ERG24_HUMAN
ID ERG24_HUMAN Reviewed; 418 AA.
AC O76062; A8K4H0; O95982; Q8IY06; Q96E64; Q96GZ1;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 3.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Delta(14)-sterol reductase TM7SF2;
DE Short=Delta-14-SR;
DE EC=1.3.1.70 {ECO:0000250|UniProtKB:Q8WMV1};
DE AltName: Full=3-beta-hydroxysterol Delta (14)-reductase {ECO:0000303|PubMed:16784888};
DE AltName: Full=Another new gene 1 protein;
DE AltName: Full=C-14 sterol reductase;
DE Short=C14SR {ECO:0000303|PubMed:16784888};
DE AltName: Full=Putative sterol reductase SR-1;
DE AltName: Full=Sterol C14-reductase;
DE AltName: Full=Transmembrane 7 superfamily member 2;
GN Name=TM7SF2; Synonyms=ANG1;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANT ILE-299.
RX PubMed=9615229; DOI=10.1006/geno.1998.5296;
RA Lemmens I.H., Kas K., Merregaert J., Van de Ven W.J.M.;
RT "Identification and molecular characterization of TM7SF2 in the FAUNA gene
RT cluster on human chromosome 11q13.";
RL Genomics 49:437-442(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT ILE-299,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9878250; DOI=10.1006/geno.1998.5615;
RA Holmer L., Pezhman A., Worman H.J.;
RT "The human lamin B receptor/sterol reductase multigene family.";
RL Genomics 54:469-476(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION.
RX PubMed=27336722; DOI=10.7554/elife.16011;
RA Tsai P.L., Zhao C., Turner E., Schlieker C.;
RT "The Lamin B receptor is essential for cholesterol synthesis and perturbed
RT by disease-causing mutations.";
RL Elife 5:0-0(2016).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-299.
RC TISSUE=Ovary;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ILE-299.
RC TISSUE=Brain, Eye, and Ovary;
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 FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16784888; DOI=10.1016/j.bbalip.2006.05.004;
RA Bennati A.M., Castelli M., Della Fazia M.A., Beccari T., Caruso D.,
RA Servillo G., Roberti R.;
RT "Sterol dependent regulation of human TM7SF2 gene expression: role of the
RT encoded 3beta-hydroxysterol Delta14-reductase in human cholesterol
RT biosynthesis.";
RL Biochim. Biophys. Acta 1761:677-685(2006).
CC -!- FUNCTION: Catalyzes the reduction of the C14-unsaturated bond of
CC lanosterol, as part of the metabolic pathway leading to cholesterol
CC biosynthesis. {ECO:0000269|PubMed:16784888}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP(+) =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + H(+) + NADPH;
CC Xref=Rhea:RHEA:18561, ChEBI:CHEBI:15378, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:18364, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.70;
CC Evidence={ECO:0000250|UniProtKB:Q8WMV1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-cholest-8,14-dien-3beta-ol + H(+) + NADPH = 5alpha-
CC cholest-8-en-3beta-ol + NADP(+); Xref=Rhea:RHEA:46456,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16608, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:86131;
CC Evidence={ECO:0000269|PubMed:16784888};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-8,14-cholestadien-3beta-ol + H(+) + NADPH = 4,4-
CC dimethyl-5alpha-cholest-8-en-3beta-ol + NADP(+);
CC Xref=Rhea:RHEA:46812, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78904, ChEBI:CHEBI:87044;
CC Evidence={ECO:0000250|UniProtKB:Q8WMV1};
CC -!- PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
CC -!- INTERACTION:
CC O76062; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2115348, EBI-3867333;
CC O76062; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-2115348, EBI-11973993;
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:Q71KT5}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9878250}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O76062-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O76062-2; Sequence=VSP_017898;
CC -!- TISSUE SPECIFICITY: Expressed in adult heart, brain, pancreas, lung,
CC liver, skeletal muscle, kidney, ovary, prostate, testis and adrenal
CC gland, but not detected in placenta, spleen, thymus, small intestine,
CC colon (mucosal lining), or peripheral blood leukocytes.
CC {ECO:0000269|PubMed:16784888, ECO:0000269|PubMed:9878250}.
CC -!- INDUCTION: By sterol starvation. {ECO:0000269|PubMed:16784888,
CC ECO:0000269|PubMed:27336722}.
CC -!- SIMILARITY: Belongs to the ERG4/ERG24 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC21450.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305};
CC Sequence=AAC21457.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305};
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DR EMBL; AF048704; AAC21457.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AF023676; AAC21450.1; ALT_FRAME; mRNA.
DR EMBL; AF096303; AAD09769.1; -; Genomic_DNA.
DR EMBL; AF096304; AAD09765.1; -; mRNA.
DR EMBL; AK290935; BAF83624.1; -; mRNA.
DR EMBL; BC009052; AAH09052.1; -; mRNA.
DR EMBL; BC012857; AAH12857.1; -; mRNA.
DR EMBL; BC038353; AAH38353.1; -; mRNA.
DR CCDS; CCDS41669.1; -. [O76062-1]
DR CCDS; CCDS60846.1; -. [O76062-2]
DR RefSeq; NP_001264162.1; NM_001277233.1. [O76062-2]
DR RefSeq; NP_003264.2; NM_003273.3. [O76062-1]
DR AlphaFoldDB; O76062; -.
DR SMR; O76062; -.
DR BioGRID; 112963; 12.
DR IntAct; O76062; 6.
DR MINT; O76062; -.
DR STRING; 9606.ENSP00000279263; -.
DR ChEMBL; CHEMBL5839; -.
DR SwissLipids; SLP:000001237; -.
DR iPTMnet; O76062; -.
DR PhosphoSitePlus; O76062; -.
DR SwissPalm; O76062; -.
DR BioMuta; TM7SF2; -.
DR EPD; O76062; -.
DR jPOST; O76062; -.
DR MassIVE; O76062; -.
DR MaxQB; O76062; -.
DR PaxDb; O76062; -.
DR PeptideAtlas; O76062; -.
DR PRIDE; O76062; -.
DR ProteomicsDB; 50368; -. [O76062-1]
DR ProteomicsDB; 50369; -. [O76062-2]
DR Antibodypedia; 29654; 123 antibodies from 23 providers.
DR DNASU; 7108; -.
DR Ensembl; ENST00000279263.14; ENSP00000279263.7; ENSG00000149809.17. [O76062-1]
DR Ensembl; ENST00000345348.9; ENSP00000329520.6; ENSG00000149809.17. [O76062-2]
DR GeneID; 7108; -.
DR KEGG; hsa:7108; -.
DR MANE-Select; ENST00000279263.14; ENSP00000279263.7; NM_003273.6; NP_003264.2.
DR UCSC; uc001oct.5; human. [O76062-1]
DR CTD; 7108; -.
DR DisGeNET; 7108; -.
DR GeneCards; TM7SF2; -.
DR HGNC; HGNC:11863; TM7SF2.
DR HPA; ENSG00000149809; Tissue enhanced (adrenal).
DR MIM; 603414; gene.
DR neXtProt; NX_O76062; -.
DR OpenTargets; ENSG00000149809; -.
DR PharmGKB; PA36564; -.
DR VEuPathDB; HostDB:ENSG00000149809; -.
DR eggNOG; KOG1435; Eukaryota.
DR GeneTree; ENSGT00390000000417; -.
DR HOGENOM; CLU_015631_0_3_1; -.
DR InParanoid; O76062; -.
DR OMA; GWIILNC; -.
DR PhylomeDB; O76062; -.
DR TreeFam; TF101179; -.
DR BRENDA; 1.3.1.70; 2681.
DR PathwayCommons; O76062; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR SignaLink; O76062; -.
DR UniPathway; UPA00063; -.
DR BioGRID-ORCS; 7108; 131 hits in 1076 CRISPR screens.
DR ChiTaRS; TM7SF2; human.
DR GeneWiki; TM7SF2; -.
DR GenomeRNAi; 7108; -.
DR Pharos; O76062; Tbio.
DR PRO; PR:O76062; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O76062; protein.
DR Bgee; ENSG00000149809; Expressed in right adrenal gland cortex and 178 other tissues.
DR ExpressionAtlas; O76062; baseline and differential.
DR Genevisible; O76062; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005637; C:nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0050613; F:delta14-sterol reductase activity; IDA:UniProtKB.
DR GO; GO:0050661; F:NADP binding; ISS:UniProtKB.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IBA:GO_Central.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR001171; ERG24_DHCR-like.
DR InterPro; IPR018083; Sterol_reductase_CS.
DR Pfam; PF01222; ERG4_ERG24; 1.
DR PROSITE; PS01017; STEROL_REDUCT_1; 1.
DR PROSITE; PS01018; STEROL_REDUCT_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Microsome; NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..418
FT /note="Delta(14)-sterol reductase TM7SF2"
FT /id="PRO_0000207500"
FT TRANSMEM 13..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 62..81
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 129..148
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..277
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..304
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..377
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 311
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 315
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 338
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 343
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 350..351
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 390
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 394..398
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 405
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT VAR_SEQ 298..324
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017898"
FT VARIANT 119
FT /note="A -> V (in dbSNP:rs11539360)"
FT /id="VAR_052153"
FT VARIANT 299
FT /note="T -> I (in dbSNP:rs1129195)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9615229,
FT ECO:0000269|PubMed:9878250"
FT /id="VAR_012716"
FT CONFLICT 179
FT /note="L -> V (in Ref. 5; AAH12857)"
FT /evidence="ECO:0000305"
FT CONFLICT 409
FT /note="V -> A (in Ref. 5; AAH38353)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 418 AA; 46406 MW; F5618ABE2BF0A911 CRC64;
MAPTQGPRAP LEFGGPLGAA ALLLLLPATM FHLLLAARSG PARLLGPPAS LPGLEVLWSP
RALLLWLAWL GLQAALYLLP ARKVAEGQEL KDKSRLRYPI NGFQALVLTA LLVGLGMSAG
LPLGALPEML LPLAFVATLT AFIFSLFLYM KAQVAPVSAL APGGNSGNPI YDFFLGRELN
PRICFFDFKY FCELRPGLIG WVLINLALLM KEAELRGSPS LAMWLVNGFQ LLYVGDALWH
EEAVLTTMDI THDGFGFMLA FGDMAWVPFT YSLQAQFLLH HPQPLGLPMA SVICLINATG
YYIFRGANSQ KNTFRKNPSD PRVAGLETIS TATGRKLLVS GWWGMVRHPN YLGDLIMALA
WSLPCGVSHL LPYFYLLYFT ALLVHREARD ERQCLQKYGL AWQEYCRRVP YRIMPYIY
