ID ALKB7_HUMAN Reviewed; 221 AA. AC Q9BT30; B2R4U9; Q53FF3; DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 27-MAR-2024, entry version 145. DE RecName: Full=Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial; DE EC=1.14.11.-; DE AltName: Full=Alkylated DNA repair protein alkB homolog 7; DE AltName: Full=Spermatogenesis cell proliferation-related protein; DE AltName: Full=Spermatogenesis-associated protein 11; DE Flags: Precursor; GN Name=ALKBH7; Synonyms=ABH7, SPATA11; ORFNames=UNQ6002/PRO34564; 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]. RA Mo Y., Li L., Lu G.; RT "Identification of a novel human testis overexpressed gene by digital RT differential display."; RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thymus; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; 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 [8] RP TISSUE SPECIFICITY. RX PubMed=17979886; DOI=10.1111/j.1582-4934.2007.00094.x; RA Tsujikawa K., Koike K., Kitae K., Shinkawa A., Arima H., Suzuki T., RA Tsuchiya M., Makino Y., Furukawa T., Konishi N., Yamamoto H.; RT "Expression and sub-cellular localization of human ABH family molecules."; RL J. Cell. Mol. Med. 11:1105-1116(2007). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-110. RX PubMed=23666923; DOI=10.1101/gad.215533.113; RA Fu D., Jordan J.J., Samson L.D.; RT "Human ALKBH7 is required for alkylation and oxidation-induced programmed RT necrosis."; RL Genes Dev. 27:1089-1100(2013). RN [12] 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 [13] RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 17-215 IN COMPLEX WITH RP 2-OXOGLUTARIC ACID AND MANGANESE, FUNCTION, COFACTOR, AND SUBUNIT. RX PubMed=25122757; DOI=10.1074/jbc.m114.590505; RA Wang G., He Q., Feng C., Liu Y., Deng Z., Qi X., Wu W., Mei P., Chen Z.; RT "The atomic-resolution structure of human Alkb homolog 7 (ALKBH7), a key RT protein for programmed necrosis and fat metabolism."; RL J. Biol. Chem. 289:27924-27936(2014). CC -!- FUNCTION: May function as protein hydroxylase; can catalyze auto- CC hydroxylation at Leu-110 (in vitro), but this activity may be due to CC the absence of the true substrate (PubMed:25122757). Required to induce CC programmed necrosis in response to DNA damage caused by cytotoxic CC alkylating agents. Acts by triggering the collapse of mitochondrial CC membrane potential and loss of mitochondrial function that leads to CC energy depletion and cell death (PubMed:23666923). ALKBH7-mediated CC necrosis is probably required to prevent the accumulation of cells with CC DNA damage (PubMed:23666923). Does not display DNA demethylase activity CC (PubMed:23666923). Involved in fatty acid metabolism (By similarity). CC {ECO:0000250|UniProtKB:Q9D6Z0, ECO:0000269|PubMed:23666923, CC ECO:0000269|PubMed:25122757}. CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:25122757}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305|PubMed:25122757}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:25122757}. CC -!- INTERACTION: CC Q9BT30; Q9BPU9: B9D2; NbExp=3; IntAct=EBI-2878075, EBI-6958971; CC Q9BT30; Q96H22-3: CENPN; NbExp=3; IntAct=EBI-2878075, EBI-19948078; CC Q9BT30; P13569: CFTR; NbExp=4; IntAct=EBI-2878075, EBI-349854; CC Q9BT30; Q9H1P6: CIMIP1; NbExp=3; IntAct=EBI-2878075, EBI-12155483; CC Q9BT30; Q5T5P2-6: KIAA1217; NbExp=3; IntAct=EBI-2878075, EBI-10188326; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:23666923}. CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in CC pancreas, followed by spleen, prostate, ovary and placenta. CC {ECO:0000269|PubMed:17979886}. CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}. CC -!- CAUTION: Was initially reported to localize both in cytoplasm and CC nucleus (PubMed:17979886). However, it was later shown it localizes in CC mitochondrion (PubMed:23666923). The discrepancy is probably due to the CC use of a fusion protein with an N-terminal tag in the initial report CC (PubMed:17979886). {ECO:0000305|PubMed:17979886, CC ECO:0000305|PubMed:23666923}. 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; AY427650; AAR24624.1; -; mRNA. DR EMBL; AY358858; AAQ89217.1; -; mRNA. DR EMBL; AK223336; BAD97056.1; -; mRNA. DR EMBL; AK311956; BAG34896.1; -; mRNA. DR EMBL; AC011491; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471139; EAW69102.1; -; Genomic_DNA. DR EMBL; BC004393; AAH04393.1; -; mRNA. DR CCDS; CCDS12163.1; -. DR RefSeq; NP_115682.1; NM_032306.3. DR PDB; 4QKB; X-ray; 2.60 A; A/B/C=17-215. DR PDB; 4QKD; X-ray; 1.35 A; A/B/C=17-215. DR PDB; 4QKF; X-ray; 1.99 A; A/B/C=17-215. DR PDBsum; 4QKB; -. DR PDBsum; 4QKD; -. DR PDBsum; 4QKF; -. DR AlphaFoldDB; Q9BT30; -. DR SMR; Q9BT30; -. DR BioGRID; 123993; 25. DR IntAct; Q9BT30; 7. DR MINT; Q9BT30; -. DR STRING; 9606.ENSP00000245812; -. DR GlyGen; Q9BT30; 1 site, 1 O-linked glycan (1 site). DR BioMuta; ALKBH7; -. DR DMDM; 74733083; -. DR EPD; Q9BT30; -. DR jPOST; Q9BT30; -. DR MassIVE; Q9BT30; -. DR MaxQB; Q9BT30; -. DR PaxDb; 9606-ENSP00000245812; -. DR PeptideAtlas; Q9BT30; -. DR ProteomicsDB; 78947; -. DR Pumba; Q9BT30; -. DR Antibodypedia; 42538; 99 antibodies from 22 providers. DR DNASU; 84266; -. DR Ensembl; ENST00000245812.8; ENSP00000245812.2; ENSG00000125652.8. DR GeneID; 84266; -. DR KEGG; hsa:84266; -. DR MANE-Select; ENST00000245812.8; ENSP00000245812.2; NM_032306.4; NP_115682.1. DR UCSC; uc002meo.3; human. DR AGR; HGNC:21306; -. DR CTD; 84266; -. DR DisGeNET; 84266; -. DR GeneCards; ALKBH7; -. DR HGNC; HGNC:21306; ALKBH7. DR HPA; ENSG00000125652; Tissue enhanced (testis). DR MIM; 613305; gene. DR neXtProt; NX_Q9BT30; -. DR OpenTargets; ENSG00000125652; -. DR PharmGKB; PA134905040; -. DR VEuPathDB; HostDB:ENSG00000125652; -. DR eggNOG; KOG4176; Eukaryota. DR GeneTree; ENSGT00390000014585; -. DR HOGENOM; CLU_092162_1_0_1; -. DR InParanoid; Q9BT30; -. DR OMA; VEPHMKR; -. DR OrthoDB; 141758at2759; -. DR PhylomeDB; Q9BT30; -. DR TreeFam; TF314197; -. DR PathwayCommons; Q9BT30; -. DR SignaLink; Q9BT30; -. DR BioGRID-ORCS; 84266; 11 hits in 1157 CRISPR screens. DR ChiTaRS; ALKBH7; human. DR GenomeRNAi; 84266; -. DR Pharos; Q9BT30; Tbio. DR PRO; PR:Q9BT30; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9BT30; Protein. DR Bgee; ENSG00000125652; Expressed in left testis and 181 other cell types or tissues. DR ExpressionAtlas; Q9BT30; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB. DR GO; GO:0010883; P:regulation of lipid storage; ISS:UniProtKB. DR GO; GO:1902445; P:regulation of mitochondrial membrane permeability involved in programmed necrotic cell death; IMP:UniProtKB. DR Gene3D; 2.60.120.590; Alpha-ketoglutarate-dependent dioxygenase AlkB-like; 1. DR InterPro; IPR027450; AlkB-like. DR InterPro; IPR037151; AlkB-like_sf. DR InterPro; IPR032870; ALKBH7-like. DR PANTHER; PTHR21052:SF0; ALPHA-KETOGLUTARATE-DEPENDENT DIOXYGENASE ALKB HOMOLOG 7, MITOCHONDRIAL; 1. DR PANTHER; PTHR21052; SPERMATOGENESIS ASSOCIATED 11-RELATED; 1. DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR Genevisible; Q9BT30; HS. PE 1: Evidence at protein level; KW 3D-structure; Dioxygenase; Iron; Metal-binding; Mitochondrion; Necrosis; KW Oxidoreductase; Reference proteome; Transit peptide. FT TRANSIT 1..20 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 21..221 FT /note="Alpha-ketoglutarate-dependent dioxygenase alkB FT homolog 7, mitochondrial" FT /id="PRO_0000239288" FT BINDING 121 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:25122757" FT BINDING 123 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:25122757" FT BINDING 165 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT BINDING 177 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:25122757" FT BINDING 197..199 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:25122757" FT BINDING 203 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT VARIANT 191 FT /note="R -> Q (in dbSNP:rs7540)" FT /id="VAR_048224" FT MUTAGEN 110 FT /note="L->Q: Does not affect ability to trigger programmed FT necrosis." FT /evidence="ECO:0000269|PubMed:23666923" FT CONFLICT 89 FT /note="L -> P (in Ref. 4; BAD97056)" FT /evidence="ECO:0000305" FT STRAND 18..22 FT /evidence="ECO:0007829|PDB:4QKD" FT HELIX 23..28 FT /evidence="ECO:0007829|PDB:4QKD" FT TURN 29..32 FT /evidence="ECO:0007829|PDB:4QKD" FT STRAND 33..36 FT /evidence="ECO:0007829|PDB:4QKD" FT HELIX 42..57 FT /evidence="ECO:0007829|PDB:4QKD" FT STRAND 69..78 FT /evidence="ECO:0007829|PDB:4QKD" FT HELIX 83..96 FT /evidence="ECO:0007829|PDB:4QKD" FT STRAND 105..121 FT /evidence="ECO:0007829|PDB:4QKD" FT TURN 125..127 FT /evidence="ECO:0007829|PDB:4QKD" FT STRAND 130..139 FT /evidence="ECO:0007829|PDB:4QKD" FT STRAND 141..149 FT /evidence="ECO:0007829|PDB:4QKD" FT STRAND 154..159 FT /evidence="ECO:0007829|PDB:4QKD" FT STRAND 164..168 FT /evidence="ECO:0007829|PDB:4QKD" FT HELIX 170..173 FT /evidence="ECO:0007829|PDB:4QKD" FT STRAND 175..179 FT /evidence="ECO:0007829|PDB:4QKD" FT HELIX 182..184 FT /evidence="ECO:0007829|PDB:4QKD" FT STRAND 197..204 FT /evidence="ECO:0007829|PDB:4QKD" SQ SEQUENCE 221 AA; 24516 MW; 3BB7DF2242A49949 CRC64; MAGTGLLALR TLPGPSWVRG SGPSVLSRLQ DAAVVRPGFL STAEEETLSR ELEPELRRRR YEYDHWDAAI HGFRETEKSR WSEASRAILQ RVQAAAFGPG QTLLSSVHVL DLEARGYIKP HVDSIKFCGA TIAGLSLLSP SVMRLVHTQE PGEWLELLLE PGSLYILRGS ARYDFSHEIL RDEESFFGER RIPRGRRISV ICRSLPEGMG PGESGQPPPA C //