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Protein

Receptor for retinol uptake STRA6

Gene

Stra6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as retinol transporter (PubMed:23839944, PubMed:24852372). Accepts all-trans retinol from the extracellular retinol-binding protein RBP4, facilitates retinol transport across the cell membrane, and then transfers retinol to the cytoplasmic retinol-binding protein RBP1. Retinol uptake is enhanced by LRAT, an enzyme that converts retinol to all-trans retinyl esters, the storage forms of vitamin A (By similarity). Contributes to the activation of a signaling cascade that depends on retinol transport and LRAT-dependent generation of retinol metabolites that then trigger activation of JAK2 and its target STAT5, and ultimately increase the expression of SOCS3 and inhibit cellular responses to insulin (PubMed:21368206, PubMed:23839944). Important for the homeostasis of vitamin A and its derivatives, such as retinoic acid and 11-cis-retinal (PubMed:22467576, PubMed:24852372). STRA6-mediated transport is particularly important in the eye, and under conditions of dietary vitamin A deficiency (PubMed:22467576, PubMed:23839944, PubMed:24852372). Does not transport retinoic acid (By similarity).By similarity4 Publications

Miscellaneous

The retinoic acid-induced activation is impaired in retinoic acid receptor gamma-null F9 cells.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processTransport
LigandRetinol-binding, Vitamin A

Protein family/group databases

TCDBi2.A.90.1.2. the vitamin a receptor/transporter (stra6) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor for retinol uptake STRA6
Alternative name(s):
Retinoic acid-responsive protein
Retinol-binding protein receptor STRA6
Stimulated by retinoic acid gene 6 protein1 Publication
Gene namesi
Name:Stra6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:107742. Stra6.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 50ExtracellularBy similarityAdd BLAST50
Transmembranei51 – 71HelicalBy similarityAdd BLAST21
Topological domaini72 – 97CytoplasmicBy similarityAdd BLAST26
Transmembranei98 – 118HelicalBy similarityAdd BLAST21
Topological domaini119 – 144ExtracellularBy similarityAdd BLAST26
Transmembranei145 – 165HelicalBy similarityAdd BLAST21
Topological domaini166 – 168CytoplasmicBy similarity3
Transmembranei169 – 189HelicalBy similarityAdd BLAST21
Topological domaini190 – 205ExtracellularBy similarityAdd BLAST16
Transmembranei206 – 226HelicalBy similarityAdd BLAST21
Topological domaini227 – 296CytoplasmicBy similarityAdd BLAST70
Transmembranei297 – 317HelicalBy similarityAdd BLAST21
Topological domaini318 – 368ExtracellularBy similarityAdd BLAST51
Transmembranei369 – 389HelicalBy similarityAdd BLAST21
Topological domaini390 – 423CytoplasmicBy similarityAdd BLAST34
Transmembranei424 – 444HelicalBy similarityAdd BLAST21
Topological domaini445 – 474ExtracellularBy similarityAdd BLAST30
Transmembranei475 – 495HelicalBy similarityAdd BLAST21
Topological domaini496 – 510CytoplasmicBy similarityAdd BLAST15
Intramembranei511 – 548HelicalBy similarityAdd BLAST38
Topological domaini549 – 670CytoplasmicBy similarityAdd BLAST122

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

No visible phenotype at birth (PubMed:22467576, PubMed:23839944, PubMed:24852372). Measurement of the eye diameter indicates a tendency towards slightly smaller eye diameter 6 weeks after birth, and this difference persists in 5 and 10 month old animals (PubMed:22467576). The retina inner and outer segments are shorter in mutant mice (PubMed:22467576, PubMed:24852372). The number of cone cells in the retina is reduced, giving rise to a reduced cone response to light stimulation (PubMed:22467576). The retinal pigment epithelium displays discolored regions, where cells have large vacuoles and a reduced melanin content (PubMed:24852372). Retina and retinal pigment epithelium from dark-adapted mutant mice display strongly reduced levels of all-trans-retinol, all-trans-retinyl palmitate, 11-cis-retinal, 11-cis-retinyl palmitate and all-trans-retinal (PubMed:22467576, PubMed:24852372). Electroretinograms (ERG) of dark-adapted retinas from mutant mice display reduced a- and b-wave amplitude in response to light (PubMed:22467576). In another knockout model, the electroretinogram shows a complete lack of response to light (PubMed:24852372). Dietary vitamin A supplements can alleviate the ocular retinoid deficiency, and can prevent the altered retinal responses to light observed in mutant mice (PubMed:24852372). Other tissues and organs (brain, heart, kidney, liver, lungs, muscle, pancreas, spleen, testis and white adipose tissue) display grossly normal retinoid levels in 12 week old mice kept on normal chow (PubMed:23839944). Embryonic development appears grossly normal, also when females are fed a vitamin A-deficient diet (PubMed:23839944). Embryonic eye development is altered, leading to persistent hyperplastic primary vitreous that forms a conical mass of cells between the optic nerve exit point and the lens in the eyes of mutant mice (PubMed:22467576). In contrast, persistent hyperplastic primary vitreous was not observed in another knockout experiment (PubMed:24852372).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003112291 – 670Receptor for retinol uptake STRA6Add BLAST670

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi8N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi128N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei644PhosphotyrosineBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residues in response to RBP4 binding (PubMed:21368206). Phosphorylation requires the presence of LRAT, suggesting it may be triggered by the uptake of retinol that is then metabolized within the cell to retinoids that function as signaling molecules (By similarity).By similarity1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO70491.
PaxDbiO70491.
PeptideAtlasiO70491.
PRIDEiO70491.

PTM databases

iPTMnetiO70491.
PhosphoSitePlusiO70491.

Expressioni

Tissue specificityi

Widely expressed in the embryo (PubMed:9203140, PubMed:23839944). Detected in adult in the retinal pigment epithelium in the eye (PubMed:9203140, PubMed:22467576, PubMed:23839944, PubMed:24852372). In the adult, is highly expressed in cells that compose blood-organ barriers in the brain (choroid plexus and the brain microvascular), in testis (the basal layer of the seminiferous epithelium), in the yolk sac, and in the chorioallantoic placenta (PubMed:9203140, PubMed:23839944). Detected in white adipose tissue and skeletal muscle, but not in liver (at protein level) (PubMed:21368206). Widely expressed in adult, with high expression levels in the eye (PubMed:24852372). Detected in brain, cerebellum, testis, pituitary, pancreas, kidney, spleen, and female genital tract; and at very low levels in heart and lung (PubMed:9203140, PubMed:24852372). Not detected in liver (PubMed:9203140).5 Publications

Developmental stagei

During embryogenesis, strongly expressed in the periocular mesenchyme, in the developing eyes, in respiratory mesenchymes, and in respiratory and bronchial epithelium, as well as in the developing central nervous system and in different embryonic gut derivatives (the epithelium of the pharyngeal pouches, mesenchyme of the esophagus, stomach, intestine, and rectum). In Sertoli cells expression depends on the stage of the spermatogenic cycle. During early placentation, is expressed in the yolk sac membrane and the chorionic plate. Expression was no longer detected in the yolk sac membrane during mid-late gestation, but was found in the labyrinthine zone of the chorioallantoic placenta. Expressed during early dorsoventral limb patterning and during endochondral ossification.3 Publications

Inductioni

By retinoic acid. Synergistically up-regulated by Wnt1 and retinoids in mammary epithelial cells.4 Publications

Gene expression databases

CleanExiMM_STRA6.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with JAK2 and STAT5. Interacts (via extracellular domains) with RBP4. Interacts (via cytoplasmic domains) with RBP1 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000034880.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni235 – 294Interaction with RBP1By similarityAdd BLAST60

Domaini

Contrary to predictions, contains nine transmembrane helices, with an extracellular N-terminus and a cytoplasmic C-terminus (By similarity). Besides, contains one long helix that dips into the membrane and then runs more or less parallel to the membrane surface (By similarity).By similarity

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IDYH. Eukaryota.
ENOG410YGRH. LUCA.
HOGENOMiHOG000154441.
HOVERGENiHBG106311.
InParanoidiO70491.
PhylomeDBiO70491.
TreeFamiTF331851.

Family and domain databases

InterProiView protein in InterPro
IPR026612. STRA6.
PANTHERiPTHR21444:SF16. PTHR21444:SF16. 1 hit.

Sequencei

Sequence statusi: Complete.

O70491-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESQASENGS QTSSGVTDDY SSWYIEEPLG AEEVQPEGVI PLCQLTAPPA
60 70 80 90 100
LLHACLASLS FLVLLLLALL VRRRRLWPRC GHRGLGLPSP VDFLAGDLSW
110 120 130 140 150
TVPAAVFVVL FSNLCLLLPD ENPLPFLNLT AASSPDGEME TSRGPWKLLA
160 170 180 190 200
LLYYPALYYP LAACASAGHQ AAFLLGTVLS WAHFGVQVWQ KAECPQDPKI
210 220 230 240 250
YKHYSLLASL PLLLGLGFLS LWYPVQLVQS LRHRTGAGSQ GLQTSYSEKY
260 270 280 290 300
LRTLLCPKKL DSCSHPASKR SLLSRAWAFS HHSIYTPQPG FRLPLKLVIS
310 320 330 340 350
ATLTGTATYQ VALLLLVSVV PTVQKVRAGI NTDVSYLLAG FGIVLSEDRQ
360 370 380 390 400
EVVELVKHHL WTVEACYISA LVLSCASTFL LLIRSLRTHR ANLQALHRGA
410 420 430 440 450
ALDLDPPLQS IHPSRQAIVS WMSFCAYQTA FSCLGLLVQQ VIFFLGTTSL
460 470 480 490 500
AFLVFVPLLH GRNLLLLRSL ESTWPFWLTV ALAVILQNIA ANWIFLRTHH
510 520 530 540 550
GYPELTNRRM LCVATFLLFP INMLVGAIMA VWRVLISSLY NTVHLGQMDL
560 570 580 590 600
SLLPQRAASL DPGYHTYQNF LRIEASQSHP GVIAFCALLL HAPSPQPRPP
610 620 630 640 650
LAPQDSLRPA EEEEGMQLLQ TKDLMAKGAG HKGSQSRARW GLAYTLLHNP
660 670
SLQAFRKAAL TSAKANGTQP
Length:670
Mass (Da):73,775
Last modified:August 1, 1998 - v1
Checksum:i6ACE69F3EE16A4F7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti234R → P in AAH75657 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF062476 mRNA. Translation: AAC16016.1.
BC075657 mRNA. Translation: AAH75657.1.
CCDSiCCDS23236.1.
RefSeqiNP_001155947.1. NM_001162475.1.
NP_001155948.1. NM_001162476.1.
NP_001155951.1. NM_001162479.1.
NP_033317.2. NM_009291.2.
XP_006511004.2. XM_006510941.3.
XP_006511006.1. XM_006510943.3.
XP_006511007.1. XM_006510944.3.
XP_006511008.1. XM_006510945.3.
XP_006511009.1. XM_006510946.3.
UniGeneiMm.10801.

Genome annotation databases

GeneIDi20897.
KEGGimmu:20897.
UCSCiuc009pwi.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiSTRA6_MOUSE
AccessioniPrimary (citable) accession number: O70491
Secondary accession number(s): Q6DIA8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: August 1, 1998
Last modified: November 22, 2017
This is version 96 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot