Q9EQL9 (SHRPN_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sharpin

Alternative name(s):
Shank-associated RH domain-interacting protein

Gene names

Name:

Sharpin

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	381 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex By similarity.
Subunit structure	Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31. LUBAC has a MW of approximative 600 kDa suggesting a heteromultimeric assembly of its subunits. Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner.Interacts with EYA1 and EYA2 By similarity. Self-associates. Interacts with SHANK1. Ref.1
Subcellular location	Cytoplasm. Note: Enriched at synaptic sites in mature neurons where it colocalizes with SHANK1. Ref.1
Tissue specificity	Expressed in brain, spleen, lung, heart, skeletal muscle, kidney and testis (at protein level). Expressed in heart and testis. Ref.1
Domain	The Ubiquitin-like domain is required for the interaction with RNF31 By similarity. The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin. Binds preferentially linear polyubiquitin chains and 'Lys-63'-linked polyubiquitin chains over 'Lys-48'-linked polyubiquitin chains. Also binds monoubiquitin By similarity.
Sequence similarities	Contains 1 RanBP2-type zinc finger. Contains 1 ubiquitin-like domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	brain development Inferred from expression pattern Ref.1. Source: RGD negative regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from sequence or structural similarity. Source: UniProtKB protein homooligomerization Inferred from direct assay Ref.1. Source: RGD protein linear polyubiquitination Inferred from sequence or structural similarity. Source: UniProtKB regulation of CD40 signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of tumor necrosis factor-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	LUBAC complex Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from sequence or structural similarity. Source: UniProtKB postsynaptic density Inferred from direct assay Ref.1. Source: RGD
Molecular function	identical protein binding Inferred from physical interaction Ref.1. Source: IntAct polyubiquitin binding Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-1394695,EBI-1394695
Shank1	Q9WV48	7	EBI-1394695,EBI-80909

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 381	381	Sharpin		PRO_0000280636
Regions
	Domain	216 – 285	70	Ubiquitin-like
	Zinc finger	342 – 371	30	RanBP2-type
	Region	1 – 177	177	Self-association
	Region	172 – 305	134	Interaction with SHANK1

Sequences

	Sequence		Length	Mass (Da)
	Q9EQL9 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 8D9A7D7D23665567	FASTA	381	40,287
	10 20 30 40 50 60 MSPPAGGAAA AADPASPVVL LAVQAAVRLL GAGHEDEAQL RKLQLKADPE RPGRFRLGLL 70 80 90 100 110 120 GIEPGAVSLE WPLESICYTI RGPNQHELQP PPGGPGTFSV HFLNSEEAQQ WAALVRDATA 130 140 150 160 170 180 EGQNGNDSTA PVPTPAMCPT SPPCSSVTPT PKATQPEMDL PQGSGNLKKE ELATHLAQAI 190 200 210 220 230 240 AGGDEKAAAQ VAAILAQHHV ALNVQLLEAW FPRGPIRLQV TVEDATSVLS SSSSAHVSLQ 250 260 270 280 290 300 IHPHCSIAAL QEQVFSEFGF PPAVQRWVIG RCLCMPERSL ASYGVSQDGD PAFLYLLSAP 310 320 330 340 350 360 REVSGHSPQH SKMDRKLGCL FPQSLELPHN LQASSSSLPS PPQPGWSCPS CTFINASNRP 370 380 GCEMCSTQRP CAWDPLTATS T

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins." Lim S., Sala C., Yoon J., Park S., Kuroda S., Sheng M., Kim E. Mol. Cell. Neurosci. 17:385-397(2001) [PubMed: 11178875] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SELF-ASSOCIATION, INTERACTION WITH SHANK1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Brain.
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF203906 mRNA. Translation: AAG43482.1. BC083553 mRNA. Translation: AAH83553.1.
IPI	IPI00190132.
RefSeq	NP_112415.1. NM_031153.2.
UniGene	Rn.38393.
3D structure databases
HSSP	HSSP built from PDB template 2CRC based on UniProtKB Q9BYM8.
ProteinModelPortal	Q9EQL9.
SMR	Q9EQL9. Positions 341-375.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9EQL9. 5 interactions.
STRING	Q9EQL9.
Proteomic databases
PRIDE	Q9EQL9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000018031; ENSRNOP00000018032; ENSRNOG00000012812.
GeneID	81859.
KEGG	rno:81859.
UCSC	NM_031153. rat.
Organism-specific databases
CTD	81858.
RGD	631353. Sharpin.
Phylogenomic databases
eggNOG	roNOG16183.
GeneTree	ENSGT00530000063620.
HOVERGEN	HBG093954.
InParanoid	Q9EQL9.
OMA	SQHELQP.
OrthoDB	EOG48SGTH.
PhylomeDB	Q9EQL9.
Gene expression databases
ArrayExpress	Q9EQL9.
Genevestigator	Q9EQL9.
Family and domain databases
InterPro	IPR001876. Znf_RanBP2. [Graphical view]
Pfam	PF00641. zf-RanBP. 1 hit. [Graphical view]
SMART	SM00547. ZnF_RBZ. 1 hit. [Graphical view]
PROSITE	PS50053. UBIQUITIN_2. False negative. PS01358. ZF_RANBP2_1. 1 hit. PS50199. ZF_RANBP2_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	615783.

Entry information

Entry name

SHRPN_RAT

Accession

Primary (citable) accession number: Q9EQL9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 2007
Last sequence update:	March 1, 2001
Last modified:	October 19, 2011
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program