Q9HAP6 (LIN7B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein lin-7 homolog B
Short name=Lin-7B
Short name=hLin7B

Alternative name(s):
Mammalian lin-seven protein 2
Short name=MALS-2
Vertebrate lin-7 homolog 2
Short name=Veli-2
Short name=hVeli2

Gene names

Name:	LIN7B
Synonyms:	MALS2, VELI2
ORF Names:	UNQ3116/PRO10200

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	207 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells. May increase the amplitude of ASIC3 acid-evoked currents by stabilizing the channel at the cell surface By similarity. Ref.1
Subunit structure	Forms two exclusive ternary complexes with CASK and APBA1 or CASKIN1. Can also interact with other modular proteins containing protein-protein interaction domains like MPP5, MPP6, MPP7, DLG1, DLG2 and DLG3 through its L27 domain. Interacts with DLG4 and GRIN2B as well as CDH1 and CTNNB1, the channels KCNJ12/Kir2.2, KCNJ4/Kir2.3 and probably KCNJ2/Kir2.1 and SLC6A12/BGT-1 via its PDZ domain. The association of LIN7A with cadherin and beta-catenin is calcium-dependent, occurs at synaptic junctions and requires the actin cytoskeleton. Interacts with EGFR, ERBB2, ERBB3 and ERBB4 with both PDZ and KID domains. Associates with KIF17 via APBA1 By similarity. Interacts with ASIC3. Interacts with TOPK. Interacts with RTKN. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7
Subcellular location	Cell membrane; Peripheral membrane protein. Basolateral cell membrane; Peripheral membrane protein. Cell junction By similarity. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density; Peripheral membrane protein By similarity. Cell junction › tight junction By similarity. Cell junction › synapse › synaptosome By similarity. Note: Enriched in synaptosomes and at epithelial cell-cell junctions By similarity. Mainly basolateral in renal epithelial cells. Ref.1 Ref.4
Domain	The kinase interacting site is required for proper delivery of ERBB2 to the basolateral membrane By similarity. The PDZ domain regulates endocytosis and recycling of the receptor at the membrane By similarity. The L27 domain mediates interaction with CASK and is involved in the formation of multimeric complexes and the association of LIN7 to membranes By similarity.
Sequence similarities	Belongs to the lin-7 family. Contains 1 L27 domain. Contains 1 PDZ (DHR) domain.

Ontologies

Keywords
Biological process	Exocytosis Protein transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse Synaptosome Tight junction
Coding sequence diversity	Alternative splicing
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	exocytosis Inferred from electronic annotation. Source: UniProtKB-KW neurotransmitter secretion Inferred from electronic annotation. Source: Compara protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	basolateral plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic density Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW tight junction Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9HAP6-1)

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.

Isoform 2 (identifier: Q9HAP6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     77-146: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 207

207

Protein lin-7 homolog B

PRO_0000189626

Regions

Domain

10 – 65

56

L27

Domain

93 – 175

83

PDZ

Motif

1 – 13

13

Kinase interacting site By similarity

Natural variations

Alternative sequence

77 – 146

70

Missing in isoform 2.

VSP_042156

Experimental info

Sequence conflict

65

1

G → R in AI826082. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

207

Helix Strand Turn

Details...

Beta strand

93 – 97

5

Beta strand

105 – 108

4

Beta strand

110 – 114

5

Beta strand

118 – 122

5

Helix

127 – 131

5

Beta strand

139 – 143

5

Helix

153 – 162

10

Beta strand

165 – 171

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 63189D82706B9B00	FASTA	207	22,896
	10 20 30 40 50 60 MAALVEPLGL ERDVSRAVEL LERLQRSGEL PPQKLQALQR VLQSRFCSAI REVYEQLYDT 70 80 90 100 110 120 LDITGSAEIR AHATAKATVA AFTASEGHAH PRVVELPKTD EGLGFNIMGG KEQNSPIYIS 130 140 150 160 170 180 RVIPGGVADR HGGLKRGDQL LSVNGVSVEG EQHEKAVELL KAAQGSVKLV VRYTPRVLEE 190 200 MEARFEKMRS ARRRQQHQSY SSLESRG
	Isoform 2 [UniParc]. Checksum: E24A181A837542DD	FASTA	137	15,620
	10 20 30 40 50 60 MAALVEPLGL ERDVSRAVEL LERLQRSGEL PPQKLQALQR VLQSRFCSAI REVYEQLYDT 70 80 90 100 110 120 LDITGSAEIR AHATAKSVEG EQHEKAVELL KAAQGSVKLV VRYTPRVLEE MEARFEKMRS 130 ARRRQQHQSY SSLESRG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Basolateral membrane expression of the Kir 2.3 channel is coordinated by PDZ interaction with Lin-7/CASK complex." Olsen O., Liu H., Wade J.B., Merot J., Welling P.A. Am. J. Physiol. 282:C183-C195(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH KCNJ4 AND CASK (ISOFORM 1). Tissue: Kidney.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"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] (ISOFORMS 1 AND 2). Tissue: Brain and Testis.
[4]	"Polar expression of ErbB-2/HER2 in epithelia. Bimodal regulation by Lin-7." Shelly M., Mosesson Y., Citri A., Lavi S., Zwang Y., Melamed-Book N., Aroeti B., Yarden Y. Dev. Cell 5:475-486(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH EGFR.
[5]	"PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current." Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J. J. Biol. Chem. 279:46962-46968(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ASIC3.
[6]	"Identification of a cell polarity-related protein, Lin-7B, as a binding partner for a Rho effector, Rhotekin, and their possible interaction in neurons." Sudo K., Ito H., Iwamoto I., Morishita R., Asano T., Nagata K. Neurosci. Res. 56:347-355(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RTKN.
[7]	"The stardust family protein MPP7 forms a tripartite complex with LIN7 and DLG1 that regulates the stability and localization of DLG1 to cell junctions." Bohl J., Brimer N., Lyons C., Vande Pol S.B. J. Biol. Chem. 282:9392-9400(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MPP7.
[8]	"Solution structure of the PDZ domain from human LIN-7 homolog B." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 93-172.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF311862 mRNA. Translation: AAG34117.1.
AY358744 mRNA. Translation: AAQ89104.1.
AI826082 mRNA. No translation available.
BC027618 mRNA. Translation: AAH27618.1.

IPI

IPI00005566.

RefSeq

NP_071448.1. NM_022165.2.

UniGene

Hs.221737.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DKR	NMR	-	A	93-172	[»]

ProteinModelPortal

Q9HAP6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9HAP6. 1 interaction.

MINT

MINT-224720.

STRING

9606.ENSP00000221459.

PTM databases

PhosphoSite

Q9HAP6.

Polymorphism databases

DMDM

59798472.

Proteomic databases

PaxDb

Q9HAP6.

PRIDE

Q9HAP6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000221459; ENSP00000221459; ENSG00000104863.
ENST00000391864; ENSP00000375737; ENSG00000104863.

GeneID

64130.

KEGG

hsa:64130.

UCSC

uc002pmp.3. human.

Organism-specific databases

CTD

64130.

GeneCards

GC19P049618.

HGNC

HGNC:17788. LIN7B.

HPA

HPA046419.

MIM

612331. gene.

neXtProt

NX_Q9HAP6.

PharmGKB

PA134914453.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG320117.

HOGENOM

HOG000285929.

HOVERGEN

HBG052329.

InParanoid

Q9HAP6.

OMA

VLQSKFC.

OrthoDB

EOG4BK556.

PhylomeDB

Q9HAP6.

Gene expression databases

Bgee

Q9HAP6.

CleanEx

HS_LIN7B.

Genevestigator

Q9HAP6.

GermOnline

ENSG00000104863. Homo sapiens.

Family and domain databases

InterPro

IPR004172. L27.
IPR014775. L27_C.
IPR017365. Lin-7_homologue.
IPR001478. PDZ.
[Graphical view]

Pfam

PF02828. L27. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]

PIRSF

PIRSF038039. Lin-7_homologue. 1 hit.

SMART

SM00569. L27. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]

SUPFAM

SSF50156. PDZ. 1 hit.

PROSITE

PS51022. L27. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9HAP6.

GenomeRNAi

64130.

NextBio

66020.

SOURCE

Search...

Entry information

Entry name

LIN7B_HUMAN

Accession

Primary (citable) accession number: Q9HAP6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 15, 2005
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.