Q9NR63 (CP26B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	512 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Craniosynostosis Disease mutation
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bone 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: Compara 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 positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of tongue muscle cell differentiation Inferred from electronic annotation. Source: Compara 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: Compara spermatogenesis Inferred from sequence or structural similarity. Source: BHF-UCL tongue 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	electron carrier activity Inferred from electronic annotation. Source: InterPro heme 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 512	512	Cytochrome P450 26B1		PRO_0000051985
Sites
	Metal binding	441	1	Iron (heme axial ligand) Potential
Natural variations
	Alternative sequence	1 – 67	67	MLFEG…GHWLL → MKNKTCVLVCVSVFGGERGQ VTVPRVGVRRPSLAGPLQKC TLRETRVWLP in isoform 3.		VSP_042967
	Alternative sequence	69 – 143	75	Missing in isoform 2.		VSP_042968
	Natural variant	146	1	S → P in RHFCA. Ref.7		VAR_067923
	Natural variant	181	1	V → M. Ref.4		VAR_038722
	Natural variant	185	1	A → V. Ref.4		VAR_038723
	Natural variant	191	1	R → H. Ref.4		VAR_038724
	Natural variant	227	1	D → N. Ref.4		VAR_038725
	Natural variant	264	1	L → S. Ref.2 Ref.3 Ref.4 Corresponds to variant rs2241057 [ dbSNP | Ensembl ].		VAR_024383
	Natural variant	363	1	R → L in RHFCA. Ref.7		VAR_067924
	Natural variant	380	1	E → K. Ref.4 Corresponds to variant rs2286965 [ dbSNP | Ensembl ].		VAR_038726
	Natural variant	420	1	A → G. Ref.4 Corresponds to variant rs7568553 [ dbSNP | Ensembl ].		VAR_038727
	Natural variant	473	1	R → C. Ref.4		VAR_038728
	Natural variant	479	1	V → I. Ref.4		VAR_038729
Experimental info
	Sequence conflict	265	1	D → G in BAH11930. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: A06D1D9944E6726F	FASTA	512	57,513
	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
	Isoform 2 [UniParc]. Checksum: 85CA080EB0045520	FASTA	437	49,007
	10 20 30 40 50 60 MLFEGLDLVS ALATLAACLV SVTLLLAVSQ QLWQLRWAAT RDKSCKLPIP KGSMGFPLIG 70 80 90 100 110 120 ETGHWLLQVF SKIFSHEALE SYLPKIQLVI QDTLRAWSSH PEAINVYQEA QKLTFRMAIR 130 140 150 160 170 180 VLLGFSIPEE DLGHLFEVYQ QFVDNVFSLP VDLPFSGYRR GIQARQILQK GLEKAIREKL 190 200 210 220 230 240 QCTQGKDYLD ALDLLIESSK EHGKEMTMQE LKDGTLELIF AAYATTASAS TSLIMQLLKH 250 260 270 280 290 300 PTVLEKLRDE LRAHGILHSG GCPCEGTLRL DTLSGLRYLD CVIKEVMRLF TPISGGYRTV 310 320 330 340 350 360 LQTFELDGFQ IPKGWSVMYS IRDTHDTAPV FKDVNVFDPD RFSQARSEDK DGRFHYLPFG 370 380 390 400 410 420 GGVRTCLGKH LAKLFLKVLA VELASTSRFE LATRTFPRIT LVPVLHPVDG LSVKFFGLDS 430 NQNEILPETE AMLSATV
	Isoform 3 [UniParc]. Checksum: F5BBD7200E20573B	FASTA	495	55,756
	10 20 30 40 50 60 MKNKTCVLVC VSVFGGERGQ VTVPRVGVRR PSLAGPLQKC TLRETRVWLP QGSGFQSSRR 70 80 90 100 110 120 EKYGNVFKTH LLGRPLIRVT GAENVRKILM GEHHLVSTEW PRSTRMLLGP NTVSNSIGDI 130 140 150 160 170 180 HRNKRKVFSK IFSHEALESY LPKIQLVIQD TLRAWSSHPE AINVYQEAQK LTFRMAIRVL 190 200 210 220 230 240 LGFSIPEEDL GHLFEVYQQF VDNVFSLPVD LPFSGYRRGI QARQILQKGL EKAIREKLQC 250 260 270 280 290 300 TQGKDYLDAL DLLIESSKEH GKEMTMQELK DGTLELIFAA YATTASASTS LIMQLLKHPT 310 320 330 340 350 360 VLEKLRDELR AHGILHSGGC PCEGTLRLDT LSGLRYLDCV IKEVMRLFTP ISGGYRTVLQ 370 380 390 400 410 420 TFELDGFQIP KGWSVMYSIR DTHDTAPVFK DVNVFDPDRF SQARSEDKDG RFHYLPFGGG 430 440 450 460 470 480 VRTCLGKHLA KLFLKVLAVE LASTSRFELA TRTFPRITLV PVLHPVDGLS VKFFGLDSNQ 490 NEILPETEAM LSATV

References

	« Hide 'large scale' referencesShow '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. , 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. , 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

SeattleSNPs

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.
IPI	IPI00008398. IPI00952755.
RefSeq	NP_063938.1. NM_019885.2.
UniGene	Hs.91546.
3D structure databases
ProteinModelPortal	Q9NR63.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000001146.
PTM databases
PhosphoSite	Q9NR63.
Polymorphism databases
DMDM	20137526.
Proteomic databases
PaxDb	Q9NR63.
PRIDE	Q9NR63.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000001146; ENSP00000001146; ENSG00000003137. ENST00000546307; ENSP00000443304; ENSG00000003137.
GeneID	56603.
KEGG	hsa:56603.
UCSC	uc002sih.1. human. uc010yra.1. human. uc010yrb.1. human.
Organism-specific databases
CTD	56603.
GeneCards	GC02M072268.
HGNC	HGNC:20581. CYP26B1.
HPA	HPA012567.
MIM	605207. gene. 614416. phenotype.
neXtProt	NX_Q9NR63.
Orphanet	293925. Lethal occipital encephalocele-skeletal dysplasia syndrome.
PharmGKB	PA134879191.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2124.
HOGENOM	HOG000220829.
HOVERGEN	HBG051099.
InParanoid	Q9NR63.
KO	K12664.
OMA	GIQARQT.
OrthoDB	EOG4D52XG.
PhylomeDB	Q9NR63.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9NR63.
Bgee	Q9NR63.
CleanEx	HS_CYP26B1.
Genevestigator	Q9NR63.
GermOnline	ENSG00000003137. Homo sapiens.
Family and domain databases
Gene3D	1.10.630.10. 1 hit.
InterPro	IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR002403. Cyt_P450_E_grp-IV. [Graphical view]
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00465. EP450IV. PR00385. P450.
SUPFAM	SSF48264. Cytochrome_P450. 1 hit.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	56603.
NextBio	62039.
SOURCE	Search...

Entry information

Entry name

CP26B_HUMAN

Accession

Primary (citable) accession number: Q9NR63
Secondary accession number(s): B2R8M7 , 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:	May 29, 2013
This is version 108 of the entry and version 1 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.