Reviewed, UniProtKB/Swiss-Prot Q5EBH1 (RASF5_MOUSE)

Names and origin

Protein names

Recommended name:
    Ras association domain-containing protein 5
Alternative name(s):
    New ras effector 1
    Regulator for cell adhesion and polarization enriched in lymphoid tissues
      Short name=RAPL

Gene names

Name:	Rassf5
Synonyms:	Nore1, Rapl

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	413 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Potental tumor suppressor. Seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T cell receptor or chemokine stimulation to integrin activation. Isoform 2 stimulates lymphocyte polarization and the patch-like distribution of ITGAL/LFA-1, resulting in an enhanced adhesion to ICAM1. Together with RAP1A may participate in regulation of microtubule growth. The association of isoform 2 with activated RAP1A is required for directional movement of endothelial cells during wound healing By similarity. May be involved in regulation of Ras apoptotic function. The RASSF5-STK4 complex may mediate HRAS1 and KRAS induced apoptosis.
Subunit structure	Interacts directly with activated HRAS1; a RASSF5-STK4 complex probably associates with activated HRAS1. Interacts with KRAS. Probably interacts with Ras-like GTPases RRAS, RRAS2, MRAS, RAP1B, RAP2A and RALA. Can self-associate. Interacts with RSSF1 isoform A. The RSSF1 isoform A-RSSF5 heterodimer probably mediates the association of RSSF1 with HRAS1. Isoform 2 interacts with activated RAP1A and ITGAL/LFA-1. Binds STK4/MST1, inhibiting STK4 autoactivation By similarity.
Subcellular location	CytoplasmBy similarity. Note= Isoform 2 is mainly located in the perinuclear region of unstimulated primary T cells. Upon stimulation translocates to the leading edge and colocalizes with ITGAL/LFA-1 in the peripheral zone of the immunological synapse. Isoform 2 is localized to growing microtubules in vascular endothelial cells and is dissociated from microtubules by activated RAP1A By similarity.
Sequence similarities	Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 Ras-associating domain. Contains 1 SARAH domain.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle
Cellular component	Cytoplasm Microtubule
Coding sequence diversity	Alternative splicing
Domain	Phorbol-ester binding Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Anti-oncogene
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW intracellular signaling cascade Inferred from electronic annotation. Source: InterPro negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW microtubule Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Ref.7 Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-960547,EBI-960547
HRAS	P01112	2	EBI-960547,EBI-350145	From a different organism.
Hras1	Q61411	2	EBI-960543,EBI-400273
Hras1	Q61411	2	EBI-960530,EBI-400273
ITGAL	P20701	1	EBI-960530,EBI-961214	From a different organism.
KRAS	P01116	1	EBI-960547,EBI-367415	From a different organism.
RAP1A	P62834	1	EBI-960530,EBI-491414	From a different organism.
RASSF1	Q9NS23-2	1	EBI-960547,EBI-438698	From a different organism.
Stk4	Q9JI11	1	EBI-960530,EBI-1181352

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5EBH1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q5EBH1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-142: Missing.
     143-188: ALRCANCKFT...ESTLTPTLNQ → MTVDSSMSSG...RNLQSKQPSK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 413

413

Ras association domain-containing protein 5

PRO_0000240402

Regions

Domain

265 – 359

95

Ras-associating

Domain

361 – 408

48

SARAH

Zinc finger

117 – 165

49

Phorbol-ester/DAG-type

Amino acid modifications

Modified residue

347

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

1 – 142

142

Missing in isoform 2.

VSP_019368

Alternative sequence

143 – 188

46

ALRCA…PTLNQ → MTVDSSMSSGYCSLDEELED CFFTAKTTFFRNLQSKQPSK in isoform 2.

VSP_019369

Experimental info

Mutagenesis

220

1

C → A: Reduced interaction with HRAS Ref.10

Mutagenesis

220

1

C → D: Strongly reduced interaction with HRAS Ref.10

Mutagenesis

221

1

L → A or D: Strongly reduced interaction with HRAS Ref.10

Mutagenesis

234

1

F → A: Reduced interaction with HRAS Ref.10

Mutagenesis

236

1

K → A: Reduced interaction with HRAS Ref.10

Mutagenesis

280

1

D → A: Reduced interaction with HRAS Ref.10

Mutagenesis

283

1

K → A: Very strong reduction of the interaction with HRAS Ref.10

Mutagenesis

284

1

Q → A: Reduced interaction with HRAS Ref.10

Mutagenesis

302

1

K → D: Reduced specificity for HRAS and diminished discrimination between HRAS and RAP1A Ref.10

Mutagenesis

303

1

K → A: Strongly reduced interaction with HRAS Ref.10

Sequence conflict

179

1

E → G in AAC08580. Ref.1

Sequence conflict

251 – 257

7

IRPQSIY → SGPSPSM in AAC08580. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

413

Helix Strand Turn

Details...

Turn

133 – 135

3

Beta strand

137 – 139

3

Turn

147 – 149

3

Helix

155 – 158

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: E6FF7DDE6BECB180	FASTA	413	46,714
	10 20 30 40 50 60 MASPAIGQRP YPLLLDPEPP RYLQSLGGTE PPPPARPRRC IPTALIPAAG ASEDRGGRRS 70 80 90 100 110 120 GRRDPEPTPR DCRHARPVRP GLQPRLRLRP GSHRPRDVRS IFEQPQDPRV LAERGEGHRF 130 140 150 160 170 180 VELALRGGPG WCDLCGREVL RQALRCANCK FTCHSECRSL IQLDCRQKGG PALDRRSPES 190 200 210 220 230 240 TLTPTLNQNV CKAVEETQHP PTIQEIKQKI DSYNSREKHC LGMKLSEDGT YTGFIKVHLK 250 260 270 280 290 300 LRRPVTVPAG IRPQSIYDAI KEVNPAATTD KRTSFYLPLD AIKQLHISST TTVSEVIQGL 310 320 330 340 350 360 LKKFMVVDNP QKFALFKRIH KDGQVLFQKL SIADYPLYLR LLAGPDTDVL SFVLKENETG 370 380 390 400 410 EVEWDAFSIP ELQNFLTILE KEEQDKIHQL QKKYNKFRQK LEEALRESQG KPG
	Isoform 2. Checksum: CF0431ED3B2D23D6		265	30,339
	10 20 30 40 50 60 MTVDSSMSSG YCSLDEELED CFFTAKTTFF RNLQSKQPSK NVCKAVEETQ HPPTIQEIKQ 70 80 90 100 110 120 KIDSYNSREK HCLGMKLSED GTYTGFIKVH LKLRRPVTVP AGIRPQSIYD AIKEVNPAAT 130 140 150 160 170 180 TDKRTSFYLP LDAIKQLHIS STTTVSEVIQ GLLKKFMVVD NPQKFALFKR IHKDGQVLFQ 190 200 210 220 230 240 KLSIADYPLY LRLLAGPDTD VLSFVLKENE TGEVEWDAFS IPELQNFLTI LEKEEQDKIH 250 260 QLQKKYNKFR QKLEEALRES QGKPG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of Nore1 as a potential Ras effector." Vavvas D., Li X., Avruch J., Zhang X.F. J. Biol. Chem. 273:5439-5442(1998) [PubMed: 9488663] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH HRAS1. Strain: BALB/c. Tissue: Brain.
[2]	"RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1." Katagiri K., Maeda A., Shimonaka M., Kinashi T. Nat. Immunol. 4:741-748(2003) [PubMed: 12845325] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: BALB/c. Tissue: Spleen.
[3]	"Prediction of the coding sequences of mouse homologues of FLJ genes: the complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H. DNA Res. 11:127-135(2004) [PubMed: 15449545] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Natural killer cell.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J and NOD. Tissue: Thymus.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Kidney.
[6]	"Identification of a novel Ras-regulated proapoptotic pathway." Khokhlatchev A., Rabizadeh S., Xavier R., Nedwidek M., Chen T., Zhang X.F., Seed B., Avruch J. Curr. Biol. 12:253-265(2002) [PubMed: 11864565] [Abstract] Cited for: FUNCTION IN APOPTOSIS, INTERACTION WITH STK4, HRAS1 AND KRAS.
[7]	"The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1." Ortiz-Vega S., Khokhlatchev A., Nedwidek M., Zhang X.F., Dammann R., Pfeifer G.P., Avruch J. Oncogene 21:1381-1390(2002) [PubMed: 11857081] [Abstract] Cited for: SELF-ASSOCIATION, INTERACTION WITH RSSF1; HRAS1; KRAS; RRAS; RRAS2; MRAS; RAP1B; RAP2A AND RALA.
[8]	Erratum Ortiz-Vega S., Khokhlatchev A., Nedwidek M., Zhang X.F., Dammann R., Pfeifer G.P., Avruch J. Oncogene 21:1943-1943(2002)
[9]	"GTP-Ras disrupts the intramolecular complex of C1 and RA domains of Nore1." Harjes E., Harjes S., Wohlgemuth S., Mueller K.H., Krieger E., Herrmann C., Bayer P. Structure 14:881-888(2006) [PubMed: 16698549] [Abstract] Cited for: STRUCTURE BY NMR OF 95-166, SUBUNIT.
[10]	"Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II." Stieglitz B., Bee C., Schwarz D., Yildiz O., Moshnikova A., Khokhlatchev A., Herrmann C. EMBO J. 27:1995-2005(2008) [PubMed: 18596699] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 200-357 OF MUTANT ASP-302 IN COMPLEX WITH HRAS, MUTAGENESIS OF CYS-220; LEU-221; PHE-234; LYS-236; ASP-280; LYS-283; GLN-284; LYS-302 AND LYS-303, INTERACTION WITH RAP1A.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF053959 mRNA. Translation: AAC08580.1.
AY261333 mRNA. Translation: AAP83361.1.
AK131147 mRNA. Translation: BAD21397.1. Different initiation.
AK088751 mRNA. Translation: BAC40546.1.
AK155534 mRNA. Translation: BAE33312.1.
AK155869 mRNA. Translation: BAE33472.1.
BC089605 mRNA. Translation: AAH89605.1.

RefSeq

NP_061220.2.

UniGene

Mm.248291

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RFH	NMR	-	A	108-166	[»]
2FNF	NMR	-	X	95-166	[»]
3DDC	X-ray	1.80	B	200-357	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:29107N.

IntAct

Q5EBH1. 12 interactions.

PTM databases

PhosphoSite

Q5EBH1.

Genome annotation databases

Ensembl

ENSMUSG00000026430. Mus musculus. [Contig view]

GeneID

54354.

KEGG

mmu:54354.

Organism-specific databases

MGI

MGI:1926375. Rassf5.

Phylogenomic databases

HOVERGEN

Q5EBH1.

Gene expression databases

ArrayExpress

Q5EBH1.

GermOnline

ENSMUSG00000026430. Mus musculus.

Family and domain databases

InterPro

IPR002219. DAG_PE_bd.
IPR000159. Ras-assoc.
IPR011524. SARAH.
[Graphical view]

Pfam

PF00130. C1_1. 1 hit.
PF00788. RA. 1 hit.
[Graphical view]

SMART

SM00109. C1. 1 hit.
SM00314. RA. 1 hit.
[Graphical view]

PROSITE

PS50200. RA. 1 hit.
PS50951. SARAH. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

311142.

SOURCE

Search...

Entry information

Entry name

RASF5_MOUSE

Accession

Primary (citable) accession number: Q5EBH1
Secondary accession number(s): O70407, Q6KAR0, Q8C2E8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 27, 2006
Last sequence update:	March 15, 2005
Last modified:	December 16, 2008
This is version 44 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)