HHLA2

Protein identityUniProt · HPA

UniProt accession

Q9UM44

Gene

HHLA2

Ensembl

ENSG00000114455

Chromosome

3

Canonical length

414 aa

Protein class

Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

This gene encodes a protein ligand found on the surface of monocytes. The encoded protein is thought to regulate cell-mediated immunity by binding to a receptor on T lymphocytes and inhibiting the proliferation of these cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Canonical amino-acid sequenceUniProt

414 residues, UniProt reviewed canonical sequence.

>Q9UM44|HHLA2
     1  MKAQTALSFF LILITSLSGS QGIFPLAFFI YVPMNEQIVI GRLDEDIILP SSFERGSEVV
    61  IHWKYQDSYK VHSYYKGSDH LESQDPRYAN RTSLFYNEIQ NGNASLFFRR VSLLDEGIYT
   121  CYVGTAIQVI TNKVVLKVGV FLTPVMKYEK RNTNSFLICS VLSVYPRPII TWKMDNTPIS
   181  ENNMEETGSL DSFSINSPLN ITGSNSSYEC TIENSLLKQT WTGRWTMKDG LHKMQSEHVS
   241  LSCQPVNDYF SPNQDFKVTW SRMKSGTFSV LAYYLSSSQN TIINESRFSW NKELINQSDF
   301  SMNLMDLNLS DSGEYLCNIS SDEYTLLTIH TVHVEPSQET ASHNKGLWIL VPSAILAAFL
   361  LIWSVKCCRA QLEARRSRHP ADGAQQERCC VPPGERCPSA PDNGEENVPL SGKV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HHLA2 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

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

130 nTPM

Expression across tissuesHPA

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)

1

gnomAD pLI

0

gnomAD missense Z

0.57

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• positive regulation of activated T cell proliferation
• positive regulation of cytokine production
• regulation of cytokine production
• T cell costimulation
• T cell receptor signaling pathway

Molecular functions

• signaling receptor binding

Cellular components

• external side of plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin C1-set
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin V-set domain
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• BTN/MOG-like
• Immunoglobulin C1-set domain
• Immunoglobulin V-set domain

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Membrane
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of HHLA2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TMIGD2