STRA6_BOVIN
ID STRA6_BOVIN Reviewed; 668 AA.
AC Q0V8E7; A5PK38;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Receptor for retinol uptake STRA6;
DE AltName: Full=Retinol-binding protein receptor STRA6;
DE AltName: Full=Stimulated by retinoic acid gene 6 protein homolog;
GN Name=STRA6;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal pons;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, INTERACTION WITH RBP4, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF LEU-256; LEU-297; GLN-310; LEU-315 AND TYR-336.
RX PubMed=17255476; DOI=10.1126/science.1136244;
RA Kawaguchi R., Yu J., Honda J., Hu J., Whitelegge J., Ping P., Wiita P.,
RA Bok D., Sun H.;
RT "A membrane receptor for retinol binding protein mediates cellular uptake
RT of vitamin A.";
RL Science 315:820-825(2007).
RN [4]
RP FUNCTION, INTERACTION WITH RBP4, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=18419130; DOI=10.1021/bi8002082;
RA Kawaguchi R., Yu J., Wiita P., Ter-Stepanian M., Sun H.;
RT "Mapping the membrane topology and extracellular ligand binding domains of
RT the retinol binding protein receptor.";
RL Biochemistry 47:5387-5395(2008).
CC -!- FUNCTION: Functions as retinol transporter. Accepts all-trans retinol
CC from the extracellular retinol-binding protein RBP4, facilitates
CC retinol transport across the cell membrane, and then transfers retinol
CC to the cytoplasmic retinol-binding protein RBP1 (PubMed:17255476,
CC PubMed:18419130). Retinol uptake is enhanced by LRAT, an enzyme that
CC converts retinol to all-trans retinyl esters, the storage forms of
CC vitamin A. Contributes to the activation of a signaling cascade that
CC depends on retinol transport and LRAT-dependent generation of retinol
CC metabolites that then trigger activation of JAK2 and its target STAT5,
CC and ultimately increase the expression of SOCS3 and inhibit cellular
CC responses to insulin. Important for the homeostasis of vitamin A and
CC its derivatives, such as retinoic acid. STRA6-mediated transport is
CC particularly important in the eye, and under conditions of dietary
CC vitamin A deficiency. Does not transport retinoic acid (By similarity).
CC {ECO:0000250|UniProtKB:Q9BX79, ECO:0000269|PubMed:17255476,
CC ECO:0000269|PubMed:18419130}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with JAK2 and STAT5.
CC Interacts (via extracellular domains) with RBP4 (PubMed:17255476,
CC PubMed:18419130). Interacts (via cytoplasmic domains) with RBP1 (By
CC similarity). {ECO:0000250|UniProtKB:F1RAX4,
CC ECO:0000250|UniProtKB:Q9BX79, ECO:0000269|PubMed:17255476,
CC ECO:0000269|PubMed:18419130}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17255476,
CC ECO:0000269|PubMed:18419130}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:17255476, ECO:0000269|PubMed:18419130}. Note=In the
CC retinal pigment epithelium localizes to the basolateral membrane.
CC {ECO:0000269|PubMed:17255476}.
CC -!- TISSUE SPECIFICITY: Expressed in placenta, spleen, retinal blood
CC vessels, and in astrocyte perivascular endfeet. Not detected in the
CC endothelial cells of the choriocapillaris (at protein level).
CC {ECO:0000269|PubMed:17255476}.
CC -!- DOMAIN: Contrary to predictions, contains nine transmembrane helices,
CC with an extracellular N-terminus and a cytoplasmic C-terminus
CC (PubMed:18419130). Besides, contains one long helix that dips into the
CC membrane and then runs more or less parallel to the membrane surface
CC (By similarity). {ECO:0000250|UniProtKB:F1RAX4,
CC ECO:0000269|PubMed:18419130}.
CC -!- PTM: Phosphorylated on tyrosine residues in response to RBP4 binding.
CC Phosphorylation requires the presence of LRAT, suggesting it may be
CC triggered by the uptake of retinol that is then metabolized within the
CC cell to retinoids that function as signaling molecules.
CC {ECO:0000250|UniProtKB:Q9BX79}.
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DR EMBL; BT026272; ABG81428.1; -; mRNA.
DR EMBL; BC142342; AAI42343.1; -; mRNA.
DR RefSeq; NP_001069198.1; NM_001075730.1.
DR AlphaFoldDB; Q0V8E7; -.
DR SMR; Q0V8E7; -.
DR STRING; 9913.ENSBTAP00000038534; -.
DR TCDB; 2.A.90.1.1; the vitamin a receptor/transporter (stra6) family.
DR PaxDb; Q0V8E7; -.
DR PRIDE; Q0V8E7; -.
DR GeneID; 515911; -.
DR KEGG; bta:515911; -.
DR CTD; 64220; -.
DR eggNOG; ENOG502QRSS; Eukaryota.
DR InParanoid; Q0V8E7; -.
DR OrthoDB; 325169at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro.
DR GO; GO:0043010; P:camera-type eye development; ISS:UniProtKB.
DR GO; GO:0034633; P:retinol transport; ISS:UniProtKB.
DR GO; GO:0071939; P:vitamin A import into cell; IBA:GO_Central.
DR InterPro; IPR026612; STRA6.
DR PANTHER; PTHR21444:SF16; PTHR21444:SF16; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Retinol-binding; Transmembrane; Transmembrane helix;
KW Transport; Vitamin A.
FT CHAIN 1..668
FT /note="Receptor for retinol uptake STRA6"
FT /id="PRO_0000311227"
FT TOPO_DOM 1..51
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:18419130"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 73..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 123..145
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 167..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 191..206
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TRANSMEM 207..227
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 228..296
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TRANSMEM 297..317
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 318..368
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TRANSMEM 369..389
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 390..423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TRANSMEM 424..444
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 445..474
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TRANSMEM 475..495
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 496..510
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT INTRAMEM 511..548
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1RAX4"
FT TOPO_DOM 549..668
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:18419130"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 236..294
FT /note="Interaction with RBP1"
FT /evidence="ECO:0000250|UniProtKB:Q9BX79"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 642
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9BX79"
FT CARBOHYD 8
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 256
FT /note="L->H: Not expressed at the cell surface; when
FT associated with H-336."
FT /evidence="ECO:0000269|PubMed:17255476"
FT MUTAGEN 297
FT /note="L->R: Not expressed at the cell surface."
FT /evidence="ECO:0000269|PubMed:17255476"
FT MUTAGEN 310
FT /note="Q->H: Expressed at the cell surface but reduced RBP
FT binding and vitamin A uptake activity; when associated with
FT P-315."
FT /evidence="ECO:0000269|PubMed:17255476"
FT MUTAGEN 315
FT /note="L->P: Expressed at the cell surface but reduced RBP
FT binding and vitamin A uptake activity; when associated with
FT H-310."
FT /evidence="ECO:0000269|PubMed:17255476"
FT MUTAGEN 336
FT /note="Y->H: Not expressed at the cell surface; when
FT associated with H-256."
FT /evidence="ECO:0000269|PubMed:17255476"
FT CONFLICT 47
FT /note="N -> S (in Ref. 2; AAI42343)"
FT /evidence="ECO:0000305"
FT CONFLICT 157
FT /note="A -> V (in Ref. 2; AAI42343)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="R -> Q (in Ref. 2; AAI42343)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 668 AA; 73762 MW; 72084B0D39DC8B6F CRC64;
MSTQAAGNQT SSGATDSEDS YDSWYIDEPQ GGQELQPEGL VPSCQPNVPP SLYHTCLAVL
SILVLFLLAM LVRRRQLWPR CGHGRPGLPS PVDFLTGDRP RTVPAAVFMV LFSSLCLLLP
TEDPLPFLSL ASPPGRDGEA ETSRGPWKIL ALLYYPALYY PLAACATVRH GAAHLLGSLL
SWAHLGVQVW QRAECPESPK IYKYYSLLAS LPLLLGLGFL SLWYPVQLVR SFGHGAATGS
KGLQSSYSEE YLRTLLCQKK LKSSSHTCKR GFASQAWMYF RHSVYIPQRG FRLPLKLVLS
VTLTGTAIYQ VALLLLVGVV PTIQKVRAGI TTDVSYLLAG FGIVLSEDRQ EVVELVKHHL
WALEVCYISA LVLSCLLTFL MLVHSLVTHR TNLRALHRGG ALDIGPLTQS PRPSRQAIFC
WMSFTAYQTA FTCLGLLVQQ ILFFLGTLTL AFLVFMPMLH GRNLLLLHYL KSSWPFWLTL
ALAVTLQNAA AHWAFLDTHH GRPGLTNRRA LYAATFLLFP VNVLVGTMVA AWRVLLSALY
NAVHLGRMDL SLLPLRAATL DPGYHTYCNF LRMEASQSHP AATAFCALLL RTQRPKPRAT
PQDGLRLGEE EEGIQLLQTK DLVAKGAGPR ARQGRARWGL AYTLLHNPAL QAFRKTALPG
ARPNGAQP
