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PR01293

Identifier
RORNUCRECPTR  [View Relations]  [View Alignment]  
Accession
PR01293
No. of Motifs
7
Creation Date
13-FEB-2000
Title
Nuclear receptor ROR family (1F nuclear receptor) signature
Database References
PRINTS; PR00398 STRDHORMONER
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
  13 codes involving  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
5 codes involving 2 elements
Composite Feature Index
713131313131313
60000000
50000000
40000000
30000000
20000550
1234567
True Positives
P97773        Q61027        Q98934        ROR1_HUMAN    
ROR1_MOUSE ROR2_HUMAN ROR3_HUMAN ROR4_HUMAN
ROR4_MOUSE RORB_HUMAN RORB_RAT RORG_HUMAN
RORG_MOUSE
True Positive Partials
Codes involving 2 elements
EAR1_HUMAN O00402 Q60674 Q63503
Q90970
Sequence Titles
P97773      RAR-RELATED ORPHAN RECEPTOR ALPHA (NUCLEAR ORPHAN RECEPTOR/TRANSCRIPTION FACTOR) 
Q61027 THYMUS ORPHAN RECEPTOR (ORPHAN RECEPTOR TOR) - MUS MUSCULUS (MOUSE).
Q98934 TRANSCRIPTION FACTOR RZRBETA - GALLUS GALLUS (CHICKEN).
ROR1_HUMAN NUCLEAR RECEPTOR ROR-ALPHA-1 - HOMO SAPIENS (HUMAN).
ROR1_MOUSE NUCLEAR RECEPTOR ROR-ALPHA-1 - MUS MUSCULUS (MOUSE).
ROR2_HUMAN NUCLEAR RECEPTOR ROR-ALPHA-2 - HOMO SAPIENS (HUMAN).
ROR3_HUMAN NUCLEAR RECEPTOR ROR-ALPHA-3 - HOMO SAPIENS (HUMAN).
ROR4_HUMAN NUCLEAR RECEPTOR ROR-ALPHA-4 (NUCLEAR RECEPTOR RZR-ALPHA) - HOMO SAPIENS (HUMAN)
ROR4_MOUSE NUCLEAR RECEPTOR ROR-ALPHA-4 (NUCLEAR RECEPTOR RZR-ALPHA) - MUS MUSCULUS (MOUSE)
RORB_HUMAN NUCLEAR RECEPTOR ROR-BETA (NUCLEAR RECEPTOR RZR-BETA) - HOMO SAPIENS (HUMAN).
RORB_RAT NUCLEAR RECEPTOR ROR-BETA (NUCLEAR RECEPTOR RZR-BETA) - RATTUS NORVEGICUS (RAT).
RORG_HUMAN NUCLEAR RECEPTOR ROR-GAMMA (NUCLEAR RECEPTOR RZR-GAMMA) - HOMO SAPIENS (HUMAN).
RORG_MOUSE NUCLEAR RECEPTOR ROR-GAMMA (NUCLEAR RECEPTOR RZR-GAMMA) - MUS MUSCULUS (MOUSE).

EAR1_HUMAN V-ERBA RELATED PROTEIN EAR-1 - HOMO SAPIENS (HUMAN).
O00402 EAR-1R - HOMO SAPIENS (HUMAN).
Q60674 THYROID HORMONE RECEPTOR ALPHA (ORPHAN NUCLEAR RECEPTOR RVR) - MUS MUSCULUS (MOU
Q63503 REV-ERBA-ALPHA PROTEIN - RATTUS NORVEGICUS (RAT).
Q90970 REV-ERBB PROTEIN - GALLUS GALLUS (CHICKEN).
Scan History
SPTR37_10f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
SFTNGETSPTVSMAELEHLAQN ROR4_HUMAN 203 203 -
SFTNGETSPTVSMAELEHLAQN ROR3_HUMAN 283 283 -
SFTNGETSPTVSMAELEHLAQN ROR2_HUMAN 291 291 -
SFTNGETSPTVSMAELEHLAQN ROR1_MOUSE 258 258 -
SFNNGQLAPGITMSEIDRIAQN RORB_RAT 197 197 -
SFCSAPEVPYASLTDIEYLVQN RORG_MOUSE 253 253 -

Motif 2 width=14
Element Seqn Id St Int Rpt
KSHLETCQYLREEL ROR4_HUMAN 227 2 -
KSHLETCQYLREEL ROR3_HUMAN 307 2 -
KSHLETCQYLREEL ROR2_HUMAN 315 2 -
KSHLETCQYLREEL ROR1_MOUSE 282 2 -
KSHLETCQYTMEEL RORB_RAT 221 2 -
KSFRETCQLRLEDL RORG_MOUSE 277 2 -

Motif 3 width=18
Element Seqn Id St Int Rpt
FLQEEIENYQNKQREVMW ROR4_HUMAN 248 7 -
FLQEEIENYQNKQREVMW ROR3_HUMAN 328 7 -
FLQEEIENYQNKQREVMW ROR2_HUMAN 336 7 -
FLQEEIENYQNKQREVMW ROR1_MOUSE 303 7 -
HTYEEIKAYQSKSREALW RORB_RAT 242 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 ROR2_HUMAN 411 57 -
TVYFDGKYASPDVFKSLG ROR1_MOUSE 378 57 -
TVLFEGKYGGMQMFKALG RORB_RAT 317 57 -
TVFFEGKYGGVELFRALG RORG_MOUSE 373 57 -

Motif 5 width=15
Element Seqn Id St Int Rpt
FEFGKSLCSMHLTED ROR4_HUMAN 349 8 -
FEFGKSLCSMHLTED ROR3_HUMAN 429 8 -
FEFGKSLCSMHLTED ROR2_HUMAN 437 8 -
FEFGKSLCSMHLTED ROR1_MOUSE 404 8 -
FDFAKNLCSLQLTEE RORB_RAT 343 8 -
FDFSHFLSALCFSED RORG_MOUSE 399 8 -

Motif 6 width=15
Element Seqn Id St Int Rpt
LRALCGRHTEKLMAF ROR4_HUMAN 422 58 -
LRALCGRHTEKLMAF ROR3_HUMAN 502 58 -
LRALCGRHTEKLMAF ROR2_HUMAN 510 58 -
LRALCGRHTEKLMAF ROR1_MOUSE 477 58 -
ITAVCNLHGEKLQVF RORB_RAT 416 58 -
LRSLCSQHVEKLQIF RORG_MOUSE 470 56 -

Motif 7 width=11
Element Seqn Id St Int Rpt
PDIVRLHFPPL ROR4_HUMAN 441 4 -
PDIVRLHFPPL ROR3_HUMAN 521 4 -
PDIVRLHFPPL ROR2_HUMAN 529 4 -
PDIVRLHFPPL ROR1_MOUSE 496 4 -
PDIVNTLFPPL RORB_RAT 435 4 -
PIVVQAAFPPL RORG_MOUSE 489 4 -
Final Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
SFTNGETSPTVSMAELEHLAQN P97773 202 202 -
SFTNGETSPTVSMAELEHLAQN ROR4_HUMAN 203 203 -
SFTNGETSPTVSMAELEHLAQN ROR3_HUMAN 283 283 -
SFTNGETSPTVSMAELEHLAQN ROR2_HUMAN 291 291 -
SFTNGETSPTVSMAELEHLAQN ROR1_MOUSE 258 258 -
SFTNGETSPTVSMAELEHLAQN ROR1_HUMAN 258 258 -
SFTNGETSPTVSMAELEHLAQN ROR4_MOUSE 194 194 -
SFNNGQLAPGITMSEIDRIAQN RORB_RAT 197 197 -
SFNNGQLAPGISMTEIDRIAQN Q98934 197 197 -
SFNNGQLAPGITMTEIDRIAQN RORB_HUMAN 197 197 -
SFCSAPEVPYASLTDIEYLVQN Q61027 253 253 -
SFCSAPEVPYASLTDIEYLVQN RORG_MOUSE 253 253 -
SFRSTPEAPYASLTEIEHLVQS RORG_HUMAN 255 255 -

Motif 2 width=14
Element Seqn Id St Int Rpt
KSHLETCQYLREEL P97773 226 2 -
KSHLETCQYLREEL ROR4_HUMAN 227 2 -
KSHLETCQYLREEL ROR3_HUMAN 307 2 -
KSHLETCQYLREEL ROR2_HUMAN 315 2 -
KSHLETCQYLREEL ROR1_MOUSE 282 2 -
KSHLETCQYLREEL ROR1_HUMAN 282 2 -
KSHLETCQYLREEL ROR4_MOUSE 218 2 -
KSHLETCQYTMEEL RORB_RAT 221 2 -
KSHLETCQYTMEEL Q98934 221 2 -
KSHLETCQYTMEEL RORB_HUMAN 221 2 -
KSFRETCQLRLEDL Q61027 277 2 -
KSFRETCQLRLEDL RORG_MOUSE 277 2 -
KSYRETCQLRLEDL RORG_HUMAN 279 2 -

Motif 3 width=18
Element Seqn Id St Int Rpt
FLQEEIENYQNKQREVMW P97773 247 7 -
FLQEEIENYQNKQREVMW ROR4_HUMAN 248 7 -
FLQEEIENYQNKQREVMW ROR3_HUMAN 328 7 -
FLQEEIENYQNKQREVMW ROR2_HUMAN 336 7 -
FLQEEIENYQNKQREVMW ROR1_MOUSE 303 7 -
FLQEEIENYQNKQREVMW ROR1_HUMAN 303 7 -
FWQEEIENYQNKQREVMW ROR4_MOUSE 239 7 -
HTYEEIKAYQSKSREALW RORB_RAT 242 7 -
HTYEEIKVYQSKTREALW Q98934 242 7 -
HTYEEIKAYQSKSREALW RORB_HUMAN 242 7 -
FSREEVTSYQRKSMWEMW Q61027 298 7 -
FSREEVTSYQRKSMWEMW RORG_MOUSE 298 7 -
FSREEVTGYQRKSMWEMW RORG_HUMAN 300 7 -

Motif 4 width=18
Element Seqn Id St Int Rpt
TVYFDGKYASPDVFKSLG P97773 322 57 -
TVYFDGKYASPDVFKSLG ROR4_HUMAN 323 57 -
TVYFDGKYASPDVFKSLG ROR3_HUMAN 403 57 -
TVYFDGKYASPDVFKSLG ROR2_HUMAN 411 57 -
TVYFDGKYASPDVFKSLG ROR1_MOUSE 378 57 -
TVYFDGKYASPDVFKSLG ROR1_HUMAN 378 57 -
TVYFDGKYASPDVFKSLG ROR4_MOUSE 314 57 -
TVLFEGKYGGMQMFKALG RORB_RAT 317 57 -
TVLFEGKYGGMQMFKALG Q98934 317 57 -
TVLFEGKYGGMQMFKALG RORB_HUMAN 317 57 -
TVFFEGKYGGVELFRALG Q61027 373 57 -
TVFFEGKYGGVELFRALG RORG_MOUSE 373 57 -
TVFFEGKYGGMELFRALG RORG_HUMAN 375 57 -

Motif 5 width=15
Element Seqn Id St Int Rpt
FEFGKSLCSMHLTED P97773 348 8 -
FEFGKSLCSMHLTED ROR4_HUMAN 349 8 -
FEFGKSLCSMHLTED ROR3_HUMAN 429 8 -
FEFGKSLCSMHLTED ROR2_HUMAN 437 8 -
FEFGKSLCSMHLTED ROR1_MOUSE 404 8 -
FEFGKSLCSMHLTED ROR1_HUMAN 404 8 -
FEFGKSLCSMHLTED ROR4_MOUSE 340 8 -
FDFAKNLCSLQLTEE RORB_RAT 343 8 -
FDFAKNLCSLQLTEE Q98934 343 8 -
FDFAKNLCSLQLTEE RORB_HUMAN 343 8 -
FDFSHFLSALCFSED Q61027 399 8 -
FDFSHFLSALCFSED RORG_MOUSE 399 8 -
FDFSHSLSALHFSED RORG_HUMAN 401 8 -

Motif 6 width=15
Element Seqn Id St Int Rpt
LRALCGRHTEKLMAF P97773 421 58 -
LRALCGRHTEKLMAF ROR4_HUMAN 422 58 -
LRALCGRHTEKLMAF ROR3_HUMAN 502 58 -
LRALCGRHTEKLMAF ROR2_HUMAN 510 58 -
LRALCGRHTEKLMAF ROR1_MOUSE 477 58 -
LRALCGRHTEKLMAF ROR1_HUMAN 477 58 -
LRALCGRHTEKLMAF ROR4_MOUSE 413 58 -
ITAVCNLHGEKLQVF RORB_RAT 416 58 -
ITALCNLHGEKLQVF Q98934 416 58 -
ITAVCNLHGEKLQVF RORB_HUMAN 416 58 -
LRSLCSQHVEKLQIF Q61027 470 56 -
LRSLCSQHVEKLQIF RORG_MOUSE 470 56 -
LRSLCSQHVERLQIF RORG_HUMAN 472 56 -

Motif 7 width=11
Element Seqn Id St Int Rpt
PDIVRLHFPPL P97773 440 4 -
PDIVRLHFPPL ROR4_HUMAN 441 4 -
PDIVRLHFPPL ROR3_HUMAN 521 4 -
PDIVRLHFPPL ROR2_HUMAN 529 4 -
PDIVRLHFPPL ROR1_MOUSE 496 4 -
PDIVRLHFPPL ROR1_HUMAN 496 4 -
PDIVRLHFPPL ROR4_MOUSE 432 4 -
PDIVNTLFPPL RORB_RAT 435 4 -
PDIVNTLFPPL Q98934 435 4 -
PEIVNTLFPPL RORB_HUMAN 435 4 -
PIVVQAAFPPL Q61027 489 4 -
PIVVQAAFPPL RORG_MOUSE 489 4 -
PIVVQAAFPPL RORG_HUMAN 491 4 -