REEP2_HUMAN
ID REEP2_HUMAN Reviewed; 252 AA.
AC Q9BRK0; Q53EM8; Q9NYF2;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Receptor expression-enhancing protein 2;
GN Name=REEP2; Synonyms=C5orf19, SGC32445;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=15550249; DOI=10.1016/j.cell.2004.11.021;
RA Saito H., Kubota M., Roberts R.W., Chi Q., Matsunami H.;
RT "RTP family members induce functional expression of mammalian odorant
RT receptors.";
RL Cell 119:679-691(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-252 (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=11161817; DOI=10.1006/geno.2000.6414;
RA Lai F., Godley L.A., Joslin J., Fernald A.A., Liu J., Espinosa R. III,
RA Zhao N., Pamintuan L., Till B.G., Larson R.A., Qian Z., Le Beau M.M.;
RT "Transcript map and comparative analysis of the 1.5-Mb commonly deleted
RT segment of human 5q31 in malignant myeloid diseases with a del(5q).";
RL Genomics 71:235-245(2001).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=16720576; DOI=10.1074/jbc.m513637200;
RA Behrens M., Bartelt J., Reichling C., Winnig M., Kuhn C., Meyerhof W.;
RT "Members of RTP and REEP gene families influence functional bitter taste
RT receptor expression.";
RL J. Biol. Chem. 281:20650-20659(2006).
RN [6]
RP FUNCTION, VARIANTS SPG72 GLU-36 AND TYR-72, AND CHARACTERIZATION OF
RP VARIANTS SPG72 GLU-36 AND TYR-72.
RX PubMed=24388663; DOI=10.1016/j.ajhg.2013.12.005;
RA Esteves T., Durr A., Mundwiller E., Loureiro J.L., Boutry M.,
RA Gonzalez M.A., Gauthier J., El-Hachimi K.H., Depienne C., Muriel M.P.,
RA Acosta Lebrigio R.F., Gaussen M., Noreau A., Speziani F.,
RA Dionne-Laporte A., Deleuze J.F., Dion P., Coutinho P., Rouleau G.A.,
RA Zuchner S., Brice A., Stevanin G., Darios F.;
RT "Loss of association of REEP2 with membranes leads to hereditary spastic
RT paraplegia.";
RL Am. J. Hum. Genet. 94:268-277(2014).
CC -!- FUNCTION: Required for endoplasmic reticulum (ER) network formation,
CC shaping and remodeling. May enhance the cell surface expression of
CC odorant receptors (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:24388663}.
CC -!- SUBUNIT: Interacts with odorant receptor proteins. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9BRK0; Q12983: BNIP3; NbExp=3; IntAct=EBI-11337973, EBI-749464;
CC Q9BRK0; O14523: C2CD2L; NbExp=3; IntAct=EBI-11337973, EBI-12822627;
CC Q9BRK0; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-11337973, EBI-11522780;
CC Q9BRK0; P78329: CYP4F2; NbExp=3; IntAct=EBI-11337973, EBI-1752413;
CC Q9BRK0; Q6NT55: CYP4F22; NbExp=3; IntAct=EBI-11337973, EBI-17509525;
CC Q9BRK0; P11215: ITGAM; NbExp=3; IntAct=EBI-11337973, EBI-2568251;
CC Q9BRK0; P11836: MS4A1; NbExp=3; IntAct=EBI-11337973, EBI-2808234;
CC Q9BRK0; Q969V5: MUL1; NbExp=3; IntAct=EBI-11337973, EBI-744120;
CC Q9BRK0; Q9UHE5: NAT8; NbExp=3; IntAct=EBI-11337973, EBI-2863634;
CC Q9BRK0; Q8N138: ORMDL3; NbExp=3; IntAct=EBI-11337973, EBI-721750;
CC Q9BRK0; Q9UI14: RABAC1; NbExp=3; IntAct=EBI-11337973, EBI-712367;
CC Q9BRK0; O00767: SCD; NbExp=3; IntAct=EBI-11337973, EBI-2684237;
CC Q9BRK0; O95562: SFT2D2; NbExp=3; IntAct=EBI-11337973, EBI-4402330;
CC Q9BRK0; O15374-3: SLC16A4; NbExp=3; IntAct=EBI-11337973, EBI-12889748;
CC Q9BRK0; Q96AG3: SLC25A46; NbExp=3; IntAct=EBI-11337973, EBI-10281975;
CC Q9BRK0; P55061: TMBIM6; NbExp=3; IntAct=EBI-11337973, EBI-1045825;
CC Q9BRK0; A0PK00: TMEM120B; NbExp=3; IntAct=EBI-11337973, EBI-10171534;
CC Q9BRK0; Q9BTX3: TMEM208; NbExp=3; IntAct=EBI-11337973, EBI-12876824;
CC Q9BRK0; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-11337973, EBI-11528917;
CC Q9BRK0; Q69YG0: TMEM42; NbExp=3; IntAct=EBI-11337973, EBI-12038591;
CC Q9BRK0; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-11337973, EBI-2852148;
CC Q9BRK0; Q9Y320: TMX2; NbExp=3; IntAct=EBI-11337973, EBI-6447886;
CC Q9BRK0; P49638: TTPA; NbExp=3; IntAct=EBI-11337973, EBI-10210710;
CC Q9BRK0; O95070: YIF1A; NbExp=3; IntAct=EBI-11337973, EBI-2799703;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BRK0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BRK0-2; Sequence=VSP_016633;
CC -!- TISSUE SPECIFICITY: Detected in brain, heart and skeletal muscle, and
CC at low levels in placenta, kidney and pancreas (PubMed:11161817).
CC Expressed in circumvallate papillae (PubMed:16720576).
CC {ECO:0000269|PubMed:11161817, ECO:0000269|PubMed:16720576}.
CC -!- DISEASE: Spastic paraplegia 72 (SPG72) [MIM:615625]: A form of spastic
CC paraplegia, a neurodegenerative disorder characterized by a slow,
CC gradual, progressive weakness and spasticity of the lower limbs. Rate
CC of progression and the severity of symptoms are quite variable. Initial
CC symptoms may include difficulty with balance, weakness and stiffness in
CC the legs, muscle spasms, and dragging the toes when walking. In some
CC forms of the disorder, bladder symptoms (such as incontinence) may
CC appear, or the weakness and stiffness may spread to other parts of the
CC body. SPG72 is a pure form of spastic paraplegia with onset of
CC difficulty walking and stiff legs associated with hyperreflexia and
CC extensor plantar responses in early childhood. Some patients may have
CC pes cavus or sphincter disturbances. Cognition, speech, and ocular
CC function are normal. SPG72 inheritance is autosomal dominant or
CC recessive. {ECO:0000269|PubMed:24388663}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DP1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF63767.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY562240; AAT70685.1; -; mRNA.
DR EMBL; AK223611; BAD97331.1; -; mRNA.
DR EMBL; BC006218; AAH06218.2; -; mRNA.
DR EMBL; AF251041; AAF63767.1; ALT_FRAME; mRNA.
DR CCDS; CCDS4205.1; -. [Q9BRK0-1]
DR CCDS; CCDS64259.1; -. [Q9BRK0-2]
DR RefSeq; NP_001258732.1; NM_001271803.1. [Q9BRK0-2]
DR RefSeq; NP_057690.2; NM_016606.3. [Q9BRK0-1]
DR AlphaFoldDB; Q9BRK0; -.
DR BioGRID; 119459; 56.
DR IntAct; Q9BRK0; 31.
DR STRING; 9606.ENSP00000367590; -.
DR iPTMnet; Q9BRK0; -.
DR PhosphoSitePlus; Q9BRK0; -.
DR BioMuta; REEP2; -.
DR DMDM; 74732895; -.
DR EPD; Q9BRK0; -.
DR jPOST; Q9BRK0; -.
DR MassIVE; Q9BRK0; -.
DR MaxQB; Q9BRK0; -.
DR PaxDb; Q9BRK0; -.
DR PeptideAtlas; Q9BRK0; -.
DR PRIDE; Q9BRK0; -.
DR ProteomicsDB; 78774; -. [Q9BRK0-1]
DR ProteomicsDB; 78775; -. [Q9BRK0-2]
DR Antibodypedia; 26670; 428 antibodies from 27 providers.
DR DNASU; 51308; -.
DR Ensembl; ENST00000254901.9; ENSP00000254901.5; ENSG00000132563.17. [Q9BRK0-1]
DR Ensembl; ENST00000378339.7; ENSP00000367590.2; ENSG00000132563.17. [Q9BRK0-2]
DR GeneID; 51308; -.
DR KEGG; hsa:51308; -.
DR MANE-Select; ENST00000378339.7; ENSP00000367590.2; NM_001271803.2; NP_001258732.1. [Q9BRK0-2]
DR UCSC; uc003lcz.5; human. [Q9BRK0-1]
DR CTD; 51308; -.
DR DisGeNET; 51308; -.
DR GeneCards; REEP2; -.
DR HGNC; HGNC:17975; REEP2.
DR HPA; ENSG00000132563; Group enriched (brain, choroid plexus, pituitary gland, retina).
DR MalaCards; REEP2; -.
DR MIM; 609347; gene.
DR MIM; 615625; phenotype.
DR neXtProt; NX_Q9BRK0; -.
DR OpenTargets; ENSG00000132563; -.
DR Orphanet; 401849; Autosomal spastic paraplegia type 72.
DR PharmGKB; PA134920985; -.
DR VEuPathDB; HostDB:ENSG00000132563; -.
DR eggNOG; KOG1726; Eukaryota.
DR GeneTree; ENSGT00940000160001; -.
DR HOGENOM; CLU_028431_0_1_1; -.
DR InParanoid; Q9BRK0; -.
DR OMA; GILCARE; -.
DR PhylomeDB; Q9BRK0; -.
DR TreeFam; TF314177; -.
DR PathwayCommons; Q9BRK0; -.
DR SignaLink; Q9BRK0; -.
DR BioGRID-ORCS; 51308; 11 hits in 1065 CRISPR screens.
DR ChiTaRS; REEP2; human.
DR GeneWiki; REEP2; -.
DR GenomeRNAi; 51308; -.
DR Pharos; Q9BRK0; Tdark.
DR PRO; PR:Q9BRK0; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9BRK0; protein.
DR Bgee; ENSG00000132563; Expressed in right hemisphere of cerebellum and 159 other tissues.
DR ExpressionAtlas; Q9BRK0; baseline and differential.
DR Genevisible; Q9BRK0; HS.
DR GO; GO:0005881; C:cytoplasmic microtubule; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IMP:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0071782; C:endoplasmic reticulum tubular network; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0031883; F:taste receptor binding; IBA:GO_Central.
DR GO; GO:0071786; P:endoplasmic reticulum tubular network organization; IMP:UniProtKB.
DR GO; GO:0032596; P:protein transport into membrane raft; IEA:Ensembl.
DR GO; GO:0032386; P:regulation of intracellular transport; IEA:Ensembl.
DR GO; GO:0050913; P:sensory perception of bitter taste; IEA:Ensembl.
DR GO; GO:0050916; P:sensory perception of sweet taste; IEA:Ensembl.
DR InterPro; IPR004345; TB2_DP1_HVA22.
DR PANTHER; PTHR12300; PTHR12300; 1.
DR Pfam; PF03134; TB2_DP1_HVA22; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Hereditary spastic paraplegia;
KW Membrane; Neurodegeneration; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..252
FT /note="Receptor expression-enhancing protein 2"
FT /id="PRO_0000101823"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 35..55
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 165..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..228
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCD6"
FT VAR_SEQ 139
FT /note="K -> KGQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11161817, ECO:0000303|Ref.2"
FT /id="VSP_016633"
FT VARIANT 36
FT /note="V -> E (in SPG72; abolishes REEP2 interaction with
FT membranes; affects correct shaping of the endoplasmic
FT reticulum; dbSNP:rs483352923)"
FT /evidence="ECO:0000269|PubMed:24388663"
FT /id="VAR_070996"
FT VARIANT 72
FT /note="F -> Y (in SPG72; reduces REEP2 interaction with
FT membranes; affects correct shaping of the endoplasmic
FT reticulum; dbSNP:rs483352925)"
FT /evidence="ECO:0000269|PubMed:24388663"
FT /id="VAR_070997"
SQ SEQUENCE 252 AA; 28261 MW; C2A4DD7F35E7F9C5 CRC64;
MVSWIISRLV VLIFGTLYPA YSSYKAVKTK NVKEYVKWMM YWIVFAFFTT AETLTDIVLS
WFPFYFELKI AFVIWLLSPY TKGSSVLYRK FVHPTLSNKE KEIDEYITQA RDKSYETMMR
VGKRGLNLAA NAAVTAAAKG VLSEKLRSFS MQDLTLIRDE DALPLQRPDG RLRPSPGSLL
DTIEDLGDDP ALSLRSSTNP ADSRTEASED DMGDKAPKRA KPIKKAPKAE PLASKTLKTR
PKKKTSGGGD SA
