HPDL_HUMAN
ID HPDL_HUMAN Reviewed; 371 AA.
AC Q96IR7; B2R9B0;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=4-hydroxyphenylpyruvate dioxygenase-like protein;
DE Short=HPD-like protein;
DE EC=1.13.-.-;
DE AltName: Full=Glyoxalase domain-containing protein 1;
GN Name=HPDL; Synonyms=GLOXD1;
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].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
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 [6]
RP INVOLVEMENT IN SPG83, INVOLVEMENT IN NEDSWMA, VARIANTS SPG83 ASP-50 AND
RP HIS-287, VARIANTS NEDSWMA ARG-157; TYR-168; CYS-179; PRO-217; PRO-234;
RP 241-GLN--ALA-371 DEL; PRO-248; GLN-251; GLU-260; THR-266 AND
RP 342-GLN--ALA-371 DEL, CHARACTERIZATION OF VARIANTS NEDSWMA ARG-157;
RP TYR-168; CYS-179 AND 342-GLN--ALA-371 DEL, AND SUBCELLULAR LOCATION.
RX PubMed=32707086; DOI=10.1016/j.ajhg.2020.06.015;
RA Husain R.A., Grimmel M., Wagner M., Hennings J.C., Marx C.,
RA Feichtinger R.G., Saadi A., Rostasy K., Radelfahr F., Bevot A.,
RA Doebler-Neumann M., Hartmann H., Colleaux L., Cordts I., Kobeleva X.,
RA Darvish H., Bakhtiari S., Kruer M.C., Besse A., Ng A.C., Chiang D.,
RA Bolduc F., Tafakhori A., Mane S., Ghasemi Firouzabadi S., Huebner A.K.,
RA Buchert R., Beck-Woedl S., Mueller A.J., Laugwitz L., Naegele T.,
RA Wang Z.Q., Strom T.M., Sturm M., Meitinger T., Klockgether T., Riess O.,
RA Klopstock T., Brandl U., Huebner C.A., Deschauer M., Mayr J.A.,
RA Bonnen P.E., Kraegeloh-Mann I., Wortmann S.B., Haack T.B.;
RT "Bi-allelic HPDL Variants Cause a Neurodegenerative Disease Ranging from
RT Neonatal Encephalopathy to Adolescent-Onset Spastic Paraplegia.";
RL Am. J. Hum. Genet. 107:364-373(2020).
RN [7]
RP VARIANT NEDSWMA PRO-176.
RX PubMed=33634263; DOI=10.1093/braincomms/fcab002;
RA Morgan N.V., Yngvadottir B., O'Driscoll M., Clark G.R., Walsh D.,
RA Martin E., Tee L., Reid E., Titheradge H.L., Maher E.R.;
RT "Evidence that autosomal recessive spastic cerebral palsy-1 (CPSQ1) is
RT caused by a missense variant in HPDL.";
RL Brain Commun. 3:fcab002-fcab002(2021).
CC -!- FUNCTION: May have dioxygenase activity. {ECO:0000305}.
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000250};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:32707086}.
CC -!- DISEASE: Neurodevelopmental disorder with progressive spasticity and
CC brain white matter abnormalities (NEDSWMA) [MIM:619026]: An autosomal
CC recessive neurodevelopmental disorder characterized by developmental
CC delay manifesting in infancy, inability to walk independently, mild to
CC severe intellectual disability, poor overall growth, progressive
CC microcephaly, and axial hypotonia. Additional variable features include
CC brainstem and cerebellar involvement, seizures, joint contractures,
CC ocular disturbances, episodic respiratory failure, and facial
CC dysmorphism. {ECO:0000269|PubMed:32707086,
CC ECO:0000269|PubMed:33634263}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Spastic paraplegia 83, autosomal recessive (SPG83)
CC [MIM:619027]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body. SPG83 is characterized
CC by juvenile onset of progressive lower limb spasticity resulting in
CC gait instability. {ECO:0000269|PubMed:32707086}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the 4HPPD family. {ECO:0000305}.
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DR EMBL; AK313714; BAG36457.1; -; mRNA.
DR EMBL; AL359540; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07002.1; -; Genomic_DNA.
DR EMBL; BC007293; AAH07293.1; -; mRNA.
DR CCDS; CCDS519.1; -.
DR RefSeq; NP_116145.1; NM_032756.2.
DR AlphaFoldDB; Q96IR7; -.
DR SMR; Q96IR7; -.
DR BioGRID; 124294; 16.
DR IntAct; Q96IR7; 1.
DR STRING; 9606.ENSP00000335060; -.
DR GlyGen; Q96IR7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96IR7; -.
DR PhosphoSitePlus; Q96IR7; -.
DR BioMuta; HPDL; -.
DR DMDM; 74751942; -.
DR EPD; Q96IR7; -.
DR jPOST; Q96IR7; -.
DR MassIVE; Q96IR7; -.
DR MaxQB; Q96IR7; -.
DR PaxDb; Q96IR7; -.
DR PeptideAtlas; Q96IR7; -.
DR PRIDE; Q96IR7; -.
DR ProteomicsDB; 76848; -.
DR Antibodypedia; 32602; 45 antibodies from 18 providers.
DR DNASU; 84842; -.
DR Ensembl; ENST00000334815.6; ENSP00000335060.3; ENSG00000186603.7.
DR GeneID; 84842; -.
DR KEGG; hsa:84842; -.
DR MANE-Select; ENST00000334815.6; ENSP00000335060.3; NM_032756.4; NP_116145.1.
DR UCSC; uc001cne.4; human.
DR CTD; 84842; -.
DR DisGeNET; 84842; -.
DR GeneCards; HPDL; -.
DR HGNC; HGNC:28242; HPDL.
DR HPA; ENSG00000186603; Tissue enhanced (intestine).
DR MalaCards; HPDL; -.
DR MIM; 618994; gene.
DR MIM; 619026; phenotype.
DR MIM; 619027; phenotype.
DR neXtProt; NX_Q96IR7; -.
DR OpenTargets; ENSG00000186603; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA162391595; -.
DR VEuPathDB; HostDB:ENSG00000186603; -.
DR eggNOG; KOG0638; Eukaryota.
DR GeneTree; ENSGT00530000063474; -.
DR HOGENOM; CLU_034004_2_0_1; -.
DR InParanoid; Q96IR7; -.
DR OMA; LYTPNIM; -.
DR OrthoDB; 1087836at2759; -.
DR PhylomeDB; Q96IR7; -.
DR TreeFam; TF300622; -.
DR PathwayCommons; Q96IR7; -.
DR SignaLink; Q96IR7; -.
DR BioGRID-ORCS; 84842; 15 hits in 1071 CRISPR screens.
DR GenomeRNAi; 84842; -.
DR Pharos; Q96IR7; Tdark.
DR PRO; PR:Q96IR7; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96IR7; protein.
DR Bgee; ENSG00000186603; Expressed in mucosa of transverse colon and 101 other tissues.
DR Genevisible; Q96IR7; HS.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0003868; F:4-hydroxyphenylpyruvate dioxygenase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009072; P:aromatic amino acid family metabolic process; IEA:InterPro.
DR CDD; cd07250; HPPD_C_like; 1.
DR CDD; cd08342; HPPD_N_like; 1.
DR Gene3D; 3.10.180.10; -; 2.
DR InterPro; IPR005956; 4OHPhenylPyrv_dOase.
DR InterPro; IPR041735; 4OHPhenylPyrv_dOase_C.
DR InterPro; IPR041736; 4OHPhenylPyrv_dOase_N.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR037523; VOC.
DR PANTHER; PTHR11959; PTHR11959; 1.
DR PIRSF; PIRSF009283; HPP_dOase; 1.
DR SUPFAM; SSF54593; SSF54593; 1.
DR PROSITE; PS51819; VOC; 2.
PE 1: Evidence at protein level;
KW Dioxygenase; Disease variant; Hereditary spastic paraplegia;
KW Intellectual disability; Iron; Metal-binding; Mitochondrion;
KW Neurodegeneration; Oxidoreductase; Reference proteome; Repeat.
FT CHAIN 1..371
FT /note="4-hydroxyphenylpyruvate dioxygenase-like protein"
FT /id="PRO_0000271119"
FT DOMAIN 7..135
FT /note="VOC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT DOMAIN 160..328
FT /note="VOC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT BINDING 163
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 258
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 339
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT VARIANT 50
FT /note="G -> D (in SPG83; dbSNP:rs1391712320)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085125"
FT VARIANT 157
FT /note="W -> R (in NEDSWMA; unknown pathological
FT significance; decreased protein abundance;
FT dbSNP:rs567130416)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085126"
FT VARIANT 168
FT /note="C -> Y (in NEDSWMA; unknown pathological
FT significance; decreased protein abundance;
FT dbSNP:rs1186696459)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085127"
FT VARIANT 176
FT /note="L -> P (in NEDSWMA; dbSNP:rs773333490)"
FT /evidence="ECO:0000269|PubMed:33634263"
FT /id="VAR_085523"
FT VARIANT 179
FT /note="W -> C (in NEDSWMA; unknown pathological
FT significance; decreased protein abundance)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085128"
FT VARIANT 217
FT /note="L -> P (in NEDSWMA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085129"
FT VARIANT 234
FT /note="L -> P (in NEDSWMA; unknown pathological
FT significance; dbSNP:rs757449403)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085130"
FT VARIANT 241..371
FT /note="Missing (in NEDSWMA)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085131"
FT VARIANT 248
FT /note="L -> P (in NEDSWMA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085132"
FT VARIANT 251
FT /note="H -> Q (in NEDSWMA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085133"
FT VARIANT 260
FT /note="G -> E (in NEDSWMA; unknown pathological
FT significance; dbSNP:rs758290491)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085134"
FT VARIANT 266
FT /note="I -> T (in NEDSWMA; unknown pathological
FT significance; dbSNP:rs769373772)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085135"
FT VARIANT 287
FT /note="Y -> H (in SPG83; unknown pathological significance;
FT dbSNP:rs777360560)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085136"
FT VARIANT 342..371
FT /note="Missing (in NEDSWMA; unknown pathological
FT significance; decreased protein abundance)"
FT /evidence="ECO:0000269|PubMed:32707086"
FT /id="VAR_085137"
SQ SEQUENCE 371 AA; 39386 MW; C52721F188E43C38 CRC64;
MAAPALRLCH IAFHVPAGQP LARNLQRLFG FQPLASREVD GWRQLALRSG DAVFLVNEGA
GSGEPLYGLD PRHAVPSATN LCFDVADAGA ATRELAALGC SVPVPPVRVR DAQGAATYAV
VSSPAGILSL TLLERAGYRG PFLPGFRPVS SAPGPGWVSR VDHLTLACTP GSSPTLLRWF
HDCLGFCHLP LSPGEDPELG LEMTAGFGLG GLRLTALQAQ PGSIVPTLVL AESLPGATTR
QDQVEQFLAR HKGPGLQHVG LYTPNIVEAT EGVATAGGQF LAPPGAYYQQ PGKERQIRAA
GHEPHLLARQ GILLDGDKGK FLLQVFTKSL FTEDTFFLEL IQRQGATGFG QGNIRALWQS
VQEQSARSQE A
