CLP1L_HUMAN
ID CLP1L_HUMAN Reviewed; 538 AA.
AC Q96KA5; D3DTC1; Q658W6; Q7LG29; Q96AZ0; Q9H3N4;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Lipid scramblase CLPTM1L {ECO:0000305|PubMed:35344438};
DE AltName: Full=Cisplatin resistance-related protein 9 {ECO:0000303|PubMed:35344438};
DE Short=CRR9p;
DE AltName: Full=Cleft lip and palate transmembrane protein 1-like protein;
DE Short=CLPTM1-like protein;
GN Name=CLPTM1L; Synonyms=CRR9;
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=Embryo;
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].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 130-538 (ISOFORM 2).
RC TISSUE=Colon, 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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-538 (ISOFORM 1), AND INDUCTION.
RX PubMed=11162647; DOI=10.1006/bbrc.2001.4250;
RA Yamamoto K., Okamoto A., Isonishi S., Ochiai K., Ohtake Y.;
RT "A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor
RT cell line, was associated with apoptosis.";
RL Biochem. Biophys. Res. Commun. 280:1148-1154(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 391-538 (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 [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-229.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [7]
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 [8]
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 [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=35344438; DOI=10.1073/pnas.2115083119;
RA Wang Y., Menon A.K., Maki Y., Liu Y.S., Iwasaki Y., Fujita M.,
RA Guerrero P.A., Silva D.V., Seeberger P.H., Murakami Y., Kinoshita T.;
RT "Genome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required
RT for efficient glycosylphosphatidylinositol biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 119:e2115083119-e2115083119(2022).
RN [10]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-313.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Scramblase that mediates the translocation of
CC glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-
CC glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic
CC reticulum (ER) membrane, from the cytosolic leaflet to the luminal
CC leaflet of the ER membrane, where it participates in the biosynthesis
CC of glycosylphosphatidylinositol (GPI) (PubMed:35344438). GPI is a lipid
CC glycoconjugate involved in post-translational modification of proteins
CC (PubMed:35344438). Can also translocate 1,2-diacyl-sn-glycero-3-
CC phospho-(1D-myo-inositol) (phosphatidylinositol or PI), as well as
CC several other phospholipids (1,2-diacyl-sn-glycero-3-phosphocholine,
CC 1,2-diacyl-sn-glycero-3-phosphoethanolamine), and N-
CC acetylglucosaminylphosphatidylinositol (GlcNAc-PI) in vitro
CC (PubMed:35344438). {ECO:0000269|PubMed:35344438}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an alpha-D-GlcN-(1->6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-
CC myo-inositol(in) = an alpha-D-GlcN-(1->6)-(1,2-diacyl-sn-glycero-3-
CC phospho)-1D-myo-inositol(out); Xref=Rhea:RHEA:71491,
CC ChEBI:CHEBI:57997; Evidence={ECO:0000269|PubMed:35344438};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-(alpha-D-glucosaminyl)-(1-octadecanoyl,2-(9Z)-octadecenoyl-
CC sn-glycero-3-phospho)-1D-myo-inositol(in) = 6-(alpha-D-glucosaminyl)-
CC (1-octadecanoyl,2-(9Z)-octadecenoyl-sn-glycero-3-phospho)-1D-myo-
CC inositol(out); Xref=Rhea:RHEA:71495, ChEBI:CHEBI:190691;
CC Evidence={ECO:0000269|PubMed:35344438};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(in) = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(out);
CC Xref=Rhea:RHEA:38691, ChEBI:CHEBI:57880;
CC Evidence={ECO:0000269|PubMed:35344438};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-
CC sn-glycero-3-phosphocholine(out); Xref=Rhea:RHEA:38571,
CC ChEBI:CHEBI:57643; Evidence={ECO:0000269|PubMed:35344438};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-
CC diacyl-sn-glycero-3-phosphoethanolamine(out); Xref=Rhea:RHEA:38895,
CC ChEBI:CHEBI:64612; Evidence={ECO:0000269|PubMed:35344438};
CC -!- INTERACTION:
CC Q96KA5; Q9H3M0: KCNF1; NbExp=3; IntAct=EBI-3216282, EBI-6918743;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:35344438}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96KA5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96KA5-2; Sequence=VSP_033157;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:35344438}.
CC -!- INDUCTION: Up-regulated by cisplatin. {ECO:0000269|PubMed:11162647}.
CC -!- SIMILARITY: Belongs to the CLPTM1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB20083.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK027306; BAB55030.1; -; mRNA.
DR EMBL; CH471102; EAX08162.1; -; Genomic_DNA.
DR EMBL; CH471102; EAX08163.1; -; Genomic_DNA.
DR EMBL; BC016399; AAH16399.1; -; mRNA.
DR EMBL; BC025305; AAH25305.1; -; mRNA.
DR EMBL; AB045223; BAB20083.1; ALT_INIT; mRNA.
DR EMBL; AL832953; CAH56333.1; -; mRNA.
DR CCDS; CCDS3862.1; -. [Q96KA5-1]
DR PIR; JC7599; JC7599.
DR RefSeq; NP_110409.2; NM_030782.4. [Q96KA5-1]
DR AlphaFoldDB; Q96KA5; -.
DR BioGRID; 123354; 124.
DR IntAct; Q96KA5; 34.
DR MINT; Q96KA5; -.
DR STRING; 9606.ENSP00000313854; -.
DR TCDB; 8.A.125.1.5; the cleft lip and palate transmembrane protein 1 (clptm1) family.
DR GlyConnect; 1117; 8 N-Linked glycans (2 sites).
DR GlyGen; Q96KA5; 4 sites, 10 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR iPTMnet; Q96KA5; -.
DR MetOSite; Q96KA5; -.
DR PhosphoSitePlus; Q96KA5; -.
DR SwissPalm; Q96KA5; -.
DR BioMuta; CLPTM1L; -.
DR DMDM; 74732209; -.
DR EPD; Q96KA5; -.
DR jPOST; Q96KA5; -.
DR MassIVE; Q96KA5; -.
DR MaxQB; Q96KA5; -.
DR PaxDb; Q96KA5; -.
DR PeptideAtlas; Q96KA5; -.
DR PRIDE; Q96KA5; -.
DR ProteomicsDB; 77054; -. [Q96KA5-1]
DR ProteomicsDB; 77055; -. [Q96KA5-2]
DR Antibodypedia; 3079; 217 antibodies from 22 providers.
DR DNASU; 81037; -.
DR Ensembl; ENST00000320895.10; ENSP00000313854.5; ENSG00000049656.14. [Q96KA5-1]
DR Ensembl; ENST00000620010.3; ENSP00000480372.1; ENSG00000274811.3. [Q96KA5-1]
DR GeneID; 81037; -.
DR KEGG; hsa:81037; -.
DR MANE-Select; ENST00000320895.10; ENSP00000313854.5; NM_030782.5; NP_110409.2.
DR UCSC; uc003jch.4; human. [Q96KA5-1]
DR CTD; 81037; -.
DR DisGeNET; 81037; -.
DR GeneCards; CLPTM1L; -.
DR HGNC; HGNC:24308; CLPTM1L.
DR HPA; ENSG00000049656; Low tissue specificity.
DR MIM; 612585; gene.
DR neXtProt; NX_Q96KA5; -.
DR OpenTargets; ENSG00000049656; -.
DR PharmGKB; PA147358156; -.
DR VEuPathDB; HostDB:ENSG00000049656; -.
DR eggNOG; KOG2489; Eukaryota.
DR GeneTree; ENSGT00530000063461; -.
DR HOGENOM; CLU_019907_4_1_1; -.
DR InParanoid; Q96KA5; -.
DR OMA; QFDRQGM; -.
DR OrthoDB; 1106937at2759; -.
DR PhylomeDB; Q96KA5; -.
DR TreeFam; TF318501; -.
DR PathwayCommons; Q96KA5; -.
DR SignaLink; Q96KA5; -.
DR BioGRID-ORCS; 81037; 8 hits in 1071 CRISPR screens.
DR ChiTaRS; CLPTM1L; human.
DR GeneWiki; CLPTM1L; -.
DR GenomeRNAi; 81037; -.
DR Pharos; Q96KA5; Tbio.
DR PRO; PR:Q96KA5; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q96KA5; protein.
DR Bgee; ENSG00000049656; Expressed in ileal mucosa and 179 other tissues.
DR ExpressionAtlas; Q96KA5; baseline and differential.
DR Genevisible; Q96KA5; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0017128; F:phospholipid scramblase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR InterPro; IPR008429; CLPTM1.
DR InterPro; IPR030434; CLPTM1L.
DR PANTHER; PTHR21347; PTHR21347; 1.
DR PANTHER; PTHR21347:SF12; PTHR21347:SF12; 1.
DR Pfam; PF05602; CLPTM1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Disease variant; Endoplasmic reticulum;
KW Glycoprotein; Lipid transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..538
FT /note="Lipid scramblase CLPTM1L"
FT /id="PRO_0000331300"
FT TOPO_DOM 1..10
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..284
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..305
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 306..324
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 325..342
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 343..346
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..364
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 365..402
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 403..423
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..428
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 429..449
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 450..538
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 325..360
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033157"
FT VARIANT 313
FT /note="K -> N (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_042754"
FT VARIANT 537
FT /note="T -> M (in dbSNP:rs33955038)"
FT /id="VAR_042755"
SQ SEQUENCE 538 AA; 62229 MW; A83FF068AED01FC7 CRC64;
MWSGRSSFTS LVVGVFVVYV VHTCWVMYGI VYTRPCSGDA NCIQPYLARR PKLQLSVYTT
TRSHLGAENN IDLVLNVEDF DVESKFERTV NVSVPKKTRN NGTLYAYIFL HHAGVLPWHD
GKQVHLVSPL TTYMVPKPEE INLLTGESDT QQIEAEKKPT SALDEPVSHW RPRLALNVMA
DNFVFDGSSL PADVHRYMKM IQLGKTVHYL PILFIDQLSN RVKDLMVINR STTELPLTVS
YDKVSLGRLR FWIHMQDAVY SLQQFGFSEK DADEVKGIFV DTNLYFLALT FFVAAFHLLF
DFLAFKNDIS FWKKKKSMIG MSTKAVLWRC FSTVVIFLFL LDEQTSLLVL VPAGVGAAIE
LWKVKKALKM TIFWRGLMPE FQFGTYSESE RKTEEYDTQA MKYLSYLLYP LCVGGAVYSL
LNIKYKSWYS WLINSFVNGV YAFGFLFMLP QLFVNYKLKS VAHLPWKAFT YKAFNTFIDD
VFAFIITMPT SHRLACFRDD VVFLVYLYQR WLYPVDKRRV NEFGESYEEK ATRAPHTD
