CPLM-021224

Genbank Nucleotide ID

Protein Synonyms/Alias

Shank-associated RH domain-interacting protein; Shank-interacting protein-like 1; hSIPL1

Homo sapiens (Human)

Position	Peptide	Type	References
189	AIAGGDEKGAAQVAA	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]
318	PSPQHPQKMDGELGR	ubiquitination	[2, 5, 8, 10]

[1] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[4] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[5] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[6] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[7] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[8] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[10] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[11] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]

Functional Description

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.

DOMAIN 219 288 Ubiquitin-like.
ZN_FING 348 377 RanBP2-type.
REGION 1 180 Self-association (By similarity).
REGION 175 310 Interaction with SHANK1 (By similarity).
MOD_RES 165 165 Phosphoserine.
MOD_RES 312 312 Phosphoserine.

3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Metal-binding; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation pathway; Zinc; Zinc-finger.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; IDA:UniProtKB.
GO:0071797; C:LUBAC complex; IDA:UniProtKB.
GO:0014069; C:postsynaptic density; IEA:Compara.
GO:0031593; F:polyubiquitin binding; IDA:UniProtKB.
GO:0008270; F:zinc ion binding; IEA:InterPro.
GO:0030262; P:apoptotic nuclear changes; IEA:Compara.
GO:0007420; P:brain development; IEA:Compara.
GO:0031424; P:keratinization; IEA:Compara.
GO:0007005; P:mitochondrion organization; IEA:Compara.
GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
GO:0051260; P:protein homooligomerization; IEA:Compara.
GO:0097039; P:protein linear polyubiquitination; IDA:UniProtKB.
GO:2000348; P:regulation of CD40 signaling pathway; IDA:UniProtKB.
GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.

IPR026168; SHARPIN.
IPR001876; Znf_RanBP2.

PS50053; UBIQUITIN_2
PS01358; ZF_RANBP2_1
PS50199; ZF_RANBP2_2