O75052 (CAPON_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein

Alternative name(s):
C-terminal PDZ ligand of neuronal nitric oxide synthase protein
Nitric oxide synthase 1 adaptor protein

Gene names

Name:	NOS1AP
Synonyms:	CAPON, KIAA0464

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	506 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adapter protein involved in neuronal nitric-oxide (NO) synthesis regulation via its association with nNOS/NOS1. The complex formed with NOS1 and synapsins is necessary for specific NO and synapsin functions at a presynaptic level. Mediates an indirect interaction between NOS1 and RASD1 leading to enhance the ability of NOS1 to activate RASD1. Competes with DLG4 for interaction with NOS1, possibly affecting NOS1 activity by regulating the interaction between NOS1 and DLG4 By similarity.
Subunit structure	Interacts with the PDZ domain of NOS1 or the second PDZ domain of DLG4 through its C-terminus. Interacts with RASD1 and SYN1, SYN2 and SYN3 via its PID domain. Forms a ternary complex with NOS1 and RASD1. Forms a ternary complex with NOS1 and SYN1 By similarity. Ref.5
Polymorphism	Genetic variation in NOS1AP influences the electrocardiographic QT interval [MIM:610141]. The QT interval is defined as the time from the beginning of the Q wave to the end of the T wave, representing the duration of ventricular electrical activity. The QT interval, a measure of cardiac repolarization, is a genetically influenced quantitative trait with considerable medical relevance: both high and low values are associated with increased risk of cardiovascular morbidity and mortality.
Sequence similarities	Contains 1 PID domain.
Sequence caution	The sequence BAA32309.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of apoptotic process Non-traceable author statement PubMed 20431962. Source: DFLAT regulation of nitric oxide biosynthetic process Non-traceable author statement PubMed 20431962. Source: DFLAT regulation of nitric-oxide synthase activity Non-traceable author statement PubMed 20431962. Source: DFLAT
Molecular_function	PDZ domain binding Inferred from sequence or structural similarity Ref.5. Source: UniProtKB nitric-oxide synthase binding Inferred from sequence or structural similarity Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75052-1)

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.

Isoform 2 (identifier: O75052-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MPSKTKYNLVDDGHDLR → MSLSSLCPVFSAAASSL
     18-312: Missing.

Isoform 3 (identifier: O75052-3)

The sequence of this isoform differs from the canonical sequence as follows:
     91-95: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 506	506	Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein		PRO_0000089316
Regions
	Domain	26 – 196	171	PID
	Region	494 – 506	13	Interaction with NOS1 By similarity
	Coiled coil	322 – 363	42	Potential
	Motif	504 – 506	3	PDZ-binding By similarity
	Compositional bias	301 – 308	8	Poly-Gln
Amino acid modifications
	Modified residue	188	1	Phosphoserine By similarity
	Modified residue	192	1	Phosphoserine By similarity
	Modified residue	266	1	Phosphoserine Ref.10
	Modified residue	374	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 17	17	MPSKT…GHDLR → MSLSSLCPVFSAAASSL in isoform 2.		VSP_042751
	Alternative sequence	18 – 312	295	Missing in isoform 2.		VSP_042752
	Alternative sequence	91 – 95	5	Missing in isoform 3.		VSP_043350

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 4, 2005. Version 3. Checksum: D969C65E87684A7C	FASTA	506	56,150
	10 20 30 40 50 60 MPSKTKYNLV DDGHDLRIPL HNEDAFQHGI CFEAKYVGSL DVPRPNSRVE IVAAMRRIRY 70 80 90 100 110 120 EFKAKNIKKK KVSIMVSVDG VKVILKKKKK LLLLQKKEWT WDESKMLVMQ DPIYRIFYVS 130 140 150 160 170 180 HDSQDLKIFS YIARDGASNI FRCNVFKSKK KSQAMRIVRT VGQAFEVCHK LSLQHTQQNA 190 200 210 220 230 240 DGQEDGESER NSNSSGDPGR QLTGAERAST ATAEETDIDA VEVPLPGNDV LEFSRGVTDL 250 260 270 280 290 300 DAVGKEGGSH TGSKVSHPQE PMLTASPRML LPSSSSKPPG LGTETPLSTH HQMQLLQQLL 310 320 330 340 350 360 QQQQQQTQVA VAQVHLLKDQ LAAEAAARLE AQARVHQLLL QNKDMLQHIS LLVKQVQELE 370 380 390 400 410 420 LKLSGQNAMG SQDSLLEITF RSGALPVLCD PTTPKPEDLH SPPLGAGLAD FAHPAGSPLG 430 440 450 460 470 480 RRDCLVKLEC FRFLPPEDTP PPAQGEALLG GLELIKFRES GIASEYESNT DESEERDSWS 490 500 QEELPRLLNV LQRQELGDGL DDEIAV
	Isoform 2 [UniParc]. Checksum: E92ED7BE06D43943	FASTA	211	22,955
	10 20 30 40 50 60 MSLSSLCPVF SAAASSLQVH LLKDQLAAEA AARLEAQARV HQLLLQNKDM LQHISLLVKQ 70 80 90 100 110 120 VQELELKLSG QNAMGSQDSL LEITFRSGAL PVLCDPTTPK PEDLHSPPLG AGLADFAHPA 130 140 150 160 170 180 GSPLGRRDCL VKLECFRFLP PEDTPPPAQG EALLGGLELI KFRESGIASE YESNTDESEE 190 200 210 RDSWSQEELP RLLNVLQRQE LGDGLDDEIA V
	Isoform 3 [UniParc]. Checksum: 365A1A9B987EE0F3	FASTA	501	55,569
	10 20 30 40 50 60 MPSKTKYNLV DDGHDLRIPL HNEDAFQHGI CFEAKYVGSL DVPRPNSRVE IVAAMRRIRY 70 80 90 100 110 120 EFKAKNIKKK KVSIMVSVDG VKVILKKKKK KKEWTWDESK MLVMQDPIYR IFYVSHDSQD 130 140 150 160 170 180 LKIFSYIARD GASNIFRCNV FKSKKKSQAM RIVRTVGQAF EVCHKLSLQH TQQNADGQED 190 200 210 220 230 240 GESERNSNSS GDPGRQLTGA ERASTATAEE TDIDAVEVPL PGNDVLEFSR GVTDLDAVGK 250 260 270 280 290 300 EGGSHTGSKV SHPQEPMLTA SPRMLLPSSS SKPPGLGTET PLSTHHQMQL LQQLLQQQQQ 310 320 330 340 350 360 QTQVAVAQVH LLKDQLAAEA AARLEAQARV HQLLLQNKDM LQHISLLVKQ VQELELKLSG 370 380 390 400 410 420 QNAMGSQDSL LEITFRSGAL PVLCDPTTPK PEDLHSPPLG AGLADFAHPA GSPLGRRDCL 430 440 450 460 470 480 VKLECFRFLP PEDTPPPAQG EALLGGLELI KFRESGIASE YESNTDESEE RDSWSQEELP 490 500 RLLNVLQRQE LGDGLDDEIA V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of cDNA clones in size-fractionated cDNA libraries from human brain." Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., Nomura N., Ohara O. DNA Res. 4:345-349(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Increased expression in dorsolateral prefrontal cortex of CAPON in schizophrenia and bipolar disorder." Xu B., Wratten N., Charych E.I., Buyske S., Firestein B.L., Brzustowicz L.M. PLoS Med. 2:E263-E263(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Brain.
[5]	"CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95." Jaffrey S.R., Snowman A.M., Eliasson M.J.L., Cohen N.A., Snyder S.H. Neuron 20:115-124(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 354-506 (ISOFORM 1), INTERACTION WITH NOS1.
[6]	"A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization." Arking D.E., Pfeufer A., Post W., Kao W.H.L., Newton-Cheh C., Ikeda M., West K., Kashuk C., Akyol M., Perz S., Jalilzadeh S., Illig T., Gieger C., Guo C.-Y., Larson M.G., Wichmann H.E., Marban E., O'Donnell C.J. , Hirschhorn J.N., Kaeaeb S., Spooner P.M., Meitinger T., Chakravarti A. Nat. Genet. 38:644-651(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN THE REGULATION OF QT INTERVALS.
[7]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB007933 mRNA. Translation: BAA32309.2. Different initiation. AY841899 mRNA. Translation: AAW57298.1. AL590408, AL450163, AL512785 Genomic DNA. Translation: CAH71497.1. AL450163, AL590408, AL512785 Genomic DNA. Translation: CAH73230.1. AL512785, AL590408, AL450163 Genomic DNA. Translation: CAI15779.1. BC112295 mRNA. Translation: AAI12296.1. BC143771 mRNA. Translation: AAI43772.1. AF037070 mRNA. Translation: AAC39656.1.
IPI	IPI00514825. IPI00893882. IPI00944541.
RefSeq	NP_001119532.2. NM_001126060.1. NP_001158229.1. NM_001164757.1. NP_055512.1. NM_014697.2.
UniGene	Hs.731942.
3D structure databases
ProteinModelPortal	O75052.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75052. 1 interaction.
STRING	9606.ENSP00000355133.
PTM databases
PhosphoSite	O75052.
Proteomic databases
PaxDb	O75052.
PeptideAtlas	O75052.
PRIDE	O75052.
Protocols and materials databases
DNASU	9722.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361897; ENSP00000355133; ENSG00000198929. ENST00000493151; ENSP00000434988; ENSG00000198929. ENST00000530878; ENSP00000431586; ENSG00000198929.
GeneID	9722.
KEGG	hsa:9722.
UCSC	uc001gbv.2. human. uc001gbw.2. human. uc009wut.1. human.
Organism-specific databases
CTD	9722.
GeneCards	GC01P162039.
HGNC	HGNC:16859. NOS1AP.
HPA	CAB018582.
MIM	605551. gene. 610141. phenotype.
neXtProt	NX_O75052.
Orphanet	101016. Romano-Ward syndrome.
PharmGKB	PA142671259.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG244289.
HOGENOM	HOG000111298.
HOVERGEN	HBG050788.
InParanoid	O75052.
KO	K16513.
OMA	QNTMGSQ.
OrthoDB	EOG49KFQP.
Gene expression databases
ArrayExpress	O75052.
Bgee	O75052.
CleanEx	HS_NOS1AP.
Genevestigator	O75052.
GermOnline	ENSG00000198929. Homo sapiens.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR011993. PH_like_dom. IPR006020. PTyr_interaction_dom. [Graphical view]
Pfam	PF00640. PID. 1 hit. [Graphical view]
SMART	SM00462. PTB. 1 hit. [Graphical view]
PROSITE	PS01179. PID. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	9722.
NextBio	36573.
SOURCE	Search...

Entry information

Entry name

CAPON_HUMAN

Accession

Primary (citable) accession number: O75052
Secondary accession number(s): B7ZLF5 , O43564, Q3T551, Q5VU95

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	January 4, 2005
Last modified:	May 29, 2013
This is version 93 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.