MIPEP_HUMAN
ID MIPEP_HUMAN Reviewed; 713 AA.
AC Q99797; Q5JV15; Q5T9Q9; Q96G65;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Mitochondrial intermediate peptidase;
DE Short=MIP;
DE EC=3.4.24.59;
DE Flags: Precursor;
GN Name=MIPEP; Synonyms=MIP;
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], AND VARIANT GLY-488.
RC TISSUE=Liver;
RX PubMed=9073519; DOI=10.1006/geno.1996.4586;
RA Chew A., Buck E.A., Peretz S., Sirugo G., Rinaldo P., Isaya G.;
RT "Cloning, expression, and chromosomal assignment of the human mitochondrial
RT intermediate peptidase gene (MIPEP).";
RL Genomics 40:493-496(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-488.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-488.
RC TISSUE=Uterus;
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 [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-126, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [6]
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 [7]
RP INVOLVEMENT IN COXPD31, AND VARIANTS COXPD31 GLN-71; PHE-306; GLU-343;
RP ASP-512 AND ARG-582.
RX PubMed=27799064; DOI=10.1186/s13073-016-0360-6;
RA Eldomery M.K., Akdemir Z.C., Voegtle F.N., Charng W.L., Mulica P.,
RA Rosenfeld J.A., Gambin T., Gu S., Burrage L.C., Al Shamsi A., Penney S.,
RA Jhangiani S.N., Zimmerman H.H., Muzny D.M., Wang X., Tang J., Medikonda R.,
RA Ramachandran P.V., Wong L.J., Boerwinkle E., Gibbs R.A., Eng C.M.,
RA Lalani S.R., Hertecant J., Rodenburg R.J., Abdul-Rahman O.A., Yang Y.,
RA Xia F., Wang M.C., Lupski J.R., Meisinger C., Sutton V.R.;
RT "MIPEP recessive variants cause a syndrome of left ventricular non-
RT compaction, hypotonia, and infantile death.";
RL Genome Med. 8:106-106(2016).
CC -!- FUNCTION: Cleaves proteins, imported into the mitochondrion, to their
CC mature size.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal octapeptide as second stage of
CC processing of some proteins imported into the mitochondrion.;
CC EC=3.4.24.59;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Activity is divalent cation-dependent. It is
CC stimulated by manganese, magnesium or calcium ions and reversibly
CC inhibited by zinc, cobalt and iron (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 31 (COXPD31)
CC [MIM:617228]: An autosomal recessive, severe mitochondrial disease with
CC multisystemic manifestations appearing soon after birth or in early
CC infancy. Clinical features include left ventricular non-compaction,
CC global developmental delay, severe hypotonia, seizures, cataract, and
CC abnormal movements. Death may occur in early childhood.
CC {ECO:0000269|PubMed:27799064}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase M3 family. {ECO:0000305}.
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DR EMBL; U80034; AAC51231.1; -; mRNA.
DR EMBL; AK291923; BAF84612.1; -; mRNA.
DR EMBL; AL157368; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139080; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445985; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009934; AAH09934.1; -; mRNA.
DR CCDS; CCDS9303.1; -.
DR RefSeq; NP_005923.2; NM_005932.3.
DR AlphaFoldDB; Q99797; -.
DR SMR; Q99797; -.
DR BioGRID; 110431; 85.
DR IntAct; Q99797; 32.
DR MINT; Q99797; -.
DR STRING; 9606.ENSP00000371607; -.
DR MEROPS; M03.006; -.
DR iPTMnet; Q99797; -.
DR MetOSite; Q99797; -.
DR PhosphoSitePlus; Q99797; -.
DR BioMuta; MIPEP; -.
DR DMDM; 182639267; -.
DR EPD; Q99797; -.
DR jPOST; Q99797; -.
DR MassIVE; Q99797; -.
DR MaxQB; Q99797; -.
DR PaxDb; Q99797; -.
DR PeptideAtlas; Q99797; -.
DR PRIDE; Q99797; -.
DR ProteomicsDB; 78477; -.
DR Antibodypedia; 22428; 400 antibodies from 28 providers.
DR DNASU; 4285; -.
DR Ensembl; ENST00000382172.4; ENSP00000371607.3; ENSG00000027001.10.
DR GeneID; 4285; -.
DR KEGG; hsa:4285; -.
DR MANE-Select; ENST00000382172.4; ENSP00000371607.3; NM_005932.4; NP_005923.3.
DR UCSC; uc001uox.5; human.
DR CTD; 4285; -.
DR DisGeNET; 4285; -.
DR GeneCards; MIPEP; -.
DR HGNC; HGNC:7104; MIPEP.
DR HPA; ENSG00000027001; Low tissue specificity.
DR MalaCards; MIPEP; -.
DR MIM; 602241; gene.
DR MIM; 617228; phenotype.
DR neXtProt; NX_Q99797; -.
DR OpenTargets; ENSG00000027001; -.
DR Orphanet; 478049; Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome.
DR PharmGKB; PA30822; -.
DR VEuPathDB; HostDB:ENSG00000027001; -.
DR eggNOG; KOG2090; Eukaryota.
DR GeneTree; ENSGT00950000183171; -.
DR HOGENOM; CLU_001805_0_2_1; -.
DR InParanoid; Q99797; -.
DR OMA; VVYCDLF; -.
DR OrthoDB; 642479at2759; -.
DR PhylomeDB; Q99797; -.
DR TreeFam; TF105715; -.
DR PathwayCommons; Q99797; -.
DR SignaLink; Q99797; -.
DR BioGRID-ORCS; 4285; 248 hits in 1079 CRISPR screens.
DR ChiTaRS; MIPEP; human.
DR GenomeRNAi; 4285; -.
DR Pharos; Q99797; Tbio.
DR PRO; PR:Q99797; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q99797; protein.
DR Bgee; ENSG00000027001; Expressed in right atrium auricular region and 160 other tissues.
DR Genevisible; Q99797; HS.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0006518; P:peptide metabolic process; IBA:GO_Central.
DR GO; GO:0006627; P:protein processing involved in protein targeting to mitochondrion; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR Gene3D; 1.10.1370.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR024077; Neurolysin/TOP_dom2.
DR InterPro; IPR045090; Pept_M3A_M3B.
DR InterPro; IPR001567; Pept_M3A_M3B_dom.
DR PANTHER; PTHR11804; PTHR11804; 2.
DR Pfam; PF01432; Peptidase_M3; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Calcium; Cobalt; Disease variant; Hydrolase; Iron; Magnesium;
KW Manganese; Metal-binding; Metalloprotease; Mitochondrion;
KW Primary mitochondrial disease; Protease; Reference proteome;
KW Transit peptide; Zinc.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT CHAIN 36..713
FT /note="Mitochondrial intermediate peptidase"
FT /id="PRO_0000028579"
FT ACT_SITE 496
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 495
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 499
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 502
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT MOD_RES 126
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VARIANT 71
FT /note="L -> Q (in COXPD31; dbSNP:rs1057518740)"
FT /evidence="ECO:0000269|PubMed:27799064"
FT /id="VAR_078009"
FT VARIANT 137
FT /note="A -> V (in dbSNP:rs2312296)"
FT /id="VAR_038934"
FT VARIANT 306
FT /note="L -> F (in COXPD31; dbSNP:rs143912947)"
FT /evidence="ECO:0000269|PubMed:27799064"
FT /id="VAR_078010"
FT VARIANT 340
FT /note="R -> Q (in dbSNP:rs11551114)"
FT /id="VAR_038935"
FT VARIANT 343
FT /note="K -> E (in COXPD31; dbSNP:rs1057518741)"
FT /evidence="ECO:0000269|PubMed:27799064"
FT /id="VAR_078011"
FT VARIANT 453
FT /note="R -> H (in dbSNP:rs12858248)"
FT /id="VAR_038936"
FT VARIANT 488
FT /note="S -> G (in dbSNP:rs7333040)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9073519"
FT /id="VAR_038937"
FT VARIANT 512
FT /note="H -> D (in COXPD31; unknown pathological
FT significance; dbSNP:rs779598020)"
FT /evidence="ECO:0000269|PubMed:27799064"
FT /id="VAR_078012"
FT VARIANT 582
FT /note="L -> R (in COXPD31; unknown pathological
FT significance; dbSNP:rs1057518739)"
FT /evidence="ECO:0000269|PubMed:27799064"
FT /id="VAR_078013"
FT CONFLICT 63..64
FT /note="RG -> AR (in Ref. 1; AAC51231)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="E -> Q (in Ref. 1; AAC51231)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="P -> A (in Ref. 1; AAC51231)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="V -> L (in Ref. 1; AAC51231)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 713 AA; 80641 MW; 9DBB26B74355B9C1 CRC64;
MLCVGRLGGL GARAAALPPR RAGRGSLEAG IRARRVSTSW SPVGAAFNVK PQGSRLDLFG
ERRGLFGVPE LSAPEGFHIA QEKALRKTEL LVDRACSTPP GPQTVLIFDE LSDSLCRVAD
LADFVKIAHP EPAFREAAEE ACRSIGTMVE KLNTNVDLYQ SLQKLLADKK LVDSLDPETR
RVAELFMFDF EISGIHLDKE KRKRAVDLNV KILDLSSTFL MGTNFPNKIE KHLLPEHIRR
NFTSAGDHII IDGLHAESPD DLVREAAYKI FLYPNAGQLK CLEELLSSRD LLAKLVGYST
FSHRALQGTI AKNPETVMQF LEKLSDKLSE RTLKDFEMIR GMKMKLNPQN SEVMPWDPPY
YSGVIRAERY NIEPSLYCPF FSLGACMEGL NILLNRLLGI SLYAEQPAKG EVWSEDVRKL
AVVHESEGLL GYIYCDFFQR ADKPHQDCHF TIRGGRLKED GDYQLPVVVL MLNLPRSSRS
SPTLLTPSMM ENLFHEMGHA MHSMLGRTRY QHVTGTRCPT DFAEVPSILM EYFANDYRVV
NQFARHYQTG QPLPKNMVSR LCESKKVCAA ADMQLQVFYA TLDQIYHGKH PLRNSTTDIL
KETQEKFYGL PYVPNTAWQL RFSHLVGYGA RYYSYLMSRA VASMVWKECF LQDPFNRAAG
ERYRREMLAH GGGREPMLMV EGMLQKCPSV DDFVSALVSD LDLDFETFLM DSE
