LLR1_HUMAN
ID LLR1_HUMAN Reviewed; 414 AA.
AC Q96L50; A5D6X3; B4DDE0; Q52M24; Q86SZ1; Q8N6H9;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2003, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Leucine-rich repeat protein 1;
DE AltName: Full=4-1BB-mediated-signaling molecule;
DE AltName: Full=4-1BBlrr;
DE AltName: Full=LRR-repeat protein 1;
DE Short=LRR-1;
DE AltName: Full=Peptidylprolyl isomerase-like 5;
GN Name=LRR1; Synonyms=PPIL5;
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] (ISOFORMS 1 AND 2), AND CHARACTERIZATION.
RC TISSUE=T-cell lymphoma;
RX PubMed=11804328;
RA Jang I.-K., Lee Z.-H., Kim H.-H., Hill J.M., Kim J.-D., Kwon B.S.;
RT "A novel leucine-rich repeat protein (LRR-1): potential involvement in 4-
RT 1BB-mediated signal transduction.";
RL Mol. Cells 12:304-312(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix carcinoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Neuroblastoma;
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].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=B-cell, Heart, and Lung;
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 IN AN E3 UBIQUITIN LIGASE COMPLEX, IDENTIFICATION BY MASS
RP SPECTROMETRY, INTERACTION WITH CUL2; RBX1; ELOB AND ELOC, AND MUTAGENESIS
RP OF 341-HIS--PRO-344.
RX PubMed=15601820; DOI=10.1101/gad.1252404;
RA Kamura T., Maenaka K., Kotoshiba S., Matsumoto M., Kohda D., Conaway R.C.,
RA Conaway J.W., Nakayama K.I.;
RT "VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1
RT and Cul5-Rbx2 modules of ubiquitin ligases.";
RL Genes Dev. 18:3055-3065(2004).
CC -!- FUNCTION: May negatively regulate the 4-1BB-mediated signaling cascades
CC which result in the activation of NK-kappaB and JNK1. Probable
CC substrate recognition subunit of an ECS (Elongin BC-CUL2/5-SOCS-box
CC protein) E3 ubiquitin-protein ligase complex which mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins. {ECO:0000269|PubMed:15601820}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with the cytoplasmic domain of TNFRSF9. Component of
CC the probable ECS(LRR1) E3 ubiquitin-protein ligase complex which
CC contains CUL2, RBX1, Elongin BC complex and LRR1. Interacts with CUL2,
CC RBX1, ELOB and ELOC. {ECO:0000269|PubMed:15601820}.
CC -!- INTERACTION:
CC Q96L50; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-2510106, EBI-742948;
CC Q96L50; Q16877: PFKFB4; NbExp=3; IntAct=EBI-2510106, EBI-764534;
CC Q96L50; Q9UL42: PNMA2; NbExp=3; IntAct=EBI-2510106, EBI-302355;
CC Q96L50; Q15645: TRIP13; NbExp=3; IntAct=EBI-2510106, EBI-358993;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LRR-1a;
CC IsoId=Q96L50-1; Sequence=Displayed;
CC Name=2; Synonyms=LRR-1b;
CC IsoId=Q96L50-2; Sequence=VSP_008363, VSP_008364;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Maximal expression was seen in the
CC heart and skeletal muscle and minimal expression seen in the kidney.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD62625.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY052405; AAL11430.1; -; mRNA.
DR EMBL; BX248298; CAD62625.1; ALT_INIT; mRNA.
DR EMBL; AK293156; BAG56701.1; -; mRNA.
DR EMBL; CH471078; EAW65761.1; -; Genomic_DNA.
DR EMBL; BC030142; AAH30142.1; -; mRNA.
DR EMBL; BC093697; AAH93697.1; -; mRNA.
DR EMBL; BC112241; AAI12242.1; -; mRNA.
DR EMBL; BC139921; AAI39922.1; -; mRNA.
DR CCDS; CCDS9686.1; -. [Q96L50-1]
DR CCDS; CCDS9687.1; -. [Q96L50-2]
DR RefSeq; NP_689542.2; NM_152329.3. [Q96L50-1]
DR RefSeq; NP_982292.1; NM_203467.1. [Q96L50-2]
DR PDB; 7PLO; EM; 2.80 A; O=1-414.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; Q96L50; -.
DR SMR; Q96L50; -.
DR BioGRID; 125793; 41.
DR IntAct; Q96L50; 22.
DR MINT; Q96L50; -.
DR STRING; 9606.ENSP00000298288; -.
DR iPTMnet; Q96L50; -.
DR PhosphoSitePlus; Q96L50; -.
DR BioMuta; LRR1; -.
DR DMDM; 37079896; -.
DR EPD; Q96L50; -.
DR jPOST; Q96L50; -.
DR MassIVE; Q96L50; -.
DR MaxQB; Q96L50; -.
DR PaxDb; Q96L50; -.
DR PeptideAtlas; Q96L50; -.
DR PRIDE; Q96L50; -.
DR ProteomicsDB; 77150; -. [Q96L50-1]
DR ProteomicsDB; 77151; -. [Q96L50-2]
DR Antibodypedia; 23515; 110 antibodies from 18 providers.
DR DNASU; 122769; -.
DR Ensembl; ENST00000298288.11; ENSP00000298288.6; ENSG00000165501.17. [Q96L50-1]
DR Ensembl; ENST00000318317.8; ENSP00000315628.4; ENSG00000165501.17. [Q96L50-2]
DR GeneID; 122769; -.
DR KEGG; hsa:122769; -.
DR MANE-Select; ENST00000298288.11; ENSP00000298288.6; NM_152329.4; NP_689542.2.
DR UCSC; uc001wwn.3; human. [Q96L50-1]
DR CTD; 122769; -.
DR DisGeNET; 122769; -.
DR GeneCards; LRR1; -.
DR HGNC; HGNC:19742; LRR1.
DR HPA; ENSG00000165501; Tissue enhanced (testis).
DR MIM; 609193; gene.
DR neXtProt; NX_Q96L50; -.
DR OpenTargets; ENSG00000165501; -.
DR PharmGKB; PA134915321; -.
DR VEuPathDB; HostDB:ENSG00000165501; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000158830; -.
DR HOGENOM; CLU_053349_1_0_1; -.
DR InParanoid; Q96L50; -.
DR OMA; SREHQIY; -.
DR PhylomeDB; Q96L50; -.
DR TreeFam; TF319257; -.
DR PathwayCommons; Q96L50; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q96L50; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 122769; 638 hits in 1072 CRISPR screens.
DR ChiTaRS; LRR1; human.
DR GenomeRNAi; 122769; -.
DR Pharos; Q96L50; Tbio.
DR PRO; PR:Q96L50; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96L50; protein.
DR Bgee; ENSG00000165501; Expressed in ileal mucosa and 143 other tissues.
DR ExpressionAtlas; Q96L50; baseline and differential.
DR Genevisible; Q96L50; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR025875; Leu-rich_rpt_4.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF12799; LRR_4; 1.
DR SMART; SM00369; LRR_TYP; 4.
DR PROSITE; PS51450; LRR; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Leucine-rich repeat;
KW Reference proteome; Repeat; Ubl conjugation pathway.
FT CHAIN 1..414
FT /note="Leucine-rich repeat protein 1"
FT /id="PRO_0000084447"
FT REPEAT 155..176
FT /note="LRR 1"
FT REPEAT 178..199
FT /note="LRR 2"
FT REPEAT 201..222
FT /note="LRR 3"
FT REPEAT 227..248
FT /note="LRR 4"
FT REPEAT 250..271
FT /note="LRR 5"
FT REPEAT 273..294
FT /note="LRR 6"
FT REPEAT 295..316
FT /note="LRR 7"
FT VAR_SEQ 95..146
FT /note="AISSSLKGFLSAMRLAHRGCNVDTPVSTLTPVKTSEFENFKTKMVITSKKDY
FT -> DSIWLSYHSIPSLPRFGYRKNLCLWKILSELFHSRNYYHESAFCCPHCGLSR (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:11804328,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_008363"
FT VAR_SEQ 147..414
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11804328,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_008364"
FT VARIANT 96
FT /note="I -> N (in dbSNP:rs17121605)"
FT /id="VAR_051095"
FT VARIANT 229
FT /note="R -> W (in dbSNP:rs7148147)"
FT /id="VAR_051096"
FT MUTAGEN 341..344
FT /note="HIIP->AAA: Abolishes interaction with CUL2 and
FT RBX1."
FT /evidence="ECO:0000269|PubMed:15601820"
FT CONFLICT 9
FT /note="V -> A (in Ref. 3; BAG56701)"
FT /evidence="ECO:0000305"
FT CONFLICT 25
FT /note="G -> V (in Ref. 1; AAL11430)"
FT /evidence="ECO:0000305"
FT CONFLICT 28
FT /note="A -> S (in Ref. 1; AAL11430)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 414 AA; 46723 MW; B19B178D6CB33C4C CRC64;
MKLHCEVEVI SRHLPALGLR NRGKGVRAVL SLCQQTSRSQ PPVRAFLLIS TLKDKRGTRY
ELRENIEQFF TKFVDEGKAT VRLKEPPVDI CLSKAISSSL KGFLSAMRLA HRGCNVDTPV
STLTPVKTSE FENFKTKMVI TSKKDYPLSK NFPYSLEHLQ TSYCGLVRVD MRMLCLKSLR
KLDLSHNHIK KLPATIGDLI HLQELNLNDN HLESFSVALC HSTLQKSLRS LDLSKNKIKA
LPVQFCQLQE LKNLKLDDNE LIQFPCKIGQ LINLRFLSAA RNKLPFLPSE FRNLSLEYLD
LFGNTFEQPK VLPVIKLQAP LTLLESSART ILHNRIPYGS HIIPFHLCQD LDTAKICVCG
RFCLNSFIQG TTTMNLHSVA HTVVLVDNLG GTEAPIISYF CSLGCYVNSS DMLK
