ID AT2L2_HUMAN Reviewed; 450 AA.
AC Q8IUZ5; A8K7P6; B3KN36; D3DWP9; Q8WYS6; Q96HW8;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 27-MAR-2024, entry version 174.
DE RecName: Full=5-phosphohydroxy-L-lysine phospho-lyase;
DE EC=4.2.3.134 {ECO:0000269|PubMed:22241472};
DE AltName: Full=Alanine--glyoxylate aminotransferase 2-like 2;
GN Name=PHYKPL; Synonyms=AGXT2L2 {ECO:0000303|PubMed:22241472};
GN ORFNames=PP9286;
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] (ISOFORM 2).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP VAL-437.
RC TISSUE=Placenta, and Stomach;
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=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
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] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, Muscle, 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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22241472; DOI=10.1074/jbc.m111.323485;
RA Veiga-da-Cunha M., Hadi F., Balligand T., Stroobant V., Van Schaftingen E.;
RT "Molecular identification of hydroxylysine kinase and of
RT ammoniophospholyases acting on 5-phosphohydroxy-L-lysine and
RT phosphoethanolamine.";
RL J. Biol. Chem. 287:7246-7255(2012).
RN [7]
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).
RN [8]
RP VARIANTS PHLU ARG-240 AND VAL-437.
RX PubMed=23242558; DOI=10.1007/s10545-012-9568-9;
RA Veiga-da-Cunha M., Verhoeven-Duif N.M., de Koning T.J., Duran M.,
RA Dorland B., Van Schaftingen E.;
RT "Mutations in the AGXT2L2 gene cause phosphohydroxylysinuria.";
RL J. Inherit. Metab. Dis. 36:961-966(2013).
CC -!- FUNCTION: Catalyzes the pyridoxal-phosphate-dependent breakdown of 5-
CC phosphohydroxy-L-lysine, converting it to ammonia, inorganic phosphate
CC and 2-aminoadipate semialdehyde. {ECO:0000269|PubMed:22241472}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5R)-5-phosphooxy-L-lysine + H2O = (S)-2-amino-6-oxohexanoate
CC + NH4(+) + phosphate; Xref=Rhea:RHEA:34091, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:43474, ChEBI:CHEBI:57882,
CC ChEBI:CHEBI:58321; EC=4.2.3.134;
CC Evidence={ECO:0000269|PubMed:22241472};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:22241472};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16 uM for 5-phosphohydroxy-L-lysine (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:22241472};
CC Vmax=256 nmol/min/mg enzyme {ECO:0000269|PubMed:22241472};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P22256}.
CC -!- INTERACTION:
CC Q8IUZ5; Q8N448: LNX2; NbExp=3; IntAct=EBI-751947, EBI-2340947;
CC Q8IUZ5; Q8IUZ5: PHYKPL; NbExp=6; IntAct=EBI-751947, EBI-751947;
CC Q8IUZ5; Q9NUX5: POT1; NbExp=2; IntAct=EBI-751947, EBI-752420;
CC Q8IUZ5; O60763: USO1; NbExp=3; IntAct=EBI-751947, EBI-356164;
CC Q8IUZ5; Q08AM6: VAC14; NbExp=4; IntAct=EBI-751947, EBI-2107455;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305|PubMed:22241472}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IUZ5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IUZ5-2; Sequence=VSP_025585;
CC Name=3;
CC IsoId=Q8IUZ5-3; Sequence=VSP_025584;
CC -!- DISEASE: Phosphohydroxylysinuria (PHLU) [MIM:615011]: A condition
CC characterized by elevated phosphohydroxylysine in the urine. There is
CC no clinical phenotype associated with this finding other than the
CC urinary metabolites. {ECO:0000269|PubMed:23242558}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class-III pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
CC -!- CAUTION: Does not seem to possess aminotransferase activity.
CC {ECO:0000305|PubMed:22241472}.
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DR EMBL; AF318375; AAL55882.1; -; mRNA.
DR EMBL; AK023470; BAG51198.1; -; mRNA.
DR EMBL; AK292061; BAF84750.1; -; mRNA.
DR EMBL; AC136601; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC136632; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471165; EAW53836.1; -; Genomic_DNA.
DR EMBL; CH471165; EAW53841.1; -; Genomic_DNA.
DR EMBL; BC008009; AAH08009.1; -; mRNA.
DR EMBL; BC037567; AAH37567.1; -; mRNA.
DR EMBL; BC110335; AAI10336.1; -; mRNA.
DR CCDS; CCDS4434.1; -. [Q8IUZ5-1]
DR RefSeq; NP_001265275.1; NM_001278346.1.
DR RefSeq; NP_699204.1; NM_153373.3. [Q8IUZ5-1]
DR AlphaFoldDB; Q8IUZ5; -.
DR SMR; Q8IUZ5; -.
DR BioGRID; 124425; 17.
DR IntAct; Q8IUZ5; 7.
DR STRING; 9606.ENSP00000310978; -.
DR DrugBank; DB00160; Alanine.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR iPTMnet; Q8IUZ5; -.
DR PhosphoSitePlus; Q8IUZ5; -.
DR BioMuta; PHYKPL; -.
DR DMDM; 74750645; -.
DR EPD; Q8IUZ5; -.
DR jPOST; Q8IUZ5; -.
DR MassIVE; Q8IUZ5; -.
DR MaxQB; Q8IUZ5; -.
DR PaxDb; 9606-ENSP00000310978; -.
DR PeptideAtlas; Q8IUZ5; -.
DR ProteomicsDB; 70633; -. [Q8IUZ5-1]
DR ProteomicsDB; 70634; -. [Q8IUZ5-2]
DR ProteomicsDB; 70635; -. [Q8IUZ5-3]
DR Antibodypedia; 29429; 183 antibodies from 26 providers.
DR DNASU; 85007; -.
DR Ensembl; ENST00000308158.10; ENSP00000310978.5; ENSG00000175309.15. [Q8IUZ5-1]
DR GeneID; 85007; -.
DR KEGG; hsa:85007; -.
DR MANE-Select; ENST00000308158.10; ENSP00000310978.5; NM_153373.4; NP_699204.1.
DR UCSC; uc003miz.5; human. [Q8IUZ5-1]
DR AGR; HGNC:28249; -.
DR CTD; 85007; -.
DR DisGeNET; 85007; -.
DR GeneCards; PHYKPL; -.
DR HGNC; HGNC:28249; PHYKPL.
DR HPA; ENSG00000175309; Low tissue specificity.
DR MalaCards; PHYKPL; -.
DR MIM; 614683; gene.
DR MIM; 615011; phenotype.
DR neXtProt; NX_Q8IUZ5; -.
DR OpenTargets; ENSG00000175309; -.
DR PharmGKB; PA162376015; -.
DR VEuPathDB; HostDB:ENSG00000175309; -.
DR eggNOG; KOG1403; Eukaryota.
DR GeneTree; ENSGT00940000159222; -.
DR HOGENOM; CLU_016922_8_0_1; -.
DR InParanoid; Q8IUZ5; -.
DR OMA; REGLNQH; -.
DR OrthoDB; 345661at2759; -.
DR PhylomeDB; Q8IUZ5; -.
DR TreeFam; TF320468; -.
DR BRENDA; 4.2.3.134; 2681.
DR PathwayCommons; Q8IUZ5; -.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-71064; Lysine catabolism.
DR SABIO-RK; Q8IUZ5; -.
DR SignaLink; Q8IUZ5; -.
DR BioGRID-ORCS; 85007; 9 hits in 1120 CRISPR screens.
DR ChiTaRS; PHYKPL; human.
DR GenomeRNAi; 85007; -.
DR Pharos; Q8IUZ5; Tbio.
DR PRO; PR:Q8IUZ5; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8IUZ5; Protein.
DR Bgee; ENSG00000175309; Expressed in pancreatic ductal cell and 180 other cell types or tissues.
DR ExpressionAtlas; Q8IUZ5; baseline and differential.
DR Genevisible; Q8IUZ5; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0008483; F:transaminase activity; IEA:InterPro.
DR CDD; cd00610; OAT_like; 1.
DR Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1.
DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1.
DR InterPro; IPR005814; Aminotrans_3.
DR InterPro; IPR049704; Aminotrans_3_PPA_site.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR45688:SF6; 5-PHOSPHOHYDROXY-L-LYSINE PHOSPHO-LYASE; 1.
DR PANTHER; PTHR45688; ALANINE--GLYOXYLATE AMINOTRANSFERASE 2, MITOCHONDRIAL; 1.
DR Pfam; PF00202; Aminotran_3; 1.
DR PIRSF; PIRSF000521; Transaminase_4ab_Lys_Orn; 1.
DR SUPFAM; SSF53383; PLP-dependent transferases; 1.
DR PROSITE; PS00600; AA_TRANSFER_CLASS_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Lyase; Mitochondrion;
KW Pyridoxal phosphate; Reference proteome.
FT CHAIN 1..450
FT /note="5-phosphohydroxy-L-lysine phospho-lyase"
FT /id="PRO_0000287667"
FT MOD_RES 278
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P22256"
FT VAR_SEQ 1..343
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15498874"
FT /id="VSP_025585"
FT VAR_SEQ 1..275
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_025584"
FT VARIANT 126
FT /note="H -> R (in dbSNP:rs7707147)"
FT /id="VAR_048233"
FT VARIANT 240
FT /note="G -> R (in PHLU; dbSNP:rs201105857)"
FT /evidence="ECO:0000269|PubMed:23242558"
FT /id="VAR_069543"
FT VARIANT 437
FT /note="E -> V (in PHLU; dbSNP:rs142181517)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:23242558"
FT /id="VAR_069544"
SQ SEQUENCE 450 AA; 49711 MW; 5EB28A6BDD44C429 CRC64;
MAADQRPKAD TLALRQRLIS SSCRLFFPED PVKIVRAQGQ YMYDEQGAEY IDCISNVAHV
GHCHPLVVQA AHEQNQVLNT NSRYLHDNIV DYAQRLSETL PEQLCVFYFL NSGSEANDLA
LRLARHYTGH QDVVVLDHAY HGHLSSLIDI SPYKFRNLDG QKEWVHVAPL PDTYRGPYRE
DHPNPAMAYA NEVKRVVSSA QEKGRKIAAF FAESLPSVGG QIIPPAGYFS QVAEHIRKAG
GVFVADEIQV GFGRVGKHFW AFQLQGKDFV PDIVTMGKSI GNGHPVACVA ATQPVARAFE
ATGVEYFNTF GGSPVSCAVG LAVLNVLEKE QLQDHATSVG SFLMQLLGQQ KIKHPIVGDV
RGVGLFIGVD LIKDEATRTP ATEEAAYLVS RLKENYVLLS TDGPGRNILK FKPPMCFSLD
NARQVVAKLD AILTDMEEKV RSCETLRLQP
//
