Reviewed, UniProtKB/Swiss-Prot Q96SB8 (SMC6_HUMAN)

Names and origin

Protein names

Recommended name:
    Structural maintenance of chromosomes protein 6
      Short name=hSMC6

Gene names

Name:	SMC6
Synonyms:	SMC6L1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1091 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Core component of the SMC5-SMC6 complex, a complex involved in 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. Ref.8
Subunit structure	Forms a heterodimer with SMC5. Component of the SMC5-SMC6 complex which consists of SMC5, SMC6, NSMCE2/MMS21 and probably NSMCE1.
Subcellular location	Nucleus. Note: Associates with chromatin. Ref.1
Tissue specificity	Widely expressed. Overexpressed in testis. Ref.1
Domain	The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC5, forming a V-shaped heterodimer By similarity.
Post-translational modification	Phosphorylated. Ref.1 Sumoylated by NSMCE2/MMS21. Ref.7
Sequence similarities	Belongs to the SMC family. SMC6 subfamily.
Sequence caution	The sequence AAH32675.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. The sequence BAB15236.1 differs from that shown. Reason: Frameshift at position 718.

Ontologies

Keywords
Biological process	DNA damage DNA recombination DNA repair
Cellular component	Chromosomal protein Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
Ligand	ATP-binding Nucleotide-binding
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW DNA repair Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	chromosome Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q96SB8-1)

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: Q96SB8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     80-80: S → SWSAVVRSRLNATSASQVQAILLFQPC

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1091	1091	Structural maintenance of chromosomes protein 6		PRO_0000270956
Regions
	Nucleotide binding	76 – 83	8	ATP Potential
	Region	452 – 659	208	Flexible hinge
	Coiled coil	226 – 451	226	Potential
	Coiled coil	660 – 914	255	Potential
	Compositional bias	987 – 1022	36	Ala/Asp-rich (DA-box)
Natural variations
	Alternative sequence	80	1	S → SWSAVVRSRLNATSASQVQA ILLFQPC in isoform 2.		VSP_022253
	Natural variant	292	1	A → V in a breast cancer sample; somatic mutation. Ref.10		VAR_035875
	Natural variant	464	1	R → G: dbSNP rs35195207. Ref.1 Ref.5		VAR_052441
	Natural variant	691	1	A → T: dbSNP rs1065381. Ref.1 Ref.5 Ref.6		VAR_029826
	Natural variant	928	1	K → Q: dbSNP rs35257753.		VAR_052442
	Natural variant	1046	1	I → M: dbSNP rs10221907.		VAR_029827
Experimental info
	Sequence conflict	483	1	N → Y in BAB15236. Ref.6
	Sequence conflict	868	1	D → N in BAB15236. Ref.6
	Sequence conflict	1082	1	V → A in BAB15236. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 9, 2007. Version 2. Checksum: 03C6F478E34285E6	FASTA	1,091	126,326
	10 20 30 40 50 60 MAKRKEENFS SPKNAKRPRQ EELEDFDKDG DEDECKGTTL TAAEVGIIES IHLKNFMCHS 70 80 90 100 110 120 MLGPFKFGSN VNFVVGNNGS GKSAVLTALI VGLGGRAVAT NRGSSLKGFV KDGQNSADIS 130 140 150 160 170 180 ITLRNRGDDA FKASVYGNSI LIQQHISIDG SRSYKLKSAT GSVVSTRKEE LIAILDHFNI 190 200 210 220 230 240 QVDNPVSVLT QEMSKQFLQS KNEGDKYKFF MKATQLEQMK EDYSYIMETK ERTKEQIHQG 250 260 270 280 290 300 EERLTELKRQ CVEKEERFQS IAGLSTMKTN LESLKHEMAW AVVNEIEKQL NAIRDNIKIG 310 320 330 340 350 360 EDRAARLDRK MEEQQVRLNE AEQKYKDIQD KLEKISEETN ARAPECMALK ADVVAKKRAY 370 380 390 400 410 420 NEAEVLYNRS LNEYKALKKD DEQLCKRIEE LKKSTDQSLE PERLERQKKI SWLKERVKAF 430 440 450 460 470 480 QNQENSVNQE IEQFQQAIEK DKEEHGKIKR EELDVKHALS YNQRQLKELK DSKTDRLKRF 490 500 510 520 530 540 GPNVPALLEA IDDAYRQGHF TYKPVGPLGA CIHLRDPELA LAIESCLKGL LQAYCCHNHA 550 560 570 580 590 600 DERVLQALMK RFYLPGTSRP PIIVSEFRNE IYDVRHRAAY HPDFPTVLTA LEIDNAVVAN 610 620 630 640 650 660 SLIDMRGIET VLLIKNNSVA RAVMQSQKPP KNCREAFTAD GDQVFAGRYY SSENTRPKFL 670 680 690 700 710 720 SRDVDSEISD LENEVENKTA QILNLQQHLS ALEKDIKHNE ELLKRCQLHY KELKMKIRKN 730 740 750 760 770 780 ISEIRELENI EEHQSVDIAT LEDEAQENKS KMKMVEEHME QQKENMEHLK SLKIEAENKY 790 800 810 820 830 840 DAIKFKINQL SELADPLKDE LNLADSEVDN QKRGKRHYEE KQKEHLDTLN KKKRELDMKE 850 860 870 880 890 900 KELEEKMSQA RQICPERIEV EKSASILDKE INRLRQKIQA EHASHGDREE IMRQYQEARE 910 920 930 940 950 960 TYLDLDSKVR TLKKFIKLLG EIMEHRFKTY QQFRRCLTLR CKLYFDNLLS QRAYCGKMNF 970 980 990 1000 1010 1020 DHKNETLSIS VQPGEGNKAA FNDMRALSGG ERSFSTVCFI LSLWSIAESP FRCLDEFDVY 1030 1040 1050 1060 1070 1080 MDMVNRRIAM DLILKMADSQ RFRQFILLTP QSMSSLPSSK LIRILRMSDP ERGQTTLPFR 1090 PVTQEEDDDQ R
	Isoform 2. Checksum: 3CB9F8CA48BC0ECE	FASTA	1,117	129,154
	10 20 30 40 50 60 MAKRKEENFS SPKNAKRPRQ EELEDFDKDG DEDECKGTTL TAAEVGIIES IHLKNFMCHS 70 80 90 100 110 120 MLGPFKFGSN VNFVVGNNGS WSAVVRSRLN ATSASQVQAI LLFQPCGKSA VLTALIVGLG 130 140 150 160 170 180 GRAVATNRGS SLKGFVKDGQ NSADISITLR NRGDDAFKAS VYGNSILIQQ HISIDGSRSY 190 200 210 220 230 240 KLKSATGSVV STRKEELIAI LDHFNIQVDN PVSVLTQEMS KQFLQSKNEG DKYKFFMKAT 250 260 270 280 290 300 QLEQMKEDYS YIMETKERTK EQIHQGEERL TELKRQCVEK EERFQSIAGL STMKTNLESL 310 320 330 340 350 360 KHEMAWAVVN EIEKQLNAIR DNIKIGEDRA ARLDRKMEEQ QVRLNEAEQK YKDIQDKLEK 370 380 390 400 410 420 ISEETNARAP ECMALKADVV AKKRAYNEAE VLYNRSLNEY KALKKDDEQL CKRIEELKKS 430 440 450 460 470 480 TDQSLEPERL ERQKKISWLK ERVKAFQNQE NSVNQEIEQF QQAIEKDKEE HGKIKREELD 490 500 510 520 530 540 VKHALSYNQR QLKELKDSKT DRLKRFGPNV PALLEAIDDA YRQGHFTYKP VGPLGACIHL 550 560 570 580 590 600 RDPELALAIE SCLKGLLQAY CCHNHADERV LQALMKRFYL PGTSRPPIIV SEFRNEIYDV 610 620 630 640 650 660 RHRAAYHPDF PTVLTALEID NAVVANSLID MRGIETVLLI KNNSVARAVM QSQKPPKNCR 670 680 690 700 710 720 EAFTADGDQV FAGRYYSSEN TRPKFLSRDV DSEISDLENE VENKTAQILN LQQHLSALEK 730 740 750 760 770 780 DIKHNEELLK RCQLHYKELK MKIRKNISEI RELENIEEHQ SVDIATLEDE AQENKSKMKM 790 800 810 820 830 840 VEEHMEQQKE NMEHLKSLKI EAENKYDAIK FKINQLSELA DPLKDELNLA DSEVDNQKRG 850 860 870 880 890 900 KRHYEEKQKE HLDTLNKKKR ELDMKEKELE EKMSQARQIC PERIEVEKSA SILDKEINRL 910 920 930 940 950 960 RQKIQAEHAS HGDREEIMRQ YQEARETYLD LDSKVRTLKK FIKLLGEIME HRFKTYQQFR 970 980 990 1000 1010 1020 RCLTLRCKLY FDNLLSQRAY CGKMNFDHKN ETLSISVQPG EGNKAAFNDM RALSGGERSF 1030 1040 1050 1060 1070 1080 STVCFILSLW SIAESPFRCL DEFDVYMDMV NRRIAMDLIL KMADSQRFRQ FILLTPQSMS 1090 1100 1110 SLPSSKLIRI LRMSDPERGQ TTLPFRPVTQ EEDDDQR

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: 11408570] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH SMC5, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION, VARIANTS GLY-464 AND THR-691.
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Amygdala.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Stomach.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-717 (ISOFORM 2), VARIANTS GLY-464 AND THR-691. Tissue: Ovary.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 467-1091, VARIANT THR-691.
[7]	"Human MMS21/NSE2 is a SUMO ligase required for DNA repair." Potts P.R., Yu H. Mol. Cell. Biol. 25:7021-7032(2005) [PubMed: 16055714] [Abstract] Cited for: INTERACTION WITH NSMCE2, SUMOYLATION.
[8]	"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: 16810316] [Abstract] Cited for: FUNCTION.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-292.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ310551 mRNA. Translation: CAC39248.1. AL136544 mRNA. Translation: CAB66479.1. AL832979 mRNA. Translation: CAH56327.1. AC097377 Genomic DNA. Translation: AAX88851.1. BC032675 mRNA. Translation: AAH32675.1. Sequence problems. BC039828 mRNA. Translation: AAH39828.1. AK025769 mRNA. Translation: BAB15236.1. Frameshift.
IPI	IPI00154528. IPI00816217.
RefSeq	NP_001135758.1. NP_078900.1.
UniGene	Hs.526728
3D structure databases
HSSP	HSSP built from PDB template 1US8 based on UniProtKB P58301.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96SB8. 2 interactions.
PTM databases
PhosphoSite	Q96SB8.
Proteomic databases
PRIDE	Q96SB8.
Genome annotation databases
Ensembl	ENSG00000163029. Homo sapiens. [Contig view]
GeneID	79677.
KEGG	hsa:79677.
Organism-specific databases
GeneCards	GC02M017708.
HGNC	HGNC:20466. SMC6.
MIM	609387. gene.
PharmGKB	PA33898.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q96SB8.
OMA	Q96SB8. INQGEER.
Gene expression databases
ArrayExpress	Q96SB8.
Bgee	Q96SB8.
CleanEx	HS_SMC6.
Family and domain databases
InterPro	IPR003395. RecF/RecN/SMC_N. [Graphical view]
Pfam	PF02463. SMC_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	68922.
SOURCE	Search...

Entry information

Entry name

SMC6_HUMAN

Accession

Primary (citable) accession number: Q96SB8
Secondary accession number(s): Q05BV4, Q9H0X3, Q9H6M0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	January 9, 2007
Last modified:	June 16, 2009
This is version 52 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)