ID P4HA2_HUMAN Reviewed; 535 AA. AC O15460; D3DQ85; D3DQ86; Q8WWN0; DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 13-FEB-2019, entry version 187. DE RecName: Full=Prolyl 4-hydroxylase subunit alpha-2; DE Short=4-PH alpha-2; DE EC=1.14.11.2; DE AltName: Full=Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-2; DE Flags: Precursor; GN Name=P4HA2; ORFNames=UNQ290/PRO330; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IIB). RC TISSUE=Lung; RX PubMed=9211872; DOI=10.1074/jbc.272.28.17342; RA Annunen P., Helaakoski T., Myllyharju J., Veijola J., Pihlajaniemi T., RA Kivirikko K.I.; RT "Cloning of the human prolyl 4-hydroxylase alpha subunit isoform RT alpha(II) and characterization of the type II enzyme tetramer. The RT alpha(I) and alpha(II) subunits do not form a mixed RT alpha(I)alpha(II)beta2 tetramer."; RL J. Biol. Chem. 272:17342-17348(1997). RN [2] RP NUCLEOTIDE SEQUENCE (ISOFORMS IIA AND IIB). RX PubMed=11606192; DOI=10.1046/j.0014-2956.2001.02464.x; RA Nokelainen M., Nissi R., Kukkola L., Helaakoski T., Myllyharju J.; RT "Characterization of the human and mouse genes for the alpha subunit RT of type II prolyl 4-hydroxylase. Identification of a previously RT unknown alternatively spliced exon and its expression in various RT tissues."; RL Eur. J. Biochem. 268:5300-5309(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IIA). 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., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IIA). RC TISSUE=Brain; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] 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., RA Buerckstuemmer T., 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 [7] RP INVOLVEMENT IN MYP25, VARIANTS IN MYP25 ARG-140; VAL-150 AND LYS-291, RP AND CHARACTERIZATION OF VARIANT MYP25 LYS-291. RX PubMed=25741866; DOI=10.1038/gim.2015.28; RA Guo H., Tong P., Liu Y., Xia L., Wang T., Tian Q., Li Y., Hu Y., RA Zheng Y., Jin X., Li Y., Xiong W., Tang B., Feng Y., Li J., Pan Q., RA Hu Z., Xia K.; RT "Mutations of P4HA2 encoding prolyl 4-hydroxylase 2 are associated RT with nonsyndromic high myopia."; RL Genet. Med. 17:300-306(2015). CC -!- FUNCTION: Catalyzes the post-translational formation of 4- CC hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other CC proteins. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + L-prolyl-[procollagen] + O2 = CO2 + CC succinate + trans-4-hydroxy-L-prolyl-[procollagen]; CC Xref=Rhea:RHEA:18945, Rhea:RHEA-COMP:11676, Rhea:RHEA- CC COMP:11680, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:50342, CC ChEBI:CHEBI:61965; EC=1.14.11.2; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE- CC ProRule:PRU00805}; CC -!- COFACTOR: CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; Evidence={ECO:0000250}; CC -!- SUBUNIT: Heterotetramer of two alpha-2 chains and two beta chains CC (the beta chain is the multi-functional PDI). CC -!- INTERACTION: CC Q13643:FHL3; NbExp=3; IntAct=EBI-10182841, EBI-741101; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=IIb; CC IsoId=O15460-1; Sequence=Displayed; CC Name=IIa; CC IsoId=O15460-2; Sequence=VSP_004506; CC -!- DISEASE: Myopia 25, autosomal dominant (MYP25) [MIM:617238]: A CC refractive error of the eye, in which parallel rays from a distant CC object come to focus in front of the retina, vision being better CC for near objects than for far. {ECO:0000269|PubMed:25741866}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the P4HA family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; U90441; AAB71339.1; -; mRNA. DR EMBL; AJ314859; CAC85688.1; -; Genomic_DNA. DR EMBL; AJ314859; CAC85689.1; -; Genomic_DNA. DR EMBL; AY358970; AAQ89329.1; -; mRNA. DR EMBL; CH471062; EAW62341.1; -; Genomic_DNA. DR EMBL; CH471062; EAW62342.1; -; Genomic_DNA. DR EMBL; CH471062; EAW62343.1; -; Genomic_DNA. DR EMBL; CH471062; EAW62346.1; -; Genomic_DNA. DR EMBL; BC035813; AAH35813.1; -; mRNA. DR CCDS; CCDS34230.1; -. [O15460-2] DR CCDS; CCDS4151.1; -. [O15460-1] DR RefSeq; NP_001017973.1; NM_001017973.1. [O15460-2] DR RefSeq; NP_001017974.1; NM_001017974.1. [O15460-2] DR RefSeq; NP_001136070.1; NM_001142598.1. [O15460-2] DR RefSeq; NP_001136071.1; NM_001142599.1. [O15460-1] DR RefSeq; NP_004190.1; NM_004199.2. [O15460-1] DR RefSeq; XP_005272173.1; XM_005272116.4. [O15460-1] DR RefSeq; XP_005272174.1; XM_005272117.4. [O15460-1] DR RefSeq; XP_005272175.1; XM_005272118.4. [O15460-1] DR RefSeq; XP_005272176.1; XM_005272119.4. [O15460-1] DR RefSeq; XP_005272177.1; XM_005272120.4. [O15460-1] DR RefSeq; XP_006714791.1; XM_006714728.3. [O15460-1] DR RefSeq; XP_006714792.1; XM_006714729.3. [O15460-2] DR RefSeq; XP_006714793.1; XM_006714730.3. [O15460-2] DR RefSeq; XP_016865500.1; XM_017010011.1. [O15460-2] DR UniGene; Hs.519568; -. DR UniGene; Hs.659712; -. DR PDB; 6EVL; X-ray; 1.87 A; A=163-257. DR PDB; 6EVM; X-ray; 2.00 A; A=163-257. DR PDB; 6EVN; X-ray; 1.48 A; A=163-257. DR PDB; 6EVO; X-ray; 1.55 A; A=163-257. DR PDB; 6EVP; X-ray; 1.68 A; A=163-257. DR PDBsum; 6EVL; -. DR PDBsum; 6EVM; -. DR PDBsum; 6EVN; -. DR PDBsum; 6EVO; -. DR PDBsum; 6EVP; -. DR ProteinModelPortal; O15460; -. DR SMR; O15460; -. DR BioGrid; 114464; 97. DR IntAct; O15460; 31. DR MINT; O15460; -. DR STRING; 9606.ENSP00000166534; -. DR ChEMBL; CHEMBL5640; -. DR DrugBank; DB00172; L-Proline. DR DrugBank; DB00139; Succinic acid. DR iPTMnet; O15460; -. DR PhosphoSitePlus; O15460; -. DR BioMuta; P4HA2; -. DR EPD; O15460; -. DR jPOST; O15460; -. DR MaxQB; O15460; -. DR PaxDb; O15460; -. DR PeptideAtlas; O15460; -. DR PRIDE; O15460; -. DR ProteomicsDB; 48680; -. DR ProteomicsDB; 48681; -. [O15460-2] DR DNASU; 8974; -. DR Ensembl; ENST00000166534; ENSP00000166534; ENSG00000072682. [O15460-1] DR Ensembl; ENST00000360568; ENSP00000353772; ENSG00000072682. [O15460-2] DR Ensembl; ENST00000379086; ENSP00000368379; ENSG00000072682. [O15460-2] DR Ensembl; ENST00000379100; ENSP00000368394; ENSG00000072682. [O15460-2] DR Ensembl; ENST00000379104; ENSP00000368398; ENSG00000072682. [O15460-1] DR Ensembl; ENST00000401867; ENSP00000384999; ENSG00000072682. [O15460-1] DR GeneID; 8974; -. DR KEGG; hsa:8974; -. DR UCSC; uc003kwg.4; human. [O15460-1] DR CTD; 8974; -. DR DisGeNET; 8974; -. DR EuPathDB; HostDB:ENSG00000072682.18; -. DR GeneCards; P4HA2; -. DR HGNC; HGNC:8547; P4HA2. DR HPA; CAB062557; -. DR HPA; HPA016997; -. DR HPA; HPA027824; -. DR MalaCards; P4HA2; -. DR MIM; 600608; gene. DR MIM; 617238; phenotype. DR neXtProt; NX_O15460; -. DR OpenTargets; ENSG00000072682; -. DR PharmGKB; PA32875; -. DR eggNOG; KOG1591; Eukaryota. DR eggNOG; ENOG410XS5J; LUCA. DR GeneTree; ENSGT00940000157695; -. DR HOGENOM; HOG000230465; -. DR HOVERGEN; HBG006834; -. DR InParanoid; O15460; -. DR KO; K00472; -. DR OMA; HHGNRTP; -. DR OrthoDB; 391515at2759; -. DR PhylomeDB; O15460; -. DR TreeFam; TF313393; -. DR BRENDA; 1.14.11.2; 2681. DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes. DR ChiTaRS; P4HA2; human. DR GeneWiki; P4HA2; -. DR GenomeRNAi; 8974; -. DR PRO; PR:O15460; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; ENSG00000072682; Expressed in 211 organ(s), highest expression level in tibia. DR ExpressionAtlas; O15460; baseline and differential. DR Genevisible; O15460; HS. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW. DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IEA:InterPro. DR GO; GO:0004656; F:procollagen-proline 4-dioxygenase activity; TAS:ProtInc. DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IBA:GO_Central. DR Gene3D; 1.25.40.10; -; 1. DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase. DR InterPro; IPR006620; Pro_4_hyd_alph. DR InterPro; IPR013547; Pro_4_hyd_alph_N. DR InterPro; IPR013026; TPR-contain_dom. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR Pfam; PF13640; 2OG-FeII_Oxy_3; 1. DR Pfam; PF08336; P4Ha_N; 1. DR SMART; SM00702; P4Hc; 1. DR SUPFAM; SSF48452; SSF48452; 1. DR PROSITE; PS51471; FE2OG_OXY; 1. DR PROSITE; PS50005; TPR; 1. DR PROSITE; PS50293; TPR_REGION; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; Dioxygenase; KW Disease mutation; Endoplasmic reticulum; Glycoprotein; Iron; KW Metal-binding; Oxidoreductase; Reference proteome; Signal; TPR repeat; KW Vitamin C. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 535 Prolyl 4-hydroxylase subunit alpha-2. FT /FTId=PRO_0000022726. FT REPEAT 207 240 TPR. FT DOMAIN 412 520 Fe2OG dioxygenase. {ECO:0000255|PROSITE- FT ProRule:PRU00805}. FT METAL 430 430 Iron. {ECO:0000255|PROSITE- FT ProRule:PRU00805}. FT METAL 432 432 Iron. {ECO:0000255|PROSITE- FT ProRule:PRU00805}. FT METAL 501 501 Iron. {ECO:0000255|PROSITE- FT ProRule:PRU00805}. FT BINDING 511 511 2-oxoglutarate. {ECO:0000255|PROSITE- FT ProRule:PRU00805}. FT MOD_RES 480 480 N6-succinyllysine. FT {ECO:0000250|UniProtKB:Q60716}. FT CARBOHYD 115 115 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 264 264 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VAR_SEQ 436 451 NDERDTFKHLGTGNRV -> RPFDSGLKTEGNRL (in FT isoform IIa). FT {ECO:0000303|PubMed:12975309, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_004506. FT VARIANT 140 140 Q -> R (in MYP25; dbSNP:rs764211125). FT {ECO:0000269|PubMed:25741866}. FT /FTId=VAR_074026. FT VARIANT 150 150 I -> V (in MYP25; unknown pathological FT significance; dbSNP:rs771208496). FT {ECO:0000269|PubMed:25741866}. FT /FTId=VAR_074027. FT VARIANT 291 291 E -> K (in MYP25; decreases protein FT abundance; dbSNP:rs758872875). FT {ECO:0000269|PubMed:25741866}. FT /FTId=VAR_074028. FT HELIX 166 178 {ECO:0000244|PDB:6EVN}. FT HELIX 182 197 {ECO:0000244|PDB:6EVN}. FT HELIX 206 219 {ECO:0000244|PDB:6EVN}. FT HELIX 223 236 {ECO:0000244|PDB:6EVN}. FT HELIX 241 253 {ECO:0000244|PDB:6EVN}. SQ SEQUENCE 535 AA; 60902 MW; FD04467B098F63CF CRC64; MKLWVSALLM AWFGVLSCVQ AEFFTSIGHM TDLIYAEKEL VQSLKEYILV EEAKLSKIKS WANKMEALTS KSAADAEGYL AHPVNAYKLV KRLNTDWPAL EDLVLQDSAA GFIANLSVQR QFFPTDEDEI GAAKALMRLQ DTYRLDPGTI SRGELPGTKY QAMLSVDDCF GMGRSAYNEG DYYHTVLWME QVLKQLDAGE EATTTKSQVL DYLSYAVFQL GDLHRALELT RRLLSLDPSH ERAGGNLRYF EQLLEEEREK TLTNQTEAEL ATPEGIYERP VDYLPERDVY ESLCRGEGVK LTPRRQKRLF CRYHHGNRAP QLLIAPFKEE DEWDSPHIVR YYDVMSDEEI ERIKEIAKPK LARATVRDPK TGVLTVASYR VSKSSWLEED DDPVVARVNR RMQHITGLTV KTAELLQVAN YGVGGQYEPH FDFSRNDERD TFKHLGTGNR VATFLNYMSD VEAGGATVFP DLGAAIWPKK GTAVFWYNLL RSGEGDYRTR HAACPVLVGC KWVSNKWFHE RGQEFLRPCG STEVD //