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UniProtKB - Q9H0F6 (SHRPN_HUMAN)

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Protein

Sharpin

Gene

SHARPIN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri348 – 377RanBP2-typePROSITE-ProRule annotationAdd BLAST30

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-6794361 Neurexins and neuroligins

Names & Taxonomyi

Protein namesi
Recommended name:
Sharpin
Alternative name(s):
Shank-associated RH domain-interacting protein
Shank-interacting protein-like 1
Short name:
hSIPL1
Gene namesi
Name:SHARPIN
Synonyms:SIPL1
ORF Names:PSEC0216
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000179526.16
HGNCiHGNC:25321 SHARPIN
MIMi611885 gene
neXtProtiNX_Q9H0F6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasm, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi114V → D: Abolishes homodimerization. 1 Publication1
Mutagenesisi272I → A: Abolishes interaction with RNF31 and ability to mediate linear polyubiquitination. 1 Publication1
Mutagenesisi354C → S: Abolishes binding to ubiquitin without affecting interaction with RNF31; when associated with S-357. 1 Publication1
Mutagenesisi357C → S: Abolishes binding to ubiquitin without affecting interaction with RNF31; when associated with S-354. 1 Publication1
Mutagenesisi358 – 359TF → LV: Abolishes binding to ubiquitin and ability to mediate linear polyubiquitination. 1 Publication2
Mutagenesisi368C → S: Abolishes binding to ubiquitin without affecting interaction with RNF31; when associated with S-371. 1 Publication1
Mutagenesisi371C → S: Abolishes binding to ubiquitin without affecting interaction with RNF31; when associated with S-368. 1 Publication1

Organism-specific databases

DisGeNETi81858
OpenTargetsiENSG00000179526
PharmGKBiPA142670925

Polymorphism and mutation databases

BioMutaiSHARPIN
DMDMi74733523

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002806341 – 387SharpinAdd BLAST387

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei165PhosphoserineCombined sources1
Modified residuei312PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9H0F6
MaxQBiQ9H0F6
PaxDbiQ9H0F6
PeptideAtlasiQ9H0F6
PRIDEiQ9H0F6
ProteomicsDBi80272
80273 [Q9H0F6-2]

PTM databases

iPTMnetiQ9H0F6
PhosphoSitePlusiQ9H0F6

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle and placenta and at lower levels in brain, heart, colon without mucosa, thymus, spleen, kidney, liver, small intestine, lung and peripheral blood leukocytes. Up-regulated in various tumor tissues such as kidney, liver, ovary and pancreas tumors.1 Publication

Gene expression databases

BgeeiENSG00000179526
CleanExiHS_SHARPIN
ExpressionAtlasiQ9H0F6 baseline and differential
GenevisibleiQ9H0F6 HS

Organism-specific databases

HPAiHPA044453

Interactioni

Subunit structurei

Monomer and homodimer. Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31. LUBAC has a MW of approximately 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, EYA2, SHANK1 and SHANK3 (via ANK repeats).4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi123608, 64 interactors
CORUMiQ9H0F6
DIPiDIP-57842N
IntActiQ9H0F6, 25 interactors
MINTiQ9H0F6
STRINGi9606.ENSP00000381698

Structurei

Secondary structure

1387
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni3 – 5Combined sources3
Beta strandi7 – 11Combined sources5
Helixi12 – 15Combined sources4
Beta strandi20 – 30Combined sources11
Helixi31 – 33Combined sources3
Beta strandi40 – 48Combined sources9
Beta strandi56 – 60Combined sources5
Beta strandi70 – 73Combined sources4
Helixi74 – 76Combined sources3
Beta strandi77 – 83Combined sources7
Beta strandi86 – 90Combined sources5
Beta strandi99 – 105Combined sources7
Helixi106 – 119Combined sources14
Beta strandi219 – 226Combined sources8
Beta strandi239 – 244Combined sources6
Helixi250 – 261Combined sources12
Helixi265 – 267Combined sources3
Beta strandi268 – 271Combined sources4
Helixi283 – 285Combined sources3
Beta strandi293 – 299Combined sources7

3D structure databases

ProteinModelPortaliQ9H0F6
SMRiQ9H0F6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini219 – 288Ubiquitin-likeAdd BLAST70

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 180Self-associationBy similarityAdd BLAST180
Regioni175 – 310Interaction with SHANK1By similarityAdd BLAST136

Domaini

The Ubiquitin-like domain is required for the interaction with RNF31.
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.

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri348 – 377RanBP2-typePROSITE-ProRule annotationAdd BLAST30

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IQMU Eukaryota
ENOG410YHH3 LUCA
GeneTreeiENSGT00530000063620
HOVERGENiHBG093954
InParanoidiQ9H0F6
KOiK20894
OMAiCEMCSTQ
OrthoDBiEOG091G0GY5
PhylomeDBiQ9H0F6
TreeFamiTF323486

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR026168 SHARPIN
IPR031912 Sharpin_PH
IPR029071 Ubiquitin-like_domsf
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
PANTHERiPTHR22770:SF36 PTHR22770:SF36, 1 hit
PfamiView protein in Pfam
PF16764 Sharpin_PH, 1 hit
SMARTiView protein in SMART
SM00547 ZnF_RBZ, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS01358 ZF_RANBP2_1, 1 hit
PS50199 ZF_RANBP2_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H0F6-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAPPAGGAAA AASDLGSAAV LLAVHAAVRP LGAGPDAEAQ LRRLQLSADP 
        60         70         80         90        100
ERPGRFRLEL LGAGPGAVNL EWPLESVSYT IRGPTQHELQ PPPGGPGTLS 
       110        120        130        140        150
LHFLNPQEAQ RWAVLVRGAT VEGQNGSKSN SPPALGPEAC PVSLPSPPEA 
       160        170        180        190        200
STLKGPPPEA DLPRSPGNLT EREELAGSLA RAIAGGDEKG AAQVAAVLAQ 
       210        220        230        240        250
HRVALSVQLQ EACFPPGPIR LQVTLEDAAS AASAASSAHV ALQVHPHCTV 
       260        270        280        290        300
AALQEQVFSE LGFPPAVQRW VIGRCLCVPE RSLASYGVRQ DGDPAFLYLL 
       310        320        330        340        350
SAPREAPATG PSPQHPQKMD GELGRLFPPS LGLPPGPQPA ASSLPSPLQP 
       360        370        380 
SWSCPSCTFI NAPDRPGCEM CSTQRPCTWD PLAAAST
Length:387
Mass (Da):39,949
Last modified:March 1, 2001 - v1
Checksum:i33EE4BF66936AB60
GO
Isoform 2 (identifier: Q9H0F6-2) [UniParc]FASTAAdd to basket
Also known as: hSIPL1A

The sequence of this isoform differs from the canonical sequence as follows:
     309-326: TGPSPQHPQKMDGELGRL → QLVLSFLHLHQCPRPPWL
     327-387: Missing.

Show »
Length:326
Mass (Da):33,878
Checksum:iC92FE8845FD1EC3E
GO

Sequence cautioni

The sequence BAC11666 differs from that shown. Reason: Frameshift at position 334.Curated
The sequence BAC53797 differs from that shown. Reason: Frameshift at position 218.Curated
The sequence BAC53798 differs from that shown. Aberrant splicing.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti238A → P in AAH02688 (Ref. 6) Curated1
Sequence conflicti243Q → R in BAC11666 (PubMed:11230166).Curated1
Sequence conflicti257V → A in AAH02688 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_047799282S → T. Corresponds to variant dbSNP:rs11541804Ensembl.1
Natural variantiVAR_047800294P → S. Corresponds to variant dbSNP:rs34674752EnsemblClinVar.1
Natural variantiVAR_047801311P → R. Corresponds to variant dbSNP:rs35844464Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023837309 – 326TGPSP…ELGRL → QLVLSFLHLHQCPRPPWL in isoform 2. 2 PublicationsAdd BLAST18
Alternative sequenceiVSP_023838327 – 387Missing in isoform 2. 2 PublicationsAdd BLAST61

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB052764 mRNA Translation: BAC53797.1 Frameshift.
AB052765 mRNA Translation: BAC53798.1 Sequence problems.
FJ655995 mRNA Translation: ACN38058.1
AL136816 mRNA Translation: CAB66750.1
AK075518 mRNA Translation: BAC11666.1 Frameshift.
AC104592 Genomic DNA No translation available.
CH471162 Genomic DNA Translation: EAW82152.1
CH471162 Genomic DNA Translation: EAW82153.1
CH471162 Genomic DNA Translation: EAW82150.1
CH471162 Genomic DNA Translation: EAW82151.1
BC002688 mRNA Translation: AAH02688.2
BC025244 mRNA Translation: AAH25244.1
BC034028 mRNA Translation: AAH34028.1
CCDSiCCDS43777.1 [Q9H0F6-1]
RefSeqiNP_112236.3, NM_030974.3 [Q9H0F6-1]
XP_016869377.1, XM_017013888.1 [Q9H0F6-2]
UniGeneiHs.529755

Genome annotation databases

EnsembliENST00000359551; ENSP00000352551; ENSG00000179526 [Q9H0F6-2]
ENST00000398712; ENSP00000381698; ENSG00000179526 [Q9H0F6-1]
GeneIDi81858
KEGGihsa:81858
UCSCiuc003zba.4 human [Q9H0F6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSHRPN_HUMAN
AccessioniPrimary (citable) accession number: Q9H0F6
Secondary accession number(s): A6NEG3
, C0L3L2, D3DWL3, Q8IXF5, Q8IXF6, Q8N2E7, Q8TB25, Q9BUE4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 1, 2001
Last modified: July 18, 2018
This is version 139 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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