SRAC1_HUMAN
ID SRAC1_HUMAN Reviewed; 654 AA.
AC Q96JX3; Q49AT1; Q5VTX3; Q6PKF3;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Protein SERAC1;
DE AltName: Full=Serine active site-containing protein 1;
GN Name=SERAC1;
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] (ISOFORM 1).
RC TISSUE=Placenta;
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 GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP THR-543.
RC TISSUE=Eye, and Testis;
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 [4]
RP INVOLVEMENT IN MEGDEL.
RX PubMed=23707711; DOI=10.1016/j.ymgme.2013.04.021;
RA Tort F., Garcia-Silva M.T., Ferrer-Cortes X., Navarro-Sastre A.,
RA Garcia-Villoria J., Coll M.J., Vidal E., Jimenez-Almazan J., Dopazo J.,
RA Briones P., Elpeleg O., Ribes A.;
RT "Exome sequencing identifies a new mutation in SERAC1 in a patient with 3-
RT methylglutaconic aciduria.";
RL Mol. Genet. Metab. 110:73-77(2013).
RN [5]
RP VARIANTS MEGDEL ASP-401; GLU-404; LEU-479 DEL AND THR-498, FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22683713; DOI=10.1038/ng.2325;
RA Wortmann S.B., Vaz F.M., Gardeitchik T., Vissers L.E., Renkema G.H.,
RA Schuurs-Hoeijmakers J.H., Kulik W., Lammens M., Christin C.,
RA Kluijtmans L.A., Rodenburg R.J., Nijtmans L.G., Grunewald A., Klein C.,
RA Gerhold J.M., Kozicz T., van Hasselt P.M., Harakalova M., Kloosterman W.,
RA Baric I., Pronicka E., Ucar S.K., Naess K., Singhal K.K., Krumina Z.,
RA Gilissen C., van Bokhoven H., Veltman J.A., Smeitink J.A., Lefeber D.J.,
RA Spelbrink J.N., Wevers R.A., Morava E., de Brouwer A.P.;
RT "Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial
RT function and intracellular cholesterol trafficking and cause dystonia and
RT deafness.";
RL Nat. Genet. 44:797-802(2012).
RN [6]
RP VARIANT MEGDEL GLU-526.
RX PubMed=28778788; DOI=10.1016/j.ejmg.2017.07.013;
RA Radha Rama Devi A., Lingappa L.;
RT "Novel mutations in SERAC1 gene in two Indian patients presenting with
RT dystonia and intellectual disability.";
RL Eur. J. Med. Genet. 61:100-103(2018).
CC -!- FUNCTION: Plays an important role in the phosphatidylglycerol
CC remodeling that is essential for both mitochondrial function and
CC intracellular cholesterol trafficking. May catalyze the remodeling of
CC phosphatidylglycerol and be involved in the transacylation-acylation
CC reaction to produce phosphatidylglycerol-36:1. May be involved in
CC bis(monoacylglycerol)phosphate biosynthetic pathway.
CC {ECO:0000269|PubMed:22683713}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:22683713}. Mitochondrion
CC {ECO:0000269|PubMed:22683713}. Note=Localizes at the endoplasmic
CC reticulum and at the endoplasmic reticulum-mitochondria interface.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96JX3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96JX3-2; Sequence=VSP_022859, VSP_022860;
CC Name=3;
CC IsoId=Q96JX3-3; Sequence=VSP_022857, VSP_022858;
CC -!- TISSUE SPECIFICITY: Widely expressed, with predominant expression in
CC fetal skeletal muscle and adult brain. In the brain, highest levels are
CC found in the frontal and occipital cortices, cerebellum and
CC hippocampus. {ECO:0000269|PubMed:22683713}.
CC -!- DISEASE: 3-methylglutaconic aciduria with deafness, encephalopathy, and
CC Leigh-like syndrome (MEGDEL) [MIM:614739]: An autosomal recessive
CC disorder characterized by childhood onset of delayed psychomotor
CC development or psychomotor regression, sensorineural deafness,
CC spasticity or dystonia, and increased excretion of 3-methylglutaconic
CC acid. Brain imaging shows cerebral and cerebellar atrophy as well as
CC lesions in the basal ganglia reminiscent of Leigh syndrome. Laboratory
CC studies show increased serum lactate and alanine, mitochondrial
CC oxidative phosphorylation defects, abnormal mitochondria, abnormal
CC phosphatidylglycerol and cardiolipin profiles in fibroblasts, and
CC abnormal accumulation of unesterified cholesterol within cells.
CC {ECO:0000269|PubMed:22683713, ECO:0000269|PubMed:23707711,
CC ECO:0000269|PubMed:28778788}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SERAC1 family. {ECO:0000305}.
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DR EMBL; AK027823; BAB55393.1; -; mRNA.
DR EMBL; AL135907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590703; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001705; AAH01705.1; -; mRNA.
DR EMBL; BC028594; AAH28594.1; -; mRNA.
DR CCDS; CCDS5255.1; -. [Q96JX3-1]
DR RefSeq; NP_116250.3; NM_032861.3. [Q96JX3-1]
DR AlphaFoldDB; Q96JX3; -.
DR BioGRID; 124380; 19.
DR IntAct; Q96JX3; 4.
DR STRING; 9606.ENSP00000356071; -.
DR ESTHER; human-SERAC1; PGAP1.
DR iPTMnet; Q96JX3; -.
DR PhosphoSitePlus; Q96JX3; -.
DR BioMuta; SERAC1; -.
DR DMDM; 74751971; -.
DR EPD; Q96JX3; -.
DR jPOST; Q96JX3; -.
DR MassIVE; Q96JX3; -.
DR MaxQB; Q96JX3; -.
DR PaxDb; Q96JX3; -.
DR PeptideAtlas; Q96JX3; -.
DR PRIDE; Q96JX3; -.
DR ProteomicsDB; 77011; -. [Q96JX3-1]
DR ProteomicsDB; 77012; -. [Q96JX3-2]
DR ProteomicsDB; 77013; -. [Q96JX3-3]
DR Antibodypedia; 20005; 103 antibodies from 21 providers.
DR DNASU; 84947; -.
DR Ensembl; ENST00000367101.5; ENSP00000356068.1; ENSG00000122335.17. [Q96JX3-2]
DR Ensembl; ENST00000647468.2; ENSP00000496731.1; ENSG00000122335.17. [Q96JX3-1]
DR GeneID; 84947; -.
DR KEGG; hsa:84947; -.
DR MANE-Select; ENST00000647468.2; ENSP00000496731.1; NM_032861.4; NP_116250.3.
DR UCSC; uc003qrc.3; human. [Q96JX3-1]
DR CTD; 84947; -.
DR DisGeNET; 84947; -.
DR GeneCards; SERAC1; -.
DR GeneReviews; SERAC1; -.
DR HGNC; HGNC:21061; SERAC1.
DR HPA; ENSG00000122335; Low tissue specificity.
DR MalaCards; SERAC1; -.
DR MIM; 614725; gene.
DR MIM; 614739; phenotype.
DR neXtProt; NX_Q96JX3; -.
DR OpenTargets; ENSG00000122335; -.
DR Orphanet; 352328; MEGDEL syndrome.
DR PharmGKB; PA134951844; -.
DR VEuPathDB; HostDB:ENSG00000122335; -.
DR eggNOG; KOG2029; Eukaryota.
DR GeneTree; ENSGT00390000003560; -.
DR HOGENOM; CLU_023317_1_0_1; -.
DR InParanoid; Q96JX3; -.
DR OMA; RRTEYIY; -.
DR OrthoDB; 1311762at2759; -.
DR PhylomeDB; Q96JX3; -.
DR TreeFam; TF319689; -.
DR PathwayCommons; Q96JX3; -.
DR SignaLink; Q96JX3; -.
DR BioGRID-ORCS; 84947; 17 hits in 1074 CRISPR screens.
DR ChiTaRS; SERAC1; human.
DR GeneWiki; SERAC1; -.
DR GenomeRNAi; 84947; -.
DR Pharos; Q96JX3; Tbio.
DR PRO; PR:Q96JX3; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q96JX3; protein.
DR Bgee; ENSG00000122335; Expressed in endothelial cell and 146 other tissues.
DR ExpressionAtlas; Q96JX3; baseline and differential.
DR Genevisible; Q96JX3; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0044233; C:mitochondria-associated endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0032367; P:intracellular cholesterol transport; IMP:UniProtKB.
DR GO; GO:0036148; P:phosphatidylglycerol acyl-chain remodeling; IMP:UniProtKB.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Deafness; Disease variant; Endoplasmic reticulum;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Mitochondrion;
KW Phospholipid biosynthesis; Phospholipid metabolism; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..654
FT /note="Protein SERAC1"
FT /id="PRO_0000274671"
FT TRANSMEM 32..54
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 163..167
FT /note="DYQYR -> GNETT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022857"
FT VAR_SEQ 168..654
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022858"
FT VAR_SEQ 469..531
FT /note="KSIAFRSNELLRKLRAAGVGDRPVVWISHSMGGLLVKKMLLEASTKPEMSTV
FT INNTRGIIFYS -> RSLLSISSGIVEGLESPLHSEATNFLGSSELLVLGIGQWFGYHI
FT AWEVFLSKRCCWKPLRSQK (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_022859"
FT VAR_SEQ 532..654
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_022860"
FT VARIANT 401
FT /note="G -> D (in MEGDEL)"
FT /evidence="ECO:0000269|PubMed:22683713"
FT /id="VAR_068442"
FT VARIANT 404
FT /note="G -> E (in MEGDEL)"
FT /evidence="ECO:0000269|PubMed:22683713"
FT /id="VAR_068443"
FT VARIANT 479
FT /note="Missing (in MEGDEL; dbSNP:rs1199625391)"
FT /evidence="ECO:0000269|PubMed:22683713"
FT /id="VAR_068444"
FT VARIANT 498
FT /note="S -> T (in MEGDEL; dbSNP:rs201941476)"
FT /evidence="ECO:0000269|PubMed:22683713"
FT /id="VAR_068445"
FT VARIANT 526
FT /note="G -> E (in MEGDEL; unknown pathological
FT significance; dbSNP:rs1554261079)"
FT /evidence="ECO:0000269|PubMed:28778788"
FT /id="VAR_080230"
FT VARIANT 543
FT /note="S -> T (in dbSNP:rs17849527)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030342"
FT CONFLICT 47
FT /note="F -> L (in Ref. 3; AAH28594)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 654 AA; 74147 MW; B40F3B41C0FBEDDE CRC64;
MSLAAYCVIC CRRIGTSTSP PKSGTHWRDI RNIIKFTGSL ILGGSLFLTY EVLALKKAVT
LDTQVVEREK MKSYIYVHTV SLDKGENHGI AWQARKELHK AVRKVLATSA KILRNPFADP
FSTVDIEDHE CAVWLLLRKS KSDDKTTRLE AVREMSETHH WHDYQYRIIA QACDPKTLIG
LARSEESDLR FFLLPPPLPS LKEDSSTEEE LRQLLASLPQ TELDECIQYF TSLALSESSQ
SLAAQKGGLW CFGGNGLPYA ESFGEVPSAT VEMFCLEAIV KHSEISTHCD KIEANGGLQL
LQRLYRLHKD CPKVQRNIMR VIGNMALNEH LHSSIVRSGW VSIMAEAMKS PHIMESSHAA
RILANLDRET VQEKYQDGVY VLHPQYRTSQ PIKADVLFIH GLMGAAFKTW RQQDSEQAVI
EKPMEDEDRY TTCWPKTWLA KDCPALRIIS VEYDTSLSDW RARCPMERKS IAFRSNELLR
KLRAAGVGDR PVVWISHSMG GLLVKKMLLE ASTKPEMSTV INNTRGIIFY SVPHHGSRLA
EYSVNIRYLL FPSLEVKELS KDSPALKTLQ DDFLEFAKDK NFQVLNFVET LPTYIGSMIK
LHVVPVESAD LGIGDLIPVD VNHLNICKPK KKDAFLYQRT LQFIREALAK DLEN