CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000332
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Hepatocyte growth factor-regulated tyrosine kinase substrate 
Protein Synonyms/Alias
 Hrs; Protein pp110 
Gene Name
 HGS 
Gene Synonyms/Alias
 HRS 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
56IKKKVNDKNPHVALYubiquitination[1, 2, 3]
86VHDEVANKQTMEELKubiquitination[1, 3, 4, 5, 6]
93KQTMEELKDLLKRQVubiquitination[4, 6]
126FRNEPKYKVVQDTYQubiquitination[1, 2, 3, 4, 5, 6]
136QDTYQIMKVEGHVFPubiquitination[1, 3, 4, 6]
146GHVFPEFKESDAMFAubiquitination[1, 3]
192CGQIFCGKCSSKYSTubiquitination[1, 2, 7]
196FCGKCSSKYSTIPKFubiquitination[1, 3]
202SKYSTIPKFGIEKEVubiquitination[1, 2, 3, 4, 5, 6, 7]
207IPKFGIEKEVRVCEPacetylation[8]
207IPKFGIEKEVRVCEPubiquitination[1, 2, 3, 4, 5, 6, 7]
222CYEQLNRKAEGKATSubiquitination[1, 3]
226LNRKAEGKATSTTELubiquitination[1, 3]
251QQSQLPPKRDETALQubiquitination[1, 3, 4, 6]
277SQSEAEEKERLRQKSubiquitination[1]
283EKERLRQKSTYTSYPubiquitination[2, 3]
291STYTSYPKAEPMPSAubiquitination[1, 3]
337LNRNYWEKKQEEARKubiquitination[1, 2, 3]
473YYEGLQDKLAQIRDAubiquitination[1, 3, 4, 5, 6]
513RQIQLAQKLEIMRQKubiquitination[1, 2, 3, 4, 5, 6]
520KLEIMRQKKQEYLEVubiquitination[2]
521LEIMRQKKQEYLEVQubiquitination[1, 2, 5]
541QRLQEQEKERQMRLEubiquitination[1]
551QMRLEQQKQTVQMRAubiquitination[1, 2, 3, 5, 9]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [8] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [9] 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] 
Functional Description
 Involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin-coated regions. Involved in down- regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. May contribute to the efficient recruitment of SMADs to the activin receptor complex. Involved in receptor recycling via its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation. 
Sequence Annotation
 DOMAIN 15 143 VHS.
 REPEAT 258 277 UIM.
 ZN_FING 160 220 FYVE-type.
 REGION 225 543 Interaction with SNX1 (By similarity).
 REGION 445 543 Interaction with SNAP25 and TRAK2 (By
 REGION 454 572 Interaction with STAM1 (By similarity).
 REGION 480 777 Interaction with NF2.
 MOD_RES 207 207 N6-acetyllysine.
 MOD_RES 216 216 Phosphotyrosine.
 MOD_RES 308 308 Phosphotyrosine (By similarity).
 MOD_RES 329 329 Phosphotyrosine (By similarity).
 MOD_RES 334 334 Phosphotyrosine (By similarity).  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Endosome; Membrane; Metal-binding; Phosphoprotein; Polymorphism; Protein transport; Reference proteome; Transport; Ubl conjugation; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 777 AA 
Protein Sequence
MGRGSGTFER LLDKATSQLL LETDWESILQ ICDLIRQGDT QAKYAVNSIK KKVNDKNPHV 60
ALYALEVMES VVKNCGQTVH DEVANKQTME ELKDLLKRQV EVNVRNKILY LIQAWAHAFR 120
NEPKYKVVQD TYQIMKVEGH VFPEFKESDA MFAAERAPDW VDAEECHRCR VQFGVMTRKH 180
HCRACGQIFC GKCSSKYSTI PKFGIEKEVR VCEPCYEQLN RKAEGKATST TELPPEYLTS 240
PLSQQSQLPP KRDETALQEE EELQLALALS QSEAEEKERL RQKSTYTSYP KAEPMPSASS 300
APPASSLYSS PVNSSAPLAE DIDPELARYL NRNYWEKKQE EARKSPTPSA PVPLTEPAAQ 360
PGEGHAAPTN VVENPLPETD SQPIPPSGGP FSEPQFHNGE SEESHEQFLK ALQNAVTTFV 420
NRMKSNHMRG RSITNDSAVL SLFQSINGMH PQLLELLNQL DERRLYYEGL QDKLAQIRDA 480
RGALSALREE HREKLRRAAE EAERQRQIQL AQKLEIMRQK KQEYLEVQRQ LAIQRLQEQE 540
KERQMRLEQQ KQTVQMRAQM PAFPLPYAQL QAMPAAGGVL YQPSGPASFP STFSPAGSVE 600
GSPMHGVYMS QPAPAAGPYP SMPSTAADPS MVSAYMYPAG ATGAQAAPQA QAGPTASPAY 660
SSYQPTPTAG YQNVASQAPQ SLPAISQPPQ SSTMGYMGSQ SVSMGYQPYN MQNLMTTLPS 720
QDASLPPQQP YIAGQQPMYQ QMAPSGGPPQ QQPPVAQQPQ AQGPPAQGSE AQLISFD 777 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005769; C:early endosome; IDA:HGNC.
 GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
 GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell.
 GO:0030141; C:secretory granule; IEA:Compara.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0016044; P:cellular membrane organization; TAS:Reactome.
 GO:0016197; P:endosomal transport; NAS:UniProtKB.
 GO:0008333; P:endosome to lysosome transport; IEA:Compara.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0006886; P:intracellular protein transport; IEA:InterPro.
 GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
 GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0046426; P:negative regulation of JAK-STAT cascade; IDA:HGNC.
 GO:0042176; P:regulation of protein catabolic process; TAS:HGNC. 
Interpro
 IPR008942; ENTH_VHS.
 IPR027426; HGS.
 IPR024641; HRS_helical.
 IPR017073; Ubi-bd_Hrs_VPS27.
 IPR003903; Ubiquitin-int_motif.
 IPR002014; VHS.
 IPR018205; VHS_subgr.
 IPR000306; Znf_FYVE.
 IPR017455; Znf_FYVE-rel.
 IPR011011; Znf_FYVE_PHD.
 IPR013083; Znf_RING/FYVE/PHD. 
Pfam
 PF01363; FYVE
 PF12210; Hrs_helical
 PF00790; VHS 
SMART
 SM00064; FYVE
 SM00726; UIM
 SM00288; VHS 
PROSITE
 PS50330; UIM
 PS50179; VHS
 PS50178; ZF_FYVE 
PRINTS