Q9CW03 (SMC3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Structural maintenance of chromosomes protein 3
Short name=SMC protein 3
Short name=SMC-3

Alternative name(s):
Basement membrane-associated chondroitin proteoglycan
Short name=Bamacan
Chondroitin sulfate proteoglycan 6
Chromosome segregation protein SmcD
Mad member-interacting protein 1

Gene names

Name:	Smc3
Synonyms:	Bam, Bmh, Cspg6, Mmip1, Smc3l1, Smcd

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	1217 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex plays also an important role in spindle pole assembly during mitosis and in chromosomes movement. Ref.2
Subunit structure	Interacts with NUMA1, and forms a ternary complex with KIF3B and KIFAP3, suggesting a function in tethering the chromosomes to the spindle pole and a function in chromosome movement. Interacts with SYCP2. Found in a complex with SMC1A, CDCA5 and RAD21, PDS5A/APRIN and PDS5B/SCC-112. Interacts with PDS5A and WAPAL; regulated by SMC3 acetylation By similarity. Forms a heterodimer with SMC1A or SMC1B in cohesin complexes. Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their hinge domain, RAD21 which link them, and one STAG protein (STAG1, STAG2 or STAG3), which interacts with RAD21. Also found in meiosis-specific cohesin complexes. Interacts with MXI1, MXD3 and MXD4. Interacts with RPGR By similarity. Ref.2 Ref.3 Ref.5 Ref.6
Subcellular location	Nucleus. Chromosome. Chromosome › centromere. Note: Associates with chromatin. Before prophase it is scattered along chromosome arms. During prophase, most of cohesin complexes dissociate from chromatin probably because of phosphorylation by PLK, except at centromeres, where cohesin complexes remain. At anaphase, the RAD21 subunit of the cohesin complex is cleaved, leading to the dissociation of the complex from chromosomes, allowing chromosome separation. The phosphorylated form at Ser-1083 is preferentially associated with unsynapsed chromosomal regions. Ref.11
Tissue specificity	Widely expressed, with higher expression in testis and brain.
Domain	The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC1A or SMC1B, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 protein, forming a ring structure By similarity.
Post-translational modification	Phosphorylated at Ser-1083 in a SPO11-dependent manner. Ref.7 Ref.11 Acetylation at Lys-105 and Lys-106 by ESCO1 is important for genome stability and S phase sister chromatid cohesion. Regulated by DSCC1, it is required for processive DNA synthesis, coupling sister chromatid cohesion establishment during S phase to DNA replication By similarity. Deacetylation by HDAC8, regulates release of the cohesin complex from chromatin By similarity.
Sequence similarities	Belongs to the SMC family. SMC3 subfamily.
Caution	Was originally isolated as a proteoglycan protein (explaining its name). Although not excluded, such secreted function is not clear.
Sequence caution	The sequence CAA75400.1 differs from that shown. Reason: Frameshift at positions 522, 1018 and 1144.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage DNA repair Meiosis Mitosis
Cellular component	Centromere Chromosome Nucleus
Domain	Coiled coil
Ligand	ATP-binding Nucleotide-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW chromosome organization Inferred from electronic annotation. Source: InterPro meiosis Inferred from sequence or structural similarity. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic spindle organization Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of DNA endoreduplication Inferred from electronic annotation. Source: Compara regulation of DNA replication Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Inferred from sequence or structural similarity. Source: UniProtKB stem cell maintenance Inferred from mutant phenotype PubMed 20720539. Source: MGI
Cellular_component	chromatin Inferred from sequence or structural similarity. Source: UniProtKB chromosome, centromeric region Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB lateral element Inferred from direct assay PubMed 15870106. Source: MGI nuclear matrix Inferred from sequence or structural similarity. Source: UniProtKB nuclear meiotic cohesin complex Inferred from direct assay PubMed 21743440. Source: MGI nucleoplasm Traceable author statement. Source: Reactome spindle pole Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW chromatin binding Inferred from direct assay PubMed 20720539. Source: MGI dynein binding Inferred from sequence or structural similarity. Source: UniProtKB mediator complex binding Inferred from direct assay PubMed 20720539. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1217

1217

Structural maintenance of chromosomes protein 3

PRO_0000119002

Regions

Nucleotide binding

32 – 39

8

ATP Potential

Region

505 – 667

163

Flexible hinge

Coiled coil

179 – 350

172

Potential

Coiled coil

393 – 503

111

Potential

Coiled coil

669 – 916

248

Potential

Coiled coil

958 – 989

32

Potential

Compositional bias

1115 – 1150

36

Ala/Asp-rich (DA-box)

Amino acid modifications

Modified residue

105

1

N6-acetyllysine By similarity

Modified residue

106

1

N6-acetyllysine By similarity

Modified residue

140

1

N6-acetyllysine By similarity

Modified residue

783

1

Phosphothreonine By similarity

Modified residue

787

1

Phosphoserine Ref.9

Modified residue

1013

1

Phosphoserine Ref.7

Modified residue

1065

1

Phosphoserine Ref.9

Modified residue

1067

1

Phosphoserine Ref.8 Ref.9 Ref.10

Modified residue

1074

1

Phosphoserine Ref.9

Modified residue

1083

1

Phosphoserine Ref.11

Modified residue

1190

1

N6-acetyllysine By similarity

Experimental info

Mutagenesis

807

1

L → P: Abolishes interaction with MXI1. Ref.3

Sequence conflict

999

1

K → R in CAA75400. Ref.3

Sequence conflict

1175

1

F → L Ref.3

Secondary structure

1

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1217

Helix Strand Turn

Details...

Helix

495 – 498

4

Turn

499 – 501

3

Helix

502 – 522

21

Helix

526 – 529

4

Beta strand

532 – 535

4

Helix

536 – 538

3

Beta strand

539 – 541

3

Helix

544 – 546

3

Helix

547 – 554

8

Helix

557 – 559

3

Beta strand

561 – 564

4

Helix

566 – 578

13

Beta strand

585 – 589

5

Turn

590 – 592

3

Beta strand

604 – 608

5

Helix

609 – 612

4

Helix

617 – 619

3

Helix

620 – 627

8

Beta strand

630 – 635

6

Helix

636 – 645

10

Beta strand

649 – 651

3

Beta strand

664 – 666

3

Helix

676 – 685

10

Sequences

	Sequence		Length	Mass (Da)
	Q9CW03 [UniParc]. Last modified March 25, 2003. Version 2. Checksum: 11FF55165BE6A88E	FASTA	1,217	141,556
	10 20 30 40 50 60 MYIKQVIIQG FRSYRDQTIV DPFSSKHNVI VGRNGSGKSN FFYAIQFVLS DEFSHLRPEQ 70 80 90 100 110 120 RLALLHEGTG PRVISAFVEI IFDNSDNRLP IDKEEVSLRR VIGAKKDQYF LDKKMVTKND 130 140 150 160 170 180 VMNLLESAGF SRSNPYYIVK QGKINQMATA PDSQRLKLLR EVAGTRVYDE RKEESISLMK 190 200 210 220 230 240 ETEGKREKIN ELLKYIEERL HTLEEEKEEL AQYQKWDKMR RALEYTIYNQ ELNETRAKLD 250 260 270 280 290 300 ELSAKRETSG EKSRQLRDAQ QDARDKMEDI ERQVRELKTK ISAMKEEKEQ LSAERQEQIK 310 320 330 340 350 360 QRTKLELKAK DLQDELAGNS EQRKRLLKER QKLLEKIEEK QKELAETEPK FNSVKEKEER 370 380 390 400 410 420 GIARLAQATQ ERTDLYAKQG RGSQFTSKEE RDKWIKKELK SLDQAINDKK RQIAAIHKDL 430 440 450 460 470 480 EDTEANKEKN LEQYNKLDQD LNEVKARVEE LDRKYYEVKN KKDELQSERN YLWREENAEQ 490 500 510 520 530 540 QALAAKREDL EKKQQLLRAA TGKAILNGID SINKVLEHFR RKGINQHVQN GYHGIVMNNF 550 560 570 580 590 600 ECEPAFYTCV EVTAGNRLFY HIVDSDEVST KILMEFNKMN LPGEVTFLPL NKLDVRDTAY 610 620 630 640 650 660 PETNDAIPMI SKLRYNPRFD KAFKHVFGKT LICRSMEVST QLARAFTMDC ITLEGDQVSH 670 680 690 700 710 720 RGALTGGYYD TRKSRLELQK DVRKAEEELG ELEAKLNENL RRNIERINNE IDQLMNQMQQ 730 740 750 760 770 780 IETQQRKFKA SRDSILSEMK MLKEKRQQSE KTFMPKQRSL QSLEASLHAM ESTRESLKAE 790 800 810 820 830 840 LGTDLLSQLS LEDQKRVDAL NDEIRQLQQE NRQLLNERIK LEGIITRVET YLNENLRKRL 850 860 870 880 890 900 DQVEQELNEL RETEGGTVLT ATTSELEAIN KRVKDTMARS EDLDNSIDKT EAGIKELQKS 910 920 930 940 950 960 MERWKNMEKE HMDAINHDTK ELEKMTNRQG MLLKKKEECM KKIRELGSLP QEAFEKYQTL 970 980 990 1000 1010 1020 SLKQLFRKLE QCNTELKKYS HVNKKALDQF VNFSEQKEKL IKRQEELDRG YKSIMELMNV 1030 1040 1050 1060 1070 1080 LELRKYEAIQ LTFKQVSKNF SEVFQKLVPG GKATLVMKKG DVEGSQSQDE GEGSGESERG 1090 1100 1110 1120 1130 1140 SGSQSSVPSV DQFTGVGIRV SFTGKQGEMR EMQQLSGGQK SLVALALIFA IQKCDPAPFY 1150 1160 1170 1180 1190 1200 LFDEIDQALD AQHRKAVSDM IMELAVHAQF ITTTFRPELL ESADKFYGVK FRNKVSHIDV 1210 ITAEMAKDFV EDDTTHG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete cDNA cloning, genomic organization, chromosomal assignment, functional characterization of the promoter, and expression of the murine Bamacan gene." Ghiselli G., Siracusa L.D., Iozzo R.V. J. Biol. Chem. 274:17384-17393(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Characterization of the components of the putative mammalian sister chromatid cohesion complex." Darwiche N., Freeman L.A., Strunnikov A. Gene 233:39-47(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, IDENTIFICATION IN A COHESIN COMPLEX WITH SMC1A AND RAD21.
[3]	"Mmip1: a novel leucine zipper protein that reverses the suppressive effects of mad family members on C-myc." Gupta K., Anand G., Yin X.Y., Prochownik E.V. Oncogene 16:1149-1159(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 478-1217, INTERACTION WITH MXI1; MXD3 AND MXD4, MUTAGENESIS OF LEU-807. Tissue: Embryo.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 887-1217. Strain: C57BL/6J. Tissue: Testis.
[5]	"Mammalian STAG3 is a cohesin specific to sister chromatid arms in meiosis I." Prieto I., Suja J.A., Pezzi N., Kremer L., Martinez-A C., Rufas J.S., Barbero J.L. Nat. Cell Biol. 3:761-766(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STAG3.
[6]	"Novel meiosis-specific isoform of mammalian SMC1." Revenkova E., Eijpe M., Heyting C., Gross B., Jessberger R. Mol. Cell. Biol. 21:6984-6998(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SMC1B.
[7]	"Phosphoproteome analysis of mouse liver using immobilized metal affinity purification and linear ion trap mass spectrometry." Jin W.-H., Dai J., Zhou H., Xia Q.-C., Zou H.-F., Zeng R. Rapid Commun. Mass Spectrom. 18:2169-2176(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-1013.
[8]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1067, MASS SPECTROMETRY. Tissue: Liver.
[9]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-787; SER-1065; SER-1067 AND SER-1074, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1067, MASS SPECTROMETRY. Tissue: Melanoma.
[11]	"Phosphorylation of chromosome core components may serve as axis marks for the status of chromosomal events during mammalian meiosis." Fukuda T., Pratto F., Schimenti J.C., Turner J.M., Camerini-Otero R.D., Hoeoeg C. PLoS Genet. 8:E1002485-E1002485(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-1083.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF141294 mRNA. Translation: AAD42073.1.
AF047601 mRNA. Translation: AAD27754.1.
Y15128 mRNA. Translation: CAA75400.1. Frameshift.
AK005647 mRNA. Translation: BAB24167.1.

IPI

IPI00132122.

RefSeq

NP_031816.2. NM_007790.3.

UniGene

Mm.14910.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WD5	X-ray	2.70	B	484-696	[»]

ProteinModelPortal

Q9CW03.

SMR

Q9CW03. Positions 1-239, 493-686, 1032-1212.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-57028N.

IntAct

Q9CW03. 8 interactions.

MINT

MINT-4134864.

PTM databases

PhosphoSite

Q9CW03.

Proteomic databases

PaxDb

Q9CW03.

PRIDE

Q9CW03.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000025930; ENSMUSP00000025930; ENSMUSG00000024974.

GeneID

13006.

KEGG

mmu:13006.

UCSC

uc008hwy.2. mouse.

Organism-specific databases

CTD

9126.

MGI

MGI:1339795. Smc3.

Phylogenomic databases

eggNOG

COG1196.

GeneTree

ENSGT00580000081628.

HOGENOM

HOG000166512.

HOVERGEN

HBG039849.

InParanoid

Q9CW03.

KO

K06669.

OMA

NKVLEHF.

OrthoDB

EOG4B5P4C.

Enzyme and pathway databases

Reactome

REACT_118161. Cell Cycle.
REACT_120463. Meiosis.
REACT_75800. Meiotic Synapsis (mouse).

Gene expression databases

ArrayExpress

Q9CW03.

Bgee

Q9CW03.

CleanEx

MM_SMC3.

Genevestigator

Q9CW03.

GermOnline

ENSMUSG00000024974. Mus musculus.

Family and domain databases

InterPro

IPR027417. P-loop_NTPase.
IPR003395. RecF/RecN/SMC.
IPR010935. SMC_hinge.
[Graphical view]

Pfam

PF06470. SMC_hinge. 1 hit.
PF02463. SMC_N. 1 hit.
[Graphical view]

SMART

SM00968. SMC_hinge. 1 hit.
[Graphical view]

SUPFAM

SSF75553. SMC_hinge. 1 hit.
SSF52540. SSF52540. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

SMC3. mouse.

EvolutionaryTrace

Q9CW03.

NextBio

282832.

SOURCE

Search...

Entry information

Entry name

SMC3_MOUSE

Accession

Primary (citable) accession number: Q9CW03
Secondary accession number(s): O35667, Q9QUS3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 25, 2003
Last sequence update:	March 25, 2003
Last modified:	May 29, 2013
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program