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PR01293

Identifier
RORNUCRECPTR  [View Relations]  [View Alignment]  
Accession
PR01293
No. of Motifs
5
Creation Date
13-FEB-2000  (UPDATE 09-JUL-2010)
Title
Nuclear receptor ROR family signature
Database References
PRINTS; PR00398 STRDHORMONER
PDB; 1K4W; 1N4H; 1N83; 1NQ7; 1S0X
SCOP; 1K4W; 1N4H; 1N83; 1NQ7; 1S0X
CATH; 1K4W; 1N4H; 1N83; 1NQ7; 1S0X
MIM; 600825; 601972; 602943
Literature References
1. NUCLEAR RECEPTORS NOMENCLATURE COMMITTEE
A unified nomenclature system for the nuclear receptor superfamily.
CELL 97 161-163 (1999).
 
2. NISHIKAWA, J-I., KITAURA, M., IMAGAWA, M. AND NISHIHARA, T.
Vitamin D receptor contains multiple dimerisation interfaces that
are functionally different.
NUCLEIC ACIDS RES. 23(4) 606-611 (1995).
 
3. DE VOS, P., SCHMITT, J., VERHOEVEN, G. AND STUNNENBERG, G.
Human androgen receptor expressed in HeLa cells activates transcription
in vitro.
NUCLEIC ACIDS RES. 22(7) 1161-1166 (1994).
 
4. GIGUERE, V., TINI, M., FLOCK, G., ONG, E., EVANS, R.M. AND OTULAKOWSKI, G.
Isoform-specific amino-terminal domains dictate DNA-binding properties of
ROR alpha, a novel family of orphan hormone nuclear receptors.
GENES DEV. 8 538-553 (1994). 

Documentation
Steroid or nuclear hormone receptors (NRs) constitute an important super-
family of transcription regulators that are involved in widely diverse 
physiological functions, including control of embryonic development, cell
differentiation and homeostasis [1]. Members of the superfamily include the
steroid hormone receptors and receptors for thyroid hormone, retinoids, 
1,25-dihydroxy-vitamin D3 and a variety of other ligands. The proteins 
function as dimeric molecules in nuclei to regulate the transcription of 
target genes in a ligand-responsive manner [2,3]. In addition to C-terminal
ligand-binding domains, these nuclear receptors contain a highly-conserved,
N-terminal zinc-finger that mediates specific binding to target DNA 
sequences, termed ligand-responsive elements. In the absence of ligand,
steroid hormone receptors are thought to be weakly associated with nuclear
components; hormone binding greatly increases receptor affinity.
 
NRs are extremely important in medical research, a large number of them
being implicated in diseases such as cancer, diabetes, hormone resistance
syndromes, etc. [1]. While several NRs act as ligand-inducible transcription
factors, many do not yet have a defined ligand and are accordingly termed 
"orphan" receptors. During the last decade, more than 300 NRs have been
described, many of which are orphans, which cannot easily be named due to 
current nomenclature confusions in the literature. However, a new system 
has recently been introduced in an attempt to rationalise the increasingly 
complex set of names used to describe superfamily members [1].
 
Three isoforms of a novel member of the steroid hormone nuclear receptor
superfamily related to retinoic acid receptors have been identified [4].
The isoforms (designated ROR alpha 1, ROR alpha 2 and ROR alpha 3) share
common DNA- and putative ligand-binding domains but are characterised by
distinct N-terminal domains generated by alternative RNA processing [4].
These differences in the N-terminal domains result in differential DNA-
binding activity for the different isoforms: ROR alpha 1 binds to and 
constitutively activates transcription from a large subset of ROR elements,
while ROR alpha 2 recognises ROR elements with strict specificity and 
displays weaker transcriptional activity [4]. The N-terminal domain and
zinc finger region work in concert to confer high affinity and specific 
DNA-binding properties to the ROR isoforms and suggest a novel strategy 
to control DNA-binding activity of nuclear receptors [4]. 
 
RORNUCRECPTR is a 5-element fingerprint that provides a signature for the
nuclear receptor ROR family. The fingerprint was derived from an initial
alignment of 6 sequences: the motifs were drawn from conserved regions 
spanning the C-terminal half of the alignment, focusing on those sections
that characterise the ROR receptors but distinguish them from the rest of
the steroid hormone receptor superfamily - motif 1 lies at the C-terminal
extremity of the hinge region, and motifs 2-5 reside in the ligand-binding
domain. Two iterations on SPTR37_10f were required to reach convergence,
at which point a true set comprising 13 sequences was identified. Five
partial matches were also found, all of which are related steroid hormone
receptors.
 
An update on SPTR57.15_40.15f identified a true set of 24 sequences, and 
twelve partial matches, all of which are translated genomic sequences that 
fail to match one or more motifs.
Summary Information
  24 codes involving  5 elements
5 codes involving 4 elements
5 codes involving 3 elements
2 codes involving 2 elements
Composite Feature Index
52424242424
435525
325530
200121
12345
True Positives
A3R3J9_DANRE  A7VL70_DANRE  B1B189_MOUSE  B2KI74_RHIFE  
B2RDT1_HUMAN B3F205_SHEEP B3KUU9_HUMAN B4DPR1_HUMAN
B6ZGS4_HUMAN B6ZGS5_HUMAN Q3TVH3_MOUSE Q3U1P4_MOUSE
Q495X4_HUMAN Q58EY0_HUMAN Q6I9R9_HUMAN Q98934
ROR1_MOUSE ROR2_HUMAN RORB_HUMAN RORB_MOUSE
RORB_RAT RORG_HUMAN RORG_MOUSE RORG_PONAB
True Positive Partials
Codes involving 4 elements
A3QU33_BOVIN B0JZJ5_DANRE B6ZGS6_HUMAN Q3U513_MOUSE
Q7ZU39_DANRE
Codes involving 3 elements
A3R3K0_DANRE B8JI61_DANRE B8JJ08_DANRE Q08D40_XENTR
Q3UUW3_MOUSE
Codes involving 2 elements
B5DFL4_RAT Q5XG07_XENLA
Sequence Titles
A3R3J9_DANRE Retinoid-related orphan receptor b - Danio rerio  
A7VL70_DANRE Retinoid-related orphan receptor alpha 2 - Danio rerio
B1B189_MOUSE RAR-related orphan receptor alpha - Mus musculus
B2KI74_RHIFE RAR-related orphan receptor C isoform a (Predicted) - Rhinolophus ferrumequinum
B2RDT1_HUMAN cDNA, FLJ96754, highly similar to Homo sapiens RAR-related orphan receptor C (RORC), mRNA - Homo sapiens
B3F205_SHEEP Retinoid-related orphan receptor beta - Ovis aries
B3KUU9_HUMAN cDNA FLJ40675 fis, clone THYMU2021714, highly similar to NUCLEAR RECEPTOR ROR-GAMMA - Homo sapiens
B4DPR1_HUMAN cDNA FLJ58518, highly similar to Nuclear receptor ROR-gamma - Homo sapiens
B6ZGS4_HUMAN Retinoid-related orphan receptor alpha - Homo sapiens
B6ZGS5_HUMAN Retinoid-related orphan receptor beta - Homo sapiens
Q3TVH3_MOUSE Putative uncharacterized protein - Mus musculus
Q3U1P4_MOUSE Putative uncharacterized protein - Mus musculus
Q495X4_HUMAN RAR-related orphan receptor A - Homo sapiens
Q58EY0_HUMAN RAR-related orphan receptor B - Homo sapiens
Q6I9R9_HUMAN RAR-related orphan receptor C - Homo sapiens
Q98934 TRANSCRIPTION FACTOR RZRBETA - GALLUS GALLUS (CHICKEN).
ROR1_MOUSE NUCLEAR RECEPTOR ROR-ALPHA-1 - MUS MUSCULUS (MOUSE).
ROR2_HUMAN NUCLEAR RECEPTOR ROR-ALPHA-2 - HOMO SAPIENS (HUMAN).
RORB_HUMAN Nuclear receptor ROR-beta - Homo sapiens
RORB_MOUSE Nuclear receptor ROR-beta - Mus musculus
RORB_RAT Nuclear receptor ROR-beta - Rattus norvegicus
RORG_HUMAN Nuclear receptor ROR-gamma - Homo sapiens
RORG_MOUSE Nuclear receptor ROR-gamma - Mus musculus
RORG_PONAB Nuclear receptor ROR-gamma - Pongo abelii

A3QU33_BOVIN RAR-related orphan receptor C - Bos taurus
B0JZJ5_DANRE Rorab protein - Danio rerio
B6ZGS6_HUMAN Retinoid-related orphan receptor gamma - Homo sapiens
Q3U513_MOUSE Putative uncharacterized protein - Mus musculus
Q7ZU39_DANRE RAR-related orphan receptor A, paralog b - Danio rerio

A3R3K0_DANRE Retinoid-related orphan receptor c - Danio rerio
B8JI61_DANRE RAR-related orphan receptor G - Danio rerio
B8JJ08_DANRE Novel protein similar to vertebrate RAR-related orphan receptor family - Danio rerio
Q08D40_XENTR RAR-related orphan receptor A - Xenopus tropicalis
Q3UUW3_MOUSE Putative uncharacterized protein - Mus musculus

B5DFL4_RAT Rorc protein - Rattus norvegicus
Q5XG07_XENLA LOC495242 protein - Xenopus laevis
Scan History
SPTR37_10f 1  50   NSINGLE    
SPTR57.15_40.15f 3 300 NSINGLE
Initial Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
SFTNGETSPTVSMAELEHLAQN ROR3_HUMAN 283 283 -
SFTNGETSPTVSMAELEHLAQN Q9Z139 258 258 -
SFTNGETSPTVSMAELEHLAQN ROR4_HUMAN 203 203 -
SFNNGQLAPGITMSEIDRIAQN RORB_RAT 197 197 -
SFCSAPEVPYASLTDIEYLVQN RORG_MOUSE 253 253 -
SFTNGETSPTVSMAELEHLAQN Q01974 291 291 -

Motif 2 width=14
Element Seqn Id St Int Rpt
KSHLETCQYLREEL ROR3_HUMAN 307 2 -
KSHLETCQYLREEL Q01974 315 2 -
KSFRETCQLRLEDL RORG_MOUSE 277 2 -
KSHLETCQYLREEL Q9Z139 282 2 -
KSHLETCQYLREEL ROR4_HUMAN 227 2 -
KSHLETCQYTMEEL RORB_RAT 221 2 -

Motif 3 width=18
Element Seqn Id St Int Rpt
HTYEEIKAYQSKSREALW RORB_RAT 242 7 -
FLQEEIENYQNKQREVMW ROR3_HUMAN 328 7 -
FLQEEIENYQNKQREVMW Q01974 336 7 -
FLQEEIENYQNKQREVMW Q9Z139 303 7 -
FLQEEIENYQNKQREVMW ROR4_HUMAN 248 7 -
FSREEVTSYQRKSMWEMW RORG_MOUSE 298 7 -

Motif 4 width=18
Element Seqn Id St Int Rpt
TVYFDGKYASPDVFKSLG ROR4_HUMAN 323 57 -
TVYFDGKYASPDVFKSLG ROR3_HUMAN 403 57 -
TVYFDGKYASPDVFKSLG Q01974 411 57 -
TVYFDGKYASPDVFKSLG Q9Z139 378 57 -
TVLFEGKYGGMQMFKALG RORB_RAT 317 57 -
TVFFEGKYGGVELFRALG RORG_MOUSE 373 57 -

Motif 5 width=11
Element Seqn Id St Int Rpt
PDIVRLHFPPL Q01974 529 4 -
PDIVRLHFPPL ROR3_HUMAN 521 4 -
PDIVNTLFPPL RORB_RAT 435 4 -
PIVVQAAFPPL RORG_MOUSE 489 4 -
PDIVRLHFPPL ROR4_HUMAN 441 4 -
PDIVRLHFPPL Q9Z139 496 4 -
Final Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
SFNNGQLAPGISMTEIDRIAQN Q98934 197 197 -
SFNNGQLAPGITMSEIDRIAQN B3F205_SHEEP 197 197 -
SFNNGQLAPGITMSEIDRIAQN RORB_RAT 197 197 -
SFNNGQLAPGITMSEIDRIAQN RORB_MOUSE 208 208 -
SFNNGQLAPGITMTEIDRIAQN B6ZGS5_HUMAN 197 197 -
SFNNGQLAPGITMTEIDRIAQN RORB_HUMAN 208 208 -
SFNNGQLAPGITMTEIDRIAQN Q58EY0_HUMAN 197 197 -
SFRSTPEAPYASLTEIEHLVQS B2RDT1_HUMAN 255 255 -
SFRSTPEAPYASLTEIEHLVQS RORG_HUMAN 255 255 -
SFRSTPEAPYASLTEIEHLVQS Q6I9R9_HUMAN 255 255 -
SFRSTPEAPYASLTEIEHLVQS B4DPR1_HUMAN 309 309 -
SFRSTPEAPYASLTEIEHLVQS RORG_PONAB 255 255 -
SFTNGETSPTVSMAELEHLAQN B1B189_MOUSE 258 258 -
SFTNGETSPTVSMAELEHLAQN ROR1_MOUSE 258 258 -
SFTNGETSPTVSMAELEHLAQN ROR2_HUMAN 291 291 -
SFTNGETSPTVSMAELEHLAQN Q495X4_HUMAN 203 203 -
SFTNGETSPTVSMAELEHLAQN Q3U1P4_MOUSE 202 202 -
SFTNGETSPTVSMAELEHLAQN B6ZGS4_HUMAN 258 258 -
SFTNGETSPTVSMAELEHLAQN A7VL70_DANRE 203 203 -
SFRSTPEAPYASLTEIEHLLQN B2KI74_RHIFE 254 254 -
SFRSTPEAPYASLTEIEHLVQS B3KUU9_HUMAN 234 234 -
SFCSAPEVPYASLTDIEYLVQN Q3TVH3_MOUSE 253 253 -
SFCSAPEVPYASLTDIEYLVQN RORG_MOUSE 253 253 -
SYQDSQLAPGVSMGELDRIAQN A3R3J9_DANRE 203 203 -

Motif 2 width=14
Element Seqn Id St Int Rpt
KSHLETCQYTMEEL Q98934 221 2 -
KSHLETCQYTMEEL B3F205_SHEEP 221 2 -
KSHLETCQYTMEEL RORB_RAT 221 2 -
KSHLETCQYTMEEL RORB_MOUSE 232 2 -
KSHLETCQYTMEEL B6ZGS5_HUMAN 221 2 -
KSHLETCQYTMEEL RORB_HUMAN 232 2 -
KSHLETCQYTMEEL Q58EY0_HUMAN 221 2 -
KSYRETCQLRLEDL B2RDT1_HUMAN 279 2 -
KSYRETCQLRLEDL RORG_HUMAN 279 2 -
KSYRETCQLRLEDL Q6I9R9_HUMAN 279 2 -
KSYRETCQLRLEDL B4DPR1_HUMAN 333 2 -
KSYRETCQLRLEDL RORG_PONAB 279 2 -
KSHLETCQYLREEL B1B189_MOUSE 282 2 -
KSHLETCQYLREEL ROR1_MOUSE 282 2 -
KSHLETCQYLREEL ROR2_HUMAN 315 2 -
KSHLETCQYLREEL Q495X4_HUMAN 227 2 -
KSHLETCQYLREEL Q3U1P4_MOUSE 226 2 -
KSHLETCQYLREEL B6ZGS4_HUMAN 282 2 -
KSHMETCQYLREEL A7VL70_DANRE 227 2 -
KSYRETCQLRLEDL B2KI74_RHIFE 278 2 -
KSYRETCQLRLEDL B3KUU9_HUMAN 258 2 -
KSFRETCQLRLEDL Q3TVH3_MOUSE 277 2 -
KSFRETCQLRLEDL RORG_MOUSE 277 2 -
KSHLETCQYTAEEL A3R3J9_DANRE 227 2 -

Motif 3 width=18
Element Seqn Id St Int Rpt
HTYEEIKVYQSKTREALW Q98934 242 7 -
HTYEEIKAYQSKSREALW B3F205_SHEEP 242 7 -
HTYEEIKAYQSKSREALW RORB_RAT 242 7 -
HTYEEIKAYQSKSREALW RORB_MOUSE 253 7 -
HTYEEIKAYQSKSREALW B6ZGS5_HUMAN 242 7 -
HTYEEIKAYQSKSREALW RORB_HUMAN 253 7 -
HTYEEIKAYQSKSREALW Q58EY0_HUMAN 242 7 -
FSREEVTGYQRKSMWEMW B2RDT1_HUMAN 300 7 -
FSREEVTGYQRKSMWEMW RORG_HUMAN 300 7 -
FSREEVTGYQRKSMWEMW Q6I9R9_HUMAN 300 7 -
FSREEVTGYQRKSMWEMW B4DPR1_HUMAN 354 7 -
FSREEVTGYQRKSMWEMW RORG_PONAB 300 7 -
FLQEEIENYQNKQREVMW B1B189_MOUSE 303 7 -
FLQEEIENYQNKQREVMW ROR1_MOUSE 303 7 -
FLQEEIENYQNKQREVMW ROR2_HUMAN 336 7 -
FLQEEIENYQNKQREVMW Q495X4_HUMAN 248 7 -
FLQEEIENYQNKQREVMW Q3U1P4_MOUSE 247 7 -
FLQEEIENYQNKQREVMW B6ZGS4_HUMAN 303 7 -
FLQEEVENYQSKPREVMW A7VL70_DANRE 248 7 -
FSREEVASYQRKSVWEMW B2KI74_RHIFE 299 7 -
FSREEVTGYQRKSMWEMW B3KUU9_HUMAN 279 7 -
FSREEVTSYQRKSMWEMW Q3TVH3_MOUSE 298 7 -
FSREEVTSYQRKSMWEMW RORG_MOUSE 298 7 -
HSYEEVKMYQSKTRDVLW A3R3J9_DANRE 248 7 -

Motif 4 width=18
Element Seqn Id St Int Rpt
TVLFEGKYGGMQMFKALG Q98934 317 57 -
TVLFEGKYGGMQMFKALG B3F205_SHEEP 317 57 -
TVLFEGKYGGMQMFKALG RORB_RAT 317 57 -
TVLFEGKYGGMQMFKALG RORB_MOUSE 328 57 -
TVLFEGKYGGMQMFKALG B6ZGS5_HUMAN 317 57 -
TVLFEGKYGGMQMFKALG RORB_HUMAN 328 57 -
TVLFEGKYGGMQMFKALG Q58EY0_HUMAN 317 57 -
TVFFEGKYGGMELFRALG B2RDT1_HUMAN 375 57 -
TVFFEGKYGGMELFRALG RORG_HUMAN 375 57 -
TVFFEGKYGGMELFRALG Q6I9R9_HUMAN 375 57 -
TVFFEGKYGGMELFRALG B4DPR1_HUMAN 429 57 -
TVFFEGKYGGMELFRALG RORG_PONAB 375 57 -
TVYFDGKYASPDVFKSLG B1B189_MOUSE 378 57 -
TVYFDGKYASPDVFKSLG ROR1_MOUSE 378 57 -
TVYFDGKYASPDVFKSLG ROR2_HUMAN 411 57 -
TVYFDGKYASPDVFKSLG Q495X4_HUMAN 323 57 -
TVYFDGKYASPDVFKSLG Q3U1P4_MOUSE 322 57 -
TVYFDGKYASPDVFKSLG B6ZGS4_HUMAN 378 57 -
TVYFDGKYAGPDVFKSLG A7VL70_DANRE 323 57 -
TVFFEGKYGGVELFRALG B2KI74_RHIFE 374 57 -
TVFFEGKYGGMELFRALG B3KUU9_HUMAN 354 57 -
TVFFEGKYGGVELFRALG Q3TVH3_MOUSE 373 57 -
TVFFEGKYGGVELFRALG RORG_MOUSE 373 57 -
TVLFEGKYGGMQIFKTLG A3R3J9_DANRE 323 57 -

Motif 5 width=11
Element Seqn Id St Int Rpt
PDIVNTLFPPL Q98934 435 100 -
PDIVNTLFPPL B3F205_SHEEP 435 100 -
PDIVNTLFPPL RORB_RAT 435 4 -
PDIVNTLFPPL RORB_MOUSE 446 100 -
PEIVNTLFPPL B6ZGS5_HUMAN 435 100 -
PEIVNTLFPPL RORB_HUMAN 446 100 -
PEIVNTLFPPL Q58EY0_HUMAN 435 100 -
PIVVQAAFPPL B2RDT1_HUMAN 491 98 -
PIVVQAAFPPL RORG_HUMAN 491 98 -
PIVVQAAFPPL Q6I9R9_HUMAN 491 98 -
PIVVQAAFPPL B4DPR1_HUMAN 545 98 -
PIVVQATFPPL RORG_PONAB 491 98 -
PDIVRLHFPPL B1B189_MOUSE 496 100 -
PDIVRLHFPPL ROR1_MOUSE 496 100 -
PDIVRLHFPPL ROR2_HUMAN 529 100 -
PDIVRLHFPPL Q495X4_HUMAN 441 100 -
PDIVRLHFPPL Q3U1P4_MOUSE 440 100 -
PDIVRLHFPPL B6ZGS4_HUMAN 496 100 -
PDIVRAHFPPL A7VL70_DANRE 441 100 -
PIVVQAAFPPL B2KI74_RHIFE 490 98 -
PIVAQAAFPPL B3KUU9_HUMAN 470 98 -
PIVVQAAFPPL Q3TVH3_MOUSE 489 98 -
PIVVQAAFPPL RORG_MOUSE 489 4 -
PETVNMLFPPL A3R3J9_DANRE 441 100 -