SIM20_RAT
ID SIM20_RAT Reviewed; 69 AA.
AC C0HLM6;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2020, sequence version 1.
DT 25-MAY-2022, entry version 5.
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:0000303|PubMed:22963497};
DE Short=PNX-14 {ECO:0000303|PubMed:22963497};
DE Contains:
DE RecName: Full=Phoenixin-20 {ECO:0000303|PubMed:22963497};
DE Short=PNX-20 {ECO:0000303|PubMed:22963497};
GN Name=Smim20 {ECO:0000312|RGD:1565192};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY, PROTEIN
RP SEQUENCE OF 47-66, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP AMIDATION AT PHE-66.
RX PubMed=22963497; DOI=10.1111/j.1365-2826.2012.02381.x;
RA Yosten G.L., Lyu R.M., Hsueh A.J., Avsian-Kretchmer O., Chang J.K.,
RA Tullock C.W., Dun S.L., Dun N., Samson W.K.;
RT "A novel reproductive peptide, phoenixin.";
RL J. Neuroendocrinol. 25:206-215(2013).
RN [2] {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 [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=27440717; DOI=10.1152/ajpregu.00191.2016;
RA Stein L.M., Tullock C.W., Mathews S.K., Garcia-Galiano D., Elias C.F.,
RA Samson W.K., Yosten G.L.;
RT "Hypothalamic action of phoenixin to control reproductive hormone secretion
RT in females: importance of the orphan G protein-coupled receptor Gpr173.";
RL Am. J. Physiol. 311:R489-R496(2016).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=28844870; DOI=10.1016/j.peptides.2017.08.004;
RA Schalla M., Prinz P., Friedrich T., Scharner S., Kobelt P.,
RA Goebel-Stengel M., Rose M., Stengel A.;
RT "Phoenixin-14 injected intracerebroventricularly but not intraperitoneally
RT stimulates food intake in rats.";
RL Peptides 96:53-60(2017).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=29364701; DOI=10.1152/ajpregu.00426.2017;
RA Gasparini S., Stein L.M., Loewen S.P., Haddock C.J., Soo J., Ferguson A.V.,
RA Kolar G.R., Yosten G.L.C., Samson W.K.;
RT "Novel regulator of vasopressin secretion: phoenixin.";
RL Am. J. Physiol. 314:R623-R628(2018).
RN [6] {ECO:0000305}
RP FUNCTION, 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 [7] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28965207; DOI=10.1007/s00018-017-2661-3;
RA Rocca C., Scavello F., Granieri M.C., Pasqua T., Amodio N., Imbrogno S.,
RA Gattuso A., Mazza R., Cerra M.C., Angelone T.;
RT "Phoenixin-14: detection and novel physiological implications in cardiac
RT modulation and cardioprotection.";
RL Cell. Mol. Life Sci. 75:743-756(2018).
RN [8] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=30930149; DOI=10.1016/j.brainres.2019.03.034;
RA Friedrich T., Schalla M.A., Scharner S., Kuehne S.G., Goebel-Stengel M.,
RA Kobelt P., Rose M., Stengel A.;
RT "Intracerebroventricular injection of phoenixin alters feeding behavior and
RT activates nesfatin-1 immunoreactive neurons in rats.";
RL Brain Res. 1715:188-195(2019).
RN [10] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=30609107; DOI=10.1111/1440-1681.13061;
RA Suszka-Switek A., Palasz A., Filipczyk L., Menezes I.C.,
RA Mordecka-Chamera K., Angelone T., Bogus K., Bacopoulou F.,
RA Worthington J.J., Wiaderkiewicz R.;
RT "The GnRH analogues affect novel neuropeptide SMIM20/phoenixin and GPR173
RT receptor expressions in the female rat hypothalamic-pituitary-gonadal (HPG)
RT axis.";
RL Clin. Exp. Pharmacol. Physiol. 46:350-359(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/Cox11 with Cox4I1 and Cox6c
CC (By similarity). Chaperone-like assembly factor required to stabilize
CC newly 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:27440717, PubMed:28844870,
CC PubMed:29364701, PubMed:28965207, PubMed:30609107). Is a ligand for
CC GPR173 (PubMed:27440717). As part of the reproductive cycle, it
CC regulates gonadotropin-releasing hormone (GnRH) signaling in the
CC hypothalamus and pituitary gland which augments the release of
CC luteinizing hormone (PubMed:22963497, PubMed:27440717). 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 (By
CC similarity). Plays a protective role in memory retention through
CC activation of GNRHR (By similarity). Regulates the secretion of AVP by
CC hypothalamic neurons (PubMed:29364701). Plays a role in the
CC transduction of the itch sensation (By similarity). Induces anxiolytic
CC effects, reducing behavior associated with anxiety (By similarity).
CC Regulates food intake as well as satiation and satiety by increasing
CC NUCB2 expression in neurons (PubMed:28844870, PubMed:30930149). In the
CC ovary, it regulates follicular growth by stimulating granulosa cell
CC proliferation by increasing the expression of GPR173, CREB1, CYP19A1,
CC KITLG, FSHR, and LHCGR (By similarity). It also increases the
CC production of estradiol (E2) (By similarity). In the heart, it
CC regulates contractility and relaxation by activating the AKT1-NOS3 and
CC MAPK1-MAPK3 signaling pathways (PubMed:28965207). It also plays a
CC cardioprotective role during ischemia, where it activates the SAFE and
CC RISK pathways (PubMed:28965207). 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 INS1 and INS2 through activation of the MAPK1-MAPK3
CC signaling pathways (PubMed:31422055). {ECO:0000250|UniProtKB:D3Z7Q2,
CC ECO:0000250|UniProtKB:Q8N5G0, ECO:0000269|PubMed:22963497,
CC ECO:0000269|PubMed:27440717, ECO:0000269|PubMed:28844870,
CC ECO:0000269|PubMed:28965207, ECO:0000269|PubMed:29364701,
CC ECO:0000269|PubMed:30251651, ECO:0000269|PubMed:30609107,
CC ECO:0000269|PubMed:30930149, ECO:0000269|PubMed:31422055}.
CC -!- FUNCTION: [Phoenixin-20]: Peptide involved in a broad spectrum of
CC regulatory functions (PubMed:27440717, PubMed:28844870,
CC PubMed:29364701, PubMed:28965207, PubMed:30609107). Is a ligand for
CC GPR173 (PubMed:27440717). As part of the reproductive cycle, it
CC regulates gonadotropin-releasing hormone (GnRH) signaling in the
CC hypothalamus and pituitary gland which augments the release of
CC luteinizing hormone (PubMed:22963497, PubMed:27440717). 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 (By
CC similarity). Plays a protective role in memory retention through
CC activation of GNRHR (By similarity). Regulates the secretion of AVP by
CC hypothalamic neurons (PubMed:29364701). Plays a role in the
CC transduction of the itch sensation (By similarity). Induces anxiolytic
CC effects, reducing behavior associated with anxiety (By similarity).
CC Regulates food intake as well as satiation and satiety by increasing
CC NUCB2 expression in neurons (PubMed:28844870, PubMed:30930149). In the
CC ovary, it regulates follicular growth by stimulating granulosa cell
CC proliferation by increasing the expression of GPR173, CREB1, CYP19A1,
CC KITLG, FSHR, and LHCGR (By similarity). It also increases the
CC production of estradiol (E2) (By similarity). In the heart, it
CC regulates contractility and relaxation by activating the AKT1-NOS3 and
CC MAPK1-MAPK3 signaling pathways (PubMed:28965207). It also plays a
CC cardioprotective role during ischemia, where it activates the SAFE and
CC RISK pathways (PubMed:28965207). 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 INS1 and INS2 through activation of the MAPK1-MAPK3
CC signaling pathways (PubMed:31422055). {ECO:0000250|UniProtKB:D3Z7Q2,
CC ECO:0000250|UniProtKB:Q8N5G0, ECO:0000269|PubMed:22963497,
CC ECO:0000269|PubMed:27440717, ECO:0000269|PubMed:28844870,
CC ECO:0000269|PubMed:28965207, ECO:0000269|PubMed:29364701,
CC ECO:0000269|PubMed:30251651, ECO:0000269|PubMed:30609107,
CC ECO:0000269|PubMed:30930149, 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:22963497, ECO:0000269|PubMed:30251651,
CC ECO:0000269|PubMed:30609107, ECO:0000269|PubMed:31422055}.
CC -!- SUBCELLULAR LOCATION: [Phoenixin-20]: Secreted
CC {ECO:0000269|PubMed:22963497, ECO:0000269|PubMed:30251651,
CC ECO:0000269|PubMed:30609107, ECO:0000269|PubMed:31422055}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the hypothalamus, substantia
CC nigra reticulata, Edinger-Westphal nucleus, and nucleus of the solitary
CC tract/dorsal motor nucleus of the vagus, the spinal cord, and sensory
CC ganglia (at protein level) (PubMed:22963497, PubMed:23912037). Also
CC expressed in the heart, thymus, esophagus, stomach, spleen, lung,
CC pituitary gland, kidney, jejunum, duodenum, ileum, cerebrum, pons, and
CC colon (at protein level) (PubMed:22963497, PubMed:23912037,
CC PubMed:28965207). Expressed in preadipocytes and apidocytes (at protein
CC level) (PubMed:30251651). Expressed in pancreatic islet cells (at
CC protein level) (PubMed:31422055). {ECO:0000269|PubMed:22963497,
CC ECO:0000269|PubMed:23912037, ECO:0000269|PubMed:28965207,
CC ECO:0000269|PubMed:30251651, ECO:0000269|PubMed:31422055}.
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DR RefSeq; NP_001128111.2; NM_001134639.2.
DR AlphaFoldDB; C0HLM6; -.
DR GeneID; 501923; -.
DR KEGG; rno:501923; -.
DR CTD; 389203; -.
DR RGD; 1565192; Smim20.
DR PRO; PR:C0HLM6; -.
DR Proteomes; UP000002494; Unplaced.
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:RGD.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; ISO:RGD.
DR InterPro; IPR027917; SMIM20.
DR PANTHER; PTHR34923; PTHR34923; 1.
DR Pfam; PF15061; DUF4538; 1.
PE 1: Evidence at protein level;
KW Amidation; Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Secreted;
KW Transit peptide; Transmembrane; Transmembrane helix.
FT CHAIN 1..69
FT /note="Small integral membrane protein 20"
FT /evidence="ECO:0000255"
FT /id="PRO_0000449033"
FT PEPTIDE 47..66
FT /note="Phoenixin-20"
FT /evidence="ECO:0000269|PubMed:22963497"
FT /id="PRO_0000449034"
FT PEPTIDE 53..66
FT /note="Phoenixin-14"
FT /id="PRO_0000449035"
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:0000269|PubMed:22963497"
SQ SEQUENCE 69 AA; 7800 MW; 3472CABBEEABC740 CRC64;
MAAARNLRTA LIFGGFISMV GAAFYPIYFR PLLRLEEYQK EQAVNRAGIV QEDVQPPGLK
VWSDPFGRK
