SIM20_HUMAN
ID SIM20_HUMAN Reviewed; 67 AA.
AC Q8N5G0; C9JYT8; Q9BRT5;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 3.
DT 03-AUG-2022, entry version 109.
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:0000303|PubMed:26321642};
DE Short=MITRAC7 {ECO:0000303|PubMed:26321642};
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; Synonyms=C4orf52, MITRAC7 {ECO:0000303|PubMed:26321642};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle, and Testis;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP FUNCTION, INTERACTION WITH COA3; COX4I1 AND MT-CO1, SUBCELLULAR LOCATION,
RP AND TOPOLOGY.
RX PubMed=26321642; DOI=10.1016/j.celrep.2015.08.009;
RA Dennerlein S., Oeljeklaus S., Jans D., Hellwig C., Bareth B., Jakobs S.,
RA Deckers M., Warscheid B., Rehling P.;
RT "MITRAC7 acts as a COX1-specific chaperone and reveals a checkpoint during
RT cytochrome c oxidase assembly.";
RL Cell Rep. 12:1644-1655(2015).
RN [6]
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 (PubMed:26321642). Promotes the progression of complex
CC assembly after the association of MT-CO1/COX1 with COX4I1 and COX6C
CC (PubMed:26321642). Chaperone-like assembly factor required to stabilize
CC newly synthesized MT-CO1/COX1 and to prevent its premature turnover
CC (PubMed:26321642). {ECO:0000269|PubMed:26321642}.
CC -!- FUNCTION: [Phoenixin-14]: Peptide involved in a broad spectrum of
CC regulatory functions (By similarity). Is a ligand for GPR173 (By
CC similarity). As part of the reproductive cycle, it regulates
CC gonadotropin-releasing hormone (GnRH) signaling in the hypothalamus and
CC pituitary gland which augments the release of luteinizing hormone (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 (By similarity). Plays a role in the transduction
CC of the itch sensation (By similarity). Induces anxiolytic effects,
CC reducing behavior associated with anxiety (By similarity). Regulates
CC food intake as well as satiation and satiety (By similarity). 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 (PubMed:30933929). It also increases the
CC production of estradiol (E2) (PubMed:30933929). In the heart, it
CC regulates contractility and relaxation (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 (By similarity). In pancreatic islet
CC cells, it induces proliferation of islet cells as well as the
CC production of INS (By similarity). {ECO:0000250|UniProtKB:C0HLM6,
CC ECO:0000250|UniProtKB:D3Z7Q2, ECO:0000269|PubMed:30933929}.
CC -!- FUNCTION: [Phoenixin-20]: Peptide involved in a broad spectrum of
CC regulatory functions (By similarity). Is a ligand for GPR173 (By
CC similarity). As part of the reproductive cycle, it regulates
CC gonadotropin-releasing hormone (GnRH) signaling in the hypothalamus and
CC pituitary gland which augments the release of luteinizing hormone (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 (By similarity). Plays a role in the transduction
CC of the itch sensation (By similarity). Induces anxiolytic effects,
CC reducing behavior associated with anxiety (By similarity). Regulates
CC food intake as well as satiation and satiety (By similarity). 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 (PubMed:30933929). It also increases the
CC production of estradiol (E2) (PubMed:30933929). In the heart, it
CC regulates contractility and relaxation (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 (By similarity). In pancreatic islet
CC cells, it induces proliferation of islet cells as well as the
CC production of INS (By similarity). {ECO:0000250|UniProtKB:C0HLM6,
CC ECO:0000250|UniProtKB:D3Z7Q2, ECO:0000269|PubMed:30933929}.
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
CC (PubMed:26321642). Interacts with COA3/MITRAC12 and COX4I1
CC (PubMed:26321642). Directly interacts with newly synthesized MT-
CC CO1/COX1 (PubMed:26321642). {ECO:0000269|PubMed:26321642}.
CC -!- SUBCELLULAR LOCATION: [Small integral membrane protein 20]:
CC Mitochondrion inner membrane {ECO:0000269|PubMed:26321642}; Single-pass
CC membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Phoenixin-14]: Secreted
CC {ECO:0000250|UniProtKB:C0HLM6}.
CC -!- SUBCELLULAR LOCATION: [Phoenixin-20]: Secreted
CC {ECO:0000250|UniProtKB:C0HLM6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N5G0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N5G0-2; Sequence=VSP_038831;
CC -!- TISSUE SPECIFICITY: Expressed in the ovary, specifically in granulosa
CC cells of follicles that have passed the primary stage and in oocytes
CC (at protein level). {ECO:0000269|PubMed:30933929}.
CC -!- MISCELLANEOUS: [Isoform 2]: Gene prediction. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH06003.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH32431.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC133961; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471069; EAW92845.1; -; Genomic_DNA.
DR EMBL; BC006003; AAH06003.1; ALT_INIT; mRNA.
DR EMBL; BC032431; AAH32431.1; ALT_INIT; mRNA.
DR CCDS; CCDS47038.1; -. [Q8N5G0-1]
DR RefSeq; NP_001138904.1; NM_001145432.1. [Q8N5G0-1]
DR AlphaFoldDB; Q8N5G0; -.
DR SMR; Q8N5G0; -.
DR BioGRID; 133034; 10.
DR CORUM; Q8N5G0; -.
DR IntAct; Q8N5G0; 6.
DR MINT; Q8N5G0; -.
DR STRING; 9606.ENSP00000427407; -.
DR iPTMnet; Q8N5G0; -.
DR PhosphoSitePlus; Q8N5G0; -.
DR BioMuta; SMIM20; -.
DR DMDM; 172046141; -.
DR EPD; Q8N5G0; -.
DR jPOST; Q8N5G0; -.
DR MassIVE; Q8N5G0; -.
DR MaxQB; Q8N5G0; -.
DR PaxDb; Q8N5G0; -.
DR PeptideAtlas; Q8N5G0; -.
DR PRIDE; Q8N5G0; -.
DR ProteomicsDB; 72047; -. [Q8N5G0-1]
DR ProteomicsDB; 72048; -. [Q8N5G0-2]
DR TopDownProteomics; Q8N5G0-1; -. [Q8N5G0-1]
DR TopDownProteomics; Q8N5G0-2; -. [Q8N5G0-2]
DR Antibodypedia; 52038; 11 antibodies from 6 providers.
DR DNASU; 389203; -.
DR Ensembl; ENST00000506197.3; ENSP00000427407.2; ENSG00000250317.9. [Q8N5G0-1]
DR GeneID; 389203; -.
DR KEGG; hsa:389203; -.
DR MANE-Select; ENST00000506197.3; ENSP00000427407.2; NM_001145432.3; NP_001138904.1.
DR UCSC; uc003grw.5; human. [Q8N5G0-1]
DR CTD; 389203; -.
DR DisGeNET; 389203; -.
DR GeneCards; SMIM20; -.
DR HGNC; HGNC:37260; SMIM20.
DR HPA; ENSG00000250317; Low tissue specificity.
DR MIM; 617465; gene.
DR neXtProt; NX_Q8N5G0; -.
DR OpenTargets; ENSG00000250317; -.
DR PharmGKB; PA165663312; -.
DR VEuPathDB; HostDB:ENSG00000250317; -.
DR eggNOG; ENOG502S83Z; Eukaryota.
DR GeneTree; ENSGT00390000002398; -.
DR HOGENOM; CLU_1598242_0_0_1; -.
DR InParanoid; Q8N5G0; -.
DR OrthoDB; 1639960at2759; -.
DR PhylomeDB; Q8N5G0; -.
DR TreeFam; TF353700; -.
DR PathwayCommons; Q8N5G0; -.
DR SignaLink; Q8N5G0; -.
DR BioGRID-ORCS; 389203; 13 hits in 1072 CRISPR screens.
DR ChiTaRS; SMIM20; human.
DR GenomeRNAi; 389203; -.
DR Pharos; Q8N5G0; Tbio.
DR PRO; PR:Q8N5G0; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8N5G0; protein.
DR Bgee; ENSG00000250317; Expressed in ileal mucosa and 175 other tissues.
DR ExpressionAtlas; Q8N5G0; baseline and differential.
DR Genevisible; Q8N5G0; HS.
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; IDA:UniProtKB.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; IDA:UniProtKB.
DR InterPro; IPR027917; SMIM20.
DR PANTHER; PTHR34923; PTHR34923; 1.
DR Pfam; PF15061; DUF4538; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Amidation; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Secreted; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..67
FT /note="Small integral membrane protein 20"
FT /id="PRO_0000326049"
FT PEPTIDE 45..64
FT /note="Phoenixin-20"
FT /id="PRO_0000449025"
FT PEPTIDE 51..64
FT /note="Phoenixin-14"
FT /id="PRO_0000449026"
FT TOPO_DOM 1..6
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:26321642"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..67
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:26321642"
FT MOD_RES 64
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000250|UniProtKB:C0HLM6"
FT VAR_SEQ 1
FT /note="M -> MVKEVWRVLREEPGRRKESRQNRARGNRVQQNSSNLNPTPAPGPHST
FT ESRGRRRAGSEAPPRPGSESLSTSSERGHGPAVGNLVSESAGRSAGQGSPGPDAM (in
FT isoform 2)"
FT /id="VSP_038831"
FT VARIANT 8
FT /note="A -> T (in dbSNP:rs4521339)"
FT /id="VAR_039968"
FT VARIANT Q8N5G0-2:41
FT /note="A -> T (in dbSNP:rs2305669)"
FT /evidence="ECO:0000305"
FT /id="VAR_082869"
FT VARIANT Q8N5G0-2:65
FT /note="S -> N (in dbSNP:rs6448414)"
FT /evidence="ECO:0000305"
FT /id="VAR_082870"
FT VARIANT Q8N5G0-2:76
FT /note="H -> N (in dbSNP:rs2305670)"
FT /evidence="ECO:0000305"
FT /id="VAR_082871"
SQ SEQUENCE 67 AA; 7702 MW; FCBA42B976E900AA CRC64;
MSRNLRTALI FGGFISLIGA AFYPIYFRPL MRLEEYKKEQ AINRAGIVQE DVQPPGLKVW
SDPFGRK
