HAND2

Protein identityUniProt · HPA

UniProt accession

P61296

Gene

HAND2

Ensembl

ENSG00000164107

Chromosome

4

Canonical length

217 aa

Protein class

Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm,Vesicles

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene belongs to the basic helix-loop-helix family of transcription factors. This gene product is one of two closely related family members, the HAND proteins, which are asymmetrically expressed in the developing ventricular chambers and play an essential role in cardiac morphogenesis. Working in a complementary fashion, they function in the formation of the right ventricle and aortic arch arteries, implicating them as mediators of congenital heart disease. In addition, this transcription factor plays an important role in limb and branchial arch development. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

217 residues, UniProt reviewed canonical sequence.

>P61296|HAND2
     1  MSLVGGFPHH PVVHHEGYPF AAAAAAAAAA AASRCSHEEN PYFHGWLIGH PEMSPPDYSM
    61  ALSYSPEYAS GAAGLDHSHY GGVPPGAGPP GLGGPRPVKR RGTANRKERR RTQSINSAFA
   121  ELRECIPNVP ADTKLSKIKT LRLATSYIAY LMDLLAKDDQ NGEAEAFKAE IKKTDVKEEK
   181  RKKELNEILK STVSSNDKKT KGRTGWPQHV WALELKQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HAND2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.6

Highest tissue expression

101 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HAND2.

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 81 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dilated cardiomyopathy 1A

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.94

gnomAD pLI

0.4

gnomAD missense Z

1.18

DepMap mean gene effect

0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult heart development
• angiogenesis
• apoptotic process involved in heart morphogenesis
• cardiac neural crest cell development involved in outflow tract morphogenesis
• cardiac neural crest cell migration involved in outflow tract morphogenesis
• cardiac right ventricle formation
• cartilage morphogenesis
• cell proliferation involved in outflow tract morphogenesis
• cellular response to retinoic acid
• coronary artery morphogenesis
• embryonic digit morphogenesis
• embryonic skeletal system development
• epithelial cell apoptotic process
• heart development
• heart looping
• in utero embryonic development
• mesenchymal cell proliferation
• negative regulation of cardiac muscle cell apoptotic process
• negative regulation of epithelial cell apoptotic process
• negative regulation of gene expression
• negative regulation of osteoblast differentiation
• noradrenergic neuron differentiation
• norepinephrine biosynthetic process
• odontogenesis of dentin-containing tooth
• osteoblast differentiation
• outflow tract morphogenesis
• peripheral nervous system neuron development
• positive regulation of cardiac muscle hypertrophy
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of gene expression
• positive regulation of p38MAPK cascade
• positive regulation of transcription by RNA polymerase II
• primary palate development
• regulation of secondary heart field cardioblast proliferation
• regulation of tissue remodeling
• regulation of transcription by RNA polymerase II
• suckling behavior
• sympathetic nervous system development
• thymus development
• tongue development
• visceral serous pericardium development
• positive regulation of semaphorin-plexin signaling pathway

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• E-box binding
• minor groove of adenine-thymine-rich DNA binding
• protein homodimerization activity
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• RNA polymerase II-specific DNA-binding transcription factor binding
• sequence-specific double-stranded DNA binding
• transcription coactivator binding

Cellular components

• chromatin
• nucleus
• protein-containing complex
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Myc-type, basic helix-loop-helix (bHLH) domain
• Helix-loop-helix DNA-binding domain superfamily
• E-box Binding Transcriptional Regulators
• Helix-loop-helix DNA-binding domain

KeywordsUniProt

• Angiogenesis
• Developmental protein
• Differentiation
• DNA-binding
• Nucleus
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of HAND2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TCF4