ID   PKHUO_HUMAN             Reviewed;          26 AA.
AC   C0HM02;
DT   25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT   25-MAY-2022, sequence version 1.
DT   03-AUG-2022, entry version 2.
DE   RecName: Full=PRKCH upstream open reading frame 2 {ECO:0000305};
DE            Short=uORF2 {ECO:0000303|PubMed:19797084};
DE   AltName: Full=Protein uPEP2 {ECO:0000303|PubMed:34593629};
GN   Name=PRKCH {ECO:0000312|HGNC:HGNC:9403};
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=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [2] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=19797084; DOI=10.1128/mcb.01044-09;
RA   Raveh-Amit H., Maissel A., Poller J., Marom L., Elroy-Stein O., Shapira M.,
RA   Livneh E.;
RT   "Translational control of protein kinase Ceta by two upstream open reading
RT   frames.";
RL   Mol. Cell. Biol. 29:6140-6148(2009).
RN   [3] {ECO:0000305}
RP   FUNCTION, INTERACTION WITH PROTEIN KINASE C ETA; PRKCD; PRKCQ AND PRKCE,
RP   AND MUTAGENESIS OF ALA-6.
RX   PubMed=34593629; DOI=10.1073/pnas.2018899118;
RA   Jayaram D.R., Frost S., Argov C., Liju V.B., Anto N.P., Muraleedharan A.,
RA   Ben-Ari A., Sinay R., Smoly I., Novoplansky O., Isakov N., Toiber D.,
RA   Keasar C., Elkabets M., Yeger-Lotem E., Livneh E.;
RT   "Unraveling the hidden role of a uORF-encoded peptide as a kinase inhibitor
RT   of PKCs.";
RL   Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
CC   -!- FUNCTION: Product of an upstream open reading frame (ORF) of PRKCH
CC       which regulates translation of the downstream protein kinase C eta
CC       (PKC-eta) ORF (PubMed:19797084, PubMed:34593629). Functions as a
CC       repressive element that maintains low basal levels of PKC-eta in
CC       growing cells but enhances its expression during stress conditions
CC       induced by amino acid starvation in a EIF2AK4/GCN2-dependent manner
CC       (PubMed:19797084, PubMed:34593629). In addition to its role in
CC       regulating PKC-eta translation, also inhibits the kinase activity of
CC       PKC-eta as well as other protein kinases including PRKCD, PRKCQ and
CC       PRKCE but not PRKCA, PRKCG or PRKCZ (PubMed:34593629).
CC       {ECO:0000269|PubMed:19797084, ECO:0000269|PubMed:34593629}.
CC   -!- SUBUNIT: Interacts with protein kinase C eta as well as other protein
CC       kinases including PRKCD, PRKCQ and PRKCE but not with PRKCG or PRKCZ;
CC       the interactions lead to inhibition of kinase activity.
CC       {ECO:0000269|PubMed:34593629}.
CC   -!- MISCELLANEOUS: Suppresses proliferation and migration of cancer cells.
CC       {ECO:0000269|PubMed:34593629}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AL138996; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   HGNC; HGNC:9403; PRKCH.
DR   Proteomes; UP000005640; Unplaced.
DR   GO; GO:0120283; F:protein serine/threonine kinase binding; IPI:UniProtKB.
DR   GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IDA:UniProtKB.
DR   GO; GO:0045182; F:translation regulator activity; IDA:UniProtKB.
DR   GO; GO:0034198; P:cellular response to amino acid starvation; IDA:UniProtKB.
DR   GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR   GO; GO:0032056; P:positive regulation of translation in response to stress; IDA:UniProtKB.
PE   1: Evidence at protein level;
KW   Protein kinase inhibitor; Reference proteome; Stress response;
KW   Translation regulation.
FT   CHAIN           1..26
FT                   /note="PRKCH upstream open reading frame 2"
FT                   /id="PRO_0000455275"
FT   MUTAGEN         6
FT                   /note="A->S,T: Abolishes kinase inhibitor activity and
FT                   converts peptide to a substrate for PRKCH and PRKCE but not
FT                   for PRKCA."
FT                   /evidence="ECO:0000269|PubMed:34593629"
SQ   SEQUENCE   26 AA;  2802 MW;  A34B57F5C35DB382 CRC64;
     MASRGALRRC LSPGLPRLLH LSRGLA