CAPON_RAT
ID CAPON_RAT Reviewed; 503 AA.
AC O54960;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein {ECO:0000305};
DE AltName: Full=C-terminal PDZ ligand of neuronal nitric oxide synthase protein;
DE AltName: Full=Nitric oxide synthase 1 adaptor protein;
GN Name=Nos1ap {ECO:0000312|RGD:620106}; Synonyms=Capon;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH
RP NOS1, AND MUTAGENESIS OF ILE-501; ALA-502 AND VAL-503.
RX PubMed=9459447; DOI=10.1016/s0896-6273(00)80439-0;
RA Jaffrey S.R., Snowman A.M., Eliasson M.J.L., Cohen N.A., Snyder S.H.;
RT "CAPON: a protein associated with neuronal nitric oxide synthase that
RT regulates its interactions with PSD95.";
RL Neuron 20:115-124(1998).
RN [2]
RP INTERACTION WITH DLG4.
RX PubMed=10623522; DOI=10.1006/jmbi.1999.3350;
RA Tochio H., Hung F., Li M., Bredt D.S., Zhang M.;
RT "Solution structure and backbone dynamics of the second PDZ domain of
RT postsynaptic density-95.";
RL J. Mol. Biol. 295:225-237(2000).
RN [3]
RP INTERACTION WITH RASD1 AND NOS1.
RX PubMed=11086993; DOI=10.1016/s0896-6273(00)00095-7;
RA Fang M., Jaffrey S.R., Sawa A., Ye K., Luo X., Snyder S.H.;
RT "Dexras1: a G protein specifically coupled to neuronal nitric oxide
RT synthase via CAPON.";
RL Neuron 28:183-193(2000).
RN [4]
RP INTERACTION WITH NOS1; SYN1; SYN2 AND SYN3.
RX PubMed=11867766; DOI=10.1073/pnas.261705799;
RA Jaffrey S.R., Benfenati F., Snowman A.M., Czernik A.J., Snyder S.H.;
RT "Neuronal nitric-oxide synthase localization mediated by a ternary complex
RT with synapsin and CAPON.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:3199-3204(2002).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=33523862; DOI=10.1126/sciadv.abe1386;
RA Majmundar A.J., Buerger F., Forbes T.A., Klaembt V., Schneider R.,
RA Deutsch K., Kitzler T.M., Howden S.E., Scurr M., Tan K.S., Krzeminski M.,
RA Widmeier E., Braun D.A., Lai E., Ullah I., Amar A., Kolb A., Eddy K.,
RA Chen C.H., Salmanullah D., Dai R., Nakayama M., Ottlewski I.,
RA Kolvenbach C.M., Onuchic-Whitford A.C., Mao Y., Mann N., Nabhan M.M.,
RA Rosen S., Forman-Kay J.D., Soliman N.A., Heilos A., Kain R., Aufricht C.,
RA Mane S., Lifton R.P., Shril S., Little M.H., Hildebrandt F.;
RT "Recessive NOS1AP variants impair actin remodeling and cause glomerulopathy
RT in humans and mice.";
RL Sci. Adv. 7:0-0(2021).
CC -!- FUNCTION: Adapter protein involved in neuronal nitric-oxide (NO)
CC synthesis regulation via its association with nNOS/NOS1. The complex
CC formed with NOS1 and synapsins is necessary for specific NO and
CC synapsin functions at a presynaptic level. Mediates an indirect
CC interaction between NOS1 and RASD1 leading to enhance the ability of
CC NOS1 to activate RASD1. Competes with DLG4 for interaction with NOS1,
CC possibly affecting NOS1 activity by regulating the interaction between
CC NOS1 and DLG4. In kidney podocytes, plays a role in podosomes and
CC filopodia formation through CDC42 activation (PubMed:33523862).
CC {ECO:0000269|PubMed:33523862, ECO:0000269|PubMed:9459447}.
CC -!- SUBUNIT: Interacts with the PDZ domain of NOS1 or the second PDZ domain
CC of DLG4 through its C-terminus. Interacts with RASD1 and SYN1, SYN2 and
CC SYN3 via its PID domain. Forms a ternary complex with NOS1 and RASD1.
CC Forms a ternary complex with NOS1 and SYN1.
CC {ECO:0000269|PubMed:10623522, ECO:0000269|PubMed:11086993,
CC ECO:0000269|PubMed:11867766, ECO:0000269|PubMed:9459447}.
CC -!- SUBCELLULAR LOCATION: Cell projection, filopodium
CC {ECO:0000269|PubMed:33523862}. Cell projection, podosome
CC {ECO:0000269|PubMed:33523862}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in brain. Highly expressed in
CC accessory olfactory bulb, caudate-putamen, cerebellum, cerebral cortex,
CC dentate gyrus of the hippocampus, islands of Calleja, olfactory bulb
CC and supraoptic nucleus. Expressed in kidney glomeruli podocytes (at
CC protein level) (PubMed:33523862). {ECO:0000269|PubMed:33523862,
CC ECO:0000269|PubMed:9459447}.
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DR EMBL; AF037071; AAC40065.1; -; mRNA.
DR RefSeq; NP_620277.1; NM_138922.1.
DR AlphaFoldDB; O54960; -.
DR SMR; O54960; -.
DR CORUM; O54960; -.
DR IntAct; O54960; 2.
DR MINT; O54960; -.
DR STRING; 10116.ENSRNOP00000038197; -.
DR PaxDb; O54960; -.
DR PeptideAtlas; O54960; -.
DR PRIDE; O54960; -.
DR GeneID; 192363; -.
DR KEGG; rno:192363; -.
DR UCSC; RGD:620106; rat.
DR CTD; 9722; -.
DR RGD; 620106; Nos1ap.
DR eggNOG; KOG4458; Eukaryota.
DR eggNOG; KOG4815; Eukaryota.
DR InParanoid; O54960; -.
DR OrthoDB; 1185572at2759; -.
DR PhylomeDB; O54960; -.
DR PRO; PR:O54960; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0002102; C:podosome; IEA:UniProtKB-SubCell.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0030018; C:Z disc; ISO:RGD.
DR GO; GO:0050998; F:nitric-oxide synthase binding; IDA:RGD.
DR GO; GO:0030165; F:PDZ domain binding; IDA:RGD.
DR GO; GO:0002020; F:protease binding; IPI:RGD.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:RGD.
DR GO; GO:0031102; P:neuron projection regeneration; IEP:RGD.
DR GO; GO:0007269; P:neurotransmitter secretion; NAS:UniProtKB.
DR GO; GO:2000170; P:positive regulation of peptidyl-cysteine S-nitrosylation; IMP:BHF-UCL.
DR GO; GO:0098974; P:postsynaptic actin cytoskeleton organization; ISO:RGD.
DR GO; GO:1902514; P:regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; IDA:BHF-UCL.
DR GO; GO:0098901; P:regulation of cardiac muscle cell action potential; IC:BHF-UCL.
DR GO; GO:0003062; P:regulation of heart rate by chemical signal; ISO:RGD.
DR GO; GO:1901841; P:regulation of high voltage-gated calcium channel activity; IDA:BHF-UCL.
DR GO; GO:0045428; P:regulation of nitric oxide biosynthetic process; TAS:DFLAT.
DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:DFLAT.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; ISO:RGD.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR Pfam; PF00640; PID; 1.
DR SMART; SM00462; PTB; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell projection; Coiled coil; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..503
FT /note="Carboxyl-terminal PDZ ligand of neuronal nitric
FT oxide synthase protein"
FT /id="PRO_0000089318"
FT DOMAIN 26..191
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 170..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 491..503
FT /note="Interaction with NOS1"
FT COILED 319..360
FT /evidence="ECO:0000255"
FT MOTIF 501..503
FT /note="PDZ-binding"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D3A8"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D3A8"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D3A8"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75052"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D3A8"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D3A8"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D3A8"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D3A8"
FT MUTAGEN 501
FT /note="I->S,A: Does not affect interaction with NOS1."
FT /evidence="ECO:0000269|PubMed:9459447"
FT MUTAGEN 502
FT /note="A->D: Abolishes interaction with NOS1."
FT /evidence="ECO:0000269|PubMed:9459447"
FT MUTAGEN 503
FT /note="V->A: Abolishes interaction with NOS1."
FT /evidence="ECO:0000269|PubMed:9459447"
SQ SEQUENCE 503 AA; 55864 MW; 801775EB2BF49EFC CRC64;
MPSKTKYNLV DDGHDLRIPL HNEDAFQHGI SFEAKYVGSL DVPRPNSRVE IVAAMRRIRY
EFKAKNIKKK KVSIMVSVDG VKVILKKKKK KKEWTWDESK MLVMQDPIYR IFYVSHDSQD
LKIFSYIARD GASNIFRCNV FKSKKKSQAM RIVRTVGQAF EVCHKLSLQH TQQNADGQED
GESERNSDGS GDPGRQLTGA ERVSTATAEE TDIDAVEVPL PGNDILEFSR GVTDLDAIGK
DGGSHIDTTV SPHPQEPMLA ASPRMLLPSS SSSKPPGLGT GTPLSTHHQM QLLQQLLQQQ
QQQTQVAVAQ VHLLKDQLAA EAAARLEAQA RVHQLLLQNK DMLQHISLLV KQVQELELKL
SGQSTMGSQD SLLEITFRSG ALPVLCESTT PKPEDLHSPL LGAGLADFAH PVGSPLGRRD
CLVKLECFRF LPAEDNQPMA QGEPLLGGLE LIKFRESGIA SEYESNTDES EERDSWSQEE
LPRLLNVLQR QELGDSLDDE IAV
