Q9NRD5 (PICK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
PRKCA-binding protein

Alternative name(s):
Protein interacting with C kinase 1
Protein kinase C-alpha-binding protein

Gene names

Name:	PICK1
Synonyms:	PRKCABP

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	415 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate heteromeric ASIC1/ASIC3 channel. Ref.12
Subunit structure	Monomer and homodimer. Interacts presynaptically with the monoamine transporters SLC6A2 and SLC6A3; with the channel proteins ASIC1 and ASIC2; with the GTP-binding proteins ARF1 and ARF3. Interacts with PRKCA; with the ephrin receptor tyrosine kinases EPHA7, EPHB1 and EPHB2; and with ERBB2. Interacts with BTG2; with the glutamate receptors GRIA2, GRIA3, the isoform A of GRM4, GRM7 and GRM8; and with NAPA and NAPB. The interaction with NAPA and NAPB disrupts the interaction with GRIA2, conducting to the internalization of GRIA2. Interacts with UNC5A By similarity. Interacts with CXADR. Interacts through its PDZ domain with the C-terminal tail of PRLHR. Interacts (via AH domain) with NCS1/FREQ; in a calcium-dependent manner By similarity. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
Subcellular location	Cytoplasm › perinuclear region. Cell junction › synapse. Note: Also present at excitatory synapses.
Tissue specificity	Ubiquitous.
Post-translational modification	Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors.
Sequence similarities	Contains 1 AH domain. Contains 1 PDZ (DHR) domain.

Ontologies

Keywords
Cellular component	Cell junction Cytoplasm Synapse
Ligand	Calcium Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA methylation involved in embryo development Non-traceable author statement PubMed 12138111. Source: UniProtKB DNA methylation involved in gamete generation Traceable author statement PubMed 12138111. Source: UniProtKB monoamine transport Inferred from direct assay Ref.8. Source: UniProtKB neuronal ion channel clustering Traceable author statement Ref.8. Source: UniProtKB protein kinase C-activating G-protein coupled receptor signaling pathway Inferred from direct assay Ref.1. Source: UniProtKB protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB protein targeting Inferred from electronic annotation. Source: Compara receptor clustering Inferred from sequence or structural similarity. Source: UniProtKB retrograde vesicle-mediated transport, Golgi to ER Non-traceable author statement Ref.1. Source: UniProtKB synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW endocytic vesicle membrane Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from direct assay Ref.8. Source: UniProtKB presynaptic membrane Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	ATPase activity Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C binding Inferred from sequence or structural similarity. Source: UniProtKB receptor binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASIC1	P78348	3	EBI-79165,EBI-79189
ASIC2	Q16515	3	EBI-79165,EBI-79149
COIL	P38432	3	EBI-79165,EBI-945751

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 415

415

PRKCA-binding protein

PRO_0000058427

Regions

Domain

22 – 105

84

PDZ

Domain

144 – 357

214

AH

Compositional bias

382 – 388

7

Poly-Glu

Sites

Metal binding

44

1

Zinc By similarity

Metal binding

46

1

Zinc By similarity

Amino acid modifications

Modified residue

82

1

Phosphothreonine Ref.12

Experimental info

Mutagenesis

27 – 28

2

KD → AA: Abolishes interaction with other proteins, but not with itself. Ref.1 Ref.8 Ref.9 Ref.11

Mutagenesis

27

1

K → E: Abolishes interaction with GRIA2, but not with PRKCA. Ref.1 Ref.8 Ref.9 Ref.11

Sequence conflict

7

1

Y → F in AAF97502. Ref.2

Sequence conflict

16

1

Missing in AAF97502. Ref.2

Sequence conflict

236

1

N → NI in AAF97502. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

415

Helix Strand Turn

Details...

Beta strand

21 – 26

6

Beta strand

34 – 39

6

Beta strand

47 – 52

6

Helix

57 – 61

5

Beta strand

69 – 73

5

Helix

83 – 92

10

Beta strand

95 – 102

8

Sequences

	Sequence		Length	Mass (Da)
	Q9NRD5 [UniParc]. Last modified August 2, 2002. Version 2. Checksum: C569FD8AA5028B90	FASTA	415	46,600
	10 20 30 40 50 60 MFADLDYDIE EDKLGIPTVP GKVTLQKDAQ NLIGISIGGG AQYCPCLYIV QVFDNTPAAL 70 80 90 100 110 120 DGTVAAGDEI TGVNGRSIKG KTKVEVAKMI QEVKGEVTIH YNKLQADPKQ GMSLDIVLKK 130 140 150 160 170 180 VKHRLVENMS SGTADALGLS RAILCNDGLV KRLEELERTA ELYKGMTEHT KNLLRAFYEL 190 200 210 220 230 240 SQTHRAFGDV FSVIGVREPQ PAASEAFVKF ADAHRSIEKF GIRLLKTIKP MLTDLNTYLN 250 260 270 280 290 300 KAIPDTRLTI KKYLDVKFEY LSYCLKVKEM DDEEYSCIAL GEPLYRVSTG NYEYRLILRC 310 320 330 340 350 360 RQEARARFSQ MRKDVLEKME LLDQKHVQDI VFQLQRLVST MSKYYNDCYA VLRDADVFPI 370 380 390 400 410 EVDLAHTTLA YGLNQEEFTD GEEEEEEEDT AAGEPSRDTR GAAGPLDKGG SWCDS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Interaction of the PDZ domain of human PICK1 with class I ADP-ribosylation factors." Takeya R., Takeshige K., Sumimoto H. Biochem. Biophys. Res. Commun. 267:149-155(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH ARF1 AND ARF3, MUTAGENESIS OF 27-LYS-ASP-28. Tissue: B-cell.
[2]	"Protein kinases interacting with the human PICK1 protein." Zhu X., Chung I., Scholl P.R. Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Reevaluating human gene annotation: a second-generation analysis of chromosome 22." Collins J.E., Goward M.E., Cole C.G., Smink L.J., Huckle E.J., Knowles S., Bye J.M., Beare D.M., Dunham I. Genome Res. 13:27-36(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Skin.
[7]	"The carboxyl terminus of the prolactin-releasing peptide receptor interacts with PDZ domain proteins involved in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor clustering." Lin S.H.S., Arai A.C., Wang Z., Nothacker H.-P., Civelli O. Mol. Pharmacol. 60:916-923(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRLHR.
[8]	"Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1." Torres G.E., Yao W.-D., Mohn A.R., Quan H., Kim K.-M., Levey A.I., Staudinger J., Caron M.G. Neuron 30:121-134(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SLC6A2 AND SLC6A3, MUTAGENESIS OF 27-LYS-ASP-28.
[9]	"Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)." Hruska-Hageman A.M., Wemmie J.A., Price M.P., Welsh M.J. Biochem. J. 361:443-450(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ASIC1 AND ASIC2, MUTAGENESIS OF 27-LYS-ASP-28.
[10]	"A role for the PDZ-binding domain of the coxsackie B virus and adenovirus receptor (CAR) in cell adhesion and growth." Ashbourne-Excoffon K.J.D., Hruska-Hageman A.M., Klotz M., Traver G.L., Zabner J. J. Cell Sci. 117:4401-4409(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CXADR.
[11]	"The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and GluR2 as interacting ligands." Dev K.K., Nakanishi S., Henley J.M. J. Biol. Chem. 279:41393-41397(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRIA2 AND PRKCA, MUTAGENESIS OF LYS-27.
[12]	"Threonine 82 at the PDZ domain of PICK1 is critical for AMPA receptor interaction and localization." Shao X., Zhu L., Wang Y., Lu Y., Wang W., Zhu J., Shen Y., Xia J., Luo J. Neurochem. Int. 56:962-970(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT THR-82.
[13]	"Structure of PICK1 and other PDZ domains obtained with the help of self-binding C-terminal extensions." Elkins J.M., Papagrigoriou E., Berridge G., Yang X., Phillips C., Gileadi C., Savitsky P., Doyle D.A. Protein Sci. 16:683-694(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.12 ANGSTROMS) OF 19-105.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB026491 mRNA. Translation: BAA89294.1.
AF231710 mRNA. Translation: AAF97502.1.
AL049654 mRNA. Translation: CAB41082.1.
CR456550 mRNA. Translation: CAG30436.1.
AL031587 Genomic DNA. Translation: CAB37478.1.
BC017561 mRNA. Translation: AAH17561.1.

IPI

IPI00160369.

PIR

JC7167.

RefSeq

NP_001034672.1. NM_001039583.1.
NP_001034673.1. NM_001039584.1.
NP_036539.1. NM_012407.3.

UniGene

Hs.180871.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GZV	X-ray	1.12	A	19-105	[»]

ProteinModelPortal

Q9NRD5.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NRD5. 17 interactions.

MINT

MINT-197903.

STRING

9606.ENSP00000349465.

PTM databases

PhosphoSite

Q9NRD5.

Polymorphism databases

DMDM

22095990.

Proteomic databases

PaxDb

Q9NRD5.

PRIDE

Q9NRD5.

Protocols and materials databases

DNASU

9463.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000356976; ENSP00000349465; ENSG00000100151.
ENST00000404072; ENSP00000385205; ENSG00000100151.

GeneID

9463.

KEGG

hsa:9463.

UCSC

uc003auq.3. human.

Organism-specific databases

CTD

9463.

GeneCards

GC22P038452.

H-InvDB

HIX0175461.

HGNC

HGNC:9394. PICK1.

HPA

CAB034049.

MIM

605926. gene.

neXtProt

NX_Q9NRD5.

PharmGKB

PA33760.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG323044.

HOGENOM

HOG000007646.

HOVERGEN

HBG053600.

InParanoid

Q9NRD5.

OMA

LCPCLYI.

OrthoDB

EOG4GQQ55.

PhylomeDB

Q9NRD5.

Enzyme and pathway databases

Reactome

REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

Q9NRD5.

Bgee

Q9NRD5.

CleanEx

HS_PICK1.

Genevestigator

Q9NRD5.

GermOnline

ENSG00000100151. Homo sapiens.

Family and domain databases

Gene3D

1.20.1270.60. 1 hit.

InterPro

IPR027267. AH/BAR-dom.
IPR010504. AH_dom.
IPR001478. PDZ.
[Graphical view]

Pfam

PF06456. Arfaptin. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]

SMART

SM01015. Arfaptin. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]

SUPFAM

SSF50156. PDZ. 1 hit.

PROSITE

PS50870. AH. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PICK1. human.

EvolutionaryTrace

Q9NRD5.

GenomeRNAi

9463.

NextBio

35452.

SOURCE

Search...

Entry information

Entry name

PICK1_HUMAN

Accession

Primary (citable) accession number: Q9NRD5
Secondary accession number(s): O95906

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 2, 2002
Last sequence update:	August 2, 2002
Last modified:	May 1, 2013
This is version 121 of the entry and version 2 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.