Q8IY18 (SMC5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Structural maintenance of chromosomes protein 5
Short name=SMC protein 5
Short name=SMC-5
Short name=hSMC5

Gene names

Name:	SMC5
Synonyms:	KIAA0594, SMC5L1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1101 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Core component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs). Required for recruitment of telomeres to PML nuclear bodies. Required for sister chromatid cohesion during prometaphase and mitotic progression; the function seems to be independent of SMC6. Ref.7 Ref.8 Ref.11
Subunit structure	Forms a heterodimer with SMC6. Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NDNL2. Ref.9
Subcellular location	Nucleus. Chromosome. Chromosome › telomere. Note: Associates with chromatin. Localizes to PML nuclear bodies in ALT cell lines. Ref.1 Ref.8 Ref.9
Tissue specificity	Widely expressed. Ref.1
Domain	The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC6, forming a V-shaped heterodimer By similarity.
Post-translational modification	Sumoylated. Ref.9 Ubiquitinated. Ref.9
Sequence similarities	Belongs to the SMC family. SMC5 subfamily.
Sequence caution	The sequence AAH17666.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage DNA recombination DNA repair Mitosis
Cellular component	Chromosome Nucleus Telomere
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Ligand	ATP-binding Nucleotide-binding
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell division Inferred from electronic annotation. Source: UniProtKB-KW cellular senescence Inferred from mutant phenotype Ref.8. Source: UniProtKB double-strand break repair via homologous recombination Inferred from mutant phenotype Ref.7. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of maintenance of mitotic sister chromatid cohesion Inferred from mutant phenotype Ref.11. Source: UniProtKB positive regulation of mitotic metaphase/anaphase transition Inferred from mutant phenotype Ref.11. Source: UniProtKB telomere maintenance via recombination Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	PML body Inferred from direct assay Ref.8. Source: UniProtKB Smc5-Smc6 complex Inferred from direct assay Ref.9. Source: UniProtKB chromosome, telomeric region Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SMC6	Q96SB8	3	EBI-605405,EBI-605415

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1101	1101	Structural maintenance of chromosomes protein 5		PRO_0000270951
Regions
	Nucleotide binding	80 – 87	8	ATP Potential
	Region	446 – 646	201	Flexible hinge
	Coiled coil	207 – 445	239	Potential
	Coiled coil	647 – 828	182	Potential
	Coiled coil	888 – 927	40	Potential
	Compositional bias	991 – 1026	36	Ala/Asp-rich (DA-box)
Amino acid modifications
	Modified residue	35	1	Phosphoserine Ref.10 Ref.12
Natural variations
	Natural variant	306	1	V → I. Ref.1 Ref.2 Ref.5 Corresponds to variant rs1180116 [ dbSNP | Ensembl ].		VAR_029824
	Natural variant	308	1	C → R. Ref.1 Ref.5 Corresponds to variant rs1180117 [ dbSNP | Ensembl ].		VAR_029825
	Natural variant	682	1	H → R. Corresponds to variant rs11142365 [ dbSNP | Ensembl ].		VAR_061869

Sequences

	Sequence		Length	Mass (Da)
	Q8IY18 [UniParc]. Last modified January 9, 2007. Version 2. Checksum: 54393D50688A914A	FASTA	1,101	128,806
	10 20 30 40 50 60 MATPSKKTST PSPQPSKRAL PRDPSSEVPS KRKNSAPQLP LLQSSGPFVE GSIVRISMEN 70 80 90 100 110 120 FLTYDICEVS PGPHLNMIVG ANGTGKSSIV CAICLGLAGK PAFMGRADKV GFFVKRGCSR 130 140 150 160 170 180 GMVEIELFRA SGNLVITREI DVAKNQSFWF INKKSTTQKI VEEKVAALNI QVGNLCQFLP 190 200 210 220 230 240 QDKVGEFAKL SKIELLEATE KSIGPPEMHK YHCELKNLRE KEKQLETSCK EKTEYLQKMV 250 260 270 280 290 300 QRNERYKQDV ERFYERKRHL DLIEMLEAKR PWVEYENVRQ EYEEVKLVRD RVKEEVRKLK 310 320 330 340 350 360 EGQIPVTCRI EEMENERHNL EARIKEKATD IKEASQKCKQ KQDVIERKDK HIEELQQALI 370 380 390 400 410 420 VKQNEELDRQ RRIGNTRKMI EDLQNELKTT ENCENLQPQI DAITNDLRRI QDEKALCEGE 430 440 450 460 470 480 IIDKRRERET LEKEKKSVDD HIVRFDNLMN QKEDKLRQRF RDTYDAVLWL RNNRDKFKQR 490 500 510 520 530 540 VCEPIMLTIN MKDNKNAKYI ENHIPSNDLR AFVFESQEDM EVFLKEVRDN KKLRVNAVIA 550 560 570 580 590 600 PKSSYADKAP SRSLNELKQY GFFSYLRELF DAPDPVMSYL CCQYHIHEVP VGTEKTRERI 610 620 630 640 650 660 ERVIQETRLK QIYTAEEKYV VKTSFYSNKV ISSNTSLKVA QFLTVTVDLE QRRHLEEQLK 670 680 690 700 710 720 EIHRKLQAVD SGLIALRETS KHLEHKDNEL RQKKKELLER KTKKRQLEQK ISSKLGSLKL 730 740 750 760 770 780 MEQDTCNLEE EERKASTKIK EINVQKAKLV TELTNLIKIC TSLHIQKVDL ILQNTTVISE 790 800 810 820 830 840 KNKLESDYMA ASSQLRLTEQ HFIELDENRQ RLLQKCKELM KRARQVCNLG AEQTLPQEYQ 850 860 870 880 890 900 TQVPTIPNGH NSSLPMVFQD LPNTLDEIDA LLTEERSRAS CFTGLNPTIV QEYTKREEEI 910 920 930 940 950 960 EQLTEELKGK KVELDQYREN ISQVKERWLN PLKELVEKIN EKFSNFFSSM QCAGEVDLHT 970 980 990 1000 1010 1020 ENEEDYDKYG IRIRVKFRSS TQLHELTPHH QSGGERSVST MLYLMALQEL NRCPFRVVDE 1030 1040 1050 1060 1070 1080 INQGMDPINE RRVFEMVVNT ACKENTSQYF FITPKLLQNL PYSEKMTVLF VYNGPHMLEP 1090 1100 NTWNLKAFQR RRRRITFTQP S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a novel human SMC heterodimer homologous to the Schizosaccharomyces pombe Rad18/Spr18 complex." Taylor E.M., Moghraby J.S., Lees J.H., Smit B., Moens P.B., Lehmann A.R. Mol. Biol. Cell 12:1583-1594(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SMC6, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS ILE-306 AND ARG-308.
[2]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-306. Tissue: Brain.
[3]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ILE-306 AND ARG-308. Tissue: Mammary gland and Uterus.
[6]	"Human MMS21/NSE2 is a SUMO ligase required for DNA repair." Potts P.R., Yu H. Mol. Cell. Biol. 25:7021-7032(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NSMCE2.
[7]	"Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks." Potts P.R., Porteus M.H., Yu H. EMBO J. 25:3377-3388(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins." Potts P.R., Yu H. Nat. Struct. Mol. Biol. 14:581-590(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]	"Identification of the proteins, including MAGEG1, that make up the human SMC5-6 protein complex." Taylor E.M., Copsey A.C., Hudson J.J., Vidot S., Lehmann A.R. Mol. Cell. Biol. 28:1197-1206(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, SUMOYLATION, UBIQUITINATION, IDENTIFICATION IN THE SMC5-SMC6 COMPLEX.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"SMC5 and MMS21 are required for chromosome cohesion and mitotic progression." Behlke-Steinert S., Touat-Todeschini L., Skoufias D.A., Margolis R.L. Cell Cycle 8:2211-2218(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ310550 mRNA. Translation: CAC39247.1. AB011166 mRNA. Translation: BAA25520.2. AL162390 Genomic DNA. Translation: CAH73243.1. BC017666 mRNA. Translation: AAH17666.1. Sequence problems. BC038225 mRNA. Translation: AAH38225.1.
IPI	IPI00413265.
RefSeq	NP_055925.2. NM_015110.3.
UniGene	Hs.534189. Hs.601181.
3D structure databases
HSSP	HSSP built from PDB template 1URQ based on UniProtKB P60881.
ProteinModelPortal	Q8IY18.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IY18. 4 interactions.
STRING	9606.ENSP00000354957.
PTM databases
PhosphoSite	Q8IY18.
Polymorphism databases
DMDM	122070387.
Proteomic databases
PaxDb	Q8IY18.
PRIDE	Q8IY18.
Protocols and materials databases
DNASU	23137.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361138; ENSP00000354957; ENSG00000198887.
GeneID	23137.
KEGG	hsa:23137.
UCSC	uc004ahr.2. human.
Organism-specific databases
CTD	23137.
GeneCards	GC09P072873.
H-InvDB	HIX0201342.
HGNC	HGNC:20465. SMC5.
HPA	HPA054900.
MIM	609386. gene.
neXtProt	NX_Q8IY18.
PharmGKB	PA134993662.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1196.
HOGENOM	HOG000154342.
HOVERGEN	HBG093963.
InParanoid	Q8IY18.
OMA	GMDPRNE.
OrthoDB	EOG4VMFDP.
Gene expression databases
Bgee	Q8IY18.
CleanEx	HS_SMC5.
Genevestigator	Q8IY18.
Family and domain databases
InterPro	IPR003395. RecF/RecN/SMC. IPR027131. SMC5. [Graphical view]
PANTHER	PTHR19306:SF1. PTHR19306:SF1. 1 hit.
Pfam	PF02463. SMC_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SMC5. human.
GenomeRNAi	23137.
NextBio	44403.
SOURCE	Search...

Entry information

Entry name

SMC5_HUMAN

Accession

Primary (citable) accession number: Q8IY18
Secondary accession number(s): A6NM81 , O60335, Q05D92, Q5VZ60, Q96SB9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	January 9, 2007
Last modified:	May 1, 2013
This is version 80 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.