PACRG_HUMAN
ID PACRG_HUMAN Reviewed; 296 AA.
AC Q96M98; E1P5B5; Q6IMB8; Q8IZM1; Q8NHP5; Q9H1V9;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Parkin coregulated gene protein;
DE AltName: Full=Molecular chaperone/chaperonin-binding protein;
DE AltName: Full=PARK2 coregulated gene protein;
GN Name=PACRG; Synonyms=GLUP;
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] (ISOFORM 2).
RX PubMed=12547187; DOI=10.1016/s0022-2836(02)01376-1;
RA West A.B., Lockhart P.J., O'Farell C., Farrer M.J.;
RT "Identification of a novel gene linked to parkin via a bi-directional
RT promoter.";
RL J. Mol. Biol. 326:11-19(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [6]
RP IDENTIFICATION, FUNCTION, AND INTERACTION WITH STIP1; PRKN; GPR37; HSPA8;
RP TCP1; CCT2; CCT3; CCT4; CCT5; CCT6A; CCT7 AND CCT8.
RX PubMed=14532270; DOI=10.1074/jbc.m309655200;
RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.;
RT "A product of the human gene adjacent to parkin is a component of Lewy
RT bodies and suppresses Pael receptor-induced cell death.";
RL J. Biol. Chem. 278:51901-51910(2003).
RN [7]
RP TISSUE SPECIFICITY, POLYMORPHISM, AND INVOLVEMENT IN LPRS2.
RX PubMed=14737177; DOI=10.1038/nature02326;
RA Mira M.T., Alcais A., Nguyen V.T., Moraes M.O., Di Flumeri C., Vu H.T.,
RA Mai C.P., Nguyen T.H., Nguyen N.B., Pham X.K., Sarno E.N., Alter A.,
RA Montpetit A., Moraes M.E., Moraes J.R., Dore C., Gallant C.J., Lepage P.,
RA Verner A., Van De Vosse E., Hudson T.J., Abel L., Schurr E.;
RT "Susceptibility to leprosy is associated with PARK2 and PACRG.";
RL Nature 427:636-640(2004).
CC -!- FUNCTION: Microtubule inner protein (MIP) part of the dynein-decorated
CC doublet microtubules (DMTs) in cilia axoneme, which is required for
CC motile cilia beating (By similarity). Suppresses cell death induced by
CC accumulation of unfolded Pael receptor (Pael-R, a substrate of Parkin).
CC Facilitates the formation of inclusions consisting of Pael-R, molecular
CC chaperones, protein degradation molecules and itself when proteasome is
CC inhibited. May play an important role in the formation of Lewy bodies
CC and protection of dopaminergic neurons against Parkinson disease
CC (PubMed:14532270). {ECO:0000250|UniProtKB:A5PK71,
CC ECO:0000269|PubMed:14532270}.
CC -!- SUBUNIT: Forms a large molecular chaperone complex containing heat
CC shock proteins 70 and 90 and chaperonin components. Interacts with
CC STIP1, PRKN, GPR37, HSPA8, TCP1/CCT1, CCT2, CCT3, CCT4, CCT5, CCT6A,
CC CCT7, CCT8. Interacts with MEIG1 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q96M98-2; Q5JSS6: MEIG1; NbExp=5; IntAct=EBI-11945452, EBI-18583441;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium axoneme
CC {ECO:0000250|UniProtKB:A5PK71}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96M98-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96M98-2; Sequence=VSP_010033;
CC -!- TISSUE SPECIFICITY: Expressed in all immune tissues, spleen, lymph
CC nodes, thymus, tonsils, leukocyte and bone marrow. Expressed also in
CC heart, brain, skeletal muscle, kidney, lung and pancreas. Expressed in
CC primary Schwann cells and very weakly by monocyte-derived macrophages
CC the primary host cells of Mycobacterium leprae, the causative agent of
CC leprosy. Component of Lewy bodies, intraneuronal inclusions found in
CC the brain of Parkinson disease patients. {ECO:0000269|PubMed:14737177}.
CC -!- POLYMORPHISM: Involved in susceptibility to leprosy (LPRS2)
CC [MIM:607572]. LPRS2 is associated with polymorphisms in the 5'-
CC regulatory region shared by the PRKN gene.
CC {ECO:0000269|PubMed:14737177}.
CC -!- MISCELLANEOUS: Linked to PRKN in a head-to-head arrangement on opposite
CC DNA strands and share a common 5'-flanking promoter region.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to exon skipping. {ECO:0000305}.
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DR EMBL; AF546872; AAN37911.1; -; mRNA.
DR EMBL; AK057286; BAB71410.1; -; mRNA.
DR EMBL; AL031121; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137182; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354942; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001576; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL078585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590286; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL603788; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47565.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47566.1; -; Genomic_DNA.
DR EMBL; BC030642; AAH30642.1; -; mRNA.
DR EMBL; BC044227; AAH44227.1; -; mRNA.
DR EMBL; BK001670; DAA02134.1; -; mRNA.
DR CCDS; CCDS43524.1; -. [Q96M98-2]
DR CCDS; CCDS5284.1; -. [Q96M98-1]
DR RefSeq; NP_001073847.1; NM_001080378.1. [Q96M98-2]
DR RefSeq; NP_001073848.1; NM_001080379.1. [Q96M98-2]
DR RefSeq; NP_689623.2; NM_152410.2. [Q96M98-1]
DR PDB; 6NDU; X-ray; 2.10 A; A=70-296.
DR PDB; 6NEP; X-ray; 2.10 A; A=70-296.
DR PDB; 6UCC; X-ray; 2.60 A; A=1-296.
DR PDBsum; 6NDU; -.
DR PDBsum; 6NEP; -.
DR PDBsum; 6UCC; -.
DR AlphaFoldDB; Q96M98; -.
DR SMR; Q96M98; -.
DR BioGRID; 126421; 28.
DR IntAct; Q96M98; 4.
DR STRING; 9606.ENSP00000337946; -.
DR iPTMnet; Q96M98; -.
DR PhosphoSitePlus; Q96M98; -.
DR BioMuta; PACRG; -.
DR DMDM; 77416872; -.
DR MassIVE; Q96M98; -.
DR PaxDb; Q96M98; -.
DR PeptideAtlas; Q96M98; -.
DR PRIDE; Q96M98; -.
DR ProteomicsDB; 77323; -. [Q96M98-1]
DR ProteomicsDB; 77324; -. [Q96M98-2]
DR Antibodypedia; 20047; 158 antibodies from 25 providers.
DR DNASU; 135138; -.
DR Ensembl; ENST00000337019.7; ENSP00000337946.3; ENSG00000112530.12. [Q96M98-1]
DR Ensembl; ENST00000366888.7; ENSP00000355854.2; ENSG00000112530.12. [Q96M98-2]
DR Ensembl; ENST00000366889.6; ENSP00000355855.2; ENSG00000112530.12. [Q96M98-2]
DR GeneID; 135138; -.
DR KEGG; hsa:135138; -.
DR MANE-Select; ENST00000366888.7; ENSP00000355854.2; NM_001080379.2; NP_001073848.1. [Q96M98-2]
DR UCSC; uc003qua.4; human. [Q96M98-1]
DR CTD; 135138; -.
DR DisGeNET; 135138; -.
DR GeneCards; PACRG; -.
DR HGNC; HGNC:19152; PACRG.
DR HPA; ENSG00000112530; Tissue enhanced (fallopian tube, testis).
DR MalaCards; PACRG; -.
DR MIM; 607572; phenotype.
DR MIM; 608427; gene.
DR neXtProt; NX_Q96M98; -.
DR OpenTargets; ENSG00000112530; -.
DR PharmGKB; PA134909011; -.
DR VEuPathDB; HostDB:ENSG00000112530; -.
DR eggNOG; KOG3961; Eukaryota.
DR GeneTree; ENSGT00940000157330; -.
DR HOGENOM; CLU_073223_1_0_1; -.
DR InParanoid; Q96M98; -.
DR OMA; INGPIHE; -.
DR OrthoDB; 1095804at2759; -.
DR PhylomeDB; Q96M98; -.
DR TreeFam; TF321123; -.
DR PathwayCommons; Q96M98; -.
DR SignaLink; Q96M98; -.
DR BioGRID-ORCS; 135138; 6 hits in 1064 CRISPR screens.
DR ChiTaRS; PACRG; human.
DR GeneWiki; PACRG; -.
DR GenomeRNAi; 135138; -.
DR Pharos; Q96M98; Tbio.
DR PRO; PR:Q96M98; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q96M98; protein.
DR Bgee; ENSG00000112530; Expressed in bronchial epithelial cell and 122 other tissues.
DR ExpressionAtlas; Q96M98; baseline and differential.
DR Genevisible; Q96M98; HS.
DR GO; GO:0005879; C:axonemal microtubule; ISS:UniProtKB.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0002177; C:manchette; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0097225; C:sperm midpiece; IEA:Ensembl.
DR GO; GO:0031982; C:vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0003779; F:actin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051087; F:chaperone binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0031072; F:heat shock protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0030544; F:Hsp70 protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051879; F:Hsp90 protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0034620; P:cellular response to unfolded protein; TAS:ParkinsonsUK-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:ParkinsonsUK-UCL.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
DR InterPro; IPR019399; Parkin_co-regulated_protein.
DR PANTHER; PTHR21207; PTHR21207; 1.
DR Pfam; PF10274; ParcG; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell projection; Cytoplasm;
KW Cytoskeleton; Reference proteome.
FT CHAIN 1..296
FT /note="Parkin coregulated gene protein"
FT /id="PRO_0000058169"
FT VAR_SEQ 205..243
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12547187,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_010033"
FT CONFLICT 93
FT /note="K -> R (in Ref. 2; BAB71410)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="A -> T (in Ref. 5; AAH30642)"
FT /evidence="ECO:0000305"
FT HELIX 70..77
FT /evidence="ECO:0007829|PDB:6NEP"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:6UCC"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 105..114
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 123..138
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 146..157
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 162..178
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 182..186
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 190..193
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 197..200
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 260..274
FT /evidence="ECO:0007829|PDB:6NEP"
FT HELIX 279..286
FT /evidence="ECO:0007829|PDB:6NEP"
SQ SEQUENCE 296 AA; 33342 MW; 4A415741D430C7FB CRC64;
MVAEKETLSL NKCPDKMPKR TKLLAQQPLP VHQPHSLVSE GFTVKAMMKN SVVRGPPAAG
AFKERPTKPT AFRKFYERGD FPIALEHDSK GNKIAWKVEI EKLDYHHYLP LFFDGLCEMT
FPYEFFARQG IHDMLEHGGN KILPVLPQLI IPIKNALNLR NRQVICVTLK VLQHLVVSAE
MVGKALVPYY RQILPVLNIF KNMNGSYSLP RLECSGAIMA RCNLDHLGSS DPPTSASQVA
EIIVNSGDGI DYSQQKRENI GDLIQETLEA FERYGGENAF INIKYVVPTY ESCLLN
