Q13702 (RAPSN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
43 kDa receptor-associated protein of the synapse
Short name=RAPsyn

Alternative name(s):
43 kDa postsynaptic protein
Acetylcholine receptor-associated 43 kDa protein
RING finger protein 205

Gene names

Name:	RAPSN
Synonyms:	RNF205

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

General annotation (Comments)

Function	Thought to play some role in anchoring or stabilizing the nicotinic acetylcholine receptor at synaptic sites. It may link the receptor to the underlying postsynaptic cytoskeleton, possibly by direct association with actin or spectrin.
Subcellular location	Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction › synapse › postsynaptic cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm › cytoskeleton. Note: Cytoplasmic surface of postsynaptic membranes.
Domain	A cysteine-rich region homologous to part of the regulatory domain of protein kinase C may be important in interactions of this protein with the lipid bilayer.
Involvement in disease	Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency (CMS-ACHRD) [MIM:608931]: A post-synaptic congenital myasthenic syndrome. Congenital myasthenic syndromes (CMS) are inherited disorders of neuromuscular transmission that stem from mutations in presynaptic, synaptic, or postsynaptic proteins. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Fetal akinesia deformation sequence (FADS) [MIM:208150]: Rare condition characterized by decreased intrauterine fetal movement, congenital limb contractures, pulmonary hypoplasia, polyhydramnios and craniofacial abnormalities. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14
Sequence similarities	Belongs to the RAPsyn family. Contains 1 RING-type zinc finger. Contains 7 TPR repeats.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Congenital myasthenic syndrome Disease mutation
Domain	Repeat TPR repeat Zinc-finger
Ligand	Metal-binding Zinc
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara synaptic transmission, cholinergic Inferred from genetic interaction PubMed 18420419. Source: MGI
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from direct assay. Source: HPA cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell neuromuscular junction Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay. Source: HPA postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	acetylcholine receptor binding Inferred from direct assay PubMed 18420419. Source: MGI zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13702-1)

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: Q13702-2)

The sequence of this isoform differs from the canonical sequence as follows:
     264-322: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 412	412	43 kDa receptor-associated protein of the synapse		PRO_0000167591
Regions
	Repeat	6 – 39	34	TPR 1
	Repeat	83 – 116	34	TPR 2
	Repeat	123 – 156	34	TPR 3
	Repeat	163 – 196	34	TPR 4
	Repeat	206 – 239	34	TPR 5
	Repeat	246 – 279	34	TPR 6
	Repeat	286 – 319	34	TPR 7
	Zinc finger	363 – 403	41	RING-type
Amino acid modifications
	Modified residue	196	1	Phosphotyrosine Potential
	Modified residue	405	1	Phosphoserine Potential
	Lipidation	2	1	N-myristoyl glycine By similarity
Natural variations
	Alternative sequence	264 – 322	59	Missing in isoform 2.		VSP_005533
	Natural variant	8	1	Q → K. Ref.4 Corresponds to variant rs11556408 [ dbSNP | Ensembl ].		VAR_043897
	Natural variant	14	1	L → P in CMS-ACHRD. Ref.2 Ref.5 Ref.6		VAR_021216
	Natural variant	45	1	V → M in CMS-ACHRD; reduced coclustering with acetylcholine receptor. Ref.12		VAR_043898
	Natural variant	81	1	F → L. Corresponds to variant rs57878668 [ dbSNP | Ensembl ].		VAR_062142
	Natural variant	88	1	N → K in CMS-ACHRD. Ref.2 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10		VAR_021217
	Natural variant	139	1	F → S in FADS. Ref.14		VAR_043899
	Natural variant	162	1	E → K in CMS-ACHRD; reduced coclustering with acetylcholine receptor. Ref.12		VAR_043900
	Natural variant	164	1	R → C in CMS-ACHRD; reduced coclustering with acetylcholine receptor. Ref.11		VAR_043901
	Natural variant	189	1	A → V in FADS. Ref.14		VAR_043902
	Natural variant	283	1	L → P in CMS-ACHRD; reduced coclustering with acetylcholine receptor. Ref.11		VAR_043903
Experimental info
	Sequence conflict	112	1	L → V in CAA83954. Ref.1
	Sequence conflict	159	1	A → T in CAA83954. Ref.1
	Sequence conflict	205	1	R → Q in CAA83954. Ref.1
	Sequence conflict	364	1	G → A in CAA83954. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 17, 2007. Version 4. Checksum: D17AC566700F5AAF	FASTA	412	46,328
	10 20 30 40 50 60 MGQDQTKQQI EKGLQLYQSN QTEKALQVWT KVLEKSSDLM GRFRVLGCLV TAHSEMGRYK 70 80 90 100 110 120 EMLKFAVVQI DTARELEDAD FLLESYLNLA RSNEKLCEFH KTISYCKTCL GLPGTRAGAQ 130 140 150 160 170 180 LGGQVSLSMG NAFLGLSVFQ KALESFEKAL RYAHNNDDAM LECRVCCSLG SFYAQVKDYE 190 200 210 220 230 240 KALFFPCKAA ELVNNYGKGW SLKYRAMSQY HMAVAYRLLG RLGSAMECCE ESMKIALQHG 250 260 270 280 290 300 DRPLQALCLL CFADIHRSRG DLETAFPRYD SAMSIMTEIG NRLGQVQALL GVAKCWVARK 310 320 330 340 350 360 ALDKALDAIE RAQDLAEEVG NKLSQLKLHC LSESIYRSKG LQRELRAHVV RFHECVEETE 370 380 390 400 410 LYCGLCGESI GEKNSRLQAL PCSHIFHLRC LQNNGTRSCP NCRRSSMKPG FV
	Isoform 2 [UniParc]. Checksum: 79A95D25A1FAA69A	FASTA	353	39,912
	10 20 30 40 50 60 MGQDQTKQQI EKGLQLYQSN QTEKALQVWT KVLEKSSDLM GRFRVLGCLV TAHSEMGRYK 70 80 90 100 110 120 EMLKFAVVQI DTARELEDAD FLLESYLNLA RSNEKLCEFH KTISYCKTCL GLPGTRAGAQ 130 140 150 160 170 180 LGGQVSLSMG NAFLGLSVFQ KALESFEKAL RYAHNNDDAM LECRVCCSLG SFYAQVKDYE 190 200 210 220 230 240 KALFFPCKAA ELVNNYGKGW SLKYRAMSQY HMAVAYRLLG RLGSAMECCE ESMKIALQHG 250 260 270 280 290 300 DRPLQALCLL CFADIHRSRG DLELSQLKLH CLSESIYRSK GLQRELRAHV VRFHECVEET 310 320 330 340 350 ELYCGLCGES IGEKNSRLQA LPCSHIFHLR CLQNNGTRSC PNCRRSSMKP GFV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of cDNA encoding human rapsyn and mapping of the RAPSN gene locus to chromosome 11p11.2-p11.1." Buckel A., Beeson D., James M., Vincent A. Genomics 35:613-616(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Muscle.
[2]	"Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome." Ohno K., Engel A.G., Shen X.-M., Selcen D., Brengman J., Harper C.M., Tsujino A., Milone M. Am. J. Hum. Genet. 70:875-885(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS CMS-ACHRD PRO-14 AND LYS-88.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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] (ISOFORM 2), VARIANT LYS-8. Tissue: Muscle.
[5]	"Identification of pathogenic mutations in the human rapsyn gene." Dunne V., Maselli R.A. J. Hum. Genet. 48:204-207(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CMS-ACHRD PRO-14 AND LYS-88.
[6]	"Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering." Maselli R.A., Dunne V., Pascual-Pascual S.I., Bowe C., Agius M., Frank R., Wollmann R.L. Muscle Nerve 28:293-301(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CMS-ACHRD PRO-14 AND LYS-88.
[7]	"Rapsyn N88K is a frequent cause of congenital myasthenic syndromes in European patients." Mueller J.S., Mildner G., Mueller-Felber W., Schara U., Krampfl K., Petersen B., Petrova S., Stucka R., Mortier W., Bufler J., Kurlemann G., Huebner A., Merlini L., Lochmuller H., Abicht A. Neurology 60:1805-1810(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMS-ACHRD LYS-88.
[8]	"Rapsyn mutations in hereditary myasthenia: distinct early- and late-onset phenotypes." Burke G., Cossins J., Maxwell S., Owens G., Vincent A., Robb S., Nicolle M., Hilton-Jones D., Newsom-Davis J., Palace J., Beeson D. Neurology 61:826-828(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMS-ACHRD LYS-88.
[9]	"Novel truncating RAPSN mutations causing congenital myasthenic syndrome responsive to 3,4-diaminopyridine." Banwell B.L., Ohno K., Sieb J.P., Engel A.G. Neuromuscul. Disord. 14:202-207(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMS-ACHRD LYS-88.
[10]	"Congenital myasthenic syndrome due to rapsyn deficiency: three cases with arthrogryposis and bulbar symptoms." Ioos C., Barois A., Richard P., Eymard B., Hantai D., Estournet-Mathiaud B. Neuropediatrics 35:246-249(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMS-ACHRD LYS-88.
[11]	"Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations." Mueller J.S., Baumeister S.K., Rasic V.M., Krause S., Todorovic S., Kugler K., Mueller-Felber W., Abicht A., Lochmueller H. Neurology 67:1159-1164(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CMS-ACHRD CYS-164 AND PRO-283, CHARACTERIZATION OF VARIANTS CMS-ACHRD CYS-164 AND PRO-283.
[12]	"Congenital myasthenic syndrome caused by two non-N88K rapsyn mutations." Maselli R.A., Dris H., Schnier J., Cockrell J.L., Wollmann R.L. Clin. Genet. 72:63-65(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CMS-ACHRD MET-45 AND LYS-162, CHARACTERIZATION OF VARIANTS CMS-ACHRD MET-45 AND LYS-162.
[13]	"Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients." Vogt J., Harrison B.J., Spearman H., Cossins J., Vermeer S., ten Cate L.N., Morgan N.V., Beeson D., Maher E.R. Am. J. Hum. Genet. 82:222-227(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN FADS.
[14]	"Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders." Michalk A., Stricker S., Becker J., Rupps R., Pantzar T., Miertus J., Botta G., Naretto V.G., Janetzki C., Yaqoob N., Ott C.-E., Seelow D., Wieczorek D., Fiebig B., Wirth B., Hoopmann M., Walther M., Koerber F. , Blankenburg M., Mundlos S., Heller R., Hoffmann K. Am. J. Hum. Genet. 82:464-476(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FADS SER-139 AND VAL-189.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z33905 mRNA. Translation: CAA83954.1. AF449218 mRNA. Translation: AAL86639.1. CH471064 Genomic DNA. Translation: EAW67914.1. BC004196 mRNA. Translation: AAH04196.1.
IPI	IPI00013319. IPI00828059.
PIR	S45064.
RefSeq	NP_005046.2. NM_005055.4. NP_116034.2. NM_032645.4.
UniGene	Hs.81218.
3D structure databases
ProteinModelPortal	Q13702.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13702. 2 interactions.
STRING	9606.ENSP00000298854.
PTM databases
PhosphoSite	Q13702.
Polymorphism databases
DMDM	145559521.
Proteomic databases
PaxDb	Q13702.
PRIDE	Q13702.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000298854; ENSP00000298854; ENSG00000165917. ENST00000352508; ENSP00000298853; ENSG00000165917.
GeneID	5913.
KEGG	hsa:5913.
UCSC	uc001nfi.2. human. uc001nfj.2. human.
Organism-specific databases
CTD	5913.
GeneCards	GC11M047459.
HGNC	HGNC:9863. RAPSN.
HPA	HPA039475.
MIM	208150. phenotype. 601592. gene. 608931. phenotype.
neXtProt	NX_Q13702.
Orphanet	994. Fetal akinesia deformation sequence. 33108. Lethal multiple pterygium syndrome. 98913. Postsynaptic congenital myasthenic syndromes.
PharmGKB	PA34224.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0457.
HOGENOM	HOG000231395.
HOVERGEN	HBG061484.
InParanoid	Q13702.
OMA	EEMELYC.
PhylomeDB	Q13702.
Gene expression databases
ArrayExpress	Q13702.
Bgee	Q13702.
CleanEx	HS_RAPSN.
Genevestigator	Q13702.
GermOnline	ENSG00000165917. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.10. 2 hits. 3.30.40.10. 1 hit.
InterPro	IPR001237. Postsynaptic. IPR018293. Postsynaptic_CS. IPR019568. Rapsyn_myristoylation/link_N. IPR001440. TPR-1. IPR013026. TPR-contain_dom. IPR011990. TPR-like_helical. IPR019734. TPR_repeat. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF10579. Rapsyn_N. 1 hit. PF00515. TPR_1. 1 hit. PF13181. TPR_8. 1 hit. PF13639. zf-RING_2. 1 hit. [Graphical view]
PRINTS	PR00217. POSTSYNAPTIC.
SMART	SM00184. RING. 1 hit. SM00028. TPR. 6 hits. [Graphical view]
PROSITE	PS00405. 43_KD_POSTSYNAPTIC. 1 hit. PS50005. TPR. 5 hits. PS50293. TPR_REGION. 1 hit. PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5913.
NextBio	23012.
SOURCE	Search...

Entry information

Entry name

RAPSN_HUMAN

Accession

Primary (citable) accession number: Q13702
Secondary accession number(s): Q8TDF3, Q9BTD9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	April 17, 2007
Last modified:	May 1, 2013
This is version 140 of the entry and version 4 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.