GFRP_HUMAN
ID GFRP_HUMAN Reviewed; 84 AA.
AC P30047; B2R4L6; B7ZLM8; Q2M1Q2; Q99749;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=GTP cyclohydrolase 1 feedback regulatory protein;
DE Short=GFRP;
DE AltName: Full=GTP cyclohydrolase I feedback regulatory protein;
DE AltName: Full=p35;
GN Name=GCHFR; Synonyms=GFRP;
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 [GENOMIC DNA].
RA Bonner T.I., Modi W.S., Milstein S.;
RT "Structure of the human GTP cyclohydrolase I feedback regulatory protein
RT gene.";
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
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=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon;
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 PROTEIN SEQUENCE OF 2-12.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16778797; DOI=10.1038/sj.jid.5700425;
RA Chavan B., Gillbro J.M., Rokos H., Schallreuter K.U.;
RT "GTP cyclohydrolase feedback regulatory protein controls cofactor 6-
RT tetrahydrobiopterin synthesis in the cytosol and in the nucleus of
RT epidermal keratinocytes and melanocytes.";
RL J. Invest. Dermatol. 126:2481-2489(2006).
RN [8]
RP INTERACTION WITH GCH1.
RX PubMed=16696853; DOI=10.1111/j.1471-4159.2006.03836.x;
RA Swick L., Kapatos G.;
RT "A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein
RT interactions.";
RL J. Neurochem. 97:1447-1455(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP IDENTIFICATION BY 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).
CC -!- FUNCTION: Mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase
CC 1. This inhibition is reversed by L-phenylalanine.
CC {ECO:0000269|PubMed:16778797}.
CC -!- SUBUNIT: Homopentamer. Forms a complex with GCH1 where a GCH1
CC homodecamer is sandwiched by two GFRP homopentamers (By similarity).
CC Interacts with GCH1. {ECO:0000250, ECO:0000269|PubMed:16696853}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16778797}. Nucleus
CC membrane {ECO:0000269|PubMed:16778797}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:16778797}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30047-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P30047-2; Sequence=VSP_055592;
CC -!- TISSUE SPECIFICITY: In epidermis, expressed predominantly in basal
CC undifferentiated keratinocytes and in some but not all melanocytes (at
CC protein level). {ECO:0000269|PubMed:16778797}.
CC -!- SIMILARITY: Belongs to the GFRP family. {ECO:0000305}.
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DR EMBL; U78190; AAB37337.1; -; Genomic_DNA.
DR EMBL; AK311872; BAG34813.1; -; mRNA.
DR EMBL; AC012476; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471125; EAW92443.1; -; Genomic_DNA.
DR EMBL; BC112262; AAI12263.1; -; mRNA.
DR EMBL; BC112264; AAI12265.1; -; mRNA.
DR EMBL; BC143904; AAI43905.1; -; mRNA.
DR CCDS; CCDS10064.1; -. [P30047-1]
DR RefSeq; NP_005249.1; NM_005258.2. [P30047-1]
DR PDB; 6Z80; EM; 3.00 A; K/L/M/N/O/P/Q/R/S/T=1-84.
DR PDB; 6Z85; EM; 2.90 A; K/L/M/N/O/P/Q/R/S/T=1-84.
DR PDB; 7ACC; X-ray; 2.04 A; A/B/C/D/E/F/G/H/I/J=1-84.
DR PDB; 7AL9; X-ray; 1.75 A; A/B/C/D/E/F/G/H/I/J=1-84.
DR PDB; 7ALA; X-ray; 1.85 A; F/G/H/I/J=1-84.
DR PDB; 7ALB; X-ray; 1.98 A; a/b/c/d/e/f/g/h/i/j/k/l/m/n/o/p/q/r/s/t=1-84.
DR PDB; 7ALC; X-ray; 1.73 A; F/G/H/I/J=1-84.
DR PDB; 7ALQ; X-ray; 2.21 A; a/b/c/d/e/f/g/h/i/j/k/l/m/n/o/p/q/r/s/t=1-84.
DR PDBsum; 6Z80; -.
DR PDBsum; 6Z85; -.
DR PDBsum; 7ACC; -.
DR PDBsum; 7AL9; -.
DR PDBsum; 7ALA; -.
DR PDBsum; 7ALB; -.
DR PDBsum; 7ALC; -.
DR PDBsum; 7ALQ; -.
DR AlphaFoldDB; P30047; -.
DR SMR; P30047; -.
DR BioGRID; 108914; 36.
DR IntAct; P30047; 12.
DR STRING; 9606.ENSP00000260447; -.
DR iPTMnet; P30047; -.
DR PhosphoSitePlus; P30047; -.
DR BioMuta; GCHFR; -.
DR DMDM; 2506906; -.
DR SWISS-2DPAGE; P30047; -.
DR EPD; P30047; -.
DR jPOST; P30047; -.
DR MassIVE; P30047; -.
DR MaxQB; P30047; -.
DR PaxDb; P30047; -.
DR PeptideAtlas; P30047; -.
DR PRIDE; P30047; -.
DR ProteomicsDB; 54627; -. [P30047-1]
DR ProteomicsDB; 7228; -.
DR Antibodypedia; 23158; 233 antibodies from 30 providers.
DR DNASU; 2644; -.
DR Ensembl; ENST00000260447.6; ENSP00000260447.4; ENSG00000137880.6. [P30047-1]
DR Ensembl; ENST00000559445.1; ENSP00000453871.1; ENSG00000137880.6. [P30047-2]
DR GeneID; 2644; -.
DR KEGG; hsa:2644; -.
DR MANE-Select; ENST00000260447.6; ENSP00000260447.4; NM_005258.3; NP_005249.1.
DR UCSC; uc001zmr.2; human. [P30047-1]
DR CTD; 2644; -.
DR DisGeNET; 2644; -.
DR GeneCards; GCHFR; -.
DR HGNC; HGNC:4194; GCHFR.
DR HPA; ENSG00000137880; Tissue enriched (liver).
DR MIM; 602437; gene.
DR neXtProt; NX_P30047; -.
DR OpenTargets; ENSG00000137880; -.
DR PharmGKB; PA28609; -.
DR VEuPathDB; HostDB:ENSG00000137880; -.
DR eggNOG; ENOG502S4A0; Eukaryota.
DR GeneTree; ENSGT00440000033849; -.
DR HOGENOM; CLU_195651_0_0_1; -.
DR InParanoid; P30047; -.
DR OMA; GQTCIWT; -.
DR OrthoDB; 1560576at2759; -.
DR PhylomeDB; P30047; -.
DR TreeFam; TF329303; -.
DR PathwayCommons; P30047; -.
DR Reactome; R-HSA-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR SignaLink; P30047; -.
DR SIGNOR; P30047; -.
DR BioGRID-ORCS; 2644; 6 hits in 1077 CRISPR screens.
DR GeneWiki; GCHFR; -.
DR GenomeRNAi; 2644; -.
DR Pharos; P30047; Tbio.
DR PRO; PR:P30047; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P30047; protein.
DR Bgee; ENSG00000137880; Expressed in right lobe of liver and 136 other tissues.
DR ExpressionAtlas; P30047; baseline and differential.
DR Genevisible; P30047; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0016597; F:amino acid binding; IEA:Ensembl.
DR GO; GO:0004857; F:enzyme inhibitor activity; IEA:Ensembl.
DR GO; GO:0044549; F:GTP cyclohydrolase binding; IBA:GO_Central.
DR GO; GO:0030742; F:GTP-dependent protein binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0009890; P:negative regulation of biosynthetic process; IEA:InterPro.
DR GO; GO:0043105; P:negative regulation of GTP cyclohydrolase I activity; IBA:GO_Central.
DR GO; GO:0042133; P:neurotransmitter metabolic process; TAS:ProtInc.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; TAS:ProtInc.
DR GO; GO:0065003; P:protein-containing complex assembly; IEA:Ensembl.
DR Gene3D; 3.30.1410.10; -; 1.
DR InterPro; IPR036717; GFRP_sf.
DR InterPro; IPR009112; GTP_CycHdrlase_I_reg.
DR PANTHER; PTHR16852; PTHR16852; 1.
DR Pfam; PF06399; GFRP; 1.
DR SUPFAM; SSF69761; SSF69761; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Membrane; Nucleus; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1286669"
FT CHAIN 2..84
FT /note="GTP cyclohydrolase 1 feedback regulatory protein"
FT /id="PRO_0000189675"
FT VAR_SEQ 13..23
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055592"
FT STRAND 3..10
FT /evidence="ECO:0007829|PDB:7ALC"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:7AL9"
FT STRAND 17..21
FT /evidence="ECO:0007829|PDB:7ALC"
FT HELIX 26..31
FT /evidence="ECO:0007829|PDB:7ALC"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:7ALC"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:7ACC"
FT STRAND 46..51
FT /evidence="ECO:0007829|PDB:7ALC"
FT HELIX 53..62
FT /evidence="ECO:0007829|PDB:7ALC"
FT STRAND 66..73
FT /evidence="ECO:0007829|PDB:7ALC"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:7ALC"
SQ SEQUENCE 84 AA; 9698 MW; 4A20FDBC6E3EE7AC CRC64;
MPYLLISTQI RMEVGPTMVG DEQSDPELMQ HLGASKRRAL GNNFYEYYVD DPPRIVLDKL
ERRGFRVLSM TGVGQTLVWC LHKE
