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Protein

HERV-H LTR-associating protein 2

Gene

HHLA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Through interaction with TMIGD2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade.1 Publication

GO - Biological processi

  • positive regulation of activated T cell proliferation Source: UniProtKB
  • positive regulation of cytokine production Source: UniProtKB
  • T cell costimulation Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
HERV-H LTR-associating protein 2
Alternative name(s):
Human endogenous retrovirus-H long terminal repeat-associating protein 2
Gene namesi
Name:HHLA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:4905. HHLA2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei345 – 36521HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29278.

Polymorphism and mutation databases

BioMutaiHHLA2.
DMDMi74762781.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence analysisAdd
BLAST
Chaini23 – 414392HERV-H LTR-associating protein 2PRO_0000249709Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi90 – 901N-linked (GlcNAc...)Sequence analysis
Glycosylationi103 – 1031N-linked (GlcNAc...)Sequence analysis
Disulfide bondi159 ↔ 210PROSITE-ProRule annotation
Disulfide bondi243 ↔ 317PROSITE-ProRule annotation
Glycosylationi318 – 3181N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UM44.
PRIDEiQ9UM44.

Expressioni

Tissue specificityi

Expressed at high levels in colon, kidney, testis, lung and pancreas, and at lower levels in small intestine, liver and skeletal muscle. In immune cells, highly expressed in B-cells, dendritic cells and macrophages. Not detected in T-cells.2 Publications

Inductioni

Up-regulated in antigen-presenting cells in response to inflammation. Induced in dendritic cells in response to IFNG, poly(I:C) or heat-killed Listeria monocytogenes (at protein level).1 Publication

Gene expression databases

BgeeiQ9UM44.
CleanExiHS_HHLA2.
ExpressionAtlasiQ9UM44. baseline and differential.
GenevisibleiQ9UM44. HS.

Organism-specific databases

HPAiHPA029417.

Interactioni

Subunit structurei

Interacts with TMIGD2.1 Publication

Protein-protein interaction databases

IntActiQ9UM44. 1 interaction.
STRINGi9606.ENSP00000350402.

Structurei

3D structure databases

ProteinModelPortaliQ9UM44.
SMRiQ9UM44. Positions 36-227, 235-320.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini61 – 13171Ig-like V-type 1Add
BLAST
Domaini138 – 22285Ig-like C1-typeAdd
BLAST
Domaini235 – 32894Ig-like V-type 2Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IW89. Eukaryota.
ENOG410YQH2. LUCA.
GeneTreeiENSGT00700000104325.
HOGENOMiHOG000069994.
HOVERGENiHBG081600.
InParanoidiQ9UM44.
OMAiEVVIHWK.
PhylomeDBiQ9UM44.
TreeFamiTF331083.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003597. Ig_C1-set.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07654. C1-set. 1 hit.
PF07686. V-set. 2 hits.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
SM00406. IGv. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UM44-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKAQTALSFF LILITSLSGS QGIFPLAFFI YVPMNEQIVI GRLDEDIILP
60 70 80 90 100
SSFERGSEVV IHWKYQDSYK VHSYYKGSDH LESQDPRYAN RTSLFYNEIQ
110 120 130 140 150
NGNASLFFRR VSLLDEGIYT CYVGTAIQVI TNKVVLKVGV FLTPVMKYEK
160 170 180 190 200
RNTNSFLICS VLSVYPRPII TWKMDNTPIS ENNMEETGSL DSFSINSPLN
210 220 230 240 250
ITGSNSSYEC TIENSLLKQT WTGRWTMKDG LHKMQSEHVS LSCQPVNDYF
260 270 280 290 300
SPNQDFKVTW SRMKSGTFSV LAYYLSSSQN TIINESRFSW NKELINQSDF
310 320 330 340 350
SMNLMDLNLS DSGEYLCNIS SDEYTLLTIH TVHVEPSQET ASHNKGLWIL
360 370 380 390 400
VPSAILAAFL LIWSVKCCRA QLEARRSRHP ADGAQQERCC VPPGERCPSA
410
PDNGEENVPL SGKV
Length:414
Mass (Da):46,850
Last modified:May 1, 2000 - v1
Checksum:iD645383E1562F70E
GO
Isoform 2 (identifier: Q9UM44-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: MKAQTALSFF...IQNGNASLFF → MVMWNILKPR...HSHNISEWIS

Note: No experimental confirmation available.
Show »
Length:350
Mass (Da):39,614
Checksum:iCA8A5348FB81487D
GO

Sequence cautioni

The sequence BAA91323.1 differs from that shown. Reason: Erroneous termination at position 221. Translated as Trp.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti30 – 301I → T.
Corresponds to variant rs6779254 [ dbSNP | Ensembl ].
VAR_027487
Natural varianti344 – 3441N → K.
Corresponds to variant rs3792332 [ dbSNP | Ensembl ].
VAR_027488
Natural varianti364 – 3641S → R.
Corresponds to variant rs6779094 [ dbSNP | Ensembl ].
VAR_027489

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 108108MKAQT…ASLFF → MVMWNILKPRTHLLCMTNMF CTRHEGTDSTVFLPHSHNIS EWIS in isoform 2. 1 PublicationVSP_054729Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126162 mRNA. Translation: AAD48396.1.
AK000692 mRNA. Translation: BAA91323.1. Sequence problems.
AK296644 mRNA. Translation: BAG59244.1.
AC078855 Genomic DNA. No translation available.
AC135308 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79727.1.
CH471052 Genomic DNA. Translation: EAW79728.1.
BC035971 mRNA. Translation: AAH35971.1.
CCDSiCCDS46883.1. [Q9UM44-1]
CCDS63713.1. [Q9UM44-2]
RefSeqiNP_001269485.1. NM_001282556.1. [Q9UM44-1]
NP_001269486.1. NM_001282557.1. [Q9UM44-1]
NP_001269487.1. NM_001282558.1.
NP_001269488.1. NM_001282559.1. [Q9UM44-2]
NP_009003.1. NM_007072.3. [Q9UM44-1]
XP_005247137.1. XM_005247080.2. [Q9UM44-1]
UniGeneiHs.225968.
Hs.252351.

Genome annotation databases

EnsembliENST00000357759; ENSP00000350402; ENSG00000114455. [Q9UM44-1]
ENST00000467562; ENSP00000418345; ENSG00000114455. [Q9UM44-2]
ENST00000467761; ENSP00000419207; ENSG00000114455. [Q9UM44-1]
ENST00000489514; ENSP00000417856; ENSG00000114455. [Q9UM44-1]
ENST00000619531; ENSP00000482187; ENSG00000114455. [Q9UM44-1]
GeneIDi11148.
KEGGihsa:11148.
UCSCiuc003dwz.5. human. [Q9UM44-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126162 mRNA. Translation: AAD48396.1.
AK000692 mRNA. Translation: BAA91323.1. Sequence problems.
AK296644 mRNA. Translation: BAG59244.1.
AC078855 Genomic DNA. No translation available.
AC135308 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79727.1.
CH471052 Genomic DNA. Translation: EAW79728.1.
BC035971 mRNA. Translation: AAH35971.1.
CCDSiCCDS46883.1. [Q9UM44-1]
CCDS63713.1. [Q9UM44-2]
RefSeqiNP_001269485.1. NM_001282556.1. [Q9UM44-1]
NP_001269486.1. NM_001282557.1. [Q9UM44-1]
NP_001269487.1. NM_001282558.1.
NP_001269488.1. NM_001282559.1. [Q9UM44-2]
NP_009003.1. NM_007072.3. [Q9UM44-1]
XP_005247137.1. XM_005247080.2. [Q9UM44-1]
UniGeneiHs.225968.
Hs.252351.

3D structure databases

ProteinModelPortaliQ9UM44.
SMRiQ9UM44. Positions 36-227, 235-320.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9UM44. 1 interaction.
STRINGi9606.ENSP00000350402.

Polymorphism and mutation databases

BioMutaiHHLA2.
DMDMi74762781.

Proteomic databases

PaxDbiQ9UM44.
PRIDEiQ9UM44.

Protocols and materials databases

DNASUi11148.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357759; ENSP00000350402; ENSG00000114455. [Q9UM44-1]
ENST00000467562; ENSP00000418345; ENSG00000114455. [Q9UM44-2]
ENST00000467761; ENSP00000419207; ENSG00000114455. [Q9UM44-1]
ENST00000489514; ENSP00000417856; ENSG00000114455. [Q9UM44-1]
ENST00000619531; ENSP00000482187; ENSG00000114455. [Q9UM44-1]
GeneIDi11148.
KEGGihsa:11148.
UCSCiuc003dwz.5. human. [Q9UM44-1]

Organism-specific databases

CTDi11148.
GeneCardsiHHLA2.
HGNCiHGNC:4905. HHLA2.
HPAiHPA029417.
MIMi604371. gene.
neXtProtiNX_Q9UM44.
PharmGKBiPA29278.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IW89. Eukaryota.
ENOG410YQH2. LUCA.
GeneTreeiENSGT00700000104325.
HOGENOMiHOG000069994.
HOVERGENiHBG081600.
InParanoidiQ9UM44.
OMAiEVVIHWK.
PhylomeDBiQ9UM44.
TreeFamiTF331083.

Miscellaneous databases

GenomeRNAii11148.
PROiQ9UM44.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UM44.
CleanExiHS_HHLA2.
ExpressionAtlasiQ9UM44. baseline and differential.
GenevisibleiQ9UM44. HS.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003597. Ig_C1-set.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07654. C1-set. 1 hit.
PF07686. V-set. 2 hits.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
SM00406. IGv. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Endogenous retroviruses provide the primary polyadenylation signal for two new human genes (HHLA2 and HHLA3)."
    Mager D.L., Hunter D.G., Schertzer M., Freeman J.D.
    Genomics 59:255-263(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Colon and Ileal mucosa.
  3. "The DNA sequence, annotation and analysis of human chromosome 3."
    Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
    , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
    Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Kidney.
  6. Cited for: FUNCTION IN T-CELL COSTIMULATION, INTERACTION WITH TMIGD2, TISSUE SPECIFICITY, INDUCTION.

Entry informationi

Entry nameiHHLA2_HUMAN
AccessioniPrimary (citable) accession number: Q9UM44
Secondary accession number(s): B4DKN2, D3DN60, Q9NWQ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.