Q96MT3 (PRIC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prickle-like protein 1

Alternative name(s):
REST/NRSF-interacting LIM domain protein 1

Gene names

Name:	PRICKLE1
Synonyms:	RILP

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	831 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure. Convergent extension is a complex morphogenetic process during which cells elongate, move mediolaterally, and intercalate between neighboring cells, leading to convergence toward the mediolateral axis and extension along the anteroposterior axis. Necessary for nuclear localization of REST. May serve as nuclear receptor. Ref.7
Subunit structure	Interacts with REST. Ref.1
Subcellular location	Nucleus membrane. Cytoplasm › cytosol. Note: A smaller amount is detected in the cytosol. Ref.1
Tissue specificity	Expressed at highest levels in placenta and at lower levels in lung, liver, kidney and pancreas. Expressed in thalamus, hippocampus, cerebral cortex, and cerebellum (in neurons rather than glia). Ref.1 Ref.4 Ref.6
Involvement in disease	Epilepsy, progressive myoclonic 1B (EPM1B) [MIM:612437]: An autosomal recessive disorder characterized by myoclonus that progressed in severity over time, tonic-clonic seizures and ataxia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.9 Neural tube defects (NTD) [MIM:182940]: Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the prickle / espinas / testin family. Contains 3 LIM zinc-binding domains. Contains 1 PET domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Epilepsy
Domain	LIM domain Repeat
Ligand	Metal-binding Zinc
PTM	Lipoprotein Methylation Phosphoprotein Prenylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 17030191. Source: BHF-UCL negative regulation of cardiac muscle cell myoblast differentiation Inferred from direct assay PubMed 21199191. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 17030191. Source: BHF-UCL neural tube closure Inferred from mutant phenotype Ref.7. Source: UniProtKB positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay PubMed 17030191. Source: BHF-UCL positive regulation of protein ubiquitination Inferred from direct assay PubMed 17030191. Source: BHF-UCL protein import into nucleus Inferred from direct assay PubMed 21199191. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay Ref.1PubMed 18922795. Source: UniProtKB nuclear membrane Inferred from direct assay Ref.1PubMed 16417580. Source: UniProtKB
Molecular_function	zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 828	828	Prickle-like protein 1		PRO_0000075889
	Propeptide	829 – 831	3	Removed in mature form Probable		PRO_0000396712
Regions
	Domain	14 – 122	109	PET
	Domain	124 – 189	66	LIM zinc-binding 1
	Domain	189 – 249	61	LIM zinc-binding 2
	Domain	249 – 313	65	LIM zinc-binding 3
	Compositional bias	655 – 682	28	Arg/His-rich
	Compositional bias	761 – 772	12	Ser-rich
	Compositional bias	816 – 821	6	Poly-Lys
Amino acid modifications
	Modified residue	681	1	Phosphoserine By similarity
	Modified residue	828	1	Cysteine methyl ester Probable
	Lipidation	828	1	S-farnesyl cysteine Ref.1 Ref.5
Natural variations
	Natural variant	69	1	I → T May be associated with NTD. Ref.7 Corresponds to variant rs141795695 [ dbSNP | Ensembl ].		VAR_066850
	Natural variant	81	1	N → H May be associated with NTD. Ref.7		VAR_066851
	Natural variant	104	1	R → Q in EPM1B; affects interaction with REST. Ref.6 Ref.9		VAR_054663
	Natural variant	121	1	V → I May be associated with NTD. Ref.7		VAR_066852
	Natural variant	124	1	A → T. Ref.7 Corresponds to variant rs79087668 [ dbSNP | Ensembl ].		VAR_066853
	Natural variant	144	1	R → H in EPM1B. Ref.9		VAR_065580
	Natural variant	275	1	T → M May be associated with NTD. Ref.7		VAR_066854
	Natural variant	472	1	Y → H in EPM1B. Ref.9		VAR_065581
	Natural variant	682	1	R → C May be associated with NTD. Ref.7		VAR_066855
	Natural variant	739	1	S → F May be associated with NTD. Ref.7 Corresponds to variant rs138452760 [ dbSNP | Ensembl ].		VAR_066856
	Natural variant	746	1	P → S. Corresponds to variant rs3827522 [ dbSNP | Ensembl ].		VAR_056164
	Natural variant	771	1	D → N May be associated with NTD. Ref.7		VAR_066857
	Natural variant	799	1	S → C May be associated with NTD. Ref.7		VAR_066858
Experimental info
	Mutagenesis	828 – 831	4	Missing: Abolishes localization to the nuclear membrane. Ref.1
	Sequence conflict	739	1	S → P in BAB71198. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q96MT3 [UniParc]. Last modified February 1, 2005. Version 2. Checksum: 753D68BD5A4D0935	FASTA	831	94,300
	10 20 30 40 50 60 MPLEMEPKMS KLAFGCQRSS TSDDDSGCAL EEYAWVPPGL RPEQIQLYFA CLPEEKVPYV 70 80 90 100 110 120 NSPGEKHRIK QLLYQLPPHD NEVRYCQSLS EEEKKELQVF SAQRKKEALG RGTIKLLSRA 130 140 150 160 170 180 VMHAVCEQCG LKINGGEVAV FASRAGPGVC WHPSCFVCFT CNELLVDLIY FYQDGKIHCG 190 200 210 220 230 240 RHHAELLKPR CSACDEIIFA DECTEAEGRH WHMKHFCCLE CETVLGGQRY IMKDGRPFCC 250 260 270 280 290 300 GCFESLYAEY CETCGEHIGV DHAQMTYDGQ HWHATEACFS CAQCKASLLG CPFLPKQGQI 310 320 330 340 350 360 YCSKTCSLGE DVHASDSSDS AFQSARSRDS RRSVRMGKSS RSADQCRQSL LLSPALNYKF 370 380 390 400 410 420 PGLSGNADDT LSRKLDDLSL SRQGTSFASE EFWKGRVEQE TPEDPEEWAD HEDYMTQLLL 430 440 450 460 470 480 KFGDKSLFQP QPNEMDIRAS EHWISDNMVK SKTELKQNNQ SLASKKYQSD MYWAQSQDGL 490 500 510 520 530 540 GDSAYGSHPG PASSRRLQEL ELDHGASGYN HDETQWYEDS LECLSDLKPE QSVRDSMDSL 550 560 570 580 590 600 ALSNITGASV DGENKPRPSL YSLQNFEEME TEDCEKMSNM GTLNSSMLHR SAESLKSLSS 610 620 630 640 650 660 ELCPEKILPE EKPVHLPVLR RSKSQSRPQQ VKFSDDVIDN GNYDIEIRQP PMSERTRRRV 670 680 690 700 710 720 YNFEERGSRS HHHRRRRSRK SRSDNALNLV TERKYSPKDR LRLYTPDNYE KFIQNKSARE 730 740 750 760 770 780 IQAYIQNADL YGQYAHATSD YGLQNPGMNR FLGLYGEDDD SWCSSSSSSS DSEEEGYFLG 790 800 810 820 830 QPIPQPRPQR FAYYTDDLSS PPSALPTPQF GQRTTKSKKK KGHKGKNCII S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"REST/NRSF-interacting LIM domain protein, a putative nuclear translocation receptor." Shimojo M., Hersh L.B. Mol. Cell. Biol. 23:9025-9031(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, ISOPRENYLATION AT CYS-828, MUTAGENESIS OF 828-CYS--SER-831, SUBCELLULAR LOCATION, INTERACTION WITH REST. Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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].
[4]	"Identification and characterization of human PRICKLE1 and PRICKLE2 genes as well as mouse Prickle1 and Prickle2 genes homologous to Drosophila tissue polarity gene prickle." Katoh M., Katoh M. Int. J. Mol. Med. 11:249-256(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, TISSUE SPECIFICITY.
[5]	"Towards complete sets of farnesylated and geranylgeranylated proteins." Maurer-Stroh S., Koranda M., Benetka W., Schneider G., Sirota F.L., Eisenhaber F. PLoS Comput. Biol. 3:634-648(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ISOPRENYLATION AT CYS-828.
[6]	"A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome." Bassuk A.G., Wallace R.H., Buhr A., Buller A.R., Afawi Z., Shimojo M., Miyata S., Chen S., Gonzalez-Alegre P., Griesbach H.L., Wu S., Nashelsky M., Vladar E.K., Antic D., Ferguson P.J., Cirak S., Voit T., Scott M.P. , Axelrod J.D., Gurnett C., Daoud A.S., Kivity S., Neufeld M.Y., Mazarib A., Straussberg R., Walid S., Korczyn A.D., Slusarski D.C., Berkovic S.F., El-Shanti H.I. Am. J. Hum. Genet. 83:572-581(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, VARIANT EPM1B GLN-104, CHARACTERIZATION OF VARIANT EPM1B GLN-104.
[7]	"Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects." Bosoi C.M., Capra V., Allache R., Trinh V.Q., De Marco P., Merello E., Drapeau P., Bassuk A.G., Kibar Z. Hum. Mutat. 32:1371-1375(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, POSSIBLE INVOLVEMENT IN NTD, VARIANTS THR-69; HIS-81; ILE-121; THR-124; MET-275; CYS-682; PHE-739; ASN-771 AND CYS-799.
[8]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Mutations in prickle orthologs cause seizures in flies, mice, and humans." Tao H., Manak J.R., Sowers L., Mei X., Kiyonari H., Abe T., Dahdaleh N.S., Yang T., Wu S., Chen S., Fox M.H., Gurnett C., Montine T., Bird T., Shaffer L.G., Rosenfeld J.A., McConnell J., Madan-Khetarpal S. , Berry-Kravis E., Griesbach H., Saneto R.P., Scott M.P., Antic D., Reed J., Boland R., Ehaideb S.N., El-Shanti H., Mahajan V.B., Ferguson P.J., Axelrod J.D., Lehesjoki A.E., Fritzsch B., Slusarski D.C., Wemmie J., Ueno N., Bassuk A.G. Am. J. Hum. Genet. 88:138-149(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EPM1B GLN-104; HIS-144 AND HIS-472.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF399844 mRNA. Translation: AAQ03035.1. AK056189 mRNA. Translation: BAB71116.1. AK056499 mRNA. Translation: BAB71198.1. BC114939 mRNA. Translation: AAI14940.1. BC114940 mRNA. Translation: AAI14941.1.
IPI	IPI00043363.
RefSeq	NP_001138353.1. NM_001144881.1. NP_001138354.1. NM_001144882.1. NP_001138355.1. NM_001144883.1. NP_694571.2. NM_153026.2.
UniGene	Hs.524348. Hs.720221.
3D structure databases
ProteinModelPortal	Q96MT3.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96MT3. 3 interactions.
STRING	9606.ENSP00000345064.
PTM databases
PhosphoSite	Q96MT3.
Polymorphism databases
DMDM	59800163.
Proteomic databases
PaxDb	Q96MT3.
PRIDE	Q96MT3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000345127; ENSP00000345064; ENSG00000139174. ENST00000445766; ENSP00000398947; ENSG00000139174. ENST00000455697; ENSP00000401060; ENSG00000139174. ENST00000548696; ENSP00000448359; ENSG00000139174. ENST00000552240; ENSP00000449819; ENSG00000139174.
GeneID	144165.
KEGG	hsa:144165.
UCSC	uc001rnl.3. human.
Organism-specific databases
CTD	144165.
GeneCards	GC12M042852.
HGNC	HGNC:17019. PRICKLE1.
HPA	HPA001379.
MIM	182940. phenotype. 608500. gene. 612437. phenotype.
neXtProt	NX_Q96MT3.
Orphanet	308. Unverricht-Lundborg disease.
PharmGKB	PA134906946.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG314122.
HOGENOM	HOG000290649.
HOVERGEN	HBG053679.
InParanoid	Q96MT3.
KO	K04511.
OMA	CCLECET.
OrthoDB	EOG4FBHS8.
PhylomeDB	Q96MT3.
Gene expression databases
ArrayExpress	Q96MT3.
Bgee	Q96MT3.
CleanEx	HS_PRICKLE1. HS_RILP.
Genevestigator	Q96MT3.
GermOnline	ENSG00000139174. Homo sapiens.
Family and domain databases
Gene3D	2.10.110.10. 3 hits.
InterPro	IPR010442. PET_domain. IPR001781. Znf_LIM. [Graphical view]
Pfam	PF00412. LIM. 3 hits. PF06297. PET. 1 hit. [Graphical view]
SMART	SM00132. LIM. 3 hits. [Graphical view]
PROSITE	PS00478. LIM_DOMAIN_1. 2 hits. PS50023. LIM_DOMAIN_2. 3 hits. PS51303. PET. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	144165.
NextBio	84850.
SOURCE	Search...

Entry information

Entry name

PRIC1_HUMAN

Accession

Primary (citable) accession number: Q96MT3
Secondary accession number(s): Q14C83, Q71QF8, Q96N00

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 2005
Last sequence update:	February 1, 2005
Last modified:	May 1, 2013
This is version 98 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.