HSDL2_HUMAN
ID HSDL2_HUMAN Reviewed; 418 AA.
AC Q6YN16; A8K1L4; A8K8X1; A8MSV3; Q658M8; Q9BT58;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Hydroxysteroid dehydrogenase-like protein 2;
DE EC=1.-.-.-;
DE AltName: Full=Short chain dehydrogenase/reductase family 13C member 1;
GN Name=HSDL2; Synonyms=C9orf99, SDR13C1;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=12834046; DOI=10.1023/a:1023377627138;
RA Dai J., Xie Y., Wu Q., Wang L., Yin G., Ye X., Zeng L., Xu J., Ji C.,
RA Gu S., Huang Q., Zhao R.C., Mao Y.;
RT "Molecular cloning and characterization of a novel human hydroxysteroid
RT dehydrogenase-like 2 (HSDL2) cDNA from fetal brain.";
RL Biochem. Genet. 41:165-174(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Hippocampus, and Testis;
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=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Blood vessel, and Uterus;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 78-418 (ISOFORM 1).
RC TISSUE=Stomach;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19703561; DOI=10.1016/j.jsbmb.2009.08.001;
RA Kowalik D., Haller F., Adamski J., Moeller G.;
RT "In search for function of two human orphan SDR enzymes: Hydroxysteroid
RT dehydrogenase like 2 (HSDL2) and short-chain dehydrogenase/reductase-orphan
RT (SDR-O).";
RL J. Steroid Biochem. Mol. Biol. 117:117-124(2009).
RN [8]
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., Buerckstuemmer T.,
RA 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 [9]
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [11]
RP HYDROXYBUTYRYLATION AT LYS-42.
RX PubMed=29192674; DOI=10.1038/cr.2017.149;
RA Huang H., Luo Z., Qi S., Huang J., Xu P., Wang X., Gao L., Li F., Wang J.,
RA Zhao W., Gu W., Chen Z., Dai L., Dai J., Zhao Y.;
RT "Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation
RT pathway.";
RL Cell Res. 28:111-125(2018).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 1-293 IN COMPLEX WITH NADP.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the catalytic domain of human hydroxysteroid
RT dehydrogenase like 2 (HSDL2).";
RL Submitted (MAR-2010) to the PDB data bank.
CC -!- FUNCTION: Has apparently no steroid dehydrogenase activity.
CC {ECO:0000269|PubMed:19703561}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:19703561}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6YN16-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6YN16-2; Sequence=VSP_031529;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:12834046}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AY093428; AAM14670.1; -; mRNA.
DR EMBL; AK292486; BAF85175.1; -; mRNA.
DR EMBL; AK289929; BAF82618.1; -; mRNA.
DR EMBL; AL162732; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471105; EAW59105.1; -; Genomic_DNA.
DR EMBL; CH471105; EAW59106.1; -; Genomic_DNA.
DR EMBL; BC004331; AAH04331.1; -; mRNA.
DR EMBL; BC095451; AAH95451.1; -; mRNA.
DR EMBL; AL833735; CAH56256.1; -; mRNA.
DR CCDS; CCDS43864.1; -. [Q6YN16-1]
DR CCDS; CCDS56582.1; -. [Q6YN16-2]
DR RefSeq; NP_001182751.1; NM_001195822.1. [Q6YN16-2]
DR RefSeq; NP_115679.2; NM_032303.4. [Q6YN16-1]
DR PDB; 3KVO; X-ray; 2.25 A; A/B=1-293.
DR PDBsum; 3KVO; -.
DR AlphaFoldDB; Q6YN16; -.
DR SMR; Q6YN16; -.
DR BioGRID; 123990; 111.
DR IntAct; Q6YN16; 37.
DR MINT; Q6YN16; -.
DR STRING; 9606.ENSP00000381785; -.
DR iPTMnet; Q6YN16; -.
DR PhosphoSitePlus; Q6YN16; -.
DR SwissPalm; Q6YN16; -.
DR BioMuta; HSDL2; -.
DR DMDM; 74749521; -.
DR UCD-2DPAGE; Q6YN16; -.
DR EPD; Q6YN16; -.
DR jPOST; Q6YN16; -.
DR MassIVE; Q6YN16; -.
DR MaxQB; Q6YN16; -.
DR PaxDb; Q6YN16; -.
DR PeptideAtlas; Q6YN16; -.
DR PRIDE; Q6YN16; -.
DR ProteomicsDB; 67855; -. [Q6YN16-1]
DR ProteomicsDB; 67856; -. [Q6YN16-2]
DR Antibodypedia; 29681; 155 antibodies from 25 providers.
DR DNASU; 84263; -.
DR Ensembl; ENST00000398803.1; ENSP00000381783.1; ENSG00000119471.15. [Q6YN16-2]
DR Ensembl; ENST00000398805.8; ENSP00000381785.3; ENSG00000119471.15. [Q6YN16-1]
DR GeneID; 84263; -.
DR KEGG; hsa:84263; -.
DR MANE-Select; ENST00000398805.8; ENSP00000381785.3; NM_032303.5; NP_115679.2.
DR UCSC; uc004bga.3; human. [Q6YN16-1]
DR CTD; 84263; -.
DR DisGeNET; 84263; -.
DR GeneCards; HSDL2; -.
DR HGNC; HGNC:18572; HSDL2.
DR HPA; ENSG00000119471; Tissue enhanced (tongue).
DR neXtProt; NX_Q6YN16; -.
DR OpenTargets; ENSG00000119471; -.
DR PharmGKB; PA134980105; -.
DR VEuPathDB; HostDB:ENSG00000119471; -.
DR eggNOG; KOG0725; Eukaryota.
DR eggNOG; KOG4170; Eukaryota.
DR GeneTree; ENSGT00940000156729; -.
DR HOGENOM; CLU_010194_25_0_1; -.
DR InParanoid; Q6YN16; -.
DR OMA; KFGMSLC; -.
DR OrthoDB; 1361949at2759; -.
DR PhylomeDB; Q6YN16; -.
DR TreeFam; TF101523; -.
DR PathwayCommons; Q6YN16; -.
DR SignaLink; Q6YN16; -.
DR BioGRID-ORCS; 84263; 11 hits in 1082 CRISPR screens.
DR ChiTaRS; HSDL2; human.
DR EvolutionaryTrace; Q6YN16; -.
DR GenomeRNAi; 84263; -.
DR Pharos; Q6YN16; Tbio.
DR PRO; PR:Q6YN16; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q6YN16; protein.
DR Bgee; ENSG00000119471; Expressed in heart right ventricle and 198 other tissues.
DR ExpressionAtlas; Q6YN16; baseline and differential.
DR Genevisible; Q6YN16; HS.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1050.10; -; 1.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR003033; SCP2_sterol-bd_dom.
DR InterPro; IPR036527; SCP2_sterol-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR Pfam; PF02036; SCP2; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF55718; SSF55718; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Hydroxylation; NADP;
KW Oxidoreductase; Peroxisome; Reference proteome.
FT CHAIN 1..418
FT /note="Hydroxysteroid dehydrogenase-like protein 2"
FT /id="PRO_0000319888"
FT DOMAIN 306..415
FT /note="SCP2"
FT ACT_SITE 168
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 17..23
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.12"
FT BINDING 42
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.12"
FT BINDING 74
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.12"
FT BINDING 172
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.12"
FT MOD_RES 42
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000269|PubMed:29192674"
FT MOD_RES 116
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q2TPA8"
FT MOD_RES 318
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q2TPA8"
FT VAR_SEQ 94..166
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_031529"
FT CONFLICT 62
FT /note="E -> G (in Ref. 2; BAF82618)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="I -> V (in Ref. 2; BAF85175)"
FT /evidence="ECO:0000305"
FT TURN 7..10
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 12..16
FT /evidence="ECO:0007829|PDB:3KVO"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 21..31
FT /evidence="ECO:0007829|PDB:3KVO"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 54..63
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 78..92
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:3KVO"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 115..124
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 126..140
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 166..185
FT /evidence="ECO:0007829|PDB:3KVO"
FT TURN 186..189
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 191..196
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 204..209
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 222..232
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 245..251
FT /evidence="ECO:0007829|PDB:3KVO"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:3KVO"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:3KVO"
SQ SEQUENCE 418 AA; 45395 MW; A8B27CC7D6F1B636 CRC64;
MLPNTGRLAG CTVFITGASR GIGKAIALKA AKDGANIVIA AKTAQPHPKL LGTIYTAAEE
IEAVGGKALP CIVDVRDEQQ ISAAVEKAIK KFGGIDILVN NASAISLTNT LDTPTKRLDL
MMNVNTRGTY LASKACIPYL KKSKVAHILN ISPPLNLNPV WFKQHCAYTI AKYGMSMYVL
GMAEEFKGEI AVNALWPKTA IHTAAMDMLG GPGIESQCRK VDIIADAAYS IFQKPKSFTG
NFVIDENILK EEGIENFDVY AIKPGHPLQP DFFLDEYPEA VSKKVESTGA VPEFKEEKLQ
LQPKPRSGAV EETFRIVKDS LSDDVVKATQ AIYLFELSGE DGGTWFLDLK SKGGNVGYGE
PSDQADVVMS MTTDDFVKMF SGKLKPTMAF MSGKLKIKGN MALAIKLEKL MNQMNARL
