SIM20_MOUSE
ID SIM20_MOUSE Reviewed; 69 AA.
AC D3Z7Q2;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Small integral membrane protein 20;
DE AltName: Full=Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 7 kDa {ECO:0000250|UniProtKB:Q8N5G0};
DE Short=MITRAC7 {ECO:0000250|UniProtKB:Q8N5G0};
DE Contains:
DE RecName: Full=Phoenixin-14 {ECO:0000250|UniProtKB:C0HLM6};
DE Short=PNX-14 {ECO:0000250|UniProtKB:C0HLM6};
DE Contains:
DE RecName: Full=Phoenixin-20 {ECO:0000250|UniProtKB:C0HLM6};
DE Short=PNX-20 {ECO:0000250|UniProtKB:C0HLM6};
GN Name=Smim20 {ECO:0000312|MGI:MGI:1913528};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|Proteomes:UP000000589};
RN [1] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2] {ECO:0007744|PubMed:21183079}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [3] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=23912037; DOI=10.1016/j.neuroscience.2013.07.057;
RA Lyu R.M., Huang X.F., Zhang Y., Dun S.L., Luo J.J., Chang J.K., Dun N.J.;
RT "Phoenixin: a novel peptide in rodent sensory ganglia.";
RL Neuroscience 250:622-631(2013).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=25687846; DOI=10.1016/j.bbr.2015.02.011;
RA Jiang J.H., He Z., Peng Y.L., Jin W.D., Mu J., Xue H.X., Wang Z., Chang M.,
RA Wang R.;
RT "Effects of Phoenixin-14 on anxiolytic-like behavior in mice.";
RL Behav. Brain Res. 286:39-48(2015).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=26505917; DOI=10.1016/j.brainres.2015.10.030;
RA Jiang J.H., He Z., Peng Y.L., Jin W.D., Wang Z., Mu L.Y., Chang M.,
RA Wang R.;
RT "Phoenixin-14 enhances memory and mitigates memory impairment induced by
RT Abeta1-42 and scopolamine in mice.";
RL Brain Res. 1629:298-308(2015).
RN [6] {ECO:0000305}
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=26415767; DOI=10.1016/j.neuroscience.2015.09.055;
RA Cowan A., Lyu R.M., Chen Y.H., Dun S.L., Chang J.K., Dun N.J.;
RT "Phoenixin: A candidate pruritogen in the mouse.";
RL Neuroscience 310:541-548(2015).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=27268078; DOI=10.1210/me.2016-1039;
RA Treen A.K., Luo V., Belsham D.D.;
RT "Phoenixin Activates Immortalized GnRH and Kisspeptin Neurons Through the
RT Novel Receptor GPR173.";
RL Mol. Endocrinol. 30:872-888(2016).
RN [8] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=30251651; DOI=10.1016/j.bbalip.2018.09.006;
RA Billert M., Wojciechowicz T., Jasaszwili M., Szczepankiewicz D., Wasko J.,
RA Kazmierczak S., Strowski M.Z., Nowak K.W., Skrzypski M.;
RT "Phoenixin-14 stimulates differentiation of 3T3-L1 preadipocytes via
RT cAMP/Epac-dependent mechanism.";
RL Biochim. Biophys. Acta 1863:1449-1457(2018).
RN [9] {ECO:0000305}
RP INDUCTION.
RX PubMed=30524225; DOI=10.3389/fnins.2018.00838;
RA McIlwraith E.K., Loganathan N., Belsham D.D.;
RT "Phoenixin Expression Is Regulated by the Fatty Acids Palmitate,
RT Docosahexaenoic Acid and Oleate, and the Endocrine Disrupting Chemical
RT Bisphenol A in Immortalized Hypothalamic Neurons.";
RL Front. Neurosci. 12:838-838(2018).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=31422055; DOI=10.1016/j.bbamcr.2019.118533;
RA Billert M., Kolodziejski P.A., Strowski M.Z., Nowak K.W., Skrzypski M.;
RT "Phoenixin-14 stimulates proliferation and insulin secretion in insulin
RT producing INS-1E cells.";
RL Biochim. Biophys. Acta 1866:118533-118533(2019).
RN [11] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=30933929; DOI=10.1530/rep-19-0025;
RA Nguyen X.P., Nakamura T., Osuka S., Bayasula B., Nakanishi N., Kasahara Y.,
RA Muraoka A., Hayashi S., Nagai T., Murase T., Goto M., Iwase A., Kikkawa F.;
RT "Effect of the Neuropeptide Phoenixin and Its Receptor GPR173 During
RT Folliculogenesis.";
RL Reproduction 158:25-34(2019).
CC -!- FUNCTION: [Small integral membrane protein 20]: Component of the MITRAC
CC (mitochondrial translation regulation assembly intermediate of
CC cytochrome c oxidase complex) complex, that regulates cytochrome c
CC oxidase assembly (By similarity). Promotes the progression of complex
CC assembly after the association of MT-CO1/COX1 with COX4I1 and COX6C (By
CC similarity). Chaperone-like assembly factor required to stabilize newly
CC synthesized MT-CO1/COX1 and to prevent its premature turnover (By
CC similarity). {ECO:0000250|UniProtKB:Q8N5G0}.
CC -!- FUNCTION: [Phoenixin-14]: Peptide involved in a broad spectrum of
CC regulatory functions (PubMed:25687846, PubMed:26505917,
CC PubMed:27268078). Is a ligand for GPR173 (By similarity). As part of
CC the reproductive cycle, it regulates gonadotropin-releasing hormone
CC (GnRH) signaling in the hypothalamus and pituitary gland which augments
CC the release of luteinizing hormone (PubMed:27268078). More
CC specifically, it regulates the expression of transcription factors
CC CEBPB and POU2F1/OCT1 through the cAMP-PKA signaling pathway, which
CC subsequently regulate the expression of GNRHR and KISS1
CC (PubMed:27268078). Plays a protective role in memory retention through
CC activation of GNRHR (PubMed:26505917). Regulates the secretion of AVP
CC by hypothalamic neurons (By similarity). Plays a role in the
CC transduction of the itch sensation (PubMed:26415767). Induces
CC anxiolytic effects, reducing behavior associated with anxiety
CC (PubMed:25687846). Regulates food intake as well as satiation and
CC satiety by increasing Nucb2 expression in neurons (By similarity). In
CC the ovary, it regulates follicular growth by stimulating granulosa cell
CC proliferation by increasing the expression of GPR173, CREB1, CYP19A1,
CC KITLG, FSHR, and LHCGR (PubMed:30933929). It also increases the
CC production of estradiol (E2) (PubMed:30933929). In the heart, it
CC regulates contractility and relaxation by activating the AKT1-NOS3 and
CC MAPK1-MAPK3 signaling pathways (By similarity). It also plays a
CC cardioprotective role during ischemia, where it activates the SAFE and
CC RISK pathways (By similarity). Stimulates the proliferation and
CC differentiation of preadipocytes (PubMed:30251651). In pancreatic islet
CC cells, it induces proliferation of islet cells as well as the
CC production of INS through activation of the MAPK1-MAPK3 signaling
CC pathways (PubMed:31422055). {ECO:0000250|UniProtKB:C0HLM6,
CC ECO:0000269|PubMed:25687846, ECO:0000269|PubMed:26415767,
CC ECO:0000269|PubMed:26505917, ECO:0000269|PubMed:27268078,
CC ECO:0000269|PubMed:30251651, ECO:0000269|PubMed:30933929,
CC ECO:0000269|PubMed:31422055}.
CC -!- FUNCTION: [Phoenixin-20]: Peptide involved in a broad spectrum of
CC regulatory functions (PubMed:25687846, PubMed:26505917,
CC PubMed:27268078). Is a ligand for GPR173 (By similarity). As part of
CC the reproductive cycle, it regulates gonadotropin-releasing hormone
CC (GnRH) signaling in the hypothalamus and pituitary gland which augments
CC the release of luteinizing hormone (PubMed:27268078). More
CC specifically, it regulates the expression of transcription factors
CC CEBPB and POU2F1/OCT1 through the cAMP-PKA signaling pathway, which
CC subsequently regulate the expression of GNRHR and KISS1
CC (PubMed:27268078). Plays a protective role in memory retention through
CC activation of GNRHR (PubMed:26505917). Regulates the secretion of AVP
CC by hypothalamic neurons (By similarity). Plays a role in the
CC transduction of the itch sensation (PubMed:26415767). Induces
CC anxiolytic effects, reducing behavior associated with anxiety
CC (PubMed:25687846). Regulates food intake as well as satiation and
CC satiety by increasing Nucb2 expression in neurons (By similarity). In
CC the ovary, it regulates follicular growth by stimulating granulosa cell
CC proliferation by increasing the expression of GPR173, CREB1, CYP19A1,
CC KITLG, FSHR, and LHCGR (PubMed:30933929). It also increases the
CC production of estradiol (E2) (PubMed:30933929). In the heart, it
CC regulates contractility and relaxation by activating the AKT1-NOS3 and
CC MAPK1-MAPK3 signaling pathways (By similarity). It also plays a
CC cardioprotective role during ischemia, where it activates the SAFE and
CC RISK pathways (By similarity). Stimulates the proliferation and
CC differentiation of preadipocytes (PubMed:30251651). In pancreatic islet
CC cells, it induces proliferation of islet cells as well as the
CC production of INS through activation of the MAPK1-MAPK3 signaling
CC pathways (PubMed:31422055). {ECO:0000250|UniProtKB:C0HLM6,
CC ECO:0000269|PubMed:25687846, ECO:0000269|PubMed:26415767,
CC ECO:0000269|PubMed:26505917, ECO:0000269|PubMed:27268078,
CC ECO:0000269|PubMed:30251651, ECO:0000269|PubMed:30933929,
CC ECO:0000269|PubMed:31422055}.
CC -!- SUBUNIT: Component of the MITRAC (mitochondrial translation regulation
CC assembly intermediate of cytochrome c oxidase complex) complex, the
CC core components of this complex being COA3/MITRAC12 and COX14 (By
CC similarity). Interacts with COA3/MITRAC12 and COX4I1 (By similarity).
CC Directly interacts with newly synthesized MT-CO1/COX1 (By similarity).
CC {ECO:0000250|UniProtKB:Q8N5G0}.
CC -!- SUBCELLULAR LOCATION: [Small integral membrane protein 20]:
CC Mitochondrion inner membrane {ECO:0000250|UniProtKB:Q8N5G0}; Single-
CC pass membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Phoenixin-14]: Secreted
CC {ECO:0000269|PubMed:30251651}.
CC -!- SUBCELLULAR LOCATION: [Phoenixin-20]: Secreted
CC {ECO:0000269|PubMed:30251651}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the hypothalamus, the spinal
CC cord, and sensory ganglia (at protein level) (PubMed:23912037,
CC PubMed:26415767). Also expressed on in the epidermis and dermis layers
CC of the skin (at protein level) (PubMed:26415767). Expressed in
CC preadipocytes and adipocytes (at protein level) (PubMed:30251651).
CC Expressed in the ovary, specifically in granulosa cells of follicles
CC that have passed the primary stage and in oocytes (at protein level)
CC (PubMed:30933929). {ECO:0000269|PubMed:23912037,
CC ECO:0000269|PubMed:26415767, ECO:0000269|PubMed:30251651,
CC ECO:0000269|PubMed:30933929}.
CC -!- INDUCTION: By fatty acids, specifically palmitate, docosahexanoic acid
CC and oleate. {ECO:0000269|PubMed:30524225}.
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DR EMBL; AC122522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC134463; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS51502.1; -.
DR RefSeq; NP_001138905.1; NM_001145433.1.
DR AlphaFoldDB; D3Z7Q2; -.
DR SMR; D3Z7Q2; -.
DR STRING; 10090.ENSMUSP00000113019; -.
DR iPTMnet; D3Z7Q2; -.
DR PhosphoSitePlus; D3Z7Q2; -.
DR MaxQB; D3Z7Q2; -.
DR PaxDb; D3Z7Q2; -.
DR PeptideAtlas; D3Z7Q2; -.
DR PRIDE; D3Z7Q2; -.
DR ProteomicsDB; 369442; -.
DR Antibodypedia; 52038; 11 antibodies from 6 providers.
DR Ensembl; ENSMUST00000147148; ENSMUSP00000121637; ENSMUSG00000061461.
DR GeneID; 66278; -.
DR KEGG; mmu:66278; -.
DR UCSC; uc008xlg.2; mouse.
DR CTD; 389203; -.
DR MGI; MGI:1913528; Smim20.
DR VEuPathDB; HostDB:ENSMUSG00000061461; -.
DR eggNOG; ENOG502S83Z; Eukaryota.
DR GeneTree; ENSGT00390000002398; -.
DR HOGENOM; CLU_175940_1_0_1; -.
DR InParanoid; D3Z7Q2; -.
DR OMA; VYPLTHK; -.
DR OrthoDB; 1639960at2759; -.
DR PhylomeDB; D3Z7Q2; -.
DR TreeFam; TF353700; -.
DR BioGRID-ORCS; 66278; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Smim20; mouse.
DR PRO; PR:D3Z7Q2; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; D3Z7Q2; protein.
DR Bgee; ENSMUSG00000061461; Expressed in right kidney and 230 other tissues.
DR ExpressionAtlas; D3Z7Q2; baseline and differential.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; ISO:MGI.
DR InterPro; IPR027917; SMIM20.
DR PANTHER; PTHR34923; PTHR34923; 1.
DR Pfam; PF15061; DUF4538; 1.
PE 1: Evidence at protein level;
KW Amidation; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Secreted; Transmembrane; Transmembrane helix.
FT CHAIN 1..69
FT /note="Small integral membrane protein 20"
FT /id="PRO_0000449030"
FT PEPTIDE 47..66
FT /note="Phoenixin-20"
FT /id="PRO_0000449031"
FT PEPTIDE 53..66
FT /note="Phoenixin-14"
FT /id="PRO_0000449032"
FT TOPO_DOM 1..8
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..69
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT MOD_RES 66
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000250|UniProtKB:C0HLM6"
SQ SEQUENCE 69 AA; 7818 MW; 3472CABBEF00DDF0 CRC64;
MAAARNLRTA LIFGGFISMV GAAFYPIYFR PLMRLEEYQK EQAVNRAGIV QEDVQPPGLK
VWSDPFGRK
