SMAD2 SMAD family member 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SMAD2provided by HGNC
Official Full Name: SMAD family member 2provided by HGNC
Primary source: HGNC:HGNC:6768
See related: Ensembl:ENSG00000175387 MIM:601366; AllianceGenome:HGNC:6768
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: JV18; LDS6; CHTD8; MADH2; MADR2; JV18-1; hMAD-2; hSMAD2
Summary: The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]
Expression: Ubiquitous expression in thyroid (RPKM 6.6), testis (RPKM 4.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 18q21.1

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	18	NC_000018.10 (47808957..47930872, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	18	NC_060942.1 (47999960..48121861, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (45335328..45457243, complement)

Chromosome 18 - NC_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Zinc-Alpha-2-Glycoprotein Peptide Downregulates Type I and III Collagen Expression via Suppression of TGF-beta and p-Smad 2/3 Pathway in Keloid Fibroblasts and Rat Incisional Model.
Title: Zinc-Alpha-2-Glycoprotein Peptide Downregulates Type I and III Collagen Expression via Suppression of TGF-β and p-Smad 2/3 Pathway in Keloid Fibroblasts and Rat Incisional Model.
SIRT3 sulfhydration using hydrogen sulfide inhibited angiotensin II-induced atrial fibrosis and vulnerability to atrial fibrillation via suppression of the TGF-beta1/smad2/3 signalling pathway.
Title: SIRT3 sulfhydration using hydrogen sulfide inhibited angiotensin II-induced atrial fibrosis and vulnerability to atrial fibrillation via suppression of the TGF-β1/smad2/3 signalling pathway.
TIPE2 inhibits the migration and invasion of epithelial ovarian cancer cells by targeting Smad2 to reverse TGF-beta1-induced EMT.
Title: TIPE2 inhibits the migration and invasion of epithelial ovarian cancer cells by targeting Smad2 to reverse TGF-β1-induced EMT.
Investigating the impact of SMAD2 and SMAD4 downregulation in colorectal cancer and their correlation with immune markers, prognosis, and drug resistance and sensitivity.
Title: Investigating the impact of SMAD2 and SMAD4 downregulation in colorectal cancer and their correlation with immune markers, prognosis, and drug resistance and sensitivity.
Exosomes derived from adipose tissue-derived stem cells alleviated H2O2-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway.
Title: Exosomes derived from adipose tissue-derived stem cells alleviated H(2)O(2)-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway.
MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFbeta2-Smad2/3 signaling pathway in cervical cancer.
Title: MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer.
TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer.
Title: TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer.
DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways.
Title: DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways.
Exosomes Derived from Human Adipose Mesenchymal Stem Cells Inhibits Fibrosis and Treats Oral Submucous Fibrosis via the miR-181a-5p/Smad2 Axis.
Title: Exosomes Derived from Human Adipose Mesenchymal Stem Cells Inhibits Fibrosis and Treats Oral Submucous Fibrosis via the miR-181a-5p/Smad2 Axis.
BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma.
Title: BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (405)

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

Associated conditions

Description	Tests
Congenital heart defects, multiple types, 8, with or without heterotaxy MedGen: C5562042 OMIM: 619657 GeneReviews: Not available	not available
Loeys-Dietz syndrome 6 MedGen: C5562041 OMIM: 619656 GeneReviews: Loeys-Dietz Syndrome	not available

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2018-06-28) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2018-06-28) ClinGen Genome Curation Page

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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Replication interactions

Interaction	Pubs
HIV-1 replication is restricted by TGFB1 and SMAD2 in Langerhans cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 and p300 synergistically increase TGF-beta, ATF-2 and activating protein-1 (AP-1) expression leading to tubular cell apoptosis; in addition, HIV-1 gp120 treatment causes phosphorylation of Smad2 and downregulation of c-Jun	PubMed
Tat	tat	HIV-1 Tat-treated pulmonary arterial smooth muscle cells downregulate levels of phosphorylated SMAD2/3 proteins and SMAD2/3-SMAD4 protein complex, which are repressed by cocaine exposure	PubMed
	tat	HIV-1 Tat enhances binding of SMAD2, -3 and -4 and their binding partner Fast1 to the JCV DNA control region (CR) to stimulate JCV gene transcription in living cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH18445 (e-PCR)
- UniSTS:62505

RH69774 (e-PCR)
- UniSTS:6449

MARC_10275-10276:998924078:1 (e-PCR)
- UniSTS:267092

L18426 (e-PCR)
- UniSTS:34648

Smad2 (e-PCR), detects polymorphism
- UniSTS:466570

WIAF-1471 (e-PCR)
- UniSTS:59533

D11S3114 (e-PCR)
- UniSTS:152207

RH12141 (e-PCR)
- UniSTS:39578

SHGC-148706 (e-PCR)
- UniSTS:176569

SHGC-64255 (e-PCR)
- UniSTS:82363

RH47015 (e-PCR)
- UniSTS:52667

RH98251 (e-PCR)
- UniSTS:86211

D18S1312 (e-PCR)
- UniSTS:31430

SHGC-16176 (e-PCR)
- UniSTS:68808

MADH2_1658 (e-PCR)
- UniSTS:277460

RH66619 (e-PCR)
- UniSTS:53990

RH17857 (e-PCR)
- UniSTS:72445

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISS Inferred from Sequence or Structural Similarity more info	PubMed
contributes_to DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables I-SMAD binding	IBA Inferred from Biological aspect of Ancestor more info
enables I-SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
enables R-SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II-specific DNA-binding transcription factor binding	IEA Inferred from Electronic Annotation more info
enables SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables cis-regulatory region sequence-specific DNA binding	IC Inferred by Curator more info	PubMed
enables co-SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
enables disordered domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables double-stranded DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables tau protein binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables transforming growth factor beta receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables type I transforming growth factor beta receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in SMAD protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within SMAD protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in SMAD protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in SMAD protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in activin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activin receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in adrenal gland development	IEA Inferred from Electronic Annotation more info
involved_in anatomical structure morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in anterior/posterior pattern specification	ISS Inferred from Sequence or Structural Similarity more info
involved_in aortic valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell fate commitment	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
involved_in determination of left/right asymmetry in lateral mesoderm	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic cranial skeleton morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic foregut morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in endocardial cushion morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in endoderm formation	IEA Inferred from Electronic Annotation more info
involved_in gastrulation	TAS Traceable Author Statement more info	PubMed
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in lung development	IEA Inferred from Electronic Annotation more info
involved_in mesoderm formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of ossification	IDA Inferred from Direct Assay more info	PubMed
involved_in nodal signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in odontoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in organ growth	IEA Inferred from Electronic Annotation more info
involved_in pancreas development	IEA Inferred from Electronic Annotation more info
involved_in paraxial mesoderm morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in pericardium development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of BMP signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of epithelial to mesenchymal transition	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in post-embryonic development	IEA Inferred from Electronic Annotation more info
involved_in primary miRNA processing	TAS Traceable Author Statement more info	PubMed
involved_in pulmonary valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of binding	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to cholesterol	IDA Inferred from Direct Assay more info	PubMed
involved_in secondary palate development	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction involved in regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in transforming growth factor beta receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transforming growth factor beta receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in ureteric bud development	IEA Inferred from Electronic Annotation more info
involved_in zygotic specification of dorsal/ventral axis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of SMAD protein complex	IDA Inferred from Direct Assay more info	PubMed
part_of activin responsive factor complex	IDA Inferred from Direct Assay more info	PubMed
located_in chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
part_of heteromeric SMAD protein complex	IBA Inferred from Biological aspect of Ancestor more info
part_of heteromeric SMAD protein complex	IDA Inferred from Direct Assay more info	PubMed
part_of heteromeric SMAD protein complex	IPI Inferred from Physical Interaction more info	PubMed
part_of heteromeric SMAD protein complex	NAS Non-traceable Author Statement more info	PubMed
part_of homomeric SMAD protein complex	IPI Inferred from Physical Interaction more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IMP Inferred from Mutant Phenotype more info	PubMed
part_of transcription regulator complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: mothers against decapentaplegic homolog 2

Names: MAD homolog 2; SMAD, mothers against DPP homolog 2; Sma- and Mad-related protein 2; mother against DPP homolog 2

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_029946.2 RefSeqGene

Range

5213..126915

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001003652.4 → NP_001003652.1 mothers against decapentaplegic homolog 2 isoform 1

See identical proteins and their annotated locations for NP_001003652.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longest transcript and encodes the longer isoform (1). Both variants 1 and 2 encode the same isoform (1).

Source sequence(s)

AC026898, AC120349, AI453799, BC025699, DB462454

Consensus CDS

CCDS11934.1

UniProtKB/Swiss-Prot

Q15796

UniProtKB/TrEMBL

A0AAQ5BHK2, Q53XR6

Related

ENSP00000384449.1, ENST00000402690.6

Conserved Domains (2) summary

cd10491
Location:8 → 172

MH1_SMAD_2_3; N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3

cd10985
Location:266 → 456

MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3
NM_001135937.3 → NP_001129409.1 mothers against decapentaplegic homolog 2 isoform 2

See identical proteins and their annotated locations for NP_001129409.1

Status: REVIEWED

Description

Transcript Variant: This variant (3, also known as SMAD2Deltaexon3) lacks an in-frame exon in the 5' coding region, compared to variant 2, resulting in an isoform (2) that is shorter than isoform 1. There are no publicly available full-length transcripts representing this variant, but it is supported by data in Taekenoshita et al. (1998; PMID: 9503010) and Yagi et al. (1999; PMID: 9873005).

Source sequence(s)

AC026898, AC120349, AI453799, AK299218, DB462454

UniProtKB/TrEMBL

A0AAQ5BHK2

Related

ENSP00000349282.4, ENST00000356825.8

Conserved Domains (2) summary

cd10491
Location:8 → 142

MH1_SMAD_2_3; N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3

cd10985
Location:236 → 426

MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3
NM_005901.6 → NP_005892.1 mothers against decapentaplegic homolog 2 isoform 1

See identical proteins and their annotated locations for NP_005892.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) uses an alternate exon (1b) in the 5' UTR compared to variant 2. Both variants 1 and 2 encode the same isoform (1).

Source sequence(s)

AC026898, AC120349, AI453799, BC014840

Consensus CDS

CCDS11934.1

UniProtKB/Swiss-Prot

Q15796

UniProtKB/TrEMBL

A0AAQ5BHK2, Q53XR6

Related

ENSP00000262160.6, ENST00000262160.11

Conserved Domains (2) summary

cd10491
Location:8 → 172

MH1_SMAD_2_3; N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3

cd10985
Location:266 → 456

MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3

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_000018.10 Reference GRCh38.p14 Primary Assembly

Range

47808957..47930872 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047437508.1 → XP_047293464.1 mothers against decapentaplegic homolog 2 isoform X1

UniProtKB/TrEMBL

K7EJX0
XM_017025749.2 → XP_016881238.1 mothers against decapentaplegic homolog 2 isoform X1

UniProtKB/TrEMBL

K7EJX0

Related

ENSP00000465355.1, ENST00000586514.5
XM_047437507.1 → XP_047293463.1 mothers against decapentaplegic homolog 2 isoform X1

UniProtKB/TrEMBL

K7EJX0

Related

ENSP00000466254.1, ENST00000587269.5

Alternate T2T-CHM13v2.0

Genomic

NC_060942.1 Alternate T2T-CHM13v2.0

Range

47999960..48121861 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054318622.1 → XP_054174597.1 mothers against decapentaplegic homolog 2 isoform X1

UniProtKB/TrEMBL

K7EJX0
XM_054318620.1 → XP_054174595.1 mothers against decapentaplegic homolog 2 isoform X1

UniProtKB/TrEMBL

K7EJX0
XM_054318621.1 → XP_054174596.1 mothers against decapentaplegic homolog 2 isoform X1

UniProtKB/TrEMBL

K7EJX0