ID TIRA_DICDI Reviewed; 1336 AA.
AC Q54HT1;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 27-MAR-2024, entry version 102.
DE RecName: Full=Protein tirA;
DE EC=3.2.2.6 {ECO:0000255|PROSITE-ProRule:PRU00204};
DE AltName: Full=TIR domain-containing protein A;
GN Name=tirA; ORFNames=DDB_G0289237;
OS Dictyostelium discoideum (Social amoeba).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=17673666; DOI=10.1126/science.1143991;
RA Chen G., Zhuchenko O., Kuspa A.;
RT "Immune-like phagocyte activity in the social amoeba.";
RL Science 317:678-681(2007).
RN [3]
RP INDUCTION [LARGE SCALE ANALYSIS].
RX PubMed=18590548; DOI=10.1186/1471-2180-8-109;
RA Carilla-Latorre S., Calvo-Garrido J., Bloomfield G., Skelton J., Kay R.R.,
RA Ivens A., Martinez J.L., Escalante R.;
RT "Dictyostelium transcriptional responses to Pseudomonas aeruginosa: common
RT and specific effects from PAO1 and PA14 strains.";
RL BMC Microbiol. 8:109-109(2008).
CC -!- FUNCTION: May regulate responses to pathogens. Required by to respond
CC appropriately to bacteria during vegetative foraging.
CC {ECO:0000269|PubMed:17673666}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC -!- DEVELOPMENTAL STAGE: Only expressed in sentinel 'S cells'.
CC {ECO:0000269|PubMed:17673666}.
CC -!- INDUCTION: Down-regulated by Pseudomonas aeruginosa, PAO1 strain and
CC up-regulated by PA14 strain infection. {ECO:0000269|PubMed:18590548}.
CC -!- DOMAIN: The TIR domain mediates NAD(+) hydrolase (NADase) activity.
CC Self-association of TIR domains is required for NADase activity.
CC {ECO:0000255|PROSITE-ProRule:PRU00204}.
CC -!- DISRUPTION PHENOTYPE: Mutant S cells are killed by an avirulent
CC Legionella strain that does not kill wild-type Dictyostelium. These
CC results indicate that, although TirA is not required for S cell
CC differentiation, it is critical for the effective response of S cells
CC to bacteria. Show growth attenuation correlated with a discernable loss
CC of cell viability. In addition, tirA mutant cells appeared to be more
CC sensitive to killing by Legionella. {ECO:0000269|PubMed:17673666}.
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DR EMBL; AAFI02000131; EAL62852.1; -; Genomic_DNA.
DR RefSeq; XP_636358.1; XM_631266.1.
DR AlphaFoldDB; Q54HT1; -.
DR SMR; Q54HT1; -.
DR STRING; 44689.Q54HT1; -.
DR PaxDb; 44689-DDB0232375; -.
DR EnsemblProtists; EAL62852; EAL62852; DDB_G0289237.
DR GeneID; 8627031; -.
DR KEGG; ddi:DDB_G0289237; -.
DR dictyBase; DDB_G0289237; tirA.
DR eggNOG; KOG0941; Eukaryota.
DR HOGENOM; CLU_258736_0_0_1; -.
DR InParanoid; Q54HT1; -.
DR OMA; WCRKELK; -.
DR PRO; PR:Q54HT1; -.
DR Proteomes; UP000002195; Chromosome 5.
DR GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR GO; GO:0019954; P:asexual reproduction; IMP:dictyBase.
DR GO; GO:0006952; P:defense response; IMP:dictyBase.
DR GO; GO:0042742; P:defense response to bacterium; IMP:dictyBase.
DR GO; GO:0006909; P:phagocytosis; IMP:dictyBase.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:dictyBase.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1.
DR Gene3D; 2.130.10.30; Regulator of chromosome condensation 1/beta-lactamase-inhibitor protein II; 1.
DR Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR45622:SF75; PROTEIN TIRA; 1.
DR PANTHER; PTHR45622; UBIQUITIN-PROTEIN LIGASE E3A-RELATED; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00415; RCC1; 1.
DR Pfam; PF13676; TIR_2; 1.
DR SMART; SM00248; ANK; 2.
DR SMART; SM00292; BRCT; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF48403; Ankyrin repeat; 1.
DR SUPFAM; SSF52113; BRCT domain; 1.
DR SUPFAM; SSF50985; RCC1/BLIP-II; 1.
DR SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
DR PROSITE; PS50172; BRCT; 1.
DR PROSITE; PS00626; RCC1_2; 1.
DR PROSITE; PS50012; RCC1_3; 1.
DR PROSITE; PS50104; TIR; 1.
PE 2: Evidence at transcript level;
KW ANK repeat; Coiled coil; Hydrolase; NAD; Reference proteome; Repeat.
FT CHAIN 1..1336
FT /note="Protein tirA"
FT /id="PRO_0000384457"
FT DOMAIN 1..110
FT /note="BRCT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REPEAT 412..462
FT /note="RCC1 1"
FT REPEAT 463..522
FT /note="RCC1 2"
FT REPEAT 529..581
FT /note="RCC1 3"
FT REPEAT 732..761
FT /note="ANK 1"
FT REPEAT 765..795
FT /note="ANK 2"
FT DOMAIN 818..935
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 186..213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1120..1140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 179..218
FT /evidence="ECO:0000255"
FT COILED 1047..1084
FT /evidence="ECO:0000255"
FT ACT_SITE 892
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
SQ SEQUENCE 1336 AA; 155247 MW; 98CFC5A0C000B206 CRC64;
MPSLFSSLKF FCFSPTKDTS DKKIKDEILK KIEVNGGTVQ YCIQKFSTNY IILCNGLDEY
DRDQHYYNFQ SNSLLFLEKS KSLGIPILSY KFINDCIGKN LIINDLQGYK ISNIIDETII
KFEYQEPEEE IKEIQEIQEI QEIQEIQEIQ EAYDDFFDLF GLDSAPIADG DVFKNMPPIS
QVLAEKAKEE KENQEKQEKE RQEKEKKEKE KSKFKSTYIS DRKLAMNQKT SPTTTSYFDN
EIDDKENINN NDDDFDIDEI DFNLFSNIDL EINEKPIEED FNLFNIGHYD DNVNRNIKTK
SKFDNLNNKI KNNGYIFQFV NKDVSLYHEK DFPNNFKSIK LFEQSSKGLS CMITEDNRCY
IWGNIKSNQK VEQLADHYQV DYCSVGGSHS VMIKRGIHTV GLNKFGQLGY KNGNTNCIGG
GGNNKLMIEN QIQRSISIIN QNFLKKVLMV SCGKDFNVLL TNEGQVFSWG KNDQGQLGLG
NSDSKENYEI KLVNFDDPYD SNSNKFISFI SCGGNHSIAI ESNSSTDGNC RLYGWGSNSQ
GQIGEKYSSV PILIKNQDQK SFNWKSPLVL CTQDTTIVVE TPLKCTTFGV KFNSFLMNLK
ENFQDLTQFD IVVLKKRIGV LVYDEYLKAS FLLRSLNYNE NYHYQLIKLI IESNKFQHSH
AVKLAKDCCE YGNLKVFKLL EHKFPLNLID PVTLESPIHY STLFNNNHLK SKIILEYCLI
NKIYSIDQLN KQKETPLHYC SRFGNYEIAT ILLVRGCNRN LKDVQGQTPL HISVSQTNHQ
LSSLLCKHGA QSIPDKTMKN PLQYCSADIK SNLQNILFTN EVFISYAHKD SEFVNNLRSN
FGLFSLRCWL DEYRLQAGCN WRAEITRGVV NSDVVVFVIS ETSINSLWCR KELKMSKKLG
KVIIPIFLQS VQIDPILYGL FTFIPKTTKK TFKEMSEKEV ISNVSSISNL IHSILNGTQD
SKLLTIQQQQ QQNFEKSVQS LSRKEFFDKC YLNDKNSGCY LLFNNADRIL FDFICDKFKE
NSIPTISSDE IIGRPSDQDD QFSLFNLMKQ KKQNSIQRKK NIELEKKLKL ENDEKLKQQW
KIKRKIEKKL EKSKLIPSDP NYQYLENYLI QLYNFKNDNE NEINENENNN NNQNNQNNQN
NIIQNNYNYN NNNNYYDDND IPILNNNFNS SELNNNYFSS STTIQIEDSY NNNNNQAIYY
DDGKTSEEEF YKQLLIEKEN EKYHSIQPLK EFIKNSLLMC ILFTRKTTKT EIEKYCLQIE
YAKSFKDEKG NQDKTIIVIT PDLSLKDNQN TPSIIKDLVW YEIDSKNIDL IFENITLMYE
VLEKTLQISN LVNNNK
//
