PRAP1_HUMAN
ID PRAP1_HUMAN Reviewed; 151 AA.
AC Q96NZ9; B7ZL57; B7ZL58; E9KL31; Q5VWY4; Q7Z4X5; Q8IWR3; Q8NCS2;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Proline-rich acidic protein 1;
DE AltName: Full=Epididymis tissue protein Li 178;
DE AltName: Full=Uterine-specific proline-rich acidic protein;
DE Flags: Precursor;
GN Name=PRAP1; Synonyms=UPA; ORFNames=UNQ608/PRO1195;
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] (ISOFORMS 1; 2 AND 4), FUNCTION, INDUCTION,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANTS GLY-54; ARG-69 AND
RP ARG-101.
RX PubMed=14583459;
RA Zhang J., Wong H., Ramanan S., Cheong D., Leong A., Hooi S.C.;
RT "The proline-rich acidic protein is epigenetically regulated and inhibits
RT growth of cancer cell lines.";
RL Cancer Res. 63:6658-6665(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-101, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Epididymis;
RX PubMed=20736409; DOI=10.1074/mcp.m110.001719;
RA Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W., Zhang C.,
RA Jin S., Liu J., Zhu P., Liu Y.;
RT "Systematic mapping and functional analysis of a family of human epididymal
RT secretory sperm-located proteins.";
RL Mol. Cell. Proteomics 9:2517-2528(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-101.
RA Zheng L.H., Yu L., Zhao S.Y.;
RT "A novel human cDNA homologous to Mus musculus uterine-specific proline-
RT rich acidic protein mRNA.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-101.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-101.
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 [6]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 4-151 (ISOFORM 3), AND VARIANT ARG-101.
RC TISSUE=Liver, 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 [8]
RP FUNCTION, AND INDUCTION.
RX PubMed=23235459; DOI=10.1038/cddis.2012.180;
RA Huang B.H., Zhuo J.L., Leung C.H., Lu G.D., Liu J.J., Yap C.T., Hooi S.C.;
RT "PRAP1 is a novel executor of p53-dependent mechanisms in cell survival
RT after DNA damage.";
RL Cell Death Dis. 3:e442-e442(2012).
RN [9]
RP FUNCTION, INTERACTION WITH MAD1L1, AND TISSUE SPECIFICITY.
RX PubMed=24374861; DOI=10.1002/path.4319;
RA Sze K.M., Chu G.K., Mak Q.H., Lee J.M., Ng I.O.;
RT "Proline-rich acidic protein 1 (PRAP1) is a novel interacting partner of
RT MAD1 and has a suppressive role in mitotic checkpoint signalling in
RT hepatocellular carcinoma.";
RL J. Pathol. 233:51-60(2014).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=32629119; DOI=10.1016/j.jcmgh.2020.06.011;
RA Wolfarth A.A., Liu X., Darby T.M., Boyer D.J., Spizman J.B., Owens J.A.,
RA Chandrasekharan B., Naudin C.R., Hanley K.Z., Robinson B.S., Ortlund E.A.,
RA Jones R.M., Neish A.S.;
RT "Proline-Rich Acidic Protein 1 (PRAP1) Protects the Gastrointestinal
RT Epithelium From Irradiation-Induced Apoptosis.";
RL Cell. Mol. Gastroenterol. Hepatol. 10:713-727(2020).
CC -!- FUNCTION: Lipid-binding protein which promotes lipid absorption by
CC facilitating MTTP-mediated lipid transfer (mainly triglycerides and
CC phospholipids) and MTTP-mediated apoB lipoprotein assembly and
CC secretion (By similarity). Protects the gastrointestinal epithelium
CC from irradiation-induced apoptosis (By similarity). May play an
CC important role in maintaining normal growth homeostasis in epithelial
CC cells (PubMed:14583459). Involved in p53/TP53-dependent cell survival
CC after DNA damage (PubMed:23235459). May down-regulate the expression of
CC MAD1L1 and exert a suppressive role in mitotic spindle assembly
CC checkpoint in hepatocellular carcinomas (PubMed:24374861).
CC {ECO:0000250|UniProtKB:Q80XD8, ECO:0000269|PubMed:14583459,
CC ECO:0000269|PubMed:23235459, ECO:0000269|PubMed:24374861}.
CC -!- SUBUNIT: Interacts with isoform 1 and isoform 3 of MAD1L1
CC (PubMed:24374861). Interacts with MTTP (By similarity).
CC {ECO:0000250|UniProtKB:Q80XD8, ECO:0000269|PubMed:24374861}.
CC -!- INTERACTION:
CC Q96NZ9; Q8IVF2-3: AHNAK2; NbExp=3; IntAct=EBI-2116102, EBI-12078468;
CC Q96NZ9; Q12797-6: ASPH; NbExp=3; IntAct=EBI-2116102, EBI-12092171;
CC Q96NZ9; Q96LK0: CEP19; NbExp=3; IntAct=EBI-2116102, EBI-741885;
CC Q96NZ9; P17066: HSPA6; NbExp=3; IntAct=EBI-2116102, EBI-355106;
CC Q96NZ9; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2116102, EBI-16439278;
CC Q96NZ9; Q9Y605: MRFAP1; NbExp=3; IntAct=EBI-2116102, EBI-995714;
CC Q96NZ9; O43765: SGTA; NbExp=9; IntAct=EBI-2116102, EBI-347996;
CC Q96NZ9; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-2116102, EBI-744081;
CC Q96NZ9; Q9UMX0: UBQLN1; NbExp=6; IntAct=EBI-2116102, EBI-741480;
CC Q96NZ9; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-2116102, EBI-10173939;
CC Q96NZ9; Q9UHD9: UBQLN2; NbExp=6; IntAct=EBI-2116102, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14583459}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q80XD8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PRAP;
CC IsoId=Q96NZ9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96NZ9-2; Sequence=VSP_027661, VSP_027662;
CC Name=3; Synonyms=PRAPV1;
CC IsoId=Q96NZ9-3; Sequence=VSP_027660;
CC Name=4; Synonyms=PRAPV2;
CC IsoId=Q96NZ9-4; Sequence=VSP_027661;
CC -!- TISSUE SPECIFICITY: Highly expressed in the intestinal epithelial cells
CC (at protein level) (PubMed:32629119). Abundantly expressed in the
CC epithelial cells of the liver, kidney and cervix. Significantly down-
CC regulated in hepatocellular carcinoma and right colon adenocarcinoma
CC compared with the respective adjacent normal tissues. Expressed in
CC epididymis (at protein level). {ECO:0000269|PubMed:14583459,
CC ECO:0000269|PubMed:20736409, ECO:0000269|PubMed:24374861,
CC ECO:0000269|PubMed:32629119}.
CC -!- INDUCTION: Up-regulated by butyrate, trichostatin A and 5'-aza-2'
CC deoxycytidine (PubMed:14583459). Induced by DNA-damaging agents in a
CC p53/TP53-dependent manner in HepG2 liver cancer cell line and HCT116
CC colon cancer cell line (PubMed:23235459). {ECO:0000269|PubMed:14583459,
CC ECO:0000269|PubMed:23235459}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP97247.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF421885; AAL16670.1; -; mRNA.
DR EMBL; AY158074; AAN87018.1; -; mRNA.
DR EMBL; AF123768; AAP97247.1; ALT_FRAME; mRNA.
DR EMBL; AY358908; AAQ89267.1; -; mRNA.
DR EMBL; GU727628; ADU87630.1; -; mRNA.
DR EMBL; AL360181; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471211; EAW61336.1; -; Genomic_DNA.
DR EMBL; BC029447; AAH29447.2; -; mRNA.
DR EMBL; BC061643; AAH61643.1; -; mRNA.
DR EMBL; BC071872; AAH71872.1; -; mRNA.
DR EMBL; BC093853; AAH93853.1; -; mRNA.
DR EMBL; BC101743; AAI01744.1; -; mRNA.
DR EMBL; BC143590; AAI43591.1; -; mRNA.
DR EMBL; BC143592; AAI43593.1; -; mRNA.
DR EMBL; BC143591; AAI43592.1; -; mRNA.
DR CCDS; CCDS44498.1; -. [Q96NZ9-4]
DR CCDS; CCDS7679.1; -. [Q96NZ9-1]
DR RefSeq; NP_001138673.1; NM_001145201.1. [Q96NZ9-4]
DR RefSeq; NP_660203.3; NM_145202.4. [Q96NZ9-1]
DR AlphaFoldDB; Q96NZ9; -.
DR BioGRID; 125610; 17.
DR IntAct; Q96NZ9; 16.
DR STRING; 9606.ENSP00000416126; -.
DR GlyGen; Q96NZ9; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q96NZ9; -.
DR PhosphoSitePlus; Q96NZ9; -.
DR BioMuta; PRAP1; -.
DR DMDM; 317373269; -.
DR MassIVE; Q96NZ9; -.
DR PaxDb; Q96NZ9; -.
DR PeptideAtlas; Q96NZ9; -.
DR PRIDE; Q96NZ9; -.
DR ProteomicsDB; 77584; -. [Q96NZ9-2]
DR ProteomicsDB; 77585; -. [Q96NZ9-3]
DR ProteomicsDB; 77586; -. [Q96NZ9-4]
DR Antibodypedia; 48788; 67 antibodies from 18 providers.
DR DNASU; 118471; -.
DR Ensembl; ENST00000433452.6; ENSP00000416126.2; ENSG00000165828.15. [Q96NZ9-1]
DR Ensembl; ENST00000463201.2; ENSP00000486265.1; ENSG00000165828.15. [Q96NZ9-4]
DR GeneID; 118471; -.
DR KEGG; hsa:118471; -.
DR MANE-Select; ENST00000433452.6; ENSP00000416126.2; NM_145202.5; NP_660203.3.
DR UCSC; uc001lmp.3; human. [Q96NZ9-1]
DR CTD; 118471; -.
DR DisGeNET; 118471; -.
DR GeneCards; PRAP1; -.
DR HGNC; HGNC:23304; PRAP1.
DR HPA; ENSG00000165828; Group enriched (intestine, liver).
DR MIM; 609776; gene.
DR neXtProt; NX_Q96NZ9; -.
DR OpenTargets; ENSG00000165828; -.
DR PharmGKB; PA134981678; -.
DR VEuPathDB; HostDB:ENSG00000165828; -.
DR eggNOG; ENOG502TDVH; Eukaryota.
DR GeneTree; ENSGT00390000012626; -.
DR InParanoid; Q96NZ9; -.
DR OMA; WVETEDI; -.
DR OrthoDB; 1574174at2759; -.
DR PhylomeDB; Q96NZ9; -.
DR TreeFam; TF337049; -.
DR PathwayCommons; Q96NZ9; -.
DR SignaLink; Q96NZ9; -.
DR BioGRID-ORCS; 118471; 6 hits in 1054 CRISPR screens.
DR ChiTaRS; PRAP1; human.
DR GenomeRNAi; 118471; -.
DR Pharos; Q96NZ9; Tbio.
DR PRO; PR:Q96NZ9; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96NZ9; protein.
DR Bgee; ENSG00000165828; Expressed in duodenum and 95 other tissues.
DR ExpressionAtlas; Q96NZ9; baseline and differential.
DR Genevisible; Q96NZ9; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0017129; F:triglyceride binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0071481; P:cellular response to X-ray; ISS:UniProtKB.
DR GO; GO:1902426; P:deactivation of mitotic spindle assembly checkpoint; IDA:UniProtKB.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:1904731; P:positive regulation of intestinal lipid absorption; ISS:UniProtKB.
DR GO; GO:2001140; P:positive regulation of phospholipid transport; ISS:UniProtKB.
DR GO; GO:1905885; P:positive regulation of triglyceride transport; ISS:UniProtKB.
DR InterPro; IPR027922; PRAP.
DR PANTHER; PTHR37861; PTHR37861; 1.
DR Pfam; PF15314; PRAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Lipid-binding;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..151
FT /note="Proline-rich acidic protein 1"
FT /id="PRO_0000299416"
FT REGION 71..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 101..127
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 43
FT /note="K -> NR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027660"
FT VAR_SEQ 79..87
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14583459,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_027661"
FT VAR_SEQ 95..151
FT /note="TEDTLGHVLSPEPDHDSLYHPPPEEDQGEERPRLWVMPNHQVLLGPEEDQDH
FT IYHPQ -> SRARP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14583459"
FT /id="VSP_027662"
FT VARIANT 54
FT /note="E -> G"
FT /evidence="ECO:0000269|PubMed:14583459"
FT /id="VAR_034815"
FT VARIANT 69
FT /note="K -> R"
FT /evidence="ECO:0000269|PubMed:14583459"
FT /id="VAR_034816"
FT VARIANT 81
FT /note="G -> S (in dbSNP:rs34780987)"
FT /id="VAR_034817"
FT VARIANT 101
FT /note="H -> R (in dbSNP:rs4369319)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14583459, ECO:0000269|PubMed:15164054,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:20736409,
FT ECO:0000269|Ref.3"
FT /id="VAR_034818"
SQ SEQUENCE 151 AA; 17208 MW; B751EDBFD24D08CA CRC64;
MRRLLLVTSL VVVLLWEAGA VPAPKVPIKM QVKHWPSEQD PEKAWGARVV EPPEKDDQLV
VLFPVQKPKL LTTEEKPRGQ GRGPILPGTK AWMETEDTLG HVLSPEPDHD SLYHPPPEED
QGEERPRLWV MPNHQVLLGP EEDQDHIYHP Q
