ID   PRR14_HUMAN             Reviewed;         585 AA.
AC   Q9BWN1; Q8WTX2;
DT   23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   24-JAN-2024, entry version 139.
DE   RecName: Full=Proline-rich protein 14;
GN   Name=PRR14;
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 MRNA].
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   [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], AND VARIANT LEU-359.
RC   TISSUE=Eye, and Pancreas;
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   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 54-VAL-VAL-55.
RX   PubMed=24209742; DOI=10.1016/j.celrep.2013.09.024;
RA   Poleshko A., Mansfield K.M., Burlingame C.C., Andrake M.D., Shah N.R.,
RA   Katz R.A.;
RT   "The human protein PRR14 tethers heterochromatin to the nuclear lamina
RT   during interphase and mitotic exit.";
RL   Cell Rep. 5:292-301(2013).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CBX5, AND MUTAGENESIS OF
RP   54-VAL-VAL-55.
RX   PubMed=25906157; DOI=10.1038/cddis.2015.103;
RA   Yang M., Yuan Z.M.;
RT   "A novel role of PRR14 in the regulation of skeletal myogenesis.";
RL   Cell Death Dis. 6:E1734-E1734(2015).
RN   [9]
RP   FUNCTION, INTERACTION WITH GRB2, AND MUTAGENESIS OF SER-101 AND GLU-566.
RX   PubMed=27041574; DOI=10.1038/onc.2016.93;
RA   Yang M., Lewinska M., Fan X., Zhu J., Yuan Z.M.;
RT   "PRR14 is a novel activator of the PI3K pathway promoting lung
RT   carcinogenesis.";
RL   Oncogene 35:5527-5538(2016).
CC   -!- FUNCTION: Functions in tethering peripheral heterochromatin to the
CC       nuclear lamina during interphase, possibly through the interaction with
CC       heterochromatin protein CBX5/HP1 alpha (PubMed:24209742). Might play a
CC       role in reattaching heterochromatin to the nuclear lamina at mitotic
CC       exit (PubMed:24209742). Promotes myoblast differentiation during
CC       skeletal myogenesis, possibly by stimulating transcription factor MyoD
CC       activity via binding to CBX5/HP1 alpha (PubMed:25906157). Involved in
CC       the positive regulation of the PI3K-Akt-mTOR signaling pathway and in
CC       promoting cell proliferation, possibly via binding to GRB2
CC       (PubMed:27041574). {ECO:0000269|PubMed:24209742,
CC       ECO:0000269|PubMed:25906157, ECO:0000269|PubMed:27041574}.
CC   -!- SUBUNIT: Interacts (via proline-rich region) with GRB2 (via SH3 domain
CC       2) (PubMed:27041574). Interacts (via N-terminus) with CBX5
CC       (PubMed:25906157). {ECO:0000269|PubMed:25906157,
CC       ECO:0000269|PubMed:27041574}.
CC   -!- INTERACTION:
CC       Q9BWN1; Q13185: CBX3; NbExp=6; IntAct=EBI-748167, EBI-78176;
CC       Q9BWN1; P45973: CBX5; NbExp=10; IntAct=EBI-748167, EBI-78219;
CC   -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:24209742}. Nucleus
CC       {ECO:0000269|PubMed:25906157}. Nucleus lamina
CC       {ECO:0000269|PubMed:24209742}. Nucleus, nucleoplasm
CC       {ECO:0000269|PubMed:24209742}. Note=During interphase, associated with
CC       peripheral heterochromatin at the nuclear lamina. Released from the
CC       nuclear lamina in mitotic prophase and remains highly dispersed in
CC       metaphase. Associates with chromatin at the onset of anaphase and
CC       relocalizes to the nuclear lamina in telophase.
CC       {ECO:0000269|PubMed:24209742}.
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; AK074783; BAC11207.1; -; mRNA.
DR   EMBL; CH471192; EAW52222.1; -; Genomic_DNA.
DR   EMBL; BC000119; AAH00119.1; -; mRNA.
DR   EMBL; BC021934; AAH21934.1; -; mRNA.
DR   EMBL; BC050677; AAH50677.1; -; mRNA.
DR   CCDS; CCDS10687.1; -.
DR   RefSeq; NP_001307393.1; NM_001320464.1.
DR   RefSeq; NP_076936.1; NM_024031.3.
DR   AlphaFoldDB; Q9BWN1; -.
DR   BioGRID; 122465; 40.
DR   IntAct; Q9BWN1; 22.
DR   MINT; Q9BWN1; -.
DR   STRING; 9606.ENSP00000441641; -.
DR   GlyGen; Q9BWN1; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9BWN1; -.
DR   PhosphoSitePlus; Q9BWN1; -.
DR   BioMuta; PRR14; -.
DR   DMDM; 74733447; -.
DR   EPD; Q9BWN1; -.
DR   jPOST; Q9BWN1; -.
DR   MassIVE; Q9BWN1; -.
DR   MaxQB; Q9BWN1; -.
DR   PaxDb; 9606-ENSP00000441641; -.
DR   PeptideAtlas; Q9BWN1; -.
DR   ProteomicsDB; 79294; -.
DR   Pumba; Q9BWN1; -.
DR   Antibodypedia; 66800; 77 antibodies from 19 providers.
DR   DNASU; 78994; -.
DR   Ensembl; ENST00000300835.9; ENSP00000300835.4; ENSG00000156858.12.
DR   Ensembl; ENST00000542965.2; ENSP00000441641.2; ENSG00000156858.12.
DR   GeneID; 78994; -.
DR   KEGG; hsa:78994; -.
DR   MANE-Select; ENST00000300835.9; ENSP00000300835.4; NM_024031.5; NP_076936.1.
DR   UCSC; uc002dyy.4; human.
DR   AGR; HGNC:28458; -.
DR   CTD; 78994; -.
DR   DisGeNET; 78994; -.
DR   GeneCards; PRR14; -.
DR   HGNC; HGNC:28458; PRR14.
DR   HPA; ENSG00000156858; Low tissue specificity.
DR   MIM; 617423; gene.
DR   neXtProt; NX_Q9BWN1; -.
DR   OpenTargets; ENSG00000156858; -.
DR   PharmGKB; PA144596393; -.
DR   VEuPathDB; HostDB:ENSG00000156858; -.
DR   eggNOG; ENOG502RJ6E; Eukaryota.
DR   GeneTree; ENSGT00520000055626; -.
DR   HOGENOM; CLU_489653_0_0_1; -.
DR   InParanoid; Q9BWN1; -.
DR   OMA; MRIVHQP; -.
DR   OrthoDB; 4255167at2759; -.
DR   PhylomeDB; Q9BWN1; -.
DR   TreeFam; TF328446; -.
DR   PathwayCommons; Q9BWN1; -.
DR   SignaLink; Q9BWN1; -.
DR   BioGRID-ORCS; 78994; 12 hits in 1158 CRISPR screens.
DR   ChiTaRS; PRR14; human.
DR   GenomeRNAi; 78994; -.
DR   Pharos; Q9BWN1; Tbio.
DR   PRO; PR:Q9BWN1; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q9BWN1; Protein.
DR   Bgee; ENSG00000156858; Expressed in granulocyte and 197 other cell types or tissues.
DR   ExpressionAtlas; Q9BWN1; baseline and differential.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005652; C:nuclear lamina; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR   InterPro; IPR026320; PRR14.
DR   InterPro; IPR028149; Tantalus-like.
DR   PANTHER; PTHR14522; EMO2-RELATED; 1.
DR   PANTHER; PTHR14522:SF2; PROLINE-RICH PROTEIN 14; 1.
DR   Pfam; PF15386; Tantalus; 1.
DR   Genevisible; Q9BWN1; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Chromosome; Myogenesis; Nucleus; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..585
FT                   /note="Proline-rich protein 14"
FT                   /id="PRO_0000307269"
FT   REGION          1..135
FT                   /note="Sufficient for heterochromatin association in
FT                   interphase and chromatin association in anaphase"
FT                   /evidence="ECO:0000269|PubMed:24209742"
FT   REGION          23..46
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          73..150
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          85..378
FT                   /note="Required for the interaction with GRB2 and
FT                   sufficient to promote the phosphorylation of AKT and cell
FT                   proliferation"
FT                   /evidence="ECO:0000269|PubMed:25906157,
FT                   ECO:0000269|PubMed:27041574"
FT   REGION          136..365
FT                   /note="Required for nuclear lamina association"
FT                   /evidence="ECO:0000269|PubMed:24209742"
FT   REGION          189..241
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          290..445
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          518..535
FT                   /note="Required for nuclear localization"
FT                   /evidence="ECO:0000269|PubMed:24209742"
FT   REGION          525..557
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        190..238
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        307..321
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        341..358
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        392..413
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        416..432
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   MOD_RES         277
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VARIANT         359
FT                   /note="P -> L (in dbSNP:rs3747481)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_035389"
FT   MUTAGEN         54..55
FT                   /note="VV->AA: Loss of heterochromatin association. Loss of
FT                   interaction with CBX5."
FT                   /evidence="ECO:0000269|PubMed:24209742,
FT                   ECO:0000269|PubMed:25906157"
FT   MUTAGEN         54..55
FT                   /note="VV->EE: Loss of heterochromatin association during
FT                   interphase and loss of chromatin association during
FT                   anaphase."
FT                   /evidence="ECO:0000269|PubMed:24209742"
FT   MUTAGEN         101
FT                   /note="S->C: Increased binding to GRB2 and enhanced cell
FT                   proliferation."
FT                   /evidence="ECO:0000269|PubMed:27041574"
FT   MUTAGEN         566
FT                   /note="E->K: Increased binding to GRB2 and enhanced cell
FT                   proliferation."
FT                   /evidence="ECO:0000269|PubMed:27041574"
SQ   SEQUENCE   585 AA;  64328 MW;  EE706853CE2D2742 CRC64;
     MDLPGDSSPP GQPRLCRQPL TRALWGARSP KRPRLQLPGA PSPLEKASRR VLAVVLEDVM
     AVHMVPVVPS KQTSIPQHHS YHQDPVHRQP PASPPRQAGW SSQARPPDPL CLCREPLSRI
     HRTSSTLRRR SRTTPGPEEG PSQKVDRAPQ PTLVVMLEDI ASPRPPAEGF IDETPNFIIP
     AQRAEPMRIV RQPTPPPGDL EPPFQPSALP ADPLESPPTA PDPALELPST PPPSSLLRPR
     LSPWGLAPLF RSVRSKLESF ADIFLTPNKT PQPPPPSPPM KLELKIAISE AEQSGAAEGT
     ASVSPRPPIR QWRTQDHNTP ALLPKPSLGR SYSCPDLGPP GPGTCTWPPA PPQPSRPRPR
     RHTVGGGEMA RAPPPPRPCL RKEVFPLGGV GASPSLTTSC SSTASTSFSE PAEPRLGSTK
     GKEPRASKDQ VLSEPETKTM GKVSRFRIRR TPARPQLNLT PMGLPRPIRL NKKEFSLEEI
     YTNKNYQSPT TRRTFETIFE EPRERNGTLI FTSSRKLRRA VEFRDSSLPR SRRPSRGVRA
     AGGRTVPPNV APSPDVGPLL QQRLEELDAL LLEEETVDRE QPHWT
//