The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Accession:
Functional site class:
WW domain ligands
Functional site description:
WW Domains are small but abundant domains found in diverse regulatory situations. The binding peptide motifs appear always to involve proline residues. Specific motifs vary for different WW domains and in some cases must be phosphorylated on a serine or threonine.
ELMs with same func. site: DOC_WW_Pin1_4  LIG_WW_1  LIG_WW_2  LIG_WW_3 
ELM Description:
Proline-directed phosphorylation is a major cellular signalling mechanism. Proline directed kinases include Map kinases and cyclin-dependent kinases. Many p(S/T)P sites act as binding motifs for recruiting proteins or placing enzymes close to their substrates. Proline isomerisation may confound the function of these sites but also provides a mechanism for their regulation. This requires a peptidyl-prolyl cis/trans isomerase (PPIase). The phospho-specific PPIase is Pin1 (for Protein interacting with NIMA 1). It belongs to the parvulin subfamily of PPIases. Pin1 homologs are highly conserved in eukaryotes. Pin1 regulates diverse cellular process, including growth-signal response, cell-cycle progression, cellular stress response, neuronal function and immune response. Pin1 is an 18 kDa protein with two domains: the N-terminal WW domain and the C-terminal PPIase domain connected by a flexible linker. The WW domain acts as the binding module to bind its substrate p(S/T)P site and bring the catalytic PPIase domain close to its substrate where it catalyses cis-trans conversions. The Pin1 WW domain interaction with substrates occurs through a conserved phosphate-binding pocket, present in Pin1 and it homologues. The pSer/Thr-Pro peptides all bind to the WW domain in the trans conformation. Only WW domains which have an arginine in loop1 will be able to bind the sequence with core motif p(S/T)P. The phosphorylated residue is recognized by the Arginine as well as by backbone interactions. The Pro residue enters a pocket bounded by the second Tryptophan.
Pattern: ...([ST])P.
Pattern Probability: 0.0154332
Present in taxons: Eukaryota Homo sapiens Saccharomyces cerevisiae
Interaction Domain:
WW (PF00397) WW domain (Stochiometry: 1 : 1)
PDB Structure: 2LB3
o See 96 Instances for DOC_WW_Pin1_4
o Abstract
WW are small modular domains of 38-40 residues long that mediate protein-protein interaction through binding of short proline-containing peptides that are typically in regions of native disordered polypeptide. WW are named after a pair of tryptophan residues that are important for structure-function. WW domains can occur singly or in clusters of up to four, as in the ubiquitin ligase Nedd4. WW domain-containing proteins are involved in many cellular processes such as ubiquitin-mediated protein degradation and mitotic regulation and they are also implicated directly or indirectly in several human diseases such as muscular distrophy and Alzheimer's and Huntington's diseases. Based on their ligand specificities, the WW domains have been divided into four classes. Group I WW domains bind proteins containing the PPXY motif, while group II recognize the PPLP motif. Group III recognise PPR motifs. There may be some overlap between the group II and III specificities. Group IV recognition is of p(ST)P sites and is dependent on phosphorylation by proline-directed kinases.
The peptidyl-prolyl cis/trans isomerases (PPIase) are evolutionarily conserved enzymes that catalyse the cis/trans isomerization of peptidyl-prolyl peptide bonds. Pin1 is a unique PPIase that recognizes only the phosphorylated S/T motif preceding a proline residue. It is a multidomain protein contains a WW domain and PPIase domain and both domains work together to target the p(S/T)P sequence. Pin1 acts a mitotic regulator by catalyzing the isomerization of p(S/T)P motifs present in a defined subset of mitosis-specific phosphoproteins and also plays essential roles in transcription, DNA damage response, neuronal survival etc. The consequence of Pin1-mediated isomerization varies in individual substrates and phosphorylation sites which make them amenable to different processes like dephosphorylation, protein degradation, cleavage and targeting to different sub cellular localization etc. It is also found that the aberrant function of pin1 is linked to many diseases like cancer, AD, asthma, ageing and microbial infection and thus it represents a major therapeutic target.
o 15 selected references:

o 11 GO-Terms:

o 96 Instances for DOC_WW_Pin1_4
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q12800 TFCP2
TFCP2_HUMAN
288 293 PEITYVNNSPSPGFNSSHSS TP 3 Homo sapiens (Human)
Q12800 TFCP2
TFCP2_HUMAN
286 291 PWPEITYVNNSPSPGFNSSH TP 3 Homo sapiens (Human)
Q12800 TFCP2
TFCP2_HUMAN
306 311 SSFSLGEGNGSPNHQPEPPP TP 3 Homo sapiens (Human)
Q12800 TFCP2
TFCP2_HUMAN
326 331 PVTDNLLPTTTPQEAQQWLH TP 3 Homo sapiens (Human)
1 
P05067-4 APP
A4_HUMAN
668 669 GVVEVDAAVTPEERHLSKMQ TP 4 Homo sapiens (Human)
1 
Q969H0 FBXW7
FBXW7_HUMAN
202 207 STTGLVPCSATPTTFGDLRA TP 4 Homo sapiens (Human)
1 
P78543 BTG2
BTG2_HUMAN
144 149 CKNQVLLGRSSPSKNYVMAV TP 3 Homo sapiens (Human)
1 
Q05397 PTK2
FAK1_HUMAN
907 912 EGVKLQPQEISPPPTANLDR TP 4 Homo sapiens (Human)
1 
Q3U182 Crtc2
CRTC2_MOUSE
133 138 DSSPYSPAYLSPPPESGWRR TP 3 Mus musculus (House mouse)
1 
1 
P46531 NOTCH1
NOTC1_HUMAN
2133 2138 GAPLGGTPTLSPPLCSPNGY TP 5 Homo sapiens (Human)
1 
2 
P46531 NOTCH1
NOTC1_HUMAN
2118 2123 RLLDEYNLVRSPQLHGAPLG TP 5 Homo sapiens (Human)
1 
1 
Q9HC98 NEK6
NEK6_HUMAN
242 247 CLLYEMAALQSPFYGDKMNL TP 2 Homo sapiens (Human)
1 
Q9HC98 NEK6
NEK6_HUMAN
212 217 HSLVGTPYYMSPERIHENGY TP 2 Homo sapiens (Human)
1 
Q90Z80 fbxo5-a
FBX5A_XENLA
7 12 MMCGFASNQSPKKLSSKKSS TP 2 Xenopus laevis (African clawed frog)
1 
O54918 Bcl2l11
B2L11_MOUSE
62 67 SPQGPLAPPASPGPFATRSP TP 4 Mus musculus (House mouse)
1 
Q96Q89-3 KIF20B
KI20B_HUMAN
1601 1606 KMAVKHPGCTTPVTVKIPKA TP 2 Homo sapiens (Human)
Q8BUV3 Gphn
GEPH_MOUSE
197 202 PPPLSPPPTTSPHKQTEDKG TP 4 Mus musculus (House mouse)
1 
Q8BUV3 Gphn
GEPH_MOUSE
191 196 EDLPSPPPPLSPPPTTSPHK TP 4 Mus musculus (House mouse)
1 
Q8QGV2 wee1-b
WEE1B_XENLA
183 188 STPQVNINPFTPDSLEIQSS TP 3 Xenopus laevis (African clawed frog)
1 
P40763 STAT3
STAT3_HUMAN
724 729 TCSNTIDLPMSPRTLDSLMQ TP 3 Homo sapiens (Human)
1 
1 
P22736 NR4A1
NR4A1_HUMAN
140 145 GSPCSAPSPSTPSFQPPQLS TP 1 Homo sapiens (Human)
1 
P22736 NR4A1
NR4A1_HUMAN
92 97 ASSTSSSSATSPASASFKFE TP 1 Homo sapiens (Human)
1 
P22736 NR4A1
NR4A1_HUMAN
428 433 AEKIPGFAELSPADQDLLLE TP 2 Homo sapiens (Human)
1 
P14598 NCF1
NCF1_HUMAN
342 347 RRRQARPGPQSPGSPLEEER TP 2 Homo sapiens (Human)
1 
P06876 Myb
MYB_MOUSE
525 530 LLKKIKQEVESPTEKSGNFF TP 3 Mus musculus (House mouse)
1 
1 
P35568 IRS1
IRS1_HUMAN
431 436 GFISSDEYGSSPCDFRSSFR TP 4 Homo sapiens (Human)
1 
Q92945 KHSRP
FUBP2_HUMAN
178 183 QQDSGCKVQISPDSGGLPER TP 2 Homo sapiens (Human)
1 
1 
Q9UER7 DAXX
DAXX_HUMAN
175 180 PTNAENTASQSPRTRGSRRQ TP 4 Homo sapiens (Human)
1 
1 
P10636-8 MAPT
TAU_HUMAN
228 233 REPKKVAVVRTPPKSPSSAK TP 3 Homo sapiens (Human)
1 
Q8CFN5 Mef2c
MEF2C_MOUSE
107 112 DPDADDSVGHSPESEDKYRK TP 6 Mus musculus (House mouse)
1 
1 
Q8CFN5 Mef2c
MEF2C_MOUSE
95 100 LRKKGLNGCDSPDPDADDSV TP 6 Mus musculus (House mouse)
1 
1 
Q9BR01 SULT4A1
ST4A1_HUMAN
5 10 MAESEAETPSTPGEFESKYF TP 5 Homo sapiens (Human)
1 
2 
P33242 Nr5a1
STF1_MOUSE
200 205 IKSEYPEPYASPPQQPGPPY TP 3 Mus musculus (House mouse)
1 
1 
Q9Y618 NCOR2
NCOR2_HUMAN
1441 1446 HEIPREELRHTPELPLAPRP TP 4 Homo sapiens (Human)
1 
1 
Q9Y618 NCOR2
NCOR2_HUMAN
1238 1243 ITYRGSITHGTPADVLYKGT TP 4 Homo sapiens (Human)
1 
1 
Q14653 IRF3
IRF3_HUMAN
336 341 LITFTEGSGRSPRYALWFCV TP 5 Homo sapiens (Human)
1 
1 
P35991 Btk
BTK_MOUSE
112 117 VYDEGPLYVFSPTEELRKRW TP 2 Mus musculus (House mouse)
1 
1 
P35991 Btk
BTK_MOUSE
18 23 LKRSQQKKKTSPLNFKKRLF TP 2 Mus musculus (House mouse)
1 
1 
Q99MK8 Adrbk1
ARBK1_MOUSE
667 672 RVPKMKNKPRSPVVELSKVP TP 2 Mus musculus (House mouse)
1 
1 
P04637 TP53
P53_HUMAN
312 317 KRALPNNTSSSPQPKKKPLD TP 2 Homo sapiens (Human)
1 
1 
P04637 TP53
P53_HUMAN
78 83 PPVAPAPAAPTPAAPAPAPS TP 2 Homo sapiens (Human)
1 
1 
P84022 SMAD3
SMAD3_HUMAN
210 215 GSPNLSPNPMSPAHNNLDLQ TP 3 Homo sapiens (Human)
2 
P84022 SMAD3
SMAD3_HUMAN
205 210 HSMDAGSPNLSPNPMSPAHN TP 3 Homo sapiens (Human)
3 
P84022 SMAD3
SMAD3_HUMAN
176 181 GIEPQSNIPETPPPGYLSED TP 4 Homo sapiens (Human)
2 
P54274 TERF1
TERF1_HUMAN
146 151 DAQFENDERITPLESALMIW TP 4 Homo sapiens (Human)
1 
Q9NY61 AATF
AATF_HUMAN
143 148 SKKSRSHSAKTPGFSVQSIS TP 4 Homo sapiens (Human)
1 
P29590 PML
PML_HUMAN
515 520 QPRPSTSKAVSPPHLDGPPS TP 3 Homo sapiens (Human)
1 
P29590 PML
PML_HUMAN
527 532 PHLDGPPSPRSPVIGSEVFL TP 3 Homo sapiens (Human)
1 
P29590 PML
PML_HUMAN
502 507 EGKEARLARSSPEQPRPSTS TP 3 Homo sapiens (Human)
1 
P29590 PML
PML_HUMAN
406 411 SKKASPEAASTPRDPIDVDL TP 3 Homo sapiens (Human)
P10276 RARA
RARA_HUMAN
74 79 SSEEIVPSPPSPPPLPRIYK TP 3 Homo sapiens (Human)
1 
Q61457 Ccne1
CCNE1_MOUSE
382 387 KAILSEQNRISPPPSVVLTP TP 3 Mus musculus (House mouse)
1 
1 
P01106 MYC
MYC_HUMAN
59 64 KFELLPTPPLSPSRRSGLCS TP 3 Homo sapiens (Human)
1 
1 
O64645 SOC1
SOC1_ARATH
192 197 ESTGRGDEESSPSSEVETQL TP 3 Arabidopsis thaliana (Thale cress)
1 
O64645 SOC1
SOC1_ARATH
46 51 CDAEVSLIIFSPKGKLYEFA TP 3 Arabidopsis thaliana (Thale cress)
1 
O82794 AGL24
AGL24_ARATH
199 204 TTNVSSYDSGTPLEDDSDTS TP 6 Arabidopsis thaliana (Thale cress)
1 
P37231-2 PPARG
PPARG_HUMAN
81 86 YQSAIKVEPASPPYYSEKTQ TP 5 Homo sapiens (Human)
1 
Q8BT07 Cep55
CEP55_MOUSE
423 428 ESRVKATSPKSPSAALNDSL TP 3 Mus musculus (House mouse)
1 
2 
P31749 AKT1
AKT1_HUMAN
447 452 EEFTAQMITITPPDQDDSME TP 4 Homo sapiens (Human)
1 
1 
P31749 AKT1
AKT1_HUMAN
89 94 TVIERTFHVETPEEREEWTT TP 4 Homo sapiens (Human)
1 
1 
P69713 X
X_HBVA3
38 43 SGPLGTLSSPSPSAVPADHG TP 2 Hepatitis B virus adw2/Rutter/1979
1 
P01101 Fos
FOS_MOUSE
371 376 GSSSNEPSSDSLSSPTLLAL TP 2 Mus musculus (House mouse)
1 
P01101 Fos
FOS_MOUSE
328 333 EPLCTPVVTCTPGCTTYTSS TP 2 Mus musculus (House mouse)
1 
P01101 Fos
FOS_MOUSE
322 327 PMVTELEPLCTPVVTCTPGC TP 2 Mus musculus (House mouse)
1 
P01101 Fos
FOS_MOUSE
229 234 DLTGGLPEASTPESEEAFTL TP 2 Mus musculus (House mouse)
1 
P03409 tax
TAX_HTL1A
157 162 SVVCMYLYQLSPPITWPLLP TP 2 Human T-cell lymphotrophic virus type 1 (strain ATK)
1 
Q01860 POU5F1
PO5F1_HUMAN
9 14 AGHLASDFAFSPPPGGGGDG TP 4 Homo sapiens (Human)
1 
1 
Q99K48 Nono
NONO_MOUSE
449 454 TMEGIGAIGGTPPAFNRPAP TP 2 Mus musculus (House mouse)
1 
Q99K48 Nono
NONO_MOUSE
427 432 TMMPDGTLGLTPPTTERFGQ TP 2 Mus musculus (House mouse)
1 
Q99K48 Nono
NONO_MOUSE
409 414 AMPPAPVPPGTPAPPGPATM TP 2 Mus musculus (House mouse)
1 
P05412 JUN
JUN_HUMAN
70 75 SPDVGLLKLASPELERLIIQ TP 3 Homo sapiens (Human)
1 
1 
P05412 JUN
JUN_HUMAN
60 65 LRAKNSDLLTSPDVGLLKLA TP 3 Homo sapiens (Human)
1 
1 
P35222 CTNNB1
CTNB1_HUMAN
243 248 GIPALVKMLGSPVDSVLFYA TP 4 Homo sapiens (Human)
1 
1 
P25322 Ccnd1
CCND1_MOUSE
283 288 EVEEEAGLACTPTDVRDVDI TP 2 Mus musculus (House mouse)
1 
1 
P46527 CDKN1B
CDN1B_HUMAN
184 189 GSPNAGSVEQTPKKPGLRRR TP 3 Homo sapiens (Human)
1 
1 
Q04206 RELA
TF65_HUMAN
251 256 VHRQVAIVFRTPPYADPSLQ TP 3 Homo sapiens (Human)
1 
O15350 TP73
P73_HUMAN
479 484 AQSMVSGSHCTPPPPYHADP TP 4 Homo sapiens (Human)
1 
2 
O15350 TP73
P73_HUMAN
439 444 GQPPPHSSAATPNLGPVGPG TP 4 Homo sapiens (Human)
2 
O15350 TP73
P73_HUMAN
409 414 LQPPSYGPVLSPMNKVHGGM TP 4 Homo sapiens (Human)
2 
P04637 TP53
P53_HUMAN
30 35 WKLLPENNVLSPLPSQAMDD TP 2 Homo sapiens (Human)
1 
1 
Q9Y6H5 SNCAIP
SNCAP_HUMAN
212 217 APFCVLSPVKSPHLRKASAV TP 5 Homo sapiens (Human)
2 
P35210 SPT23
SPT23_YEAST
651 656 IAKRIVGSDSSPSNNNAGLH TP 3 Saccharomyces cerevisiae S288c
1 
1 
Q80Z64 Nanog
NANOG_MOUSE
62 67 PSSEDLPLQGSPDSSTSPKQ TP 3 Mus musculus (House mouse)
1 
1 
Q80Z64 Nanog
NANOG_MOUSE
49 54 ATEMLCTEAASPRPSSEDLP TP 3 Mus musculus (House mouse)
1 
1 
P34152-3 Ptk2
FAK1_MOUSE
907 912 EGVKLQPQEISPPPTANLDR TP 5 Mus musculus (House mouse)
1 
P05067 APP
A4_HUMAN
740 745 HGVVEVDAAVTPEERHLSKM TP 1 Homo sapiens (Human)
Q8BT07 Cep55
CEP55_MOUSE
420 425 REPESRVKATSPKSPSAALN TP 3 Mus musculus (House mouse)
2 
P46531 NOTCH1
NOTC1_HUMAN
2129 2134 PQLHGAPLGGTPTLSPPLCS TP 5 Homo sapiens (Human)
2 
Q8BUV3 Gphn
GEPH_MOUSE
185 190 EVHDELEDLPSPPPPLSPPP TP 4 Mus musculus (House mouse)
1 
P22736 NR4A1
NR4A1_HUMAN
137 142 DYYGSPCSAPSPSTPSFQPP TP 1 Homo sapiens (Human)
1 
Q9BR01 SULT4A1
ST4A1_HUMAN
8 13 MAESEAETPSTPGEFESKYF TP 5 Homo sapiens (Human)
2 
P84022 SMAD3
SMAD3_HUMAN
201 206 HQMNHSMDAGSPNLSPNPMS TP 3 Homo sapiens (Human)
2 
P29590 PML
PML_HUMAN
524 529 VSPPHLDGPPSPRSPVIGSE TP 3 Homo sapiens (Human)
1 
P29590 PML
PML_HUMAN
400 405 GKDAAVSKKASPEAASTPRD TP 3 Homo sapiens (Human)
1 
P01106 MYC
MYC_HUMAN
55 60 DIWKKFELLPTPPLSPSRRS TP 3 Homo sapiens (Human)
1 
Q9Y6H5 SNCAIP
SNCAP_HUMAN
208 213 SSNMAPFCVLSPVKSPHLRK TP 5 Homo sapiens (Human)
2 
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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