Q8C7W7 (DCR1B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5' exonuclease Apollo
EC=3.1.-.-

Alternative name(s):
DNA cross-link repair 1B protein
SNM1 homolog B

Gene names

Name:	Dclre1b
Synonyms:	Snm1b

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	541 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways. Together with TERF2, required to protect telomeres from replicative damage during replication by controlling the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Also involved in response to DNA damage: plays a role in response to DNA interstrand cross-links (ICLs) by facilitating double-strand break formation. In case of spindle stress, involved in prophase checkpoint. Ref.4 Ref.5
Subunit structure	Interacts with MUS81, MRE11 and FANCD2. Interacts with HSPA2, HSPA8 and HSPA14. Interacts with SPAG5 By similarity. Interacts with TERF2; the interaction is direct. Ref.5
Subcellular location	Chromosome › telomere. Nucleus By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Note: Mainly localizes to telomeres, recruited via its interaction with TERF2. During mitosis, localizes to the centrosome. Ref.4 Ref.5
Domain	The TBM domain mediates interaction with TERF2 By similarity.
Post-translational modification	Ubiquitinated, leading to its degradation. Interaction with TERF2 protects it from ubiquitination By similarity.
Disruption phenotype	Embryos are smaller than wild-type embryos and neonates die at postnatal day 0 (P0). Cells activate the ATM kinase at their telomeres in S phase and show leading-end telomere fusions which are accompanied by a reduction in the telomeric overhang signal. Ref.4 Ref.5
Sequence similarities	Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.
Sequence caution	The sequence AAH11094.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAC39165.1 differs from that shown. Reason: Frameshift at position 55. The sequence BAE23379.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Chromosome Cytoplasm Cytoskeleton Nucleus Telomere
Coding sequence diversity	Alternative splicing
Molecular function	Exonuclease Hydrolase Nuclease
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle checkpoint Inferred from sequence or structural similarity. Source: UniProtKB nucleotide-excision repair Inferred from sequence alignment PubMed 10848582. Source: MGI protection from non-homologous end joining at telomere Inferred from mutant phenotype Ref.4Ref.5. Source: UniProtKB telomeric 3' overhang formation Inferred from mutant phenotype Ref.4Ref.5. Source: UniProtKB telomeric loop formation Inferred from mutant phenotype Ref.5. Source: UniProtKB
Cellular_component	centrosome Inferred from sequence or structural similarity. Source: UniProtKB chromosome, telomeric region Inferred from direct assay Ref.4Ref.5. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from sequence alignment PubMed 10848582. Source: MGI
Molecular_function	5'-3' exonuclease activity Inferred from mutant phenotype Ref.4Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8C7W7-1)

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: Q8C7W7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-126: Missing.

Isoform 3 (identifier: Q8C7W7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     181-213: LYSLGKESLLEQLALEFRTWVVLSPQRLELVQL → ERFPFFFHSCLVNQNSLKVLIVFQIFVPCSPFL
     214-541: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 541	541	5' exonuclease Apollo		PRO_0000209120
Regions
	Motif	492 – 507	16	TBM
Natural variations
	Alternative sequence	1 – 126	126	Missing in isoform 2.		VSP_015174
	Alternative sequence	181 – 213	33	LYSLG…ELVQL → ERFPFFFHSCLVNQNSLKVL IVFQIFVPCSPFL in isoform 3.		VSP_015175
	Alternative sequence	214 – 541	328	Missing in isoform 3.		VSP_015176
Experimental info
	Mutagenesis	14	1	D → A: Abolishes exonuclease activity without affecting the telomere localization, leading to impaired 3'-overhang at the leading end telomeres. Ref.4
	Mutagenesis	31 – 35	5	HMHCD → AMACN: Abolishes exonuclease activity, leading to activate the ATM signaling pathway; when associated with A-230. Ref.5
	Mutagenesis	230	1	H → A: Abolishes exonuclease activity, leading to activate the ATM signaling pathway; when associated with 31-A--N-35. Ref.5
	Mutagenesis	500 – 504	5	Missing: Abolishes interaction with TERF2 and localization to telomeres, leading to activate the ATM signaling pathway. Ref.5
	Sequence conflict	49	1	Y → D in BAE23379. Ref.1
	Sequence conflict	162	1	T → S in BAC33550. Ref.1
	Sequence conflict	327	1	Y → H in AAI25278. Ref.3
	Sequence conflict	412	1	P → L in AAI25278. Ref.3
	Sequence conflict	540	1	V → D in BAE23700. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 16, 2005. Version 2. Checksum: 884FB1A8E452A76C	FASTA	541	61,069
	10 20 30 40 50 60 MNGVVIPQTP IAVDFWSLRR AGSARLFFLT HMHCDHTVGL SSTWARPLYC SPITACLLHR 70 80 90 100 110 120 RLQVSKHWIR ALEVGESHVL PLDEIGQETM TVTLIDANHC PGSVMFLFEG YFGTILYTGD 130 140 150 160 170 180 FRYTPSMLKE PALILGKQIH TLYLDNTNCN PALVLPSRQE ATQQIVQLIR QFPQHNIKIG 190 200 210 220 230 240 LYSLGKESLL EQLALEFRTW VVLSPQRLEL VQLLGLADVF TVEEEAGRIH AVDHTEICHS 250 260 270 280 290 300 AMLQWNQSHP TIAIFPTSRK VRSPHPSIYT VPYSDHSSYS ELRAFVAALR PCQVVPIVHQ 310 320 330 340 350 360 KPCGEFFQDS LSPRLAMPLI PHSVQQYMSS SSRKTNVLWQ LERRLKRPRT QGVVFESPEE 370 380 390 400 410 420 KANQVKVDRD SKKHKKENLS PWAGHLERLC PHPLQARKQL FPDFCRKERD EPVLFCDSNK 430 440 450 460 470 480 MATVLTAPLE FSVQLQPIDE FLFPETREKI GLESPLLSRG DSGSPARGNQ SDCVGCGSPP 490 500 510 520 530 540 AHISRAVPLT PESRGLALKY LLTPVHFLQA GFSSRNFDKQ VEKHQRVQRS SPAVLSPVDV G
	Isoform 2 [UniParc]. Checksum: D887FB35BE7747E3	FASTA	415	46,864
	10 20 30 40 50 60 MLKEPALILG KQIHTLYLDN TNCNPALVLP SRQEATQQIV QLIRQFPQHN IKIGLYSLGK 70 80 90 100 110 120 ESLLEQLALE FRTWVVLSPQ RLELVQLLGL ADVFTVEEEA GRIHAVDHTE ICHSAMLQWN 130 140 150 160 170 180 QSHPTIAIFP TSRKVRSPHP SIYTVPYSDH SSYSELRAFV AALRPCQVVP IVHQKPCGEF 190 200 210 220 230 240 FQDSLSPRLA MPLIPHSVQQ YMSSSSRKTN VLWQLERRLK RPRTQGVVFE SPEEKANQVK 250 260 270 280 290 300 VDRDSKKHKK ENLSPWAGHL ERLCPHPLQA RKQLFPDFCR KERDEPVLFC DSNKMATVLT 310 320 330 340 350 360 APLEFSVQLQ PIDEFLFPET REKIGLESPL LSRGDSGSPA RGNQSDCVGC GSPPAHISRA 370 380 390 400 410 VPLTPESRGL ALKYLLTPVH FLQAGFSSRN FDKQVEKHQR VQRSSPAVLS PVDVG
	Isoform 3 [UniParc]. Checksum: 56845E3156F33971	FASTA	213	24,254
	10 20 30 40 50 60 MNGVVIPQTP IAVDFWSLRR AGSARLFFLT HMHCDHTVGL SSTWARPLYC SPITACLLHR 70 80 90 100 110 120 RLQVSKHWIR ALEVGESHVL PLDEIGQETM TVTLIDANHC PGSVMFLFEG YFGTILYTGD 130 140 150 160 170 180 FRYTPSMLKE PALILGKQIH TLYLDNTNCN PALVLPSRQE ATQQIVQLIR QFPQHNIKIG 190 200 210 ERFPFFFHSC LVNQNSLKVL IVFQIFVPCS PFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). Strain: C57BL/6J and NOD. Tissue: Adipose tissue, Bone, Eye, Spinal cord and Testis.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 82-541 (ISOFORM 1). Strain: Czech II. Tissue: Brain and Mammary gland.
[4]	"SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair." Lam Y.C., Akhter S., Gu P., Ye J., Poulet A., Giraud-Panis M.J., Bailey S.M., Gilson E., Legerski R.J., Chang S. EMBO J. 29:2230-2241(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, MUTAGENESIS OF ASP-14.
[5]	"Apollo contributes to G overhang maintenance and protects leading-end telomeres." Wu P., van Overbeek M., Rooney S., de Lange T. Mol. Cell 39:606-617(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TERF2, DISRUPTION PHENOTYPE, MUTAGENESIS OF 31-HIS--ASP-35; HIS-230 AND 500-TYR--PRO-504.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK046571 mRNA. Translation: BAC32791.1. AK049115 mRNA. Translation: BAC33550.1. AK084347 mRNA. Translation: BAC39165.1. Frameshift. AK134324 mRNA. Translation: BAE22098.1. AK137495 mRNA. Translation: BAE23379.1. Different initiation. AK138568 mRNA. Translation: BAE23700.1. AK154124 mRNA. Translation: BAE32389.1. CU210953 Genomic DNA. Translation: CAQ12168.1. CU210953 Genomic DNA. Translation: CAQ12169.1. BC011094 mRNA. Translation: AAH11094.1. Different initiation. BC067017 mRNA. Translation: AAH67017.1. BC125277 mRNA. Translation: AAI25278.1.
IPI	IPI00226917. IPI00403798. IPI00458408.
RefSeq	NP_001020483.1. NM_001025312.1. NP_598626.2. NM_133865.2.
UniGene	Mm.374850.
3D structure databases
ProteinModelPortal	Q8C7W7.
SMR	Q8C7W7. Positions 6-299.
ModBase	Search...
Proteomic databases
PRIDE	Q8C7W7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000029435; ENSMUSP00000029435; ENSMUSG00000027845. ENSMUST00000063502; ENSMUSP00000067695; ENSMUSG00000027845. ENSMUST00000106832; ENSMUSP00000102445; ENSMUSG00000027845. ENSMUST00000106834; ENSMUSP00000102447; ENSMUSG00000027845.
GeneID	140917.
KEGG	mmu:140917.
UCSC	uc008qtl.1. mouse. uc008qtm.1. mouse. uc008qto.1. mouse.
Organism-specific databases
CTD	64858.
MGI	MGI:2156057. Dclre1b.
Phylogenomic databases
eggNOG	COG1236.
GeneTree	ENSGT00530000063183.
HOVERGEN	HBG081420.
InParanoid	B0V3P0.
KO	K15341.
OMA	KYLLTPV.
OrthoDB	EOG43R3N5.
Gene expression databases
ArrayExpress	Q8C7W7.
Bgee	Q8C7W7.
Genevestigator	Q8C7W7.
GermOnline	ENSMUSG00000027845. Mus musculus.
Family and domain databases
InterPro	IPR001279. Beta-lactamas-like. IPR011084. DRMBL. [Graphical view]
Pfam	PF07522. DRMBL. 1 hit. [Graphical view]
SMART	SM00849. Lactamase_B. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	370035.
SOURCE	Search...

Entry information

Entry name

DCR1B_MOUSE

Accession

Primary (citable) accession number: Q8C7W7
Secondary accession number(s): A0JLW2 , B0V3N9, B0V3P0, Q3U4P2, Q3UUC7, Q3UV92, Q6NXL4, Q8BN95, Q8BQS8, Q921S0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	August 16, 2005
Last modified:	May 1, 2013
This is version 72 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program