NAL14_HUMAN
ID NAL14_HUMAN Reviewed; 1093 AA.
AC Q86W24; Q7RTR6;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 14;
DE AltName: Full=Nucleotide-binding oligomerization domain protein 5 {ECO:0000303|PubMed:12766759};
GN Name=NLRP14; Synonyms=NALP14, NOD5 {ECO:0000303|PubMed:12766759};
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].
RX PubMed=12563287; DOI=10.1038/nrm1019;
RA Tschopp J., Martinon F., Burns K.;
RT "NALPs: a novel protein family involved in inflammation.";
RL Nat. Rev. Mol. Cell Biol. 4:95-104(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12766759; DOI=10.1038/nri1086;
RA Inohara N., Nunez G.;
RT "NODs: intracellular proteins involved in inflammation and apoptosis.";
RL Nat. Rev. Immunol. 3:371-382(2003).
RN [3]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND VARIANTS THR-48; GLN-55;
RP VAL-86; ARG-92; LEU-98; THR-375; ILE-397; MET-441; GLY-522; LYS-808;
RP THR-951; SER-954; PHE-1010 AND ILE-1019.
RX PubMed=16931801; DOI=10.1093/humrep/del293;
RA Westerveld G.H., Korver C.M., van Pelt A.M.M., Leschot N.J.,
RA van der Veen F., Repping S., Lombardi M.P.;
RT "Mutations in the testis-specific NALP14 gene in men suffering from
RT spermatogenic failure.";
RL Hum. Reprod. 21:3178-3184(2006).
RN [4] {ECO:0007744|PDB:4N1J, ECO:0007744|PDB:4N1K, ECO:0007744|PDB:4N1L}
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 1-100 OF WILD-TYPE AND VARIANT
RP VAL-86, DOMAIN, CHARACTERIZATION OF VARIANT VAL-86, AND MUTAGENESIS OF
RP LEU-84.
RX PubMed=25004977; DOI=10.1107/s1399004714010311;
RA Eibl C., Hessenberger M., Wenger J., Brandstetter H.;
RT "Structures of the NLRP14 pyrin domain reveal a conformational switch
RT mechanism regulating its molecular interactions.";
RL Acta Crystallogr. D 70:2007-2018(2014).
RN [5]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-779.
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).
RN [6]
RP VARIANT VAL-86.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- FUNCTION: May be involved in inflammation and spermatogenesis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6B966}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:16931801}.
CC -!- DEVELOPMENTAL STAGE: In the testis, expressed mainly in A dark
CC spermatogonia, mid and late spermatocytes and spermatids but not in
CC mitotically active A pale and B spermatogonia.
CC {ECO:0000269|PubMed:16931801}.
CC -!- DOMAIN: Upon heterologous expression, a small proportion of the
CC isolated Pyrin domain forms homodimers and higher oligomers.
CC {ECO:0000269|PubMed:25004977}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
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DR EMBL; AY154469; AAO18165.1; -; mRNA.
DR EMBL; BK001107; DAA01240.1; -; mRNA.
DR CCDS; CCDS7776.1; -.
DR RefSeq; NP_789792.1; NM_176822.3.
DR PDB; 4N1J; X-ray; 2.60 A; A/B/C/D=1-100.
DR PDB; 4N1K; X-ray; 3.00 A; A/B/C/D=1-100.
DR PDB; 4N1L; X-ray; 1.99 A; A=1-100.
DR PDBsum; 4N1J; -.
DR PDBsum; 4N1K; -.
DR PDBsum; 4N1L; -.
DR AlphaFoldDB; Q86W24; -.
DR SMR; Q86W24; -.
DR BioGRID; 130710; 2.
DR IntAct; Q86W24; 3.
DR MINT; Q86W24; -.
DR STRING; 9606.ENSP00000299481; -.
DR iPTMnet; Q86W24; -.
DR PhosphoSitePlus; Q86W24; -.
DR BioMuta; NLRP14; -.
DR DMDM; 38372322; -.
DR jPOST; Q86W24; -.
DR MassIVE; Q86W24; -.
DR PaxDb; Q86W24; -.
DR PeptideAtlas; Q86W24; -.
DR PRIDE; Q86W24; -.
DR ProteomicsDB; 70103; -.
DR Antibodypedia; 42308; 53 antibodies from 22 providers.
DR DNASU; 338323; -.
DR Ensembl; ENST00000299481.5; ENSP00000299481.5; ENSG00000158077.5.
DR GeneID; 338323; -.
DR KEGG; hsa:338323; -.
DR MANE-Select; ENST00000299481.5; ENSP00000299481.5; NM_176822.4; NP_789792.1.
DR UCSC; uc001mfb.2; human.
DR CTD; 338323; -.
DR DisGeNET; 338323; -.
DR GeneCards; NLRP14; -.
DR HGNC; HGNC:22939; NLRP14.
DR HPA; ENSG00000158077; Not detected.
DR MIM; 609665; gene.
DR neXtProt; NX_Q86W24; -.
DR OpenTargets; ENSG00000158077; -.
DR PharmGKB; PA162397917; -.
DR VEuPathDB; HostDB:ENSG00000158077; -.
DR eggNOG; ENOG502SBIG; Eukaryota.
DR GeneTree; ENSGT00940000162005; -.
DR HOGENOM; CLU_002274_2_1_1; -.
DR InParanoid; Q86W24; -.
DR OMA; MISKDWP; -.
DR OrthoDB; 114368at2759; -.
DR PhylomeDB; Q86W24; -.
DR TreeFam; TF340267; -.
DR PathwayCommons; Q86W24; -.
DR SignaLink; Q86W24; -.
DR BioGRID-ORCS; 338323; 4 hits in 1064 CRISPR screens.
DR ChiTaRS; NLRP14; human.
DR GeneWiki; NLRP14; -.
DR GenomeRNAi; 338323; -.
DR Pharos; Q86W24; Tbio.
DR PRO; PR:Q86W24; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q86W24; protein.
DR Bgee; ENSG00000158077; Expressed in oocyte and 18 other tissues.
DR Genevisible; Q86W24; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR007111; NACHT_NTPase.
DR InterPro; IPR041267; NLRP_HD2.
DR InterPro; IPR041075; NOD2_WH.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF13516; LRR_6; 4.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF17776; NLRC4_HD2; 1.
DR Pfam; PF17779; NOD2_WH; 1.
DR Pfam; PF02758; PYRIN; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Developmental protein;
KW Differentiation; Leucine-rich repeat; Nucleotide-binding;
KW Reference proteome; Repeat; Spermatogenesis.
FT CHAIN 1..1093
FT /note="NACHT, LRR and PYD domains-containing protein 14"
FT /id="PRO_0000080901"
FT DOMAIN 1..97
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 177..499
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 730..750
FT /note="LRR 1"
FT REPEAT 759..780
FT /note="LRR 2"
FT REPEAT 787..807
FT /note="LRR 3"
FT REPEAT 816..836
FT /note="LRR 4"
FT REPEAT 844..864
FT /note="LRR 5"
FT REPEAT 873..894
FT /note="LRR 6"
FT REPEAT 901..921
FT /note="LRR 7"
FT REPEAT 930..951
FT /note="LRR 8"
FT REPEAT 958..978
FT /note="LRR 9"
FT REPEAT 987..1008
FT /note="LRR 10"
FT REPEAT 1015..1035
FT /note="LRR 11"
FT REGION 102..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 183..190
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT VARIANT 21
FT /note="E -> K (in dbSNP:rs11041150)"
FT /id="VAR_053622"
FT VARIANT 48
FT /note="N -> T (in dbSNP:rs12801277)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031932"
FT VARIANT 55
FT /note="R -> Q (in dbSNP:rs61063081)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031933"
FT VARIANT 86
FT /note="D -> V (increased tendency to form aggregates;
FT dbSNP:rs199735773)"
FT /evidence="ECO:0000269|PubMed:16931801,
FT ECO:0000269|PubMed:25004977, ECO:0000269|PubMed:27535533"
FT /id="VAR_031934"
FT VARIANT 92
FT /note="K -> R (in dbSNP:rs16921697)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031935"
FT VARIANT 98
FT /note="S -> L (in dbSNP:rs117823353)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031936"
FT VARIANT 375
FT /note="A -> T (in dbSNP:rs368562565)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031937"
FT VARIANT 397
FT /note="T -> I (in dbSNP:rs76670455)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031938"
FT VARIANT 441
FT /note="V -> M (in dbSNP:rs147389856)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031939"
FT VARIANT 511
FT /note="L -> F (in dbSNP:rs11041151)"
FT /id="VAR_053623"
FT VARIANT 522
FT /note="D -> G (in dbSNP:rs1044378174)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031940"
FT VARIANT 779
FT /note="S -> C (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036387"
FT VARIANT 808
FT /note="E -> K (in dbSNP:rs10839708)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_024180"
FT VARIANT 951
FT /note="S -> T (in dbSNP:rs117124176)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031941"
FT VARIANT 954
FT /note="L -> S (in dbSNP:rs117583918)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031942"
FT VARIANT 1010
FT /note="L -> F (in dbSNP:rs17280682)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031943"
FT VARIANT 1019
FT /note="M -> I (in dbSNP:rs115776642)"
FT /evidence="ECO:0000269|PubMed:16931801"
FT /id="VAR_031944"
FT MUTAGEN 84
FT /note="L->R: Increased thermal stability of the Pyrin
FT domain."
FT /evidence="ECO:0000269|PubMed:25004977"
FT HELIX 9..12
FT /evidence="ECO:0007829|PDB:4N1L"
FT HELIX 14..19
FT /evidence="ECO:0007829|PDB:4N1L"
FT HELIX 24..38
FT /evidence="ECO:0007829|PDB:4N1L"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:4N1L"
FT HELIX 45..52
FT /evidence="ECO:0007829|PDB:4N1L"
FT HELIX 55..65
FT /evidence="ECO:0007829|PDB:4N1L"
FT HELIX 69..81
FT /evidence="ECO:0007829|PDB:4N1L"
FT HELIX 85..100
FT /evidence="ECO:0007829|PDB:4N1L"
SQ SEQUENCE 1093 AA; 124733 MW; 124EEACE22A11D6F CRC64;
MADSSSSSFF PDFGLLLYLE ELNKEELNTF KLFLKETMEP EHGLTPWNEV KKARREDLAN
LMKKYYPGEK AWSVSLKIFG KMNLKDLCER AKEEINWSAQ TIGPDDAKAG ETQEDQEAVL
GDGTEYRNRI KEKFCITWDK KSLAGKPEDF HHGIAEKDRK LLEHLFDVDV KTGAQPQIVV
LQGAAGVGKT TLVRKAMLDW AEGSLYQQRF KYVFYLNGRE INQLKERSFA QLISKDWPST
EGPIEEIMYQ PSSLLFIIDS FDELNFAFEE PEFALCEDWT QEHPVSFLMS SLLRKVMLPE
ASLLVTTRLT TSKRLKQLLK NHHYVELLGM SEDAREEYIY QFFEDKRWAM KVFSSLKSNE
MLFSMCQVPL VCWAACTCLK QQMEKGGDVT LTCQTTTALF TCYISSLFTP VDGGSPSLPN
QAQLRRLCQV AAKGIWTMTY VFYRENLRRL GLTQSDVSSF MDSNIIQKDA EYENCYVFTH
LHVQEFFAAM FYMLKGSWEA GNPSCQPFED LKSLLQSTSY KDPHLTQMKC FLFGLLNEDR
VKQLERTFNC KMSLKIKSKL LQCMEVLGNS DYSPSQLGFL ELFHCLYETQ DKAFISQAMR
CFPKVAINIC EKIHLLVSSF CLKHCRCLRT IRLSVTVVFE KKILKTSLPT NTWDGDRITH
CWQDLCSVLH TNEHLRELDL YHSNLDKSAM NILHHELRHP NCKLQKLLLK FITFPDGCQD
ISTSLIHNKN LMHLDLKGSD IGDNGVKSLC EALKHPECKL QTLRLESCNL TVFCCLNISN
ALIRSQSLIF LNLSTNNLLD DGVQLLCEAL RHPKCYLERL SLESCGLTEA GCEYLSLALI
SNKRLTHLCL ADNVLGDGGV KLMSDALQHA QCTLKSLVLR RCHFTSLSSE YLSTSLLHNK
SLTHLDLGSN WLQDNGVKLL CDVFRHPSCN LQDLELMGCV LTNACCLDLA SVILNNPNLR
SLDLGNNDLQ DDGVKILCDA LRYPNCNIQR LGLEYCGLTS LCCQDLSSAL ICNKRLIKMN
LTQNTLGYEG IVKLYKVLKS PKCKLQVLGL CKEAFDEEAQ KLLEAVGVSN PHLIIKPDCN
YHNEEDVSWW WCF
