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Protein

Protein NLRC5

Gene

NLRC5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Probable regulator of the NF-kappa-B and type I interferon signaling pathways. May also regulate the type II interferon signaling pathway. Plays a role in homeostatic control of innate immunity and in antiviral defense mechanisms.2 Publications

Caution

Supposed to contain a CARD domain at the N-terminus (PubMed:20434986). However, this domain is not detected by Pfam, PROSITE or SMART. Has a weak similarity with a DAPIN domain.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi228 – 235ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

  • defense response to virus Source: UniProtKB
  • innate immune response Source: UniProtKB
  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • negative regulation of type I interferon-mediated signaling pathway Source: UniProtKB
  • negative regulation of type I interferon production Source: Reactome
  • positive regulation of interferon-gamma-mediated signaling pathway Source: UniProtKB
  • positive regulation of MHC class I biosynthetic process Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of type I interferon-mediated signaling pathway Source: UniProtKB
  • regulation of kinase activity Source: UniProtKB

Keywordsi

Biological processImmunity, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Protein NLRC5
Alternative name(s):
Caterpiller protein 16.1
Short name:
CLR16.1
Nucleotide-binding oligomerization domain protein 27
Nucleotide-binding oligomerization domain protein 4
Gene namesi
Name:NLRC5
Synonyms:NOD27, NOD4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000140853.15
HGNCiHGNC:29933 NLRC5
MIMi613537 gene
neXtProtiNX_Q86WI3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi84166
OpenTargetsiENSG00000140853
PharmGKBiPA162397694

Polymorphism and mutation databases

BioMutaiNLRC5
DMDMi269849666

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002961891 – 1866Protein NLRC5Add BLAST1866

Proteomic databases

EPDiQ86WI3
MaxQBiQ86WI3
PaxDbiQ86WI3
PeptideAtlasiQ86WI3
PRIDEiQ86WI3

PTM databases

iPTMnetiQ86WI3
PhosphoSitePlusiQ86WI3

Expressioni

Tissue specificityi

Expressed in spleen, thymus, lung, brain, tonsil, heart and prostate.2 Publications

Inductioni

By IFNG/IFN-gamma.1 Publication

Gene expression databases

BgeeiENSG00000140853
CleanExiHS_NLRC5
ExpressionAtlasiQ86WI3 baseline and differential
GenevisibleiQ86WI3 HS

Organism-specific databases

HPAiHPA059120
HPA060405

Interactioni

Subunit structurei

Interacts with CHUK and IKBKB; prevents CHUK and IKBKB phosphorylation and inhibits their kinase activity. Interacts with DDX58 and IFIH1; blocks the interaction of MAVS to DDX58.1 Publication

Protein-protein interaction databases

BioGridi1239224 interactors.
IntActiQ86WI3 2 interactors.
STRINGi9606.ENSP00000262510

Structurei

3D structure databases

ProteinModelPortaliQ86WI3
SMRiQ86WI3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini222 – 539NACHTPROSITE-ProRule annotationAdd BLAST318
Repeati599 – 622LRR 1Add BLAST24
Repeati713 – 737LRR 2Add BLAST25
Repeati741 – 765LRR 3Add BLAST25
Repeati769 – 792LRR 4Add BLAST24
Repeati869 – 892LRR 5Add BLAST24
Repeati897 – 921LRR 6Add BLAST25
Repeati930 – 953LRR 7Add BLAST24
Repeati976 – 1000LRR 8Add BLAST25
Repeati1004 – 1026LRR 9Add BLAST23
Repeati1031 – 1058LRR 10Add BLAST28
Repeati1138 – 1161LRR 11Add BLAST24
Repeati1162 – 1184LRR 12Add BLAST23
Repeati1242 – 1265LRR 13Add BLAST24
Repeati1272 – 1294LRR 14Add BLAST23
Repeati1462 – 1488LRR 15Add BLAST27
Repeati1493 – 1516LRR 16Add BLAST24
Repeati1521 – 1544LRR 17Add BLAST24
Repeati1554 – 1577LRR 18Add BLAST24
Repeati1578 – 1600LRR 19Add BLAST23
Repeati1605 – 1628LRR 20Add BLAST24
Repeati1633 – 1656LRR 21Add BLAST24
Repeati1661 – 1684LRR 22Add BLAST24
Repeati1687 – 1714LRR 23Add BLAST28
Repeati1715 – 1739LRR 24Add BLAST25
Repeati1741 – 1762LRR 25Add BLAST22
Repeati1795 – 1818LRR 26Add BLAST24

Sequence similaritiesi

Belongs to the NLRP family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4308 Eukaryota
ENOG4112B0K LUCA
GeneTreeiENSGT00860000133673
HOVERGENiHBG108194
InParanoidiQ86WI3
OMAiCPLEPHC
OrthoDBiEOG091G01CG
PhylomeDBiQ86WI3

Family and domain databases

Gene3Di3.80.10.108 hits
InterProiView protein in InterPro
IPR001611 Leu-rich_rpt
IPR025875 Leu-rich_rpt_4
IPR006553 Leu-rich_rpt_Cys-con_subtyp
IPR032675 LRR_dom_sf
IPR007111 NACHT_NTPase
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF12799 LRR_4, 1 hit
PF13516 LRR_6, 4 hits
SMARTiView protein in SMART
SM00367 LRR_CC, 9 hits
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 13 hits
PS50837 NACHT, 1 hit

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86WI3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDPVGLQLGN KNLWSCLVRL LTKDPEWLNA KMKFFLPNTD LDSRNETLDP
60 70 80 90 100
EQRVILQLNK LHVQGSDTWQ SFIHCVCMQL EVPLDLEVLL LSTFGYDDGF
110 120 130 140 150
TSQLGAEGKS QPESQLHHGL KRPHQSCGSS PRRKQCKKQQ LELAKKYLQL
160 170 180 190 200
LRTSAQQRYR SQIPGSGQPH AFHQVYVPPI LRRATASLDT PEGAIMGDVK
210 220 230 240 250
VEDGADVSIS DLFNTRVNKG PRVTVLLGKA GMGKTTLAHR LCQKWAEGHL
260 270 280 290 300
NCFQALFLFE FRQLNLITRF LTPSELLFDL YLSPESDHDT VFQYLEKNAD
310 320 330 340 350
QVLLIFDGLD EALQPMGPDG PGPVLTLFSH LCNGTLLPGC RVMATSRPGK
360 370 380 390 400
LPACLPAEAA MVHMLGFDGP RVEEYVNHFF SAQPSREGAL VELQTNGRLR
410 420 430 440 450
SLCAVPALCQ VACLCLHHLL PDHAPGQSVA LLPNMTQLYM QMVLALSPPG
460 470 480 490 500
HLPTSSLLDL GEVALRGLET GKVIFYAKDI APPLIAFGAT HSLLTSFCVC
510 520 530 540 550
TGPGHQQTGY AFTHLSLQEF LAALHLMASP KVNKDTLTQY VTLHSRWVQR
560 570 580 590 600
TKARLGLSDH LPTFLAGLAS CTCRPFLSHL AQGNEDCVGA KQAAVVQVLK
610 620 630 640 650
KLATRKLTGP KVVELCHCVD ETQEPELASL TAQSLPYQLP FHNFPLTCTD
660 670 680 690 700
LATLTNILEH REAPIHLDFD GCPLEPHCPE ALVGCGQIEN LSFKSRKCGD
710 720 730 740 750
AFAEALSRSL PTMGRLQMLG LAGSKITARG ISHLVKALPL CPQLKEVSFR
760 770 780 790 800
DNQLSDQVVL NIVEVLPHLP RLRKLDLSSN SICVSTLLCL ARVAVTCPTV
810 820 830 840 850
RMLQAREADL IFLLSPPTET TAELQRAPDL QESDGQRKGA QSRSLTLRLQ
860 870 880 890 900
KCQLQVHDAE ALIALLQEGP HLEEVDLSGN QLEDEGCRLM AEAASQLHIA
910 920 930 940 950
RKLDLSNNGL SVAGVHCVLR AVSACWTLAE LHISLQHKTV IFMFAQEPEE
960 970 980 990 1000
QKGPQERAAF LDSLMLQMPS ELPLSSRRMR LTHCGLQEKH LEQLCKALGG
1010 1020 1030 1040 1050
SCHLGHLHLD FSGNALGDEG AARLAQLLPG LGALQSLNLS ENGLSLDAVL
1060 1070 1080 1090 1100
GLVRCFSTLQ WLFRLDISFE SQHILLRGDK TSRDMWATGS LPDFPAAAKF
1110 1120 1130 1140 1150
LGFRQRCIPR SLCLSECPLE PPSLTRLCAT LKDCPGPLEL QLSCEFLSDQ
1160 1170 1180 1190 1200
SLETLLDCLP QLPQLSLLQL SQTGLSPKSP FLLANTLSLC PRVKKVDLRS
1210 1220 1230 1240 1250
LHHATLHFRS NEEEEGVCCG RFTGCSLSQE HVESLCWLLS KCKDLSQVDL
1260 1270 1280 1290 1300
SANLLGDSGL RCLLECLPQV PISGLLDLSH NSISQESALY LLETLPSCPR
1310 1320 1330 1340 1350
VREASVNLGS EQSFRIHFSR EDQAGKTLRL SECSFRPEHV SRLATGLSKS
1360 1370 1380 1390 1400
LQLTELTLTQ CCLGQKQLAI LLSLVGRPAG LFSLRVQEPW ADRARVLSLL
1410 1420 1430 1440 1450
EVCAQASGSV TEISISETQQ QLCVQLEFPR QEENPEAVAL RLAHCDLGAH
1460 1470 1480 1490 1500
HSLLVGQLME TCARLQQLSL SQVNLCEDDD ASSLLLQSLL LSLSELKTFR
1510 1520 1530 1540 1550
LTSSCVSTEG LAHLASGLGH CHHLEELDLS NNQFDEEGTK ALMRALEGKW
1560 1570 1580 1590 1600
MLKRLDLSHL LLNSSTLALL THRLSQMTCL QSLRLNRNSI GDVGCCHLSE
1610 1620 1630 1640 1650
ALRAATSLEE LDLSHNQIGD AGVQHLATIL PGLPELRKID LSGNSISSAG
1660 1670 1680 1690 1700
GVQLAESLVL CRRLEELMLG CNALGDPTAL GLAQELPQHL RVLHLPFSHL
1710 1720 1730 1740 1750
GPGGALSLAQ ALDGSPHLEE ISLAENNLAG GVLRFCMELP LLRQIDLVSC
1760 1770 1780 1790 1800
KIDNQTAKLL TSSFTSCPAL EVILLSWNLL GDEAAAELAQ VLPQMGRLKR
1810 1820 1830 1840 1850
VDLEKNQITA LGAWLLAEGL AQGSSIQVIR LWNNPIPCDM AQHLKSQEPR
1860
LDFAFFDNQP QAPWGT
Length:1,866
Mass (Da):204,595
Last modified:November 24, 2009 - v3
Checksum:i4E3BDED8E1624967
GO
Isoform 2 (identifier: Q86WI3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1307-1328: NLGSEQSFRIHFSREDQAGKTL → KCLGSWHVWAPCFPRPFSLQPGL
     1329-1866: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:1,329
Mass (Da):146,203
Checksum:i88549300F78231D0
GO
Isoform 3 (identifier: Q86WI3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     721-1866: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:720
Mass (Da):79,324
Checksum:i88BA764FA11781C7
GO
Isoform 4 (identifier: Q86WI3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1221-1249: Missing.

Note: No experimental confirmation available.
Show »
Length:1,837
Mass (Da):201,300
Checksum:i3DEED7B4B9E094E2
GO
Isoform 5 (identifier: Q86WI3-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1221-1249: Missing.
     1385-1385: R → S
     1386-1866: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:1,356
Mass (Da):148,956
Checksum:iF6BE709CA4115698
GO
Isoform 6 (identifier: Q86WI3-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1501-1551: LTSSCVSTEG...LMRALEGKWM → IQSSQDPGRL...LPPLGGAGLV
     1552-1866: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:1,551
Mass (Da):170,417
Checksum:i4F701C542D352429
GO

Sequence cautioni

The sequence BAB55096 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB55098 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB85008 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti808 – 810ADL → RTI in AAO59377 (PubMed:12615073).Curated3
Sequence conflicti808 – 810ADL → RTI in ABO40479 (Ref. 2) Curated3
Sequence conflicti1411T → A in BAB55096 (PubMed:14702039).Curated1
Sequence conflicti1411T → A in BAB55098 (PubMed:14702039).Curated1
Sequence conflicti1715S → F in BAB55096 (PubMed:14702039).Curated1
Sequence conflicti1715S → F in BAB55098 (PubMed:14702039).Curated1
Sequence conflicti1794Q → K in AAO59377 (PubMed:12615073).Curated1
Sequence conflicti1794Q → K in ABO40479 (Ref. 2) Curated1
Sequence conflicti1794Q → K in AAH63566 (PubMed:15489334).Curated1
Sequence conflicti1803L → P in BAB55096 (PubMed:14702039).Curated1
Sequence conflicti1803L → P in BAB55098 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034607210S → L. Corresponds to variant dbSNP:rs16965150Ensembl.1
Natural variantiVAR_036388361M → I in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_034608453P → L1 PublicationCorresponds to variant dbSNP:rs9938543Ensembl.1
Natural variantiVAR_034609500C → R1 PublicationCorresponds to variant dbSNP:rs28438857Ensembl.1
Natural variantiVAR_034610833S → N. Corresponds to variant dbSNP:rs35534915Ensembl.1
Natural variantiVAR_060589907N → D3 PublicationsCorresponds to variant dbSNP:rs1672867Ensembl.1
Natural variantiVAR_0346111105Q → K2 PublicationsCorresponds to variant dbSNP:rs289723Ensembl.1
Natural variantiVAR_0346121455V → A. Corresponds to variant dbSNP:rs7190199Ensembl.1
Natural variantiVAR_0346131466Q → R. Corresponds to variant dbSNP:rs7185320Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_027150721 – 1866Missing in isoform 3. 1 PublicationAdd BLAST1146
Alternative sequenceiVSP_0271511221 – 1249Missing in isoform 4 and isoform 5. 2 PublicationsAdd BLAST29
Alternative sequenceiVSP_0271521307 – 1328NLGSE…AGKTL → KCLGSWHVWAPCFPRPFSLQ PGL in isoform 2. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_0271531329 – 1866Missing in isoform 2. 1 PublicationAdd BLAST538
Alternative sequenceiVSP_0271541385R → S in isoform 5. 1 Publication1
Alternative sequenceiVSP_0271551386 – 1866Missing in isoform 5. 1 PublicationAdd BLAST481
Alternative sequenceiVSP_0271561501 – 1551LTSSC…EGKWM → IQSSQDPGRLLPDLLPFDPH QADLQLCEHRGPRPPGIWSG PLPPLGGAGLV in isoform 6. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_0271571552 – 1866Missing in isoform 6. 1 PublicationAdd BLAST315

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF389420 mRNA Translation: AAO59377.1
EF452236 mRNA Translation: ABO40479.1
AK074133 mRNA Translation: BAB84959.1
AK074182 mRNA Translation: BAB85008.1 Different initiation.
AC009090 Genomic DNA No translation available.
AC023825 Genomic DNA No translation available.
AK090439 mRNA Translation: BAC03420.1
BC050527 mRNA Translation: AAH50527.1
BC063566 mRNA Translation: AAH63566.1
AK027414 mRNA Translation: BAB55096.1 Different initiation.
AK027416 mRNA Translation: BAB55098.1 Different initiation.
CCDSiCCDS10773.1 [Q86WI3-1]
CCDS81985.1 [Q86WI3-4]
RefSeqiNP_001317481.1, NM_001330552.1 [Q86WI3-4]
NP_115582.4, NM_032206.4 [Q86WI3-1]
XP_005256250.1, XM_005256193.2 [Q86WI3-1]
XP_005256251.1, XM_005256194.3 [Q86WI3-1]
XP_005256254.1, XM_005256197.2 [Q86WI3-4]
XP_006721360.1, XM_006721297.2 [Q86WI3-1]
XP_011521675.1, XM_011523373.2 [Q86WI3-1]
UniGeneiHs.528836

Genome annotation databases

EnsembliENST00000262510; ENSP00000262510; ENSG00000140853 [Q86WI3-1]
ENST00000436936; ENSP00000389739; ENSG00000140853 [Q86WI3-1]
ENST00000539144; ENSP00000441727; ENSG00000140853 [Q86WI3-4]
ENST00000539881; ENSP00000441679; ENSG00000140853 [Q86WI3-3]
GeneIDi84166
KEGGihsa:84166
UCSCiuc010ccq.2 human [Q86WI3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNLRC5_HUMAN
AccessioniPrimary (citable) accession number: Q86WI3
Secondary accession number(s): B5MEF1
, C9JMD8, Q6P4A6, Q86VM7, Q8NF42, Q8TEE2, Q8TEJ1, Q969L7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: November 24, 2009
Last modified: April 25, 2018
This is version 132 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome