LRC14_HUMAN
ID LRC14_HUMAN Reviewed; 493 AA.
AC Q15048; A8K0A8; D3DWM8;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Leucine-rich repeat-containing protein 14 {ECO:0000305};
GN Name=LRRC14 {ECO:0000312|HGNC:HGNC:20419};
GN Synonyms=KIAA0014 {ECO:0000303|PubMed:7584026};
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].
RC TISSUE=Bone marrow;
RX PubMed=7584026; DOI=10.1093/dnares/1.1.27;
RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S.,
RA Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I. The
RT coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of
RT randomly sampled cDNA clones from human immature myeloid cell line KG-1.";
RL DNA Res. 1:27-35(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [5]
RP INDUCTION, SUBCELLULAR LOCATION, INTERACTION WITH CHUK AND IKBKB, AND
RP FUNCTION.
RX PubMed=27426725; DOI=10.1016/j.yexcr.2016.07.011;
RA Wu C., Yang Y., Ou J., Zhu L., Zhao W., Cui J.;
RT "LRRC14 attenuates Toll-like receptor-mediated NF-kappa-B signaling through
RT disruption of IKK complex.";
RL Exp. Cell Res. 347:65-73(2016).
CC -!- FUNCTION: Negatively regulates Toll-like receptor-mediated NF-kappa-B
CC signaling by disrupting IKK core complex formation through interaction
CC with IKBKB. {ECO:0000269|PubMed:27426725}.
CC -!- SUBUNIT: Interacts with IKBKB; disrupts IKBKB-IKBKG interaction
CC preventing I-kappa-B-kinase (IKK) core complex formation and leading to
CC a decrease of IKBKB phosphorylation and NF-kappaB activation
CC (PubMed:27426725). Interacts with CHUK (PubMed:27426725).
CC {ECO:0000269|PubMed:27426725}.
CC -!- INTERACTION:
CC Q15048; Q13617: CUL2; NbExp=6; IntAct=EBI-2510124, EBI-456179;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27426725}.
CC -!- INDUCTION: Down-regulated in response to toll-like receptor ligand.
CC {ECO:0000269|PubMed:27426725}.
CC -!- SIMILARITY: Belongs to the PRAME family. LRRC14 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04946.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D25216; BAA04946.2; ALT_INIT; mRNA.
DR EMBL; AK289473; BAF82162.1; -; mRNA.
DR EMBL; CH471162; EAW82066.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82067.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82068.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82069.1; -; Genomic_DNA.
DR EMBL; BC011377; AAH11377.1; -; mRNA.
DR CCDS; CCDS6432.1; -.
DR RefSeq; NP_001258965.1; NM_001272036.1.
DR RefSeq; NP_055480.1; NM_014665.3.
DR RefSeq; XP_005272415.1; XM_005272358.4.
DR RefSeq; XP_005272416.1; XM_005272359.4.
DR AlphaFoldDB; Q15048; -.
DR SMR; Q15048; -.
DR BioGRID; 115037; 10.
DR IntAct; Q15048; 5.
DR STRING; 9606.ENSP00000292524; -.
DR iPTMnet; Q15048; -.
DR PhosphoSitePlus; Q15048; -.
DR BioMuta; LRRC14; -.
DR DMDM; 6686102; -.
DR EPD; Q15048; -.
DR jPOST; Q15048; -.
DR MassIVE; Q15048; -.
DR MaxQB; Q15048; -.
DR PaxDb; Q15048; -.
DR PeptideAtlas; Q15048; -.
DR PRIDE; Q15048; -.
DR ProteomicsDB; 60400; -.
DR TopDownProteomics; Q15048; -.
DR Antibodypedia; 14965; 59 antibodies from 16 providers.
DR DNASU; 9684; -.
DR Ensembl; ENST00000292524.6; ENSP00000292524.1; ENSG00000160959.8.
DR Ensembl; ENST00000529022.5; ENSP00000434768.1; ENSG00000160959.8.
DR GeneID; 9684; -.
DR KEGG; hsa:9684; -.
DR MANE-Select; ENST00000292524.6; ENSP00000292524.1; NM_014665.4; NP_055480.1.
DR UCSC; uc003zdk.4; human.
DR CTD; 9684; -.
DR DisGeNET; 9684; -.
DR GeneCards; LRRC14; -.
DR HGNC; HGNC:20419; LRRC14.
DR HPA; ENSG00000160959; Low tissue specificity.
DR MIM; 619368; gene.
DR neXtProt; NX_Q15048; -.
DR OpenTargets; ENSG00000160959; -.
DR PharmGKB; PA134914089; -.
DR VEuPathDB; HostDB:ENSG00000160959; -.
DR eggNOG; ENOG502QWSJ; Eukaryota.
DR GeneTree; ENSGT01030000234531; -.
DR HOGENOM; CLU_039635_0_1_1; -.
DR InParanoid; Q15048; -.
DR OMA; VTECELM; -.
DR OrthoDB; 563553at2759; -.
DR PhylomeDB; Q15048; -.
DR TreeFam; TF332708; -.
DR PathwayCommons; Q15048; -.
DR SignaLink; Q15048; -.
DR BioGRID-ORCS; 9684; 14 hits in 1079 CRISPR screens.
DR ChiTaRS; LRRC14; human.
DR GenomeRNAi; 9684; -.
DR Pharos; Q15048; Tdark.
DR PRO; PR:Q15048; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q15048; protein.
DR Bgee; ENSG00000160959; Expressed in lower esophagus mucosa and 159 other tissues.
DR ExpressionAtlas; Q15048; baseline and differential.
DR Genevisible; Q15048; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IDA:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR026292; LRRC14.
DR PANTHER; PTHR14224:SF9; PTHR14224:SF9; 1.
DR Pfam; PF13516; LRR_6; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; Leucine-rich repeat; Reference proteome; Repeat.
FT CHAIN 1..493
FT /note="Leucine-rich repeat-containing protein 14"
FT /id="PRO_0000156974"
FT REPEAT 111..146
FT /note="LRR 1; degenerate"
FT /evidence="ECO:0000250|UniProtKB:Q3UWY1"
FT REPEAT 194..218
FT /note="LRR 2; degenerate"
FT /evidence="ECO:0000250|UniProtKB:Q3UWY1"
FT REPEAT 219..246
FT /note="LRR 3; degenerate"
FT /evidence="ECO:0000250|UniProtKB:Q3UWY1"
FT REPEAT 247..282
FT /note="LRR 4; degenerate"
FT /evidence="ECO:0000250|UniProtKB:Q3UWY1"
FT REPEAT 283..307
FT /note="LRR 5"
FT /evidence="ECO:0000250|UniProtKB:Q3UWY1"
FT REPEAT 308..339
FT /note="LRR 6"
FT /evidence="ECO:0000250|UniProtKB:Q3UWY1"
FT REPEAT 340..360
FT /note="LRR 7"
FT /evidence="ECO:0000250|UniProtKB:Q3UWY1"
FT REPEAT 364..391
FT /note="LRR 8"
FT /evidence="ECO:0000250|UniProtKB:Q3UWY1"
FT REPEAT 392..416
FT /note="LRR 9"
FT /evidence="ECO:0000250|UniProtKB:Q3UWY1"
FT VARIANT 437
FT /note="G -> D (in dbSNP:rs3735854)"
FT /id="VAR_053603"
FT CONFLICT 230
FT /note="N -> S (in Ref. 2; BAF82162)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 493 AA; 54513 MW; 1B02E6D0FAF06A88 CRC64;
MHTLVFLSTR QVLQCQPAAC QALPLLPREL FPLLFKVAFM DKKTVVLREL VHTWPFPLLS
FQQLLQECAH CSRALLQERP STESMQAVIL GLTARLHTSE PGASTQPLCR KHALRVLDMT
GLLDDGVEQD PGTMSMWDCT AAVARTCIAQ QQGGAAEPGP APIPVEVRVD LRVNRASYAF
LREALRSSVG SPLRLCCRDL RAEDLPMRNT VALLQLLDAG CLRRVDLRFN NLGLRGLSVI
IPHVARFQHL ASLRLHYVHG DSRQPSVDGE DNFRYFLAQM GRFTCLRELS MGSSLLSGRL
DQLLSTLQSP LESLELAFCA LLPEDLRFLA RSPHAAHLKK LDLSGNDLSG SQLAPFQGLL
QASAATLLHL ELTECQLADT QLLATLPILT QCASLRYLGL YGNPLSMAGL KELLRDSVAQ
AELRTVVHPF PVDCYEGLPW PPPASVLLEA SINEEKFARV EAELHQLLLA SGRAHVLWTT
DIYGRLAADY FSL