SDHF2_HUMAN
ID SDHF2_HUMAN Reviewed; 166 AA.
AC Q9NX18;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Succinate dehydrogenase assembly factor 2, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03057};
DE Short=SDH assembly factor 2 {ECO:0000255|HAMAP-Rule:MF_03057};
DE Short=SDHAF2 {ECO:0000255|HAMAP-Rule:MF_03057};
DE Flags: Precursor;
GN Name=SDHAF2 {ECO:0000255|HAMAP-Rule:MF_03057};
GN Synonyms=C11orf79, PGL2 {ECO:0000255|HAMAP-Rule:MF_03057},
GN SDH5 {ECO:0000255|HAMAP-Rule:MF_03057};
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 MRNA].
RC TISSUE=Lung;
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 [3]
RP VARIANT PGL2 ARG-78, CHARACTERIZATION OF VARIANT PGL2 ARG-78, FUNCTION,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SDHA.
RX PubMed=19628817; DOI=10.1126/science.1175689;
RA Hao H.-X., Khalimonchuk O., Schraders M., Dephoure N., Bayley J.-P.,
RA Kunst H., Devilee P., Cremers C.W.R.J., Schiffman J.D., Bentz B.G.,
RA Gygi S.P., Winge D.R., Kremer H., Rutter J.;
RT "SDH5, a gene required for flavination of succinate dehydrogenase, is
RT mutated in paraganglioma.";
RL Science 325:1139-1142(2009).
CC -!- FUNCTION: Plays an essential role in the assembly of succinate
CC dehydrogenase (SDH), an enzyme complex (also referred to as respiratory
CC complex II) that is a component of both the tricarboxylic acid (TCA)
CC cycle and the mitochondrial electron transport chain, and which couples
CC the oxidation of succinate to fumarate with the reduction of ubiquinone
CC (coenzyme Q) to ubiquinol. Required for flavinylation (covalent
CC attachment of FAD) of the flavoprotein subunit SDHA of the SDH
CC catalytic dimer. {ECO:0000255|HAMAP-Rule:MF_03057,
CC ECO:0000269|PubMed:19628817}.
CC -!- SUBUNIT: Interacts with SDHA within the SDH catalytic dimer.
CC {ECO:0000255|HAMAP-Rule:MF_03057, ECO:0000269|PubMed:19628817}.
CC -!- INTERACTION:
CC Q9NX18; P78329: CYP4F2; NbExp=3; IntAct=EBI-713250, EBI-1752413;
CC Q9NX18; P31040: SDHA; NbExp=3; IntAct=EBI-713250, EBI-1057265;
CC Q9NX18; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-713250, EBI-8652744;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000255|HAMAP-
CC Rule:MF_03057, ECO:0000269|PubMed:19628817}.
CC -!- DISEASE: Paragangliomas 2 (PGL2) [MIM:601650]: A neural crest tumor
CC usually derived from the chromoreceptor tissue of a paraganglion.
CC Paragangliomas can develop at various body sites, including the head,
CC neck, thorax and abdomen. Most commonly, they are located in the head
CC and neck region, specifically at the carotid bifurcation, the jugular
CC foramen, the vagal nerve, and in the middle ear.
CC {ECO:0000269|PubMed:19628817}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SDHAF2 family. {ECO:0000255|HAMAP-
CC Rule:MF_03057}.
CC -!- WEB RESOURCE: Name=TCA Cycle Gene Mutation Database;
CC URL="https://databases.lovd.nl/shared/genes/SDHAF2";
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DR EMBL; AK000494; BAA91204.1; -; mRNA.
DR EMBL; BC002331; AAH02331.1; -; mRNA.
DR CCDS; CCDS8007.1; -.
DR RefSeq; NP_060311.1; NM_017841.2.
DR PDB; 6VAX; X-ray; 2.59 A; B/D=1-166.
DR PDBsum; 6VAX; -.
DR AlphaFoldDB; Q9NX18; -.
DR SMR; Q9NX18; -.
DR BioGRID; 120288; 33.
DR DIP; DIP-61728N; -.
DR IntAct; Q9NX18; 18.
DR STRING; 9606.ENSP00000301761; -.
DR GlyGen; Q9NX18; 1 site.
DR iPTMnet; Q9NX18; -.
DR PhosphoSitePlus; Q9NX18; -.
DR BioMuta; SDHAF2; -.
DR DMDM; 74734683; -.
DR EPD; Q9NX18; -.
DR jPOST; Q9NX18; -.
DR MassIVE; Q9NX18; -.
DR MaxQB; Q9NX18; -.
DR PaxDb; Q9NX18; -.
DR PeptideAtlas; Q9NX18; -.
DR PRIDE; Q9NX18; -.
DR ProteomicsDB; 83023; -.
DR TopDownProteomics; Q9NX18; -.
DR Antibodypedia; 51652; 62 antibodies from 23 providers.
DR DNASU; 54949; -.
DR Ensembl; ENST00000301761.7; ENSP00000301761.3; ENSG00000167985.7.
DR GeneID; 54949; -.
DR KEGG; hsa:54949; -.
DR MANE-Select; ENST00000301761.7; ENSP00000301761.3; NM_017841.4; NP_060311.1.
DR UCSC; uc001nrt.4; human.
DR CTD; 54949; -.
DR DisGeNET; 54949; -.
DR GeneCards; SDHAF2; -.
DR GeneReviews; SDHAF2; -.
DR HGNC; HGNC:26034; SDHAF2.
DR HPA; ENSG00000167985; Low tissue specificity.
DR MalaCards; SDHAF2; -.
DR MIM; 601650; phenotype.
DR MIM; 613019; gene.
DR neXtProt; NX_Q9NX18; -.
DR OpenTargets; ENSG00000167985; -.
DR Orphanet; 29072; Hereditary pheochromocytoma-paraganglioma.
DR PharmGKB; PA165543618; -.
DR VEuPathDB; HostDB:ENSG00000167985; -.
DR eggNOG; KOG3326; Eukaryota.
DR GeneTree; ENSGT00390000001149; -.
DR HOGENOM; CLU_103054_0_2_1; -.
DR InParanoid; Q9NX18; -.
DR OMA; HVKNHEK; -.
DR OrthoDB; 1492851at2759; -.
DR PhylomeDB; Q9NX18; -.
DR TreeFam; TF300175; -.
DR PathwayCommons; Q9NX18; -.
DR SignaLink; Q9NX18; -.
DR SIGNOR; Q9NX18; -.
DR BioGRID-ORCS; 54949; 306 hits in 1080 CRISPR screens.
DR ChiTaRS; SDHAF2; human.
DR GenomeRNAi; 54949; -.
DR Pharos; Q9NX18; Tbio.
DR PRO; PR:Q9NX18; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9NX18; protein.
DR Bgee; ENSG00000167985; Expressed in islet of Langerhans and 159 other tissues.
DR ExpressionAtlas; Q9NX18; baseline and differential.
DR Genevisible; Q9NX18; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0006121; P:mitochondrial electron transport, succinate to ubiquinone; IMP:UniProtKB.
DR GO; GO:0034553; P:mitochondrial respiratory chain complex II assembly; IBA:GO_Central.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IMP:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; IGI:MGI.
DR GO; GO:0018293; P:protein-FAD linkage; IMP:UniProtKB.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR Gene3D; 1.10.150.250; -; 1.
DR HAMAP; MF_03057; SDHAF2; 1.
DR InterPro; IPR005631; SDH.
DR InterPro; IPR036714; SDH_sf.
DR InterPro; IPR028882; SDHAF2.
DR Pfam; PF03937; Sdh5; 1.
DR SUPFAM; SSF109910; SSF109910; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chaperone; Disease variant; Mitochondrion;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 30..166
FT /note="Succinate dehydrogenase assembly factor 2,
FT mitochondrial"
FT /id="PRO_0000294357"
FT VARIANT 78
FT /note="G -> R (in PGL2; abolishes interaction with SDHA and
FT flavination of SDHA; dbSNP:rs113560320)"
FT /evidence="ECO:0000269|PubMed:19628817"
FT /id="VAR_058705"
FT HELIX 63..75
FT /evidence="ECO:0007829|PDB:6VAX"
FT HELIX 80..93
FT /evidence="ECO:0007829|PDB:6VAX"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:6VAX"
FT HELIX 99..110
FT /evidence="ECO:0007829|PDB:6VAX"
FT HELIX 115..122
FT /evidence="ECO:0007829|PDB:6VAX"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:6VAX"
FT HELIX 135..144
FT /evidence="ECO:0007829|PDB:6VAX"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:6VAX"
SQ SEQUENCE 166 AA; 19599 MW; AB31FD150E1B6ECA CRC64;
MAVSTVFSTS SLMLALSRHS LLSPLLSVTS FRRFYRGDSP TDSQKDMIEI PLPPWQERTD
ESIETKRARL LYESRKRGML ENCILLSLFA KEHLQHMTEK QLNLYDRLIN EPSNDWDIYY
WATEAKPAPE IFENEVMALL RDFAKNKNKE QRLRAPDLEY LFEKPR
