STRA6_DANRE
ID STRA6_DANRE Reviewed; 670 AA.
AC F1RAX4; A4IGB6; Q1ECX5;
DT 22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Receptor for retinol uptake stra6 {ECO:0000303|PubMed:27563101};
DE AltName: Full=Stimulated by retinoic acid gene 6 protein homolog;
GN Name=stra6 {ECO:0000312|Ensembl:ENSDARP00000067478,
GN ECO:0000312|ZFIN:ZDB-GENE-060616-252};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|Proteomes:UP000000437};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2] {ECO:0000312|EMBL:AAI35018.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Singapore {ECO:0000312|EMBL:AAI35018.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAI35018.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP DISRUPTION PHENOTYPE, FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=18316031; DOI=10.1016/j.cmet.2008.01.009;
RA Isken A., Golczak M., Oberhauser V., Hunzelmann S., Driever W.,
RA Imanishi Y., Palczewski K., von Lintig J.;
RT "RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal
RT model for Matthew-Wood syndrome.";
RL Cell Metab. 7:258-268(2008).
RN [4] {ECO:0007744|PDB:5K8Q, ECO:0007744|PDB:5SY1}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) IN COMPLEX WITH
RP CALMODULIN, X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 600-62 IN COMPLEX
RP WITH CALMODULIN, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, AND
RP DOMAIN.
RX PubMed=27563101; DOI=10.1126/science.aad8266;
RA Chen Y., Clarke O.B., Kim J., Stowe S., Kim Y.K., Assur Z., Cavalier M.,
RA Godoy-Ruiz R., von Alpen D.C., Manzini C., Blaner W.S., Frank J.,
RA Quadro L., Weber D.J., Shapiro L., Hendrickson W.A., Mancia F.;
RT "Structure of the STRA6 receptor for retinol uptake.";
RL Science 353:0-0(2016).
CC -!- FUNCTION: Retinol transporter. Accepts retinol from the extracellular
CC retinol-binding protein rbp4, mediates retinol transport across the
CC cell membrane, and then transmits retinol to the cytoplasmic retinol-
CC binding protein rbp1 (PubMed:27563101). Required for normal vitamin A
CC homeostasis (PubMed:18316031). {ECO:0000269|PubMed:18316031,
CC ECO:0000269|PubMed:27563101}.
CC -!- SUBUNIT: Homodimer. Interacts (via C-terminus) with calmodulin.
CC {ECO:0000269|PubMed:27563101}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27563101};
CC Multi-pass membrane protein {ECO:0000269|PubMed:27563101}.
CC -!- DEVELOPMENTAL STAGE: Detected in embryos (at protein level). Detected
CC in the yolk syncytium and in mesendodermal cells in the head and trunk
CC region during early somitogenesis. Detected in the developing eyes, the
CC anterior midbrain, the pineal gland and in anterior somites at 24 hpf.
CC Detected only in the eyes and the pineal gland at 3 and 4 dpf. Detected
CC in retinal pigment epithelium at 4 dpf. {ECO:0000269|PubMed:18316031}.
CC -!- DOMAIN: Contrary to predictions, contains nine transmembrane helices,
CC with an extracellular N-terminus and a cytoplasmic C-terminus. Besides,
CC contains one long helix that dips into the membrane and then runs more
CC or less parallel to the membrane surface.
CC {ECO:0000269|PubMed:27563101}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown causes severe defects in
CC embryonic development, with microphthalmia, a curved body axis and
CC heart edema. The morphant hearts do not loop normally, heart atria are
CC strongly dilated and blood circulation is severely impaired. Morphants
CC have an altered morphology of the craniofacial skeleton, with
CC malformation of the first and second arches and absence of the
CC branchial arches. Embryonic heads at 4 dpf display reduced total
CC retinyl ester levels and reduced levels of the visual pigment 11-cis-
CC retinal. Morpholino knockdown of both stra6 and rbp4 alleviates the
CC developmental impairment that is observed in stra6 morphants,
CC suggesting the phenotype is due to impaired vitamin A homeostasis and
CC excessive accumulation of retinoic acid. {ECO:0000269|PubMed:18316031}.
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DR EMBL; CR855275; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117633; AAI17634.1; -; mRNA.
DR EMBL; BC135017; AAI35018.1; -; mRNA.
DR RefSeq; NP_001038777.1; NM_001045312.1.
DR RefSeq; XP_005170746.1; XM_005170689.3.
DR PDB; 5K8Q; X-ray; 1.74 A; B=600-626.
DR PDB; 5SY1; EM; 3.90 A; A/B=1-670.
DR PDBsum; 5K8Q; -.
DR PDBsum; 5SY1; -.
DR AlphaFoldDB; F1RAX4; -.
DR SMR; F1RAX4; -.
DR STRING; 7955.ENSDARP00000067478; -.
DR TCDB; 2.A.90.1.4; the vitamin a receptor/transporter (stra6) family.
DR PaxDb; F1RAX4; -.
DR Ensembl; ENSDART00000067479; ENSDARP00000067478; ENSDARG00000051874.
DR Ensembl; ENSDART00000152096; ENSDARP00000126450; ENSDARG00000051874.
DR Ensembl; ENSDART00000161559; ENSDARP00000131530; ENSDARG00000051874.
DR Ensembl; ENSDART00000190851; ENSDARP00000146793; ENSDARG00000115031.
DR GeneID; 724007; -.
DR KEGG; dre:724007; -.
DR CTD; 64220; -.
DR ZFIN; ZDB-GENE-060616-252; stra6.
DR eggNOG; ENOG502QRSS; Eukaryota.
DR GeneTree; ENSGT00940000153246; -.
DR InParanoid; F1RAX4; -.
DR OMA; HICITVI; -.
DR OrthoDB; 325169at2759; -.
DR PhylomeDB; F1RAX4; -.
DR TreeFam; TF331851; -.
DR Reactome; R-DRE-2453902; The canonical retinoid cycle in rods (twilight vision).
DR PRO; PR:F1RAX4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 25.
DR Bgee; ENSDARG00000051874; Expressed in intestine and 25 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:ZFIN.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IDA:ZFIN.
DR GO; GO:0042802; F:identical protein binding; IPI:ZFIN.
DR GO; GO:0016918; F:retinal binding; IEA:UniProtKB-KW.
DR GO; GO:0019841; F:retinol binding; IEA:UniProtKB-KW.
DR GO; GO:0034632; F:retinol transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro.
DR GO; GO:0043009; P:chordate embryonic development; IMP:ZFIN.
DR GO; GO:0034633; P:retinol transport; IDA:ZFIN.
DR GO; GO:0071939; P:vitamin A import into cell; IBA:GO_Central.
DR DisProt; DP02583; -.
DR InterPro; IPR026612; STRA6.
DR PANTHER; PTHR21444:SF16; PTHR21444:SF16; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calmodulin-binding; Cell membrane; Membrane; Receptor;
KW Reference proteome; Retinol-binding; Transmembrane; Transmembrane helix;
KW Transport; Vitamin A.
FT CHAIN 1..670
FT /note="Receptor for retinol uptake stra6"
FT /id="PRO_0000442341"
FT TOPO_DOM 1..38
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TRANSMEM 39..59
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 60..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 109..121
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 143..145
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 167..182
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 204..274
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TRANSMEM 275..295
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 296..346
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 368..401
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TRANSMEM 402..422
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 423..452
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TRANSMEM 453..473
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 474..488
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27563101"
FT INTRAMEM 489..526
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27563101"
FT TOPO_DOM 527..670
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27563101"
FT REGION 600..626
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000269|PubMed:27563101"
FT REGION 640..670
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 133
FT /note="A -> T (in Ref. 2; AAI35018)"
FT /evidence="ECO:0000305"
FT CONFLICT 657
FT /note="N -> K (in Ref. 2; AAI17634/AAI35018)"
FT /evidence="ECO:0000305"
FT CONFLICT 660
FT /note="S -> N (in Ref. 2; AAI35018)"
FT /evidence="ECO:0000305"
FT HELIX 603..618
FT /evidence="ECO:0007829|PDB:5K8Q"
FT HELIX 620..622
FT /evidence="ECO:0007829|PDB:5K8Q"
SQ SEQUENCE 670 AA; 75397 MW; 3A94024BA4BD8552 CRC64;
MSAETVNNYD YSDWYENAAP TKAPVEVIPP CDPTADEGLF HICIAAISLV VMLVLAILAR
RQKLSDNQRG LTGLLSPVNF LDHTQHKGLA VAVYGVLFCK LVGMVLSHHP LPFTKEVANK
EFWMILALLY YPALYYPLLA CGTLHNKVGY VLGSLLSWTH FGILVWQKVD CPKTPQIYKY
YALFGSLPQI ACLAFLSFQY PLLLFKGLQN TETANASEDL SSSYYRDYVK KILKKKKPTK
ISSSTSKPKL FDRLRDAVKS YIYTPEDVFR FPLKLAISVV VAFIALYQMA LLLISGVLPT
LHIVRRGVDE NIAFLLAGFN IILSNDRQEV VRIVVYYLWC VEICYVSAVT LSCLVNLLML
MRSMVLHRSN LKGLYRGDSL NVFNCHRSIR PSRPALVCWM GFTSYQAAFL CLGMAIQTLV
FFICILFAVF LIIIPILWGT NLMLFHIIGN LWPFWLTLVL AALIQHVASR FLFIRKDGGT
RDLNNRGSLF LLSYILFLVN VMIGVVLGIW RVVITALFNI VHLGRLDISL LNRNVEAFDP
GYRCYSHYLK IEVSQSHPVM KAFCGLLLQS SGQDGLSAQR IRDAEEGIQL VQQEKKQNKV
SNAKRARAHW QLLYTLVNNP SLVGSRKHFQ CQSSESFING ALSRTSKEGS KKDGSVNEPS
KEAESAAASN
