TSPO2_CANLF
ID TSPO2_CANLF Reviewed; 172 AA.
AC E2RDM9; A0A6M3RDU1; A0A6M3RRT7;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Translocator protein 2 {ECO:0000303|PubMed:32358067};
GN Name=TSPO2 {ECO:0000303|PubMed:32358067};
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615 {ECO:0000312|Proteomes:UP000002254};
RN [1] {ECO:0000312|EMBL:QJD20749.1, ECO:0000312|EMBL:QJD20750.1, ECO:0000312|EMBL:QJD20751.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND CHARACTERIZATION OF VARIANTS HK TYR-40; PHE-89; PHE-98 DEL
RP AND ILE-120.
RX PubMed=32358067; DOI=10.1074/jbc.ra119.011679;
RA Kiatpakdee B., Sato K., Otsuka Y., Arashiki N., Chen Y., Tsumita T.,
RA Otsu W., Yamamoto A., Kawata R., Yamazaki J., Sugimoto Y., Takada K.,
RA Mohandas N., Inaba M.;
RT "Cholesterol-binding protein TSPO2 coordinates maturation and proliferation
RT of terminally differentiating erythroblasts.";
RL J. Biol. Chem. 295:8048-8063(2020).
RN [2] {ECO:0000312|Proteomes:UP000002254}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer {ECO:0000312|Proteomes:UP000002254};
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
CC -!- FUNCTION: Cholesterol-binding protein involved in the redistribution of
CC cholesterol from lipid droplets to the endoplasmic reticulum
CC (PubMed:32358067). Required to meet cholesterol demands during
CC erythropoietic differentiation (PubMed:32358067). May play a role in
CC transport processes at the plasma membrane of erythrocytes, including
CC regulating VDAC-mediated ATP export, and import of the heme precursors
CC protoporphyrin IX and 5-aminolevulinic acid (By similarity).
CC {ECO:0000250|UniProtKB:Q5TGU0, ECO:0000269|PubMed:32358067}.
CC -!- SUBUNIT: Homotetramer. May also form homodimer.
CC {ECO:0000250|UniProtKB:Q5TGU0}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q5TGU0}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:32358067}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Localizes to the plasma membrane
CC and intracellular membranes in developing and mature erythrocytes.
CC {ECO:0000250|UniProtKB:Q5TGU0}.
CC -!- TISSUE SPECIFICITY: Expressed in erythrocytes (at protein level).
CC {ECO:0000269|PubMed:32358067}.
CC -!- DOMAIN: The C-terminal region mediates cholesterol-binding.
CC {ECO:0000250|UniProtKB:Q9CRZ8}.
CC -!- DISEASE: Note=Defects in TSPO2 functioning alter the cation composition
CC of canine erythrocytes so that they are high in potassium and low in
CC sodium (HK phenotype) (PubMed:32358067). Although HK erythrocytes have
CC a tendency to hemolyze they do not cause serious disease, but the
CC phenotype may lead to misdiagnosis of hyperkalemia in HK canines and
CC blood transfusions using HK blood may induce hyperkalemia
CC (PubMed:32358067). This phenotype has been identified in the Shiba
CC breed (PubMed:32358067). {ECO:0000269|PubMed:32358067}.
CC -!- SIMILARITY: Belongs to the TspO/BZRP family. {ECO:0000305}.
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DR EMBL; MN397823; QJD20749.1; -; mRNA.
DR EMBL; MN397824; QJD20750.1; -; mRNA.
DR EMBL; MN397825; QJD20751.1; -; mRNA.
DR EMBL; AAEX03008323; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; E2RDM9; -.
DR SMR; E2RDM9; -.
DR STRING; 9612.ENSCAFP00000002289; -.
DR PaxDb; E2RDM9; -.
DR Ensembl; ENSCAFT00030012352; ENSCAFP00030010806; ENSCAFG00030006716.
DR Ensembl; ENSCAFT00040043569; ENSCAFP00040038005; ENSCAFG00040023442.
DR Ensembl; ENSCAFT00845026413; ENSCAFP00845020815; ENSCAFG00845014773.
DR VEuPathDB; HostDB:ENSCAFG00845014773; -.
DR eggNOG; KOG3797; Eukaryota.
DR GeneTree; ENSGT00390000012980; -.
DR HOGENOM; CLU_091805_2_1_1; -.
DR InParanoid; E2RDM9; -.
DR OMA; RDSLCPE; -.
DR OrthoDB; 1592225at2759; -.
DR TreeFam; TF342852; -.
DR Proteomes; UP000002254; Chromosome 12.
DR Bgee; ENSCAFG00000001574; Expressed in bone marrow and 4 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0140485; F:5-aminolevulinic acid transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015485; F:cholesterol binding; IBA:GO_Central.
DR GO; GO:0140484; P:5-aminolevulinic acid import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0043353; P:enucleate erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0098739; P:import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0032367; P:intracellular cholesterol transport; IMP:UniProtKB.
DR GO; GO:0034389; P:lipid droplet organization; IMP:UniProtKB.
DR CDD; cd15904; TSPO_MBR; 1.
DR Gene3D; 1.20.1260.100; -; 1.
DR InterPro; IPR038330; TspO/MBR-related_sf.
DR InterPro; IPR004307; TspO_MBR.
DR PANTHER; PTHR10057; PTHR10057; 1.
DR Pfam; PF03073; TspO_MBR; 1.
DR PIRSF; PIRSF005859; PBR; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Endoplasmic reticulum; Membrane; Receptor;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..172
FT /note="Translocator protein 2"
FT /id="PRO_0000451410"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..65
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..150
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 40
FT /note="C -> Y (in HK; decreases TSPO2 expression levels.
FT Abnormal chromosome condensation and chromosome segregation
FT in differentiating erythrocytes, resulting in abnormal
FT cytokinesis and differentiation)"
FT /evidence="ECO:0000269|PubMed:32358067"
FT VARIANT 89
FT /note="V -> F (in HK; associated in cis with F-98 DEL and
FT I-120; decreases TSPO2 expression levels)"
FT /evidence="ECO:0000269|PubMed:32358067"
FT VARIANT 98
FT /note="Missing (in HK; associated in cis with F-89 and I-
FT 120; decreases TSPO2 expression levels)"
FT /evidence="ECO:0000269|PubMed:32358067"
FT VARIANT 120
FT /note="T -> I (in HK; associated in cis with F-89 and F-98
FT DEL; decreases TSPO2 expression levels)"
FT /evidence="ECO:0000269|PubMed:32358067"
SQ SEQUENCE 172 AA; 19357 MW; F5746F1570C35888 CRC64;
MQPQGAIFVA LPHLGPILVS LLTRHRMIRW YDIPKKPPWC PPHKVLLAGW ITIYFVMGYA
SYLVWKDLGG GFGRPLALPL GLYAVQLAVS WAVLIFFFAA HAHGLALLHM LLLYGLVVST
ALIWHPINKL AAVLLLPYLA WLTVTASIAY HLWRDSLCPN HHQPLPMGEK RD
