KDSR_HUMAN
ID KDSR_HUMAN Reviewed; 332 AA.
AC Q06136; B2R5Y1; B4DMX0;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=3-ketodihydrosphingosine reductase;
DE Short=KDS reductase;
DE EC=1.1.1.102;
DE AltName: Full=3-dehydrosphinganine reductase;
DE AltName: Full=Follicular variant translocation protein 1;
DE Short=FVT-1;
DE AltName: Full=Short chain dehydrogenase/reductase family 35C member 1;
DE Flags: Precursor;
GN Name=KDSR; Synonyms=FVT1, SDR35C1;
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 CHROMOSOMAL TRANSLOCATION WITH
RP KDSR.
RX PubMed=8417785;
RA Rimokh R., Gadoux M., Bertheas M.-F., Berger F., Garoscio M., Deleage G.,
RA Germain D., Magaud J.-P.;
RT "FVT-1, a novel human transcription unit affected by variant translocation
RT t(2;18)(p11;q21) of follicular lymphoma.";
RL Blood 81:136-142(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Amygdala, and Heart;
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 GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [7]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MEMBRANE TOPOLOGY.
RX PubMed=15328338; DOI=10.1074/jbc.m405915200;
RA Kihara A., Igarashi Y.;
RT "FVT-1 is a mammalian 3-ketodihydrosphingosine reductase with an active
RT site that faces the cytosolic side of the endoplasmic reticulum membrane.";
RL J. Biol. Chem. 279:49243-49250(2004).
RN [8]
RP VARIANTS EKVP4 55-GLN-GLY-56 DELINS ARG; 86-VAL--GLN-107 DEL; PHE-186 AND
RP 260-GLN--GLN-293 DEL, CHARACTERIZATION OF VARIANTS EKVP4 55-GLN-GLY-56
RP DELINS ARG; 86-VAL--GLN-107 DEL AND 260-GLN--GLN-293 DEL, AND FUNCTION.
RX PubMed=28575652; DOI=10.1016/j.ajhg.2017.05.003;
RA Boyden L.M., Vincent N.G., Zhou J., Hu R., Craiglow B.G., Bayliss S.J.,
RA Rosman I.S., Lucky A.W., Diaz L.A., Goldsmith L.A., Paller A.S.,
RA Lifton R.P., Baserga S.J., Choate K.A.;
RT "Mutations in KDSR cause recessive progressive symmetric
RT erythrokeratoderma.";
RL Am. J. Hum. Genet. 100:978-984(2017).
CC -!- FUNCTION: Catalyzes the reduction of 3-ketodihydrosphingosine (KDS) to
CC dihydrosphingosine (DHS). {ECO:0000269|PubMed:28575652}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + sphinganine = 3-oxosphinganine + H(+) + NADPH;
CC Xref=Rhea:RHEA:22640, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:57817, ChEBI:CHEBI:58299, ChEBI:CHEBI:58349;
CC EC=1.1.1.102; Evidence={ECO:0000269|PubMed:15328338};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC -!- INTERACTION:
CC Q06136; P04792: HSPB1; NbExp=3; IntAct=EBI-3909166, EBI-352682;
CC Q06136; O60333-2: KIF1B; NbExp=3; IntAct=EBI-3909166, EBI-10975473;
CC Q06136; P02766: TTR; NbExp=3; IntAct=EBI-3909166, EBI-711909;
CC Q06136; O76024: WFS1; NbExp=3; IntAct=EBI-3909166, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15328338}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15328338}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q06136-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q06136-2; Sequence=VSP_056641;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined. Highest
CC expression in placenta. High expression in lung, kidney, stomach and
CC small intestine, low expression in heart, spleen and skeletal muscle.
CC Weakly expressed in normal hematopoietic tissues. Higher expression in
CC some T-cell malignancies and PHA-stimulated lymphocytes.
CC -!- DISEASE: Note=A chromosomal aberration involving KDSR is a cause of
CC follicular lymphoma; also known as type II chronic lymphatic leukemia.
CC Translocation t(2;18)(p11;q21) with a Ig J kappa chain region
CC (PubMed:8417785). {ECO:0000269|PubMed:8417785}.
CC -!- DISEASE: Erythrokeratodermia variabilis et progressiva 4 (EKVP4)
CC [MIM:617526]: A form of erythrokeratodermia variabilis et progressiva,
CC a genodermatosis characterized by the coexistence of two independent
CC skin lesions: transient erythema and hyperkeratosis that is usually
CC localized but occasionally occurs in its generalized form. Clinical
CC presentation varies significantly within a family and from one family
CC to another. Palmoplantar keratoderma is present in around 50% of cases.
CC {ECO:0000269|PubMed:28575652}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; X63657; CAA45197.1; -; mRNA.
DR EMBL; BT006782; AAP35428.1; -; mRNA.
DR EMBL; AK297670; BAG60032.1; -; mRNA.
DR EMBL; AK312360; BAG35278.1; -; mRNA.
DR EMBL; AC021803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC036176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471096; EAW63140.1; -; Genomic_DNA.
DR EMBL; BC008797; AAH08797.1; -; mRNA.
DR CCDS; CCDS11982.1; -. [Q06136-1]
DR PIR; S37652; S37652.
DR RefSeq; NP_002026.1; NM_002035.2. [Q06136-1]
DR AlphaFoldDB; Q06136; -.
DR SMR; Q06136; -.
DR BioGRID; 108807; 157.
DR IntAct; Q06136; 17.
DR MINT; Q06136; -.
DR STRING; 9606.ENSP00000385083; -.
DR SwissLipids; SLP:000000155; -.
DR iPTMnet; Q06136; -.
DR PhosphoSitePlus; Q06136; -.
DR SwissPalm; Q06136; -.
DR BioMuta; KDSR; -.
DR DMDM; 544358; -.
DR EPD; Q06136; -.
DR jPOST; Q06136; -.
DR MassIVE; Q06136; -.
DR MaxQB; Q06136; -.
DR PaxDb; Q06136; -.
DR PeptideAtlas; Q06136; -.
DR PRIDE; Q06136; -.
DR ProteomicsDB; 4650; -.
DR ProteomicsDB; 58417; -. [Q06136-1]
DR Antibodypedia; 23084; 144 antibodies from 24 providers.
DR DNASU; 2531; -.
DR Ensembl; ENST00000326575.9; ENSP00000312939.5; ENSG00000119537.18. [Q06136-2]
DR Ensembl; ENST00000645214.2; ENSP00000494352.1; ENSG00000119537.18. [Q06136-1]
DR GeneID; 2531; -.
DR KEGG; hsa:2531; -.
DR MANE-Select; ENST00000645214.2; ENSP00000494352.1; NM_002035.4; NP_002026.1.
DR UCSC; uc010dpw.4; human. [Q06136-1]
DR CTD; 2531; -.
DR DisGeNET; 2531; -.
DR GeneCards; KDSR; -.
DR HGNC; HGNC:4021; KDSR.
DR HPA; ENSG00000119537; Low tissue specificity.
DR MalaCards; KDSR; -.
DR MIM; 136440; gene.
DR MIM; 617526; phenotype.
DR neXtProt; NX_Q06136; -.
DR OpenTargets; ENSG00000119537; -.
DR Orphanet; 317; Erythrokeratodermia variabilis.
DR Orphanet; 316; Progressive symmetric erythrokeratodermia.
DR PharmGKB; PA162392777; -.
DR VEuPathDB; HostDB:ENSG00000119537; -.
DR eggNOG; KOG1210; Eukaryota.
DR GeneTree; ENSGT00940000156961; -.
DR InParanoid; Q06136; -.
DR OMA; NCAGMAI; -.
DR PhylomeDB; Q06136; -.
DR TreeFam; TF105430; -.
DR BioCyc; MetaCyc:HS04306-MON; -.
DR BRENDA; 1.1.1.102; 2681.
DR PathwayCommons; Q06136; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; Q06136; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 2531; 230 hits in 1083 CRISPR screens.
DR ChiTaRS; KDSR; human.
DR GeneWiki; 3-dehydrosphinganine_reductase; -.
DR GenomeRNAi; 2531; -.
DR Pharos; Q06136; Tbio.
DR PRO; PR:Q06136; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q06136; protein.
DR Bgee; ENSG00000119537; Expressed in endothelial cell and 199 other tissues.
DR ExpressionAtlas; Q06136; baseline and differential.
DR Genevisible; Q06136; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0047560; F:3-dehydrosphinganine reductase activity; IDA:MGI.
DR GO; GO:0006666; P:3-keto-sphinganine metabolic process; IDA:MGI.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IBA:GO_Central.
DR CDD; cd08939; KDSR-like_SDR_c; 1.
DR InterPro; IPR045022; KDSR-like.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromosomal rearrangement; Disease variant;
KW Endoplasmic reticulum; Lipid metabolism; Membrane; NADP; Oxidoreductase;
KW Palmoplantar keratoderma; Proto-oncogene; Reference proteome; Signal;
KW Sphingolipid metabolism; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..332
FT /note="3-ketodihydrosphingosine reductase"
FT /id="PRO_0000031982"
FT TOPO_DOM 26..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..293
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..314
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 315..332
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 186
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT ACT_SITE 190
FT /evidence="ECO:0000305"
FT BINDING 36..60
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000305"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 139..202
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056641"
FT VARIANT 55..56
FT /note="QG -> R (in EKVP4; loss of 3-dehydrosphinganine
FT reductase activity)"
FT /evidence="ECO:0000269|PubMed:28575652"
FT /id="VAR_079185"
FT VARIANT 86..107
FT /note="Missing (in EKVP4; loss of 3-dehydrosphinganine
FT reductase activity)"
FT /evidence="ECO:0000269|PubMed:28575652"
FT /id="VAR_079186"
FT VARIANT 186
FT /note="Y -> F (in EKVP4; dbSNP:rs1114167452)"
FT /evidence="ECO:0000269|PubMed:28575652"
FT /id="VAR_079187"
FT VARIANT 260..293
FT /note="Missing (in EKVP4; loss of 3-dehydrosphinganine
FT reductase activity)"
FT /evidence="ECO:0000269|PubMed:28575652"
FT /id="VAR_079188"
SQ SEQUENCE 332 AA; 36187 MW; CB4BA5D020858F0C CRC64;
MLLLAAAFLV AFVLLLYMVS PLISPKPLAL PGAHVVVTGG SSGIGKCIAI ECYKQGAFIT
LVARNEDKLL QAKKEIEMHS INDKQVVLCI SVDVSQDYNQ VENVIKQAQE KLGPVDMLVN
CAGMAVSGKF EDLEVSTFER LMSINYLGSV YPSRAVITTM KERRVGRIVF VSSQAGQLGL
FGFTAYSASK FAIRGLAEAL QMEVKPYNVY ITVAYPPDTD TPGFAEENRT KPLETRLISE
TTSVCKPEQV AKQIVKDAIQ GNFNSSLGSD GYMLSALTCG MAPVTSITEG LQQVVTMGLF
RTIALFYLGS FDSIVRRCMM QREKSENADK TA
