acid synthesis defect type 3.
PharmGKBiPA27124.

Polymorphism and mutation databases

BioMutaiCYP7B1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 50650625-hydroxycholesterol 7-alpha-hydroxylasePRO_0000051906Add
BLAST

Proteomic databases

MaxQBiO75881.
PaxDbiO75881.
PRIDEiO75881.

PTM databases

PhosphoSiteiO75881.

Expressioni

Tissue specificityi

Brain, testis, ovary, prostate, liver, colon, kidney, and small intestine.

Gene expression databases

BgeeiO75881.
CleanExiHS_CYP7B1.
GenevestigatoriO75881.

Organism-specific databases

HPAiHPA017761.

Interactioni

Protein-protein interaction databases

BioGridi114813. 1 interaction.
STRINGi9606.ENSP00000310721.

Structurei

3D structure databases

ProteinModelPortaliO75881.
SMRiO75881. Positions 39-505.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00550000074551.
HOGENOMiHOG000231026.
HOVERGENiHBG051100.
InParanoidiO75881.
KOiK07430.
OMAiQYQLVIK.
OrthoDBiEOG7J9VP6.
PhylomeDBiO75881.
TreeFamiTF105090.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR024204. Cyt_P450_CYP7A1-type.
IPR002403. Cyt_P450_E_grp-IV.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PIRSFiPIRSF000047. Cytochrome_CYPVIIA1. 1 hit.
PRINTSiPR00465. EP450IV.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.

Sequencei

Sequence statusi: Complete.

O75881-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGEVSAATG RFSLERLGLP GLALAAALLL LALCLLVRRT RRPGEPPLIK
60 70 80 90 100
GWLPYLGVVL NLRKDPLRFM KTLQKQHGDT FTVLLGGKYI TFILDPFQYQ
110 120 130 140 150
LVIKNHKQLS FRVFSNKLLE KAFSISQLQK NHDMNDELHL CYQFLQGKSL
160 170 180 190 200
DILLESMMQN LKQVFEPQLL KTTSWDTAEL YPFCSSIIFE ITFTTIYGKV
210 220 230 240 250
IVCDNNKFIS ELRDDFLKFD DKFAYLVSNI PIELLGNVKS IREKIIKCFS
260 270 280 290 300
SEKLAKMQGW SEVFQSRQDV LEKYYVHEDL EIGAHHLGFL WASVANTIPT
310 320 330 340 350
MFWAMYYLLR HPEAMAAVRD EIDRLLQSTG QKKGSGFPIH LTREQLDSLI
360 370 380 390 400
CLESSIFEAL RLSSYSTTIR FVEEDLTLSS ETGDYCVRKG DLVAIFPPVL
410 420 430 440 450
HGDPEIFEAP EEFRYDRFIE DGKKKTTFFK RGKKLKCYLM PFGTGTSKCP
460 470 480 490 500
GRFFALMEIK QLLVILLTYF DLEIIDDKPI GLNYSRLLFG IQYPDSDVLF

RYKVKS
Length:506
Mass (Da):58,256
Last modified:February 11, 2002 - v2
Checksum:i07D3D4B801B6DBD9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti324 – 3241R → H in AAC95426 (PubMed:9802883).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti57 – 571G → R in SPG5A. 1 Publication
VAR_044382
Natural varianti216 – 2161F → S in SPG5A. 1 Publication
VAR_044383
Natural varianti363 – 3631S → F in SPG5A. 1 Publication
VAR_044384
Natural varianti417 – 4171R → H in SPG5A. 1 Publication
VAR_044385

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6180.1.
RefSeqiNP_004811.1. NM_004820.3.
UniGeneiHs.667720.

Genome annotation databases

EnsembliENST00000310193; ENSP00000310721; ENSG00000172817.
GeneIDi9420.
KEGGihsa:9420.
UCSCiuc003xvj.2. human.

Polymorphism and mutation databases

BioMutaiCYP7B1.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6180.1.
RefSeqiNP_004811.1. NM_004820.3.
UniGeneiHs.667720.

3D structure databases

ProteinModelPortaliO75881.
SMRiO75881. Positions 39-505.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114813. 1 interaction.
STRINGi9606.ENSP00000310721.

PTM databases

PhosphoSiteiO75881.

Polymorphism and mutation databases

BioMutaiCYP7B1.

Proteomic databases

MaxQBiO75881.
PaxDbiO75881.
PRIDEiO75881.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310193; ENSP00000310721; ENSG00000172817.
GeneIDi9420.
KEGGihsa:9420.
UCSCiuc003xvj.2. human.

Organism-specific databases

CTDi9420.
GeneCardsiGC08M065500.
HGNCiHGNC:2652. CYP7B1.
HPAiHPA017761.
MIMi270800. phenotype.
603711. gene.
613812. phenotype.
neXtProtiNX_O75881.
Orphaneti100986. Autosomal recessive spastic paraplegia type 5A.
79302. Congenital bile acid synthesis defect type 3.
PharmGKBiPA27124.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00550000074551.
HOGENOMiHOG000231026.
HOVERGENiHBG051100.
InParanoidiO75881.
KOiK07430.
OMAiQYQLVIK.
OrthoDBiEOG7J9VP6.
PhylomeDBiO75881.
TreeFamiTF105090.

Enzyme and pathway databases

UniPathwayiUPA00221.
BRENDAi1.14.13.100. 2681.
ReactomeiREACT_11041. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
REACT_11048. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
REACT_11054. Synthesis of bile acids and bile salts.
REACT_13812. Endogenous sterols.
REACT_267709. Defective CYP7B1 causes Spastic paraplegia 5A, autosomal recessive (SPG5A) and Congenital bile acid synthesis defect 3 (CBAS3).
REACT_268444. Orphan transporters.

Miscellaneous databases

GeneWikiiCYP7B1.
GenomeRNAii9420.
NextBioi35286.
PROiO75881.
SOURCEiSearch...

Gene expression databases

BgeeiO75881.
CleanExiHS_CYP7B1.
GenevestigatoriO75881.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR024204. Cyt_P450_CYP7A1-type.
IPR002403. Cyt_P450_E_grp-IV.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PIRSFiPIRSF000047. Cytochrome_CYPVIIA1. 1 hit.
PRINTSiPR00465. EP450IV.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. Cited for: VARIANTS SPG5A ARG-57; SER-216; PHE-363 AND HIS-417.

Entry informationi

Entry nameiCP7B1_HUMAN
AccessioniPrimary (citable) accession number: O75881
Secondary accession number(s): B2RN07, Q9UNF5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: February 11, 2002
Last modified: April 29, 2015
This is version 139 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

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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.