ALKB7_HUMAN
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 03-AUG-2022, entry version 136.
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; Q9H1P6: C20orf85; NbExp=3; IntAct=EBI-2878075, EBI-12155483;
CC Q9BT30; Q96H22-3: CENPN; NbExp=3; IntAct=EBI-2878075, EBI-19948078;
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}.
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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; 24.
DR IntAct; Q9BT30; 6.
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; Q9BT30; -.
DR PeptideAtlas; Q9BT30; -.
DR PRIDE; Q9BT30; -.
DR ProteomicsDB; 78947; -.
DR Antibodypedia; 42538; 81 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 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; 1181737at2759; -.
DR PhylomeDB; Q9BT30; -.
DR TreeFam; TF314197; -.
DR PathwayCommons; Q9BT30; -.
DR SignaLink; Q9BT30; -.
DR BioGRID-ORCS; 84266; 11 hits in 1080 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 179 other tissues.
DR ExpressionAtlas; Q9BT30; baseline and differential.
DR Genevisible; Q9BT30; HS.
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:cellular response to DNA damage stimulus; 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; -; 1.
DR InterPro; IPR027450; AlkB-like.
DR InterPro; IPR037151; AlkB-like_sf.
DR InterPro; IPR032870; ALKBH7.
DR PANTHER; PTHR21052; PTHR21052; 1.
DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1.
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
