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Q9NR63 (CP26B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome P450 26B1

EC=1.14.-.-
Alternative name(s):
Cytochrome P450 26A2
Cytochrome P450 retinoic acid-inactivating 2
Short name=Cytochrome P450RAI-2
Retinoic acid-metabolizing cytochrome
Gene names
Name:CYP26B1
Synonyms:CYP26A2, P450RAI2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length512 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the metabolism of retinoic acid (RA), rendering this classical morphogen inactive through oxidation. Involved in the specific inactivation of all-trans-retinoic acid (all-trans-RA), with a preference for the following substrates: all-trans-RA > 9-cis-RA > 13-cis-RA. Generates several hydroxylated forms of RA, including 4-OH-RA, 4-oxo-RA, and 18-OH-RA. Esential for postnatal survival. Plays a central role in germ cell development: acts by degrading RA in the developing testis, preventing STRA8 expression, thereby leading to delay of meiosis. Required for the maintenance of the undifferentiated state of male germ cells during embryonic development in Sertoli cells, inducing arrest in G0 phase of the cell cycle and preventing meiotic entry. Plays a role in skeletal development, both at the level of patterning and in the ossification of bone and the establishment of some synovial joints. Ref.1 Ref.7

Cofactor

Heme group By similarity.

Subcellular location

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

Tissue specificity

Highly expressed in brain, particularly in the cerebellum and pons. Ref.1

Induction

By retinoic acid.

Involvement in disease

Radiohumeral fusions with other skeletal and craniofacial anomalies (RHFCA) [MIM:614416]: A disease characterized by craniofacial malformations, occipital encephalocele, radiohumeral fusions, oligodactyly, advanced osseous maturation, and calvarial mineralization defects.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the cytochrome P450 family.

Sequence caution

The sequence BAH12154.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCraniosynostosis
Disease mutation
   LigandHeme
Iron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbone morphogenesis

Inferred from mutant phenotype Ref.7. Source: UniProtKB

cell fate determination

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

embryonic limb morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

male meiosis

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of retinoic acid receptor signaling pathway

Traceable author statement PubMed 14532297. Source: BHF-UCL

oxidation-reduction process

Inferred from direct assay Ref.1. Source: BHF-UCL

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of tongue muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

proximal/distal pattern formation

Inferred from sequence or structural similarity. Source: BHF-UCL

retinoic acid catabolic process

Inferred from direct assay Ref.1. Source: BHF-UCL

retinoic acid receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

spermatogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

tongue morphogenesis

Inferred from electronic annotation. Source: Ensembl

vitamin metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

   Molecular_functionheme binding

Non-traceable author statement Ref.1. Source: BHF-UCL

iron ion binding

Inferred from electronic annotation. Source: InterPro

retinoic acid 4-hydroxylase activity

Inferred from direct assay Ref.1. Source: BHF-UCL

retinoic acid binding

Inferred from direct assay Ref.1. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NR63-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9NR63-2)

The sequence of this isoform differs from the canonical sequence as follows:
     69-143: Missing.
Isoform 3 (identifier: Q9NR63-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-67: MLFEGLDLVS...LIGETGHWLL → MKNKTCVLVC...TLRETRVWLP
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 512512Cytochrome P450 26B1
PRO_0000051985

Sites

Metal binding4411Iron (heme axial ligand) Potential

Natural variations

Alternative sequence1 – 6767MLFEG…GHWLL → MKNKTCVLVCVSVFGGERGQ VTVPRVGVRRPSLAGPLQKC TLRETRVWLP in isoform 3.
VSP_042967
Alternative sequence69 – 14375Missing in isoform 2.
VSP_042968
Natural variant1461S → P in RHFCA. Ref.7
Corresponds to variant rs281875232 [ dbSNP | Ensembl ].
VAR_067923
Natural variant1811V → M. Ref.4
VAR_038722
Natural variant1851A → V. Ref.4
VAR_038723
Natural variant1911R → H. Ref.4
Corresponds to variant rs76025186 [ dbSNP | Ensembl ].
VAR_038724
Natural variant2271D → N. Ref.4
VAR_038725
Natural variant2641L → S. Ref.2 Ref.3 Ref.4
Corresponds to variant rs2241057 [ dbSNP | Ensembl ].
VAR_024383
Natural variant3631R → L in RHFCA. Ref.7
Corresponds to variant rs281875231 [ dbSNP | Ensembl ].
VAR_067924
Natural variant3801E → K. Ref.4
Corresponds to variant rs2286965 [ dbSNP | Ensembl ].
VAR_038726
Natural variant4201A → G. Ref.4
Corresponds to variant rs7568553 [ dbSNP | Ensembl ].
VAR_038727
Natural variant4731R → C. Ref.4
Corresponds to variant rs61751056 [ dbSNP | Ensembl ].
VAR_038728
Natural variant4791V → I. Ref.4
Corresponds to variant rs148075682 [ dbSNP | Ensembl ].
VAR_038729

Experimental info

Sequence conflict2651D → G in BAH11930. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: A06D1D9944E6726F

FASTA51257,513
        10         20         30         40         50         60 
MLFEGLDLVS ALATLAACLV SVTLLLAVSQ QLWQLRWAAT RDKSCKLPIP KGSMGFPLIG 

        70         80         90        100        110        120 
ETGHWLLQGS GFQSSRREKY GNVFKTHLLG RPLIRVTGAE NVRKILMGEH HLVSTEWPRS 

       130        140        150        160        170        180 
TRMLLGPNTV SNSIGDIHRN KRKVFSKIFS HEALESYLPK IQLVIQDTLR AWSSHPEAIN 

       190        200        210        220        230        240 
VYQEAQKLTF RMAIRVLLGF SIPEEDLGHL FEVYQQFVDN VFSLPVDLPF SGYRRGIQAR 

       250        260        270        280        290        300 
QILQKGLEKA IREKLQCTQG KDYLDALDLL IESSKEHGKE MTMQELKDGT LELIFAAYAT 

       310        320        330        340        350        360 
TASASTSLIM QLLKHPTVLE KLRDELRAHG ILHSGGCPCE GTLRLDTLSG LRYLDCVIKE 

       370        380        390        400        410        420 
VMRLFTPISG GYRTVLQTFE LDGFQIPKGW SVMYSIRDTH DTAPVFKDVN VFDPDRFSQA 

       430        440        450        460        470        480 
RSEDKDGRFH YLPFGGGVRT CLGKHLAKLF LKVLAVELAS TSRFELATRT FPRITLVPVL 

       490        500        510 
HPVDGLSVKF FGLDSNQNEI LPETEAMLSA TV 

« Hide

Isoform 2 [UniParc].

Checksum: 85CA080EB0045520
Show »

FASTA43749,007
Isoform 3 [UniParc].

Checksum: F5BBD7200E20573B
Show »

FASTA49555,756

References

« Hide 'large scale' references
[1]"Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism."
White J.A., Ramshaw H., Taimi M., Stangle W., Zhang A., Everingham S., Creighton S., Tam S.-P., Jones G., Petkovich M.
Proc. Natl. Acad. Sci. U.S.A. 97:6403-6408(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
Tissue: Retina.
[2]"A spliced version of the human cytochrome P450 26B1 has an alternative function in retinoic acid metabolism."
Savenstrand H., Kumawat A., Karlsson M., Eriksson L.A., Sirsjo A., Strid A.
Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT SER-264.
Tissue: Vascular smooth muscle.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT SER-264.
Tissue: Brain, Cerebellum and Hippocampus.
[4]SeattleSNPs variation discovery resource
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-181; VAL-185; HIS-191; ASN-227; SER-264; LYS-380; GLY-420; CYS-473 AND ILE-479.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 1).
[7]"Craniosynostosis and multiple skeletal anomalies in humans and zebrafish result from a defect in the localized degradation of retinoic acid."
Laue K., Pogoda H.M., Daniel P.B., van Haeringen A., Alanay Y., von Ameln S., Rachwalski M., Morgan T., Gray M.J., Breuning M.H., Sawyer G.M., Sutherland-Smith A.J., Nikkels P.G., Kubisch C., Bloch W., Wollnik B., Hammerschmidt M., Robertson S.P.
Am. J. Hum. Genet. 89:595-606(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANTS RHFCA PRO-146 AND LEU-363.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF252297 mRNA. Translation: AAF76003.1.
FJ467289 mRNA. Translation: ACR19332.1.
AK294814 mRNA. Translation: BAH11892.1.
AK294933 mRNA. Translation: BAH11930.1.
AK295683 mRNA. Translation: BAH12154.1. Different initiation.
AK313433 mRNA. Translation: BAG36224.1.
AC007002 Genomic DNA. Translation: AAY14690.1.
BC069443 mRNA. Translation: AAH69443.1.
BC109205 mRNA. Translation: AAI09206.1.
CCDSCCDS1919.1. [Q9NR63-1]
CCDS62934.1. [Q9NR63-2]
RefSeqNP_001264671.1. NM_001277742.1. [Q9NR63-2]
NP_063938.1. NM_019885.3. [Q9NR63-1]
UniGeneHs.91546.

3D structure databases

ProteinModelPortalQ9NR63.
SMRQ9NR63. Positions 32-493.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121153. 2 interactions.
STRING9606.ENSP00000001146.

PTM databases

PhosphoSiteQ9NR63.

Polymorphism databases

DMDM20137526.

Proteomic databases

MaxQBQ9NR63.
PaxDbQ9NR63.
PRIDEQ9NR63.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000001146; ENSP00000001146; ENSG00000003137. [Q9NR63-1]
ENST00000546307; ENSP00000443304; ENSG00000003137. [Q9NR63-2]
GeneID56603.
KEGGhsa:56603.
UCSCuc002sih.2. human. [Q9NR63-1]
uc010yra.1. human. [Q9NR63-3]
uc010yrb.2. human. [Q9NR63-2]

Organism-specific databases

CTD56603.
GeneCardsGC02M072268.
HGNCHGNC:20581. CYP26B1.
HPAHPA012567.
MIM605207. gene.
614416. phenotype.
neXtProtNX_Q9NR63.
Orphanet293925. Lethal occipital encephalocele-skeletal dysplasia syndrome.
PharmGKBPA134879191.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000220829.
HOVERGENHBG051099.
InParanoidQ9NR63.
KOK12664.
OMAWSSQPEA.
OrthoDBEOG7F24SP.
PhylomeDBQ9NR63.
TreeFamTF105093.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ9NR63.
BgeeQ9NR63.
CleanExHS_CYP26B1.
GenevestigatorQ9NR63.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002403. Cyt_P450_E_grp-IV.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00465. EP450IV.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCYP26B1.
GenomeRNAi56603.
NextBio62039.
PROQ9NR63.
SOURCESearch...

Entry information

Entry nameCP26B_HUMAN
AccessionPrimary (citable) accession number: Q9NR63
Secondary accession number(s): B2R8M7 expand/collapse secondary AC list , B7Z2K6, B7Z2P4, B7Z3B8, E4W5W7, Q32MC0, Q53TW1, Q9NP41
Entry history
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 121 of the entry and version 1 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

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 2

Human chromosome 2: entries, gene names and cross-references to MIM