ID   MP31_HUMAN              Reviewed;          31 AA.
AC   C0HLV8;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   02-JUN-2021, sequence version 1.
DT   03-AUG-2022, entry version 4.
DE   RecName: Full=PTEN upstream open reading frame MP31 {ECO:0000305};
DE   AltName: Full=Micropeptide 31 {ECO:0000303|PubMed:33406399};
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] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [2] {ECO:0000305}
RP   PROTEIN SEQUENCE OF 4-19, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION,
RP   INTERACTION WITH LDHA AND LDHB, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   PHARMACEUTICAL, AND MUTAGENESIS OF SER-5 AND TYR-12.
RX   PubMed=33406399; DOI=10.1016/j.cmet.2020.12.008;
RA   Huang N., Li F., Zhang M., Zhou H., Chen Z., Ma X., Yang L., Wu X.,
RA   Zhong J., Xiao F., Yang X., Zhao K., Li X., Xia X., Liu Z., Gao S.,
RA   Zhang N.;
RT   "An Upstream Open Reading Frame in Phosphatase and Tensin Homolog Encodes a
RT   Circuit Breaker of Lactate Metabolism.";
RL   Cell Metab. 33:128-144(2021).
RN   [3] {ECO:0000305}
RP   ERRATUM OF PUBMED:33406399.
RX   PubMed=33535099; DOI=10.1016/j.cmet.2021.01.008;
RA   Huang N., Li F., Zhang M., Zhou H., Chen Z., Ma X., Yang L., Wu X.,
RA   Zhong J., Xiao F., Yang X., Zhao K., Li X., Xia X., Liu Z., Gao S.,
RA   Zhang N.;
RL   Cell Metab. 33:454-454(2021).
CC   -!- FUNCTION: Inhibits lactate dehydrogenase (LDH)-mediated conversion of
CC       lactate to pyruvate in mitochondria by competing with mitochondrial LDH
CC       for binding to NAD(+) (PubMed:33406399). Also inhibits cellular lactate
CC       utilization (PubMed:33406399). {ECO:0000269|PubMed:33406399}.
CC   -!- SUBUNIT: Interacts with lactate dehydrogenases LDHA and LDHB;
CC       interaction with mitochondrial LDH leads to inhibition of lactate
CC       dehydrogenase activity, preventing conversion of lactate to pyruvate.
CC       {ECO:0000269|PubMed:33406399}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:33406399}.
CC   -!- TISSUE SPECIFICITY: Expressed in brain (at protein level)
CC       (PubMed:33406399). Expressed at lower levels in glioblastomas than in
CC       normal brain tissue (at protein level) (PubMed:33406399).
CC       {ECO:0000269|PubMed:33406399}.
CC   -!- PHARMACEUTICAL: Recombinant MP31 administered intraperitoneally
CC       penetrates the blood-brain barrier and inhibits mice glioblastoma
CC       xenografts without neurological toxicity, suggesting a potential role
CC       in gliobastoma treatment. {ECO:0000269|PubMed:33406399}.
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DR   EMBL; AC022016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; C0HLV8; -.
DR   neXtProt; NX_C0HLV8; -.
DR   Proteomes; UP000005640; Unplaced.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0019516; P:lactate oxidation; IMP:UniProtKB.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Mitochondrion; Pharmaceutical;
KW   Reference proteome.
FT   CHAIN           1..31
FT                   /note="PTEN upstream open reading frame MP31"
FT                   /id="PRO_0000453000"
FT   MUTAGEN         5
FT                   /note="S->A: Abolishes interaction with LDHA and LDHB."
FT                   /evidence="ECO:0000269|PubMed:33406399"
FT   MUTAGEN         12
FT                   /note="Y->A: Abolishes interaction with LDHA and LDHB."
FT                   /evidence="ECO:0000269|PubMed:33406399"
SQ   SEQUENCE   31 AA;  3336 MW;  E6B0E33D07E7988F CRC64;
     MWRDSLCAAA GYALGAGTRL RSVLSSRKLQ P