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 27-MAR-2024, entry version 161. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 137. DR IntAct; Q96KA5; 35. 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 GlyCosmos; Q96KA5; 4 sites, 9 glycans. 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; 9606-ENSP00000313854; -. DR PeptideAtlas; Q96KA5; -. DR ProteomicsDB; 77054; -. [Q96KA5-1] DR ProteomicsDB; 77055; -. [Q96KA5-2] DR Pumba; Q96KA5; -. DR Antibodypedia; 3079; 242 antibodies from 23 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 AGR; HGNC:24308; -. 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; TTMWRAF; -. DR OrthoDB; 31537at2759; -. DR PhylomeDB; Q96KA5; -. DR TreeFam; TF318501; -. DR PathwayCommons; Q96KA5; -. DR SignaLink; Q96KA5; -. DR BioGRID-ORCS; 81037; 8 hits in 1149 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 181 other cell types or tissues. DR ExpressionAtlas; Q96KA5; baseline and differential. DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. 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 PANTHER; PTHR21347; CLEFT LIP AND PALATE ASSOCIATED TRANSMEMBRANE PROTEIN-RELATED; 1. DR PANTHER; PTHR21347:SF0; CLEFT LIP AND PALATE TRANSMEMBRANE PROTEIN 1-LIKE PROTEIN; 1. DR Pfam; PF05602; CLPTM1; 1. DR Genevisible; Q96KA5; HS. 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 //