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Protein

Receptor for retinol uptake STRA6

Gene

STRA6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as retinol transporter. 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 (PubMed:9452451, PubMed:18316031, PubMed:22665496). Retinol uptake is enhanced by LRAT, an enzyme that converts retinol to all-trans retinyl esters, the storage forms of vitamin A (PubMed:18316031, PubMed:22665496). 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:22665496). Important for the homeostasis of vitamin A and its derivatives, such as retinoic acid (PubMed:18316031). STRA6-mediated transport is particularly important in the eye, and under conditions of dietary vitamin A deficiency (Probable). Does not transport retinoic acid (PubMed:18316031).Curated4 Publications

GO - Molecular functioni

  • receptor activity Source: InterPro
  • retinol transporter activity Source: UniProtKB

GO - Biological processi

  • adrenal gland development Source: DFLAT
  • alveolar primary septum development Source: DFLAT
  • artery morphogenesis Source: DFLAT
  • blood vessel development Source: DFLAT
  • camera-type eye development Source: UniProtKB
  • cognition Source: DFLAT
  • developmental growth Source: DFLAT
  • diaphragm development Source: DFLAT
  • digestive tract morphogenesis Source: DFLAT
  • ductus arteriosus closure Source: DFLAT
  • ear development Source: DFLAT
  • embryonic camera-type eye formation Source: DFLAT
  • embryonic digestive tract development Source: DFLAT
  • eyelid development in camera-type eye Source: DFLAT
  • face morphogenesis Source: DFLAT
  • feeding behavior Source: DFLAT
  • female genitalia development Source: DFLAT
  • head development Source: DFLAT
  • head morphogenesis Source: DFLAT
  • heart development Source: DFLAT
  • kidney development Source: DFLAT
  • learning Source: DFLAT
  • lung alveolus development Source: DFLAT
  • lung development Source: DFLAT
  • lung vasculature development Source: DFLAT
  • neuromuscular process Source: DFLAT
  • nose morphogenesis Source: DFLAT
  • paramesonephric duct development Source: DFLAT
  • positive regulation of behavior Source: DFLAT
  • pulmonary artery morphogenesis Source: DFLAT
  • pulmonary valve morphogenesis Source: DFLAT
  • retinoid metabolic process Source: Reactome
  • retinol transport Source: UniProtKB
  • smooth muscle tissue development Source: DFLAT
  • uterus morphogenesis Source: DFLAT
  • ventricular septum development Source: DFLAT
  • vocal learning Source: DFLAT

Keywordsi

Molecular functionReceptor
Biological processTransport
LigandRetinol-binding, Vitamin A

Enzyme and pathway databases

ReactomeiR-HSA-2453864. Retinoid cycle disease events.
R-HSA-2453902. The canonical retinoid cycle in rods (twilight vision).

Protein family/group databases

TCDBi2.A.90.1.3. the vitamin a receptor/transporter (stra6) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor for retinol uptake STRA6
Alternative name(s):
Retinol-binding protein receptor STRA62 Publications
Stimulated by retinoic acid gene 6 protein homolog
Gene namesi
Name:STRA6
ORF Names:PP14296, UNQ3126/PRO10282/PRO19578
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000137868.18.
HGNCiHGNC:30650. 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 – 100CytoplasmicBy similarityAdd BLAST29
Transmembranei101 – 121HelicalBy similarityAdd BLAST21
Topological domaini122 – 144ExtracellularBy similarityAdd BLAST23
Transmembranei145 – 165HelicalBy similarityAdd BLAST21
Topological domaini166 – 168CytoplasmicBy similarity3
Transmembranei169 – 189HelicalBy similarityAdd BLAST21
Topological domaini190 – 205ExtracellularBy similarityAdd BLAST16
Transmembranei206 – 226HelicalBy similarityAdd BLAST21
Topological domaini227 – 295CytoplasmicBy similarityAdd BLAST69
Transmembranei296 – 316HelicalBy similarityAdd BLAST21
Topological domaini317 – 367ExtracellularBy similarityAdd BLAST51
Transmembranei368 – 388HelicalBy similarityAdd BLAST21
Topological domaini389 – 422CytoplasmicBy similarityAdd BLAST34
Transmembranei423 – 443HelicalBy similarityAdd BLAST21
Topological domaini444 – 473ExtracellularBy similarityAdd BLAST30
Transmembranei474 – 494HelicalBy similarityAdd BLAST21
Topological domaini495 – 509CytoplasmicBy similarityAdd BLAST15
Intramembranei510 – 547HelicalBy similarityAdd BLAST38
Topological domaini548 – 667CytoplasmicBy similarityAdd BLAST120

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Microphthalmia, syndromic, 9 (MCOPS9)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
See also OMIM:601186
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03716890P → L in MCOPS9. 1 PublicationCorresponds to variant dbSNP:rs118203961Ensembl.1
Natural variantiVAR_037169293P → L in MCOPS9. 1 PublicationCorresponds to variant dbSNP:rs118203958Ensembl.1
Natural variantiVAR_066849304G → K in MCOPS9; also found in a family with isolated colobomatous microphthalmia; affects STRA6 cell surface expression and retinol uptake; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs151341424Ensembl.1
Natural variantiVAR_037170321T → P in MCOPS9. 1 PublicationCorresponds to variant dbSNP:rs118203962Ensembl.1
Natural variantiVAR_037174644T → M in MCOPS9; loss of tyrosine phosphorylation. 2 PublicationsCorresponds to variant dbSNP:rs118203960Ensembl.1
Natural variantiVAR_037175655R → C in MCOPS9. 1 PublicationCorresponds to variant dbSNP:rs118203959Ensembl.1
Mutations in STRA6 may be a cause of isolated colobomatous microphthalmia, a disorder of the eye characterized by an abnormally small ocular globe.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi255L → A: Loss of interaction with RBP1. 1 Publication1
Mutagenesisi643Y → F: Loss of tyrosine phosphorylation. 1 Publication1

Keywords - Diseasei

Disease mutation, Microphthalmia

Organism-specific databases

DisGeNETi64220.
MalaCardsiSTRA6.
MIMi601186. phenotype.
OpenTargetsiENSG00000137868.
Orphaneti98938. Colobomatous microphthalmia.
2470. Matthew-Wood syndrome.
PharmGKBiPA134956551.

Polymorphism and mutation databases

BioMutaiSTRA6.
DMDMi74733466.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003112281 – 667Receptor for retinol uptake STRA6Add BLAST667

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi8N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei643Phosphotyrosine1 Publication1

Post-translational modificationi

Phosphorylated on tyrosine residues in response to RBP4 binding (PubMed:21368206, PubMed:22665496). 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 (PubMed:22665496).2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9BX79.
MaxQBiQ9BX79.
PaxDbiQ9BX79.
PeptideAtlasiQ9BX79.
PRIDEiQ9BX79.

PTM databases

iPTMnetiQ9BX79.
PhosphoSitePlusiQ9BX79.

Expressioni

Tissue specificityi

Broad expression. In adult eye expressed in sclera, retina, retinal pigment epithelium, and trabecular meshwork but not in choroid and iris.1 Publication

Inductioni

Up-regulated in the colorectal cancer cell line WiDr by the administration of retinoic acid and in tumors with frequent defects in Wnt-1 signaling.2 Publications

Gene expression databases

BgeeiENSG00000137868.
CleanExiHS_STRA6.
ExpressionAtlasiQ9BX79. baseline and differential.
GenevisibleiQ9BX79. HS.

Organism-specific databases

HPAiHPA040839.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with JAK2 and STAT5 (PubMed:21368206). Interacts (via extracellular domains) with RBP4 (PubMed:22665496). Interacts (via cytoplasmic domains) with RBP1 (PubMed:22665496).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GLRX3O760034EBI-12140683,EBI-374781

Protein-protein interaction databases

BioGridi122110. 2 interactors.
IntActiQ9BX79. 2 interactors.
MINTiMINT-4722094.
STRINGi9606.ENSP00000456609.

Structurei

3D structure databases

ProteinModelPortaliQ9BX79.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni235 – 293Interaction with RBP11 PublicationAdd BLAST59

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.
GeneTreeiENSGT00390000015272.
HOVERGENiHBG106311.
InParanoidiQ9BX79.
OMAiAIFCWMS.
OrthoDBiEOG091G05AQ.
PhylomeDBiQ9BX79.
TreeFamiTF331851.

Family and domain databases

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

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BX79-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSSQPAGNQT SPGATEDYSY GSWYIDEPQG GEELQPEGEV PSCHTSIPPG
60 70 80 90 100
LYHACLASLS ILVLLLLAML VRRRQLWPDC VRGRPGLPSP VDFLAGDRPR
110 120 130 140 150
AVPAAVFMVL LSSLCLLLPD EDALPFLTLA SAPSQDGKTE APRGAWKILG
160 170 180 190 200
LFYYAALYYP LAACATAGHT AAHLLGSTLS WAHLGVQVWQ RAECPQVPKI
210 220 230 240 250
YKYYSLLASL PLLLGLGFLS LWYPVQLVRS FSRRTGAGSK GLQSSYSEEY
260 270 280 290 300
LRNLLCRKKL GSSYHTSKHG FLSWARVCLR HCIYTPQPGF HLPLKLVLSA
310 320 330 340 350
TLTGTAIYQV ALLLLVGVVP TIQKVRAGVT TDVSYLLAGF GIVLSEDKQE
360 370 380 390 400
VVELVKHHLW ALEVCYISAL VLSCLLTFLV LMRSLVTHRT NLRALHRGAA
410 420 430 440 450
LDLSPLHRSP HPSRQAIFCW MSFSAYQTAF ICLGLLVQQI IFFLGTTALA
460 470 480 490 500
FLVLMPVLHG RNLLLFRSLE SSWPFWLTLA LAVILQNMAA HWVFLETHDG
510 520 530 540 550
HPQLTNRRVL YAATFLLFPL NVLVGAMVAT WRVLLSALYN AIHLGQMDLS
560 570 580 590 600
LLPPRAATLD PGYYTYRNFL KIEVSQSHPA MTAFCSLLLQ AQSLLPRTMA
610 620 630 640 650
APQDSLRPGE EDEGMQLLQT KDSMAKGARP GASRGRARWG LAYTLLHNPT
660
LQVFRKTALL GANGAQP
Length:667
Mass (Da):73,503
Last modified:June 1, 2001 - v1
Checksum:iD20840A46998BA2E
GO
Isoform 2 (identifier: Q9BX79-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     145-667: AWKILGLFYY...ALLGANGAQP → NLPKITELRLVRAWI

Note: No experimental confirmation available.
Show »
Length:159
Mass (Da):17,190
Checksum:i7FB62BED986EC3B9
GO
Isoform 3 (identifier: Q9BX79-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     89-97: Missing.

Show »
Length:658
Mass (Da):72,601
Checksum:i54052F7AE58F82C9
GO
Isoform 4 (identifier: Q9BX79-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGGKGGGDTRGPVLFPCQLAQALSPRRAFPRELKEKGQRM

Note: No experimental confirmation available.
Show »
Length:706
Mass (Da):77,696
Checksum:iCC091BBE74255CDA
GO
Isoform 5 (identifier: Q9BX79-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQIRLLRAELVVPLWQFIRQWPPGSDGWGQMEEKGQRM

Show »
Length:704
Mass (Da):77,922
Checksum:i8E952666FFAAE051
GO
Isoform 6 (identifier: Q9BX79-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MDSQGDWAAQEKGQRM

Note: No experimental confirmation available.
Show »
Length:682
Mass (Da):75,192
Checksum:i24CE3B0CC96D9FA5
GO

Sequence cautioni

The sequence BAB14122 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAH13848 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAD97655 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti95A → V in BAH12965 (PubMed:14702039).Curated1
Sequence conflicti408R → Q in CAD97655 (PubMed:17974005).Curated1
Sequence conflicti417I → M in BAH12965 (PubMed:14702039).Curated1
Sequence conflicti635G → S in BAH13848 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03716890P → L in MCOPS9. 1 PublicationCorresponds to variant dbSNP:rs118203961Ensembl.1
Natural variantiVAR_060203217G → E in anophthalmia/microphthalmia. 1 Publication1
Natural variantiVAR_037169293P → L in MCOPS9. 1 PublicationCorresponds to variant dbSNP:rs118203958Ensembl.1
Natural variantiVAR_066849304G → K in MCOPS9; also found in a family with isolated colobomatous microphthalmia; affects STRA6 cell surface expression and retinol uptake; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs151341424Ensembl.1
Natural variantiVAR_037170321T → P in MCOPS9. 1 PublicationCorresponds to variant dbSNP:rs118203962Ensembl.1
Natural variantiVAR_037171339G → S2 PublicationsCorresponds to variant dbSNP:rs17852249Ensembl.1
Natural variantiVAR_060204438Q → R in anophthalmia/microphthalmia. 1 PublicationCorresponds to variant dbSNP:rs869025269Ensembl.1
Natural variantiVAR_037172517L → F. Corresponds to variant dbSNP:rs11545567Ensembl.1
Natural variantiVAR_037173527M → I3 PublicationsCorresponds to variant dbSNP:rs736118Ensembl.1
Natural variantiVAR_060205638R → P in anophthalmia/microphthalmia. 1 PublicationCorresponds to variant dbSNP:rs144691445Ensembl.1
Natural variantiVAR_037174644T → M in MCOPS9; loss of tyrosine phosphorylation. 2 PublicationsCorresponds to variant dbSNP:rs118203960Ensembl.1
Natural variantiVAR_037175655R → C in MCOPS9. 1 PublicationCorresponds to variant dbSNP:rs118203959Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0294371M → MGGKGGGDTRGPVLFPCQLA QALSPRRAFPRELKEKGQRM in isoform 4. 1 Publication1
Alternative sequenceiVSP_0467761M → MQIRLLRAELVVPLWQFIRQ WPPGSDGWGQMEEKGQRM in isoform 5. 1 Publication1
Alternative sequenceiVSP_0474971M → MDSQGDWAAQEKGQRM in isoform 6. 1 Publication1
Alternative sequenceiVSP_02943889 – 97Missing in isoform 3. 2 Publications9
Alternative sequenceiVSP_029439145 – 667AWKIL…NGAQP → NLPKITELRLVRAWI in isoform 2. 1 PublicationAdd BLAST523

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF352728 mRNA. Translation: AAK30289.1.
AF352729 mRNA. Translation: AAK30290.1.
AY358748 mRNA. Translation: AAQ89108.1.
AY359089 mRNA. Translation: AAQ89447.1.
BX537413 mRNA. Translation: CAD97655.1. Different initiation.
AK022603 mRNA. Translation: BAB14122.1. Different initiation.
AK291966 mRNA. Translation: BAF84655.1.
AK299191 mRNA. Translation: BAH12965.1.
AK302932 mRNA. Translation: BAH13848.1. Different initiation.
AF370419 mRNA. Translation: AAQ15255.2.
AC023545 Genomic DNA. No translation available.
CH471136 Genomic DNA. Translation: EAW99353.1.
CH471136 Genomic DNA. Translation: EAW99356.1.
BC015881 mRNA. Translation: AAH15881.1.
BC025256 mRNA. Translation: AAH25256.1.
CCDSiCCDS10261.1. [Q9BX79-1]
CCDS45301.1. [Q9BX79-3]
CCDS45302.1. [Q9BX79-2]
CCDS55973.1. [Q9BX79-4]
CCDS55974.1. [Q9BX79-5]
CCDS58387.1. [Q9BX79-6]
RefSeqiNP_001136089.1. NM_001142617.1. [Q9BX79-1]
NP_001136090.1. NM_001142618.1. [Q9BX79-1]
NP_001136091.1. NM_001142619.1. [Q9BX79-3]
NP_001136092.1. NM_001142620.1. [Q9BX79-2]
NP_001185969.1. NM_001199040.1. [Q9BX79-5]
NP_001185970.1. NM_001199041.1. [Q9BX79-6]
NP_001185971.1. NM_001199042.1. [Q9BX79-4]
NP_071764.3. NM_022369.3. [Q9BX79-1]
XP_011520185.1. XM_011521883.1. [Q9BX79-1]
XP_016877968.1. XM_017022479.1. [Q9BX79-1]
UniGeneiHs.24553.

Genome annotation databases

EnsembliENST00000323940; ENSP00000326085; ENSG00000137868. [Q9BX79-1]
ENST00000395105; ENSP00000378537; ENSG00000137868. [Q9BX79-1]
ENST00000423167; ENSP00000413012; ENSG00000137868. [Q9BX79-3]
ENST00000432245; ENSP00000407176; ENSG00000137868. [Q9BX79-2]
ENST00000449139; ENSP00000410221; ENSG00000137868. [Q9BX79-1]
ENST00000535552; ENSP00000440238; ENSG00000137868. [Q9BX79-5]
ENST00000563965; ENSP00000456609; ENSG00000137868. [Q9BX79-4]
ENST00000574278; ENSP00000458827; ENSG00000137868. [Q9BX79-6]
ENST00000616000; ENSP00000479112; ENSG00000137868. [Q9BX79-1]
GeneIDi64220.
KEGGihsa:64220.
UCSCiuc002axj.5. human. [Q9BX79-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSTRA6_HUMAN
AccessioniPrimary (citable) accession number: Q9BX79
Secondary accession number(s): A8K7F1
, B7Z5M9, B7Z862, D3DW54, F5GYI8, I3L1G8, Q6PJF8, Q71RB9, Q7L9G1, Q7Z3U9, Q8TB21, Q9BX78, Q9H9U8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: June 1, 2001
Last modified: November 22, 2017
This is version 115 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot