SMC4 structural maintenance of chromosomes 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SMC4provided by HGNC
Official Full Name: structural maintenance of chromosomes 4provided by HGNC
Primary source: HGNC:HGNC:14013
See related: Ensembl:ENSG00000113810 MIM:605575; AllianceGenome:HGNC:14013
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CAPC; CAP-C; SMC-4; SMC4L1
Summary: This gene belongs to the 'structural maintenance of chromosomes' (SMC) gene family. Members of this gene family play a role in two changes in chromosome structure during mitotic segregation of chromosomes- chromosome condensation and sister chromatid cohesion. The protein encoded by this gene is likely a subunit of the 13S condensin complex, which is involved in chromosome condensation. A pseudogene related to this gene is located on chromosome 2. [provided by RefSeq, Jun 2016]
Expression: Broad expression in testis (RPKM 22.9), bone marrow (RPKM 22.6) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q25.33

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (160399650..160434953)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (163174262..163209567)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (160117438..160152741)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Screening Differential CircRNAs Expression Profiles Reveals the Regulatory Role of the has_circTPT1_003-has-miR-218-5p-CCNE2/SMC4 Signaling Axis in Bladder Carcinoma Progression.
Title: Screening Differential CircRNAs Expression Profiles Reveals the Regulatory Role of the has_circTPT1_003-has-miR-218-5p-CCNE2/SMC4 Signaling Axis in Bladder Carcinoma Progression.
Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/beta-catenin Signaling Pathway.
Title: Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/β-catenin Signaling Pathway.
FoxO1 promotes ovarian cancer by increasing transcription and METTL14-mediated m[6]A modification of SMC4.
Title: FoxO1 promotes ovarian cancer by increasing transcription and METTL14-mediated m(6)A modification of SMC4.
TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway.
Title: TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway.
MiR-433-3p restrains the proliferation, migration and invasion of glioma cells via targeting SMC4.
Title: MiR-433-3p restrains the proliferation, migration and invasion of glioma cells via targeting SMC4.
SMC4 knockdown inhibits malignant biological behaviors of endometrial cancer cells by regulation of FoxO1 activity.
Title: SMC4 knockdown inhibits malignant biological behaviors of endometrial cancer cells by regulation of FoxO1 activity.
Study found that mRNA expression of SMC4 was upregulated in invasive breast cancer cells. Patients with high mRNA level of SMC4 suffered different survival with triple negative breast cancer (TNBC) and non-TNBC. These results suggest that SMC4 could be a good biomarker for predicting the prognosis.
Title: The Prognostic Value of the Expression of SMC4 mRNA in Breast Cancer.
study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in hepatocellular carcinoma cells.
Title: HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition.
this paper shows that condensin Smc4 promotes inflammatory innate immune response by epigenetically enhancing NEMO transcription
Title: Condensin Smc4 promotes inflammatory innate immune response by epigenetically enhancing NEMO transcription.
Study examined the expression of SMC4 in acute myeloid leukemia (AML) pediatric patients cells and normal cells and revealed that SMC4 was significantly higher than control. Utilizing SMC4 gene knockdown in the established MLL-AF9 AML mouse model study found that SMC4 knockdown inhibited AML progression by maintaining leukemia stem cells.
Title: Structural maintenance of chromosomes 4 is required for leukemia stem cell maintenance in MLL-AF9 induced acute myeloid leukemia.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Interaction of HIV-1 Tat with SMC4 in T-cells is identified by a proteomic strategy based on affinity chromatography coupled with mass spectrometry	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-W93650 (e-PCR)
- UniSTS:54057

G38154 (e-PCR)
- UniSTS:53341

SHGC-52508 (e-PCR)
- UniSTS:67982

RH98841 (e-PCR)
- UniSTS:87478

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	TAS Traceable Author Statement more info	PubMed
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded DNA binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in kinetochore organization	IEA Inferred from Electronic Annotation more info
involved_in meiotic chromosome condensation	IEA Inferred from Electronic Annotation more info
involved_in meiotic chromosome segregation	IEA Inferred from Electronic Annotation more info
involved_in mitotic chromosome condensation	IDA Inferred from Direct Assay more info	PubMed
involved_in mitotic sister chromatid segregation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of chromosome condensation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chromosome condensation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of chromosome segregation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of chromosome separation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in chromosome, centromeric region	IEA Inferred from Electronic Annotation more info
located_in condensed nuclear chromosome	ISO Inferred from Sequence Orthology more info
part_of condensin complex	IDA Inferred from Direct Assay more info	PubMed
part_of condensin complex	NAS Non-traceable Author Statement more info	PubMed
part_of condensin complex	TAS Traceable Author Statement more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nuclear speck	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: structural maintenance of chromosomes protein 4

Names: SMC protein 4; SMC4 structural maintenance of chromosomes 4-like 1; chromosome-associated polypeptide C

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_050987.1 RefSeqGene

Range

5347..40650

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001002800.3 → NP_001002800.1 structural maintenance of chromosomes protein 4 isoform 1

See identical proteins and their annotated locations for NP_001002800.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) is the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AB019987, AL136877, BC106033

Consensus CDS

CCDS3189.1

UniProtKB/Swiss-Prot

A6NLT9, D3DNL8, O95752, Q8NDL4, Q9NTJ3, Q9UNT9

UniProtKB/TrEMBL

B3KXX5

Related

ENSP00000349961.3, ENST00000357388.8

Conserved Domains (4) summary

cd03274
Location:82 → 241

ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins

smart00968
Location:613 → 727

SMC_hinge; SMC proteins Flexible Hinge Domain

pfam02463
Location:83 → 1274

SMC_N; RecF/RecN/SMC N terminal domain

cl23887
Location:327 → 427

DUF4349; Domain of unknown function (DUF4349)
NM_001288753.2 → NP_001275682.1 structural maintenance of chromosomes protein 4 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate splice site in the 5' coding region, compared to variant 2. The resulting isoform (2) lacks an internal segment, compared to isoform 1.

Source sequence(s)

AK128143, AL136877

Consensus CDS

CCDS75046.1

UniProtKB/TrEMBL

B3KXX5, E9PD53

Related

ENSP00000417964.1, ENST00000469762.5

Conserved Domains (4) summary

cd03274
Location:57 → 216

ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins

smart00968
Location:588 → 702

SMC_hinge; SMC proteins Flexible Hinge Domain

pfam02463
Location:58 → 1249

SMC_N; RecF/RecN/SMC N terminal domain

cl23887
Location:302 → 402

DUF4349; Domain of unknown function (DUF4349)
NM_005496.3 → NP_005487.3 structural maintenance of chromosomes protein 4 isoform 1

See identical proteins and their annotated locations for NP_005487.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 2. Both variants 1 and 2 encode the same isoform (1).

Source sequence(s)

AL136877, AL833949

Consensus CDS

CCDS3189.1

UniProtKB/Swiss-Prot

A6NLT9, D3DNL8, O95752, Q8NDL4, Q9NTJ3, Q9UNT9

UniProtKB/TrEMBL

B3KXX5

Related

ENSP00000341382.5, ENST00000344722.5

Conserved Domains (4) summary

cd03274
Location:82 → 241

ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins

smart00968
Location:613 → 727

SMC_hinge; SMC proteins Flexible Hinge Domain

pfam02463
Location:83 → 1274

SMC_N; RecF/RecN/SMC N terminal domain

cl23887
Location:327 → 427

DUF4349; Domain of unknown function (DUF4349)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

160399650..160434953

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011512311.3 → XP_011510613.1 structural maintenance of chromosomes protein 4 isoform X1

See identical proteins and their annotated locations for XP_011510613.1

UniProtKB/Swiss-Prot

A6NLT9, D3DNL8, O95752, Q8NDL4, Q9NTJ3, Q9UNT9

UniProtKB/TrEMBL

B3KXX5

Conserved Domains (4) summary

cd03274
Location:82 → 241

ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins

smart00968
Location:613 → 727

SMC_hinge; SMC proteins Flexible Hinge Domain

pfam02463
Location:83 → 1274

SMC_N; RecF/RecN/SMC N terminal domain

cl23887
Location:327 → 427

DUF4349; Domain of unknown function (DUF4349)
XM_006713459.5 → XP_006713522.1 structural maintenance of chromosomes protein 4 isoform X3

UniProtKB/TrEMBL

B3KXX5

Conserved Domains (4) summary

cd03274
Location:82 → 241

ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins

smart00968
Location:535 → 649

SMC_hinge; SMC proteins Flexible Hinge Domain

pfam02463
Location:83 → 1196

SMC_N; RecF/RecN/SMC N terminal domain

cl23887
Location:327 → 427

DUF4349; Domain of unknown function (DUF4349)
XM_011512312.3 → XP_011510614.1 structural maintenance of chromosomes protein 4 isoform X2

UniProtKB/TrEMBL

B3KXX5

Conserved Domains (3) summary

cd03274
Location:10 → 169

ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins

smart00968
Location:541 → 655

SMC_hinge; SMC proteins Flexible Hinge Domain

pfam02463
Location:11 → 1202

SMC_N; RecF/RecN/SMC N terminal domain

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

163174262..163209567

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054344823.1 → XP_054200798.1 structural maintenance of chromosomes protein 4 isoform X1

UniProtKB/Swiss-Prot

A6NLT9, D3DNL8, O95752, Q8NDL4, Q9NTJ3, Q9UNT9
XM_054344825.1 → XP_054200800.1 structural maintenance of chromosomes protein 4 isoform X3
XM_054344824.1 → XP_054200799.1 structural maintenance of chromosomes protein 4 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001002799.1: Suppressed sequence

Description

NM_001002799.1: This RefSeq was permanently suppressed because it contains an unsupported deletion in the CDS that causes a frameshift resulting in premature translation termination. NM_001002799.1 is therefore a nonsense-mediated m